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Training to recognise the early signs of recurrence in schizophrenia

  1. Richard Morriss1,
  2. Indira Vinjamuri2,*,
  3. Mohammad Amir Faizal3,
  4. Catherine A Bolton4,
  5. James P McCarthy5

Editorial Group: Cochrane Schizophrenia Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 24 SEP 2012

DOI: 10.1002/14651858.CD005147.pub2


How to Cite

Morriss R, Vinjamuri I, Faizal MA, Bolton CA, McCarthy JP. Training to recognise the early signs of recurrence in schizophrenia. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD005147. DOI: 10.1002/14651858.CD005147.pub2.

Author Information

  1. 1

    University of Nottingham, Psychiatry, Nottingham, UK

  2. 2

    Mersey Care NHS Trust, Liverpool, UK

  3. 3

    Mersey Care NHS Trust, Psychiatry, Liverpool, UK

  4. 4

    Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

  5. 5

    Merseycare NHS Trust, Ferndale Unit, Liverpool, UK

*Indira Vinjamuri, Mersey Care NHS Trust, Broadoak Unit, Liverpool, L14 3PJ, UK. indira.vinjamuri@merseycare.nhs.uk. vinjamuriindira@hotmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Anzai 2002

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 9 weeks.

Design: parallel.

Setting: secondary care.
Country: Tokyo.


ParticipantsDiagnosis: schizophrenia (ICD-10 and DSM-IV).

N = 32.
Age: average ˜47 years (SD 11).
Sex: not reported.
History: persistent and refractory symptoms of psychosis and poor insight into their illness. Mean duration of the current hospitalisation 4 ± 4.3 years, mean duration of illness 20.5 ± 11.6 years.


Interventions1. Psychoeducation + TAU: CREP (Community Re-entry Program) includes identifying and keeping track of warning signs of relapse with a relapse prevention plan, group therapy, 18 one-hour sessions, twice a week (N = 16).

2. TAU + other: occupational rehabilitation activities (N = 16).


OutcomesSocial functioning: REHAB scale.

Unable to use:

Service use: re-hospitalisation (number not reported).
Mental state: PANSS (no mean and SD).

Knowledge: related to self management of illness, HOW (mean and SD not reported for the TAU group).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomised" no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"Before training started, two participants in the training group and one in the control group were discharged from the hospital. These patients were not included in calculations of the discharge rates". No further details provided.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskSmall sample size. Protocol not available. Source of funding not reported.

Bauml 2007

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 2 years*.

Design: parallel.
Setting: secondary care.
Country: Germany.


ParticipantsDiagnosis: Schizophrenia (DSM-III-R and ICD-9).

N = 101.
Age: average ˜34 years (SD 11).
Sex: M 51, F 50.
History: indication for an antipsychotic relapse prevention for a period of at least 12 months.


Interventions1. Psychoeducation + TAU: Patients had 4 weekly sessions of 60 minutes, then 4 more monthly sessions. Relatives were separately invited to 8 bi-weekly sessions of 90 to 120 minutes. Sessions were conducted by psychiatrists. Comprehensive information given about symptoms, aetiology, treatment, relapse prevention, etc. and individual crisis plans drawn up (N = 51).

2. TAU: maintenance therapy with antipsychotic medication, outpatient appointments (N = 50).


OutcomesService use: re-hospitalisation rate, (2-year follow-up reported in review, 7-year follow-up data available for a subgroup but not reported in review), time to re-hospitalisation**.
Mental state: BPRS.
Social functioning: GAF.

Quality of life: Lancashire quality of life profile (German).
Adverse events: death***.


NotesResults based only on Technical University of Munich study centre.

*48 participants also followed up at 7 years.

**Time to relapse was imputed using method 7 from Tierney 2007 (report presents P value and events on each arm and randomisation ratio is 1:1).

***1 suicide at 12-month follow-up in the intervention group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation of 8 to 12 patients, "the randomisation list for each study centre was generated by a computerised random sampling in the study evaluation centre".

Allocation concealment (selection bias)Low risk"The study centres could learn to which treatment condition the group was assigned via telephone".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"The treating study psychiatrists were blind to the randomisation".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNineteen patients excluded prior to index discharge and 34 patients dropped out during the 7-year follow-up. Missing patients were not included in the final analysis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Bradley 2006

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 12 months.

Design: parallel.
Setting: secondary care.
Country: Australia.


ParticipantsDiagnosis: Schizophrenia (DSM-IV).

N = 59*.
Age: Average ˜34 years (SD 8).
Sex: M 15, F 35.
History: number of previous episodes: treatment group mean 0.6 (SD 1.5), control group 0.29 (SD 0.86).


Interventions1. Psychoeducation + TAU: 26 sessions of multiple family group intervention for patients and families which involved recognising early warning signs, 26 sessions over 12 months (N = 25).

2. TAU: Regular appointments with case manager/doctor and individual psychosocial rehabilitation. Family contact (direct or on telephone) focused on psychoeducation, monitoring mental state and general support (N = 25).


OutcomesLost to follow-up.

Relapse**: rate of relapse, time to relapse.

Mental state: BPRS, SANS.

Social functioning: HONOS.

Quality of life: Quality of life scale.
Adverse events: death***.

Burden of care: FBIS (Family Burden Interview Schedule).

Unable to use -

Relapse**: time to relapse (hazard ratio not reported), duration (no mean and SD).


Notes*59 consumer-caregiver pairs. 34 pairs were English speaking and 25 were Vietnamese speaking.

**Relapse is defined as the reemergence of frank psychotic symptoms after a period of remission of such symptoms, persisting continuously for a minimum of 7 days and requiring intensive community treatment or hospital admission. Time to relapse was imputed using method 4 from Tierney 2007 (report presents HR and events on each arm and randomisation ratio is 1:1).

***1 participant in the treatment group died from a heroin overdose.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"randomised" - participants divided into English speaking and Vietnamese speaking, randomly allocated within their group by drawing names form a canister.

Allocation concealment (selection bias)Unclear risk"A staff member drew names from a canister and without looking at the names, assigned them to experimental and control groups".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Independent researchers, who were blind to study condition, conducted assessments".

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"Nine pairs did not complete the data collection procedure after treatment or at 18 months (four in the control group and five in the treatment group". Missing patients were not included in the final analysis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Buchkremer 1997

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 2 years*.

Design: parallel.
Setting: secondary care.
Country: Germany.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).

N = 191.
Age: average ˜ 31 years (SD 7).
Sex: M 111, F 80.
History: mean number of hospitalisations 4.7 (SD 3.6); at least two acute psychotic episodes within the past 5 years; at least 4 weeks of psychopathological stabilization.


Interventions1. Psychoeducational medication management (PMT) + TAU: all patients given detailed individualised information about schizophrenia and treatment; trained to recognize early symptoms, individual crisis schedules drawn up and medication management skills promoted. 10 sessions, first 5 at weekly intervals and 5 at fortnightly intervals (N = 32).

2. PMT + TAU + Key counselling (KC): Key-person counselling: relatives and carers were given information about schizophrenia and recognition of impending relapses, with coping strategies. 20 sessions (N = 35).

3. PMT + TAU + cognitive psychotherapy (CP): Cognitive psychotherapy: mediation of problem solving skills and improve coping strategies. 15 sessions, 7 sessions at weekly and 8 sessions at fortnightly intervals (N = 34).

4. PMT + TAU + CP + KP: (N = 33).

5. TAU: regular leisure time group activities. (N = 57).


OutcomesMental state: BPRS.

Service use: re-hospitalisation rate, time to re-hospitalisation**.
Social functioning: Global Assessment Scale (GAS).

Unable to use -

Mental state: SANS (no mean and SD).

Knowledge: Illness related attitudes - KK-Skala scale (no mean and SD).


NotesMulti-centre study: 7 centres in Germany.

* 126 participants also followed up at 5 years.

**re-hospitalisation is reported as 36 hour full hospitalisation or 5-day partial hospitalisation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" - initial homogeneity of the groups was ensured by applying a randomisation technique in which the prognostic factors of sex, Strauss-Carpenter prognosis score and medication compliance were balanced by preliminary matching; then randomly assigned to one of five groups with an allocation ratio of 1:1:1:1:2.

Allocation concealment (selection bias)Low risk"Randomisation was carried out by an independent institution".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskFor the outcome re-hospitalisation there was blinding: "Where necessary, rehospitalisation data were obtained directly from the pertaining psychiatric institutions with the consent of the patient. As the project staff had no influence on the re-hospitalisation decision, this is an independent outcome criterion. Referral to hospital was accordingly 'blind' with respect to allocation to one treatment condition".

Other outcome measurements were not blind: "data were recorded by trained project staff who were not blind with respect to the group to which the patients were assigned".

Incomplete outcome data (attrition bias)
All outcomes
Low risk"In a modified intention-to-treat approach all patients who had attended at least one group session were included in the main analysis"; "44 patients who were re-hospitalised or dropped out for other reasons during the period between randomization and the start of group treatment (2 to 6 months) had to be excluded. However, these patients were followed up as completely as possible."

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Chan 2007

MethodsAllocation: randomised.
Blinding: no details.
Duration: 12 months.
Design: parallel.
Setting: inpatient secondary care.
Country: Hong Kong.


ParticipantsDiagnosis: schizophrenia or schizo-affective disorder (DSM-IV).

N = 81.

Age: 18-63 years, mean: 35.82 years.

Sex: M 81.

History: not reported.


Interventions1. Psychoeducation + TAU: Transforming Relapse and Installing Prosperity (TRIP) programme to improve illness insight and health, ten 50-minute sessions over two weeks, includes relapse prevention plan development and symptom management (N = 44).
2. TAU + other: traditional ward occupational therapy of equivalent frequency and length, including a routine of work, rest and leisure activities (n = 37).


OutcomesService utilisation: Number of re-hospitalisations*.
Knowledge: Scale of Unawareness of Mental Disorder (SUMD)**.

Unable to use -

Short Form Health Survey (SF-36) questionnaire** (overall score not reported).

Time to relapse (unable to read data from curve).


Notes*Number of re-hospitalisations was classified as relapse in the study, but as service utilisation in our review.
**Translated to Chinese.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomly assigned", no further details reported.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
High riskNumber of patients randomised not reported. Data reported on treatment completers only.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available. Source of funding not reported.

Chen 2003

MethodsAllocation: randomised.

Blinding: double-blind.
Duration: 10 weeks, follow-up 1 year.

Design: parallel.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: schizophrenia (ICD-10 and CCMD-3).

N = 64.
Age: 15-55 years, average ˜31 years (SD 9).
Sex: M 35, F 28.
History: average length of illness: 7.12 ± 5.45 years (N = 32, intervention group)vs. 8. 03 ± 5.95 years (N = 32, control group).


Interventions1. Psychoeducation + TAU: teamwork education, medication management skills training module, symptom management skills training module. (N = 32).

2. TAU: antipsychotic therapy (N = 32).


OutcomesRelapse: relapse rate.

Service use: re-hospitalisation rate (hospital stay ≥ 4 weeks).
Mental state: PANSS;
Social functioning: SDSS (Social dysfunction screening scale), NOSIE, not employed (no work after discharge ≥ half a year).

Adverse events: lost to follow-up.

Knowledge: ITAQ (Insight and treatment attitude questionnaire)

Not used in the review:

MRSS (Morningside Rehabilitation Status Scale)


NotesAssessment of curative effect: based on PANSS scale score.
Relapse: score of items P2, P3 , P6 , G5 or G9 ≥ 5, or two of which ≥ 4.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using draw lots.

Allocation concealment (selection bias)Unclear riskNot stated.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"Double blind."

Incomplete outcome data (attrition bias)
All outcomes
Low riskOne person dropped out of the control group due to myocardial infarction. The reason for this is unlikely to be related to the true outcome.

Selective reporting (reporting bias)Low riskAll measured outcomes were reported.

Other biasLow riskNone obvious.

Chien 2004

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 18 months.

Design: parallel.
Setting: secondary care.
Country: Hong Kong.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 96*.
Age: average ˜42 years (SD 7).

Sex: M 128, F 72.

History: the relative with schizophrenia had no other mental illness, and the duration of the schizophrenia was 3 years or less at the time of recruitment.


Interventions1. Psychoeducation + TAU: 12 bi-weekly 2-hour sessions over 6 months by trained psychiatric nurses to educate, improve illness management including recognising early warning signs and improve coping skills, multiple family group intervention (N = 33).

2. TAU: routine psychiatric outpatient and family support services (N = 31).
3. TAU + mutual support: peer-led group for information, support and coping skills for caregiving, 12 bi-weekly 2-hour sessions over 6 months, and did not include the patients (N = 32).


OutcomesLost to follow-up.
Mental state: BPRS (Positive symptoms).
Social functioning: SLOF (Specific level of functioning scale).

Burden of care: FBIS (Family Burden Interview Schedule).

Not used-

Service use: mean number of re-hospitalisations.


Notes*96 families of out-patients with schizophrenia.

Data used only from interventions 1. and 2.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomised" - computer-generated random numbers table.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskClinic staff were blinded, blinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"An independent trained assessor (research assistant) undertook measurements at baseline (Time 1), 6 months (Time 2) and 18 months (Time 3), using a set of questionnaires. Both assessor and clinic staff were masked to treatment allocation".

Incomplete outcome data (attrition bias)
All outcomes
Low riskAnalysis of data was on an intention-to-treat basis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Drury 1996

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 9 months*.

Design: parallel.
Setting: secondary care.
Country: UK.


ParticipantsDiagnosis: schizophrenia (ICD-9).

N = 62**.
Age: average ˜30 years (SD 9)
Sex: M 25, F 15.

History: mean number of previous episodes: treatment group 3.5 (SD 3.5), control group 3.0 (SD 2.7).


Interventions1. Psychoeducation + TAU: four individual and group cognitive therapy, and family engagement. Cognitive therapy involved individual and group procedures including early warning signs recognition and strategies for coping (N = 30).

2. TAU: care of psychiatrist + recreation and informal support (N = 32).


OutcomesLost to follow-up*.

Mental state: PAS (Psychiatric assessment scale)*.

Unable to use:

Mental state: self report measure of delusional conviction (no mean and SD).


Notes*Usable data reported after 12 weeks of treatment.

**Demographic data given only for participants completing the study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Prescribing clinicians were blind to group allocation", blinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"All patients were rated by the first author and a random subset of patients were blindly rated by MB and JFM".

Incomplete outcome data (attrition bias)
All outcomes
High risk22 patients were excluded after randomisation and not included in the final analyses.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskSmall sample size. Protocol not available. Source of funding not reported.

Garety 2008

MethodsAllocation: randomised.

Blinding: single blind.
Duration: 24 months.
Design: parallel.

Setting: secondary care.

Country: UK


ParticipantsDiagnosis: non-affective psychoses (ICD-10 or DSM-IV).

N = 301.

Age: 18-65 years.

Sex: M 211 F 90.

History: Patients with recent relapse, whether or not they had been admitted.


InterventionsThere were two randomisation pathways:

Patients without carers:

1. CBT + TAU: Cognitive behavioural therapy focused on relapse prevention including pragmatic relapse prevention plan and identification of early signs, 12-20 sessions over nine weeks,  (N = 106)
2. TAU (N = 112)

Patients with carers:

1. CBT + TAU: Cognitive behavioural therapy focused on relapse prevention including pragmatic relapse prevention plan and identification of early signs, 12-20 sessions over nine weeks,  (N = 27)
2. TAU (N = 28)

3. Family Intervention + TAU: Family intervention focused on relapse prevention including how family members might understand warning signs, 12-20 sessions over nine weeks, (N = 28)


OutcomesRate of relapse*.
Mental state: PANSS.
Social functioning: Time-budget interview, SOFAS (Social and Occupational Assessment Scale)
Quality of Life: EuroQol
Adverse events: death, suicide attempts, violent incidence, lost to follow-up.

Not used-

Mental health: BDI (Beck Depression Inventory), BAI (Beck Anxiety Inventory).

Days on hospital and number of admissions.
Unable to use -

PSYRATS (Psychotic Symptom Rating Scale) (reported on two subscales).


Notes*Measured in a subgroup of participants that relapsed after partial or full remission.

Protocol: ISRCTN83557988.

For the patients with carers pathway, data for the TAU group were split in two in the analyses: total number of participants were divided and the means and standard deviations remained the same.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomisation schedules were independently generated by a trial randomisation service in a separate location from all trial centres using randomised permuted blocks"

Allocation concealment (selection bias)Low riskCentral randomisation "Randomisation schedules were independently generated by a trial randomisation service"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Trial research assessors were independent of treatment delivery and every effort was made to ensure they were kept masked to allocation" "Patients were reminded by the assessors not to talk about treatment allocation". "The primary outcome variable, relapse, was assessed by masked panel evaluation"

Incomplete outcome data (attrition bias)
All outcomes
Low risk96% followed up for primary outcome data, secondary outcome data were available for 82% of the total sample at 12 months and for 80% at 24 months. No reasons for losses reported.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasLow riskProtocol pre-published (ISRCTN83557988). Source of funding: Wellcome Trust.

Granholm 2005

MethodsAllocation: randomised.
Blinding: single blind.

Duration: 6 months.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 76.
Age: average ˜54 years (SD 7).
Sex: M 56, F 20.

History: not reported.


Interventions1. Psychoeducation + TAU: 24 weekly 2 hour group cognitive behavioural therapy sessions, including early detection and management of symptoms (N = 37).

2. TAU: ongoing care as usual (N = 39).


OutcomesLost to follow-up.

Unable to use -

Mental state:PANSS (Positive and negative syndrome scale); HDRS (Hamilton Depression Rating Scale); Beck Cognitive insight scale (mean and SD not reported).

Social functioning: Independent Living Skills Survey; UCSD performance based skills assessment; coping skills (mean and SD not reported).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"randomised" - sequential list of random numbers.

Allocation concealment (selection bias)Unclear risk"The project coordinator assigned participants to treatments in the order that they consented, and the coordinator was the only staff person other than therapists with knowledge of group membership".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe assessors were blinded to treatment group.

Incomplete outcome data (attrition bias)
All outcomes
Low risk"Intent-to-treat analyses were used to examine all outcome variables".

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskProtocol not available.

Gumley 2003

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 12 months.

Design: parallel.
Setting: secondary care.
Country: UK.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 144.
Age: average ˜36 years (SD 10).
Sex: M 66. F 134.

History: receiving antipsychotic medication, prone to relapse.


Interventions1. Psychoeducation + TAU: clinical psychologist provided CBT, 5-session engagement phase and intensive targeted phase of 2-3 sessions per week at the appearance of relapse. Individualised case formulation of the cognitive behavioural factors associated with relapse, an idiosyncratic early signs questionnaire incorporating these factors was developed (N = 72).

2.TAU: Treatment overseen by consultant psychiatrist for ongoing medication, regular reviews, follow-up from a community mental health nurse (N = 72).


OutcomesLost to follow-up.

Relapse*: relapse number, time to relapse.

Service use: Re-hospitalisation rate.
Mental state: PANSS positive, PANSS negative.

Unable to use -

Service use: time to re-hospitalisation.

Mental state: Personal beliefs about Illness questionnaire (overall score not reported); Brief symptom inventory (only baseline data reported).

Social functioning: Social Functioning Scale (overall score not reported).


Notes*Increase in participant's self-reported early signs, failure to return questionnaire more than once, treating team reported symptom changes or circumstances/stressors suggestive of relapse. Time to relapse data was log transformed.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Patient randomised according to predetermined envelopes containing the treatment group, devised by researcher, which was unbeknown to the assessors, therapist or participants".

Allocation concealment (selection bias)Unclear risk"A member of the research team opened an envelope that informed as to which group individual participants were to be allocated. Another member of the team witnessed this procedure, and the envelope was placed in the participant's case file".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
High risk"Two research nurses, who were not blind to the treatment allocation of participants, conducted follow-up assessments".

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll data analysed on an intention-to-treat basis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Harris 2009

MethodsAllocation: Cluster randomised, community health professional unit of randomisation.

Blinding: Not blinded.

Duration: 9 months.

Design: Parallel.
Setting: Mental health trusts.
Country: England.


ParticipantsCommunity mental health professionals (CMHPs) with caseloads of service users (SU) with a diagnosis of schizophrenia (DSM-IV).

CMHP
N = 28 pairs; service users N = 169.
Age: CMHP – Experimental : 39, Control: 40; SU -  Experimental : 44, Control: 41.4  

Sex: CMHP : 20 male, 36 female; SU:  96 male, 73 female.

History: SU length of illness – Experimental : 17.25 years, Control: 12 years  


Interventions1. Experimental medication management training programme, including early warning signs work and relapse prevention, (N = 28 CMHP; N = 88 SU).

2. Waiting list (N = 28 CMHP; N = 81 SU).


OutcomesMental state: KGV (M) Version 6.

Social functioning scale: SFS.

Knowledge: Drug attitude inventory (DAI).

Satsifaction with care: The Californian Psychopharmacology Alliance Scale (CALPAS).

Unable to use-

Leaving the study early (number lost from each group not reported).

Not used-

Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).


NotesResults adjusted for clustering: "Based on experience of similar studies with process outcomes a value of 0.05 was assumed for the ICC."


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Service users were randomly selected from each CMHP’s sample frame to form their ‘study caseload’ before CMHPs were randomised to either the training programme or training waiting list." Does not report method of randomisation.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
High risk“There was no ‘blind’ assessment of service user level outcomes.”

Incomplete outcome data (attrition bias)
All outcomes
Low risk6 CMHPs withdrew from the study, 3 that had been randomised to the intervention and 3 randomised to the control group. "34 [service users] withdrew from the study and 12 were lost to follow-up"; 16 from the intervention group and 30 from the control group.

Intention-to-treat analysis used.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasLow riskNone obvious.

Herz 2000

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 18 months.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).

N = 82.
Age: average ˜29 years (SD 9)
Sex: M 53, F 29.

History: increased risk for relapse (at least 1 hospitalisation in past 3 years or 2 or more lifetime hospital admissions).


Interventions1. Psychoeducation + TAU: 5 components of PRP (Program for relapse prevention): education for patients and family about relapse and recognizing prodromal symptoms and behaviours, active monitoring of prodromal symptoms by team, immediate clinical intervention within 24 to 48 hours, supportive group/individual therapy improving coping skills, multifamily psychoeducation (N = 41).

2. TAU: individual supportive therapy and medication management biweekly for 15-30 min (N = 41).


OutcomesRelapse*: relapse rate, time to relapse.

Service use: re-hospitalisation rate.

Unable to use -

Mental state: PANSS; Early Signs Questionnaire (no mean and SD).

Social functioning: GAS (no mean and SD).


Notes*defined as increase in any PANSS to moderately severe or higher and a GAS score of 30 or less. Time to relapse data was log transformed.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"randomised" - computer-generated cards.

Allocation concealment (selection bias)Low riskSealed envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Assessments were done by research interviewers who were master's-level mental health professionals, blinded as to patient group assignment, not associated with clinical care and instructed not to inquire about a patient's treatment during interviews".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe study did not address this outcome.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Hogarty 1997a

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 3 years.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia.

N = 97.
Age: average ˜28 years (SD 7).
Sex: M 56, F 41.

History: not reported.


Interventions1. Personal therapy + TAU: taught awareness of one's own individual prodromes of psychosis (N = 23).

2. Family psychoeducation/management (family therapy) + TAU: included the three broad phases of joining, survival skills training and reintegration within the home, and reintegration into the community (N = 26).
3. Personal therapy + family therapy + TAU: (N = 26).
4. TAU: supportive therapy, active listening, correct empathy, reassurance (N = 24).

Treatment sessions were 30-45 min weekly for about 3 years. Personal and family therapy patients also received 1.9 additional monthly medication management sessions in years 1 and 2, and an additional 1.3 sessions each month in year 3.


OutcomesRelapse*: rate of relapse.

Unable to use -

Time to relapse: defined as also including early treatment termination.

Service use: re-hospitalisation rate (only reported for patients who had relapse episodes).
Mental state: BPRS; Raskin negative symptom scale; Covi anxiety scale; Wing negative symptom scale (no mean and SD).
Social functioning: GAS (no data for TAU group).


Notes*Defined as mild or less to greater than mild on two or more of the four psychotic symptoms on the BPRS or a 2 point increase on one or more severe symptoms + decrease of 10 points or more on GAS.

Data for intervention groups 1, 2 and 3 were combined.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot intention-to-treat: "Since missing data were relatively few and not different among treatment conditions, only the data collected were analysed."

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Horan 2009

MethodsAllocation: randomised.

Blinding: no details.

Duration: 6 weeks.

Design: parallel.

Setting: outpatient secondary care.

Country: USA.


ParticipantsDiagnosis: schizophrenia or schizoaffective disorder (DSM-IV).

N = 34.

Age: mean age social cognition: 50.7; mean age control (relapse prevention): 45.9 years.
Sex: social cognition: 87% M; control (relapse prevention): 100% M.

History: Clinically stable outpatients with no psychiatric hospitalisations in the past 6 months and the same antipsychotic medication for previous 3 months.


Interventions1. Social cognition: social skills training (N = 17)
2. Control*: illness self-management and relapse prevention skills including identifying and managing warning signs of relapse (n = 7).
Both programmes consisted of 12 one-hour groups that met twice weekly.


OutcomesLoss to follow-up
Unable to use -
Mental state: BPRS (total scores not reported)

Satisfaction with treatment (not validated scale)

Not used -

Facial Emotion Identification Test, Half-profile of Nonverbal Sensitivity, Ambiguous Intentions Hostility Questionnaire, The  Awareness of Social Inference Test , MATRICS Consensus Cognitive Battery (MCCB): cognitive performance


Notes*EWS training was the control group, social skills the intervention.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomly assigned", no further information.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThree participants out of 34 dropped out.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskProtocol not available. Source of funding:  US Mental Illness Research, Eduation and Clinical Center.

Kopelowicz 1998a

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 1 month.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 70*.
Age: average ˜35 years (SD 11).
Sex: M 42, F 17.
History: mean duration of illness 12 years (SD 9).


Interventions1. Psychoeducation + TAU: (CREP) community re-entry programme: eight sessions each 45 minutes, in groups, twice a day, four days a week schedule, over 2 weeks.; including teaching patients early warning signs of relapse (N = 28).

2. TAU+ other: occupational therapy sessions conducted by certified therapists (N = 31).


OutcomesLost to follow-up.

Unable to use -

Knowledge and performance of skills (no mean and SD).


Notes*Data were reported on 59 subjects that completed participation, defined as attending at least four sessions.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomised" -no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskData reported on treatment completers only.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskProtocol not available. Source of funding not reported.

Kopelowicz 2003

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 9 months.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 92.
Age: average ˜38 years (SD 11).
Sex: M 62, F 30.

History: not reported.


Interventions1. Psychoeducation + TAU: skills training groups met for 90-minute sessions four times per week for 3 months. Skills training for patients and relatives included medication management and symptom management (identification and intervention of early warning signs) (N = 45).

2. TAU: monthly psychiatric visits for medication management and case management by social workers (N = 47).


OutcomesLost to follow-up.

Service use: re-hospitalisation rate.
Mental state: PANSS.
Social functioning: ILSS (Independent Living Skills Survey).

Medication compliance.

Unable to use -

Quality of life: Quality of life interview (no data).

Knowledge: Skill acquisition and generalisation (no overall scores).

Burden of care: FBIS (no SD).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" -no further details.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"All of the raters were blind to the treatment condition of the patients and relatives", "to ensure blindness the raters were instructed to remind patients and relative subjects at each visit to not disclose what kinds if treatment they were receiving".

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"Baseline comparisons were conducted with all 92 subjects who were randomised, but all subsequent analyses included only those subjects who were assessed at all three time points".

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Kuipers 1997

MethodsAllocation: randomised.
Blinding: not blind.
Duration: 9 months.

Design: parallel.
Setting: secondary care.
Country: UK.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 60.
Age: average ˜40 years.
Sex: M 38, F 22.
History: at least one current positive psychotic symptom that was distressing, unremitting, and medication resistant.


Interventions1. Psychoeducation + TAU: 9 months of individual CBT weekly or fortnightly, individual CBT included discussion of relapse signatures, trigger identification and seeking help (N = 28).

2. TAU: case management and medication, including involvement of a key worker (N = 32).


OutcomesLost to follow-up.

Mental state: BPRS.

Economic burden (cost of care).

Unable to use -

Mental state: Insight; BDI; BAI; Beck Hopelessness Scale; NART; Quick test (no data).

Social functioning: SFS (Social Functioning Scale) (no data).

Satisfaction of care: Satisfaction with therapy questionnaire (results not reported for TAU group).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised permuted blocking, block size of six.

Allocation concealment (selection bias)Low riskCarried out by the trial statistician.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"In a trial of psychological treatment it is extremely difficult to make assessments that are totally blind to the treatment condition and this was not attempted. However, all assessments were carried out by independent research workers who were not involved in the treatments".

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk'Decision to treat' analysis using the standard 'carry forward' method to impute missing values reported.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasHigh riskProtocol not available. Charitable donation from Janssen Pharmaceutica.

Li 2003

MethodsAllocation: cluster-randomised (ward unit of randomisation).
Blinding: not reported.
Duration: 9 months.

Design: parallel.
Setting: secondary care.
Country: Hong Kong.


ParticipantsDiagnosis: schizophrenia (CCMD-II-R).

N = 101.
Age: experimental group 16-61 years, mean age 32.9 (SD 9.7); control group 15-49 years, mean 32.2 (SD 8.9)
Sex: M 43, F 58 .
History: number of hospitalisations ranged from first to sixth time, duration of illness ranged from 0 to 21 years.


Interventions1. Comprehensive patient/family education guide (CP/FEG): Nurse initiated patient/family education strategy. 8 hours with patients, 36 hours with families in hospital, then 2 hours per month for 3 months. Included early warning signs of relapse and responding to early warning signs training for families (N = 46, 4 wards).

2. TAU (N = 55, 4 wards).


OutcomesRelapse rate.

Re-hospitalisation rate.

Pychotic symptoms of patient: Chinese version of the BPRS (Zhang 1998).

Social functioning: Chinese version of the NOSIE (measured at discharge) and GAS (Zhang 1998).

Knowledge (of relative): Chinese version of Knowledge about Schizophrenia Interview (KASI) (Tsang, Chan & Tam 1999).

Burden of care: FAS.

Medication compliance.


NotesResults not adjusted for randomisation. ICC of 0.1 used to impute data.

Relapse defined as re-hospitalisation, recurrence of schizophrenic symptoms or a marked increase in the number or intensity of symptoms measured by a BPRS score of 5 or above on the relapse scale indicating exacerbation of the illness.

EWS part of training only delivered to family.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Random assignment", no further details reported.

Allocation concealment (selection bias)Unclear riskNo details reported.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo details reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThere were 10 dropouts in the experimental group and 22 dropouts in the control group.

Selective reporting (reporting bias)Unclear riskNumber of participants for the outcome burden of care (FAS) not reported.

Other biasUnclear riskNone obvious.

Liberman 1998

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 2 years.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia.

N = 84.
Age: 37.1 years (SD 8.8).
Sex: M 84.
History: outpatients with persistent and unremitting forms of schizophrenia.


Interventions1. Social skills training: UCLA Social and Independent Living Skills Program consisting of basic conversation, recreation for leisure, medication management, and symptom management, including Identifying warning signs of relapse and developing a relapse prevention plan, over 6 months, 3 hours per day, 4 days a week (N = 42)*.

2. Psychosocial occupational therapy: expressive, artistic, and recreational activities that mediated supportive therapy in groups and individually, over 6 months, 3 hours per day, 4 days a week (N = 42)*.


OutcomesMental state: BPRS**

Social functioning: Independent Living Skills Survey (ILSS)**

Social functioning: Global Assessment Scale (GAS)**

Adverse events: Lost to follow-up*

Quality of life: Lehman Quality of Life Scale (LQoLS)**

Not used in the review-

Profile of Adaptation to Life subscales

Rosenberg Self-Esteem Scale

Brief Symptom Inventory (BSI)

Social Activities Scale (SAS) (not a validated scale)


Notes*Total included participants for each group was not clearly reported "assigned half to psychosocial occupational therapy and half to skills training", assumed this to be 42 in each treatment group.

**Data reported for 80 participants at 2 years follow-up, number in each group not reported, assumed to be 40 in each group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised "Cohorts of 10–12 outpatients with persistent and unremitting forms of schizophrenia were entered into the study through a randomization procedure".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskBlinding of outcome assessors "psychiatrists were blind to the psychosocial treatment assignment", "Blindness of the assessors was promoted by geographically distancing the treatment program from the locales for pharmacotherapy and ratings of outcome and by repeatedly instructing the subjects to refrain from mentioning their psychosocial treatment".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskTotal included participants for each group was not clearly reported. "Attrition was minimal; only 14 of 84 subjects dropped out during the 2-year period (four in the control group and 10 in the social skills training group; x2 = 2.44, df = 1, P = 0.12). Almost all of the dropouts were accounted for by individuals moving to new geographical areas of the state or country and becoming unavailable for assessments."

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasLow riskFunded by Department of Veterans Affairs and NIMH.

McDonell 2006

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 3 years.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia, schizoaffective disorder, other psychotic disorders (DSM-IV).

N = 97*.
Age: average ˜32 years (SD 9).

Sex: M 74, F 21.

History: mean illness duration ˜10 years (SD 8.5).


Interventions1. Psychoeducation + TAU: multiple-family group treatment delivered by two clinicians to groups of 5-8 families over 2 years, including early warning signs work and relapse prevention, 24 sessions in year 1 and 12 sessions in year 2 (N = 53).

2. TAU: outpatient services, medication management and case management (N = 44).


OutcomesService use: re-hospitalisation rate*.

Unable to use -

Mental state: BPRS; MSANS (Modified scale for the assessment of negative symptoms) (only baseline data reported).

Burden of care: care givers' social support (no mean and SD).

Economic outcomes: Inpatient and outpatient service utilisation (no SD).


Notes*Demographic data not reported for 2 participants.

**Community hospitalisation when imminent danger to oneself or others, grave disability, or medically necessary. State hospitalisation when need for long-term care not possible at a community hospital or direct referral from the justice system.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation of participants conducted by (1) separating participants on the basis of 'atypical v conventional medication at status; (2) assigning a number and (3) pulling a piece of paper with the number from a hat giving a 50% chance of being in either group.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData analysed on an intention-to-treat basis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Merinder 1999

MethodsAllocation: randomised.
Blinding: single blind.
Duration: 1 year.

Design: parallel.
Setting: secondary care.
Country: Denmark.


ParticipantsDiagnosis: schizophrenia (ICD-10, OPCRIT).

N=46.
Age: average ˜36 years (SD 35).
Sex: M 24, F 22.

History: 8.2 years with a median of five earlier admissions.


Interventions1. Psychoeducation + TAU: 8 session psychoeducation programme for patients and relatives including sessions called "Stress and early signs of relapse, emergency plan" and "What can you and your family do about it?", 8 weekly sessions separately for patients and relatives (N = 23).

2. TAU+ other: pharmacological intervention, psychosocial rehabilitation, supportive psychotherapy (N = 23).


OutcomesLost to follow-up.

Rate of relapse, time to relapse*.

Rate of re-hospitalisations**

Mental state: BPRS.
Social functioning: GAF (Global Assessment of Function).

Satisfaction with care: VSSS (Verona Service Satisfaction scale).

Knowledge: Insight scale***.

Unable to use -

Relapse*: time to (no hazard ratio).

Knowledge of schizophrenia scale (not validated scale).

GCSI (Global Clinical Assessment of Severity of Side Effects; results not reported for separately for treatment groups).


Notes*3 levels rated: Type 1- aggravation of symptoms without change of treatment; Type 2- aggravation of symptoms with change in medication, Type 3- aggravation of symptoms with admission to hospital. Time to relapse was imputed using method 7 from Tierney 2007 (report presents P value and events on each arm and randomisation ratio is 1:1).

**Re-hospitalisation rate was added to the analysis as the number of participants with Type 3 relapse.
***Translated to Danish.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskPatients were block randomised, stratified for gender and for illness duration.

Allocation concealment (selection bias)Unclear riskRandomisation by an independent institution, no further details provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"The ratings of psychopathology and psychosocial function were performed by researchers not involved in the intervention and not informed of the treatment allocation".

Incomplete outcome data (attrition bias)
All outcomes
Low riskData analyses on an intention-to-treat basis.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasHigh riskProtocol not available. Part funded by Lunbeck A/S, Denmark.

Norman 2002

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 1 year.

Design: parallel.
Setting: secondary care.
Country: Canada.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).

N = 130*.
Age: Average ˜34 years (SD 9).
Sex: M 81, F 40.

History: clinically stable.


Interventions1. Psychoeducation + TAU: 12 weeks of group sessions+ 12 individual sessions emphasizing on three aspects of stress management. Stress management program included 12 aspects, one of which included recognition and reporting any increase in symptoms and learning to recognise and avoid situations that trigger symptoms. (N = 64).

2. TAU: social activities programme, including mutual support and recreational activities (N = 66).


OutcomesLost to follow-up.

Service use: Re-hospitalisation rate.

Unable to use -

Mental state: SAPS; SANS (no SD).

Social functioning: Life Skills Profile (no SD).


Notes* Demogaphic data reported for participants completing the study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants were randomly assigned within matching by gender and number of previous hospitalisations, no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskData was collected by psychiatrists who "were not responsible for the clinical care of the relevant clients and were kept blind as to the assignment of clients to the stress management or social activities conditions".

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"Nine clients were lost to follow-up (five did not complete the intervention and four were unavailable for 1 year post-test assessments), leaving a net sample of 121 clients, 60 of whom were assigned to the stress management condition and 61 to the social activities. Because of sporadic instances of missing data, analyses are based on sample sizes varying between 112 and 121".

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Shin 2002

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 10 weeks.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 48.
Age: Average ˜38 years (SD 8).
Sex: M 20, F 28.
History: not reported.


Interventions1. Psychoeducation + TAU: 90 minutes long, 10 weekly group therapy. Culturally sensitive psychoeducational group program (including early warning signs recognition and relapse prevention) and individual supportive therapy and family work. (N = 24).

2. TAU: individual supportive therapy (N = 24).


OutcomesLost to follow-up.

Mental state: BPRS.


NotesAll sessions and outcome measures were conducted in Korean.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"The BPRS was completed before and after the intervention in Korean by a bilingual Korean psychiatrist, who was blinded to participants' treatment modality [...] the other scales were verbally presented to the study participants by the first author in Korean and self-report answers were written down by the participants".

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients accounted for.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskProtocol not available. Source of funding not reported.

Shon 2002

MethodsAllocation: randomised.
Blinding: unclear.
Duration: unclear, 12 sessions.

Design: parallel.
Setting: secondary care.
Country: Korea.


ParticipantsDiagnosis: schizophrenia, delusional disorders, mood disorders (DSM-IV).

N = 40*.
Age: average ˜32 years (SD 8).
Sex: M 22, F 16.
History: not reported.


Interventions1. Psychoeducation + TAU: medication compliance and symptom management program consisting of 12 sessions, each lasting 70 minutes and included developing skills to recognize symptoms and effective methods of preventing relapse (N = 18).

2. TAU: standard psychiatric treatment post discharge (N = 20).


OutcomesLost to follow-up.

Unable to use -

Mental state: Relapse symptom measurement (not validated scale).

Medication compliance: Medication use scale; Scale for family support in medication compliance (not validated scales).


Notes*Two participants were excluded from the experimental group during the randomisation process.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomised" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe study does not address this outcome.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskProtocol not available.

Tait 2002

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 10 months*.

Design: parallel.
Setting: secondary care.
Country: UK.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 20.
Age: average ˜39 years.
Sex: M 14, F 6.
History:


Interventions1. Psychoeducation + TAU: initial engagement and formulation for 5 one-hour sessions, early signs monitoring fortnightly for 10 months, targeted cognitive therapy intensively for a brief period, about 2-3 sessions per week (N = 9).

2.TAU: routine appointments with psychiatrist and key worker (CPN, social worker or OT) (N = 11).


OutcomesRelapse**: relapse rate.

Unable to use -

Mental state: Early signs monitoring; PANSS (no data).


Notes*Average follow-up 10 months (range from 5-13 months).

**Relapse defined as i) significant increase in early signs; ii) presence of relevant psychosocial factors associated with previous relapses; iii) non return of early sings monitoring questionnaires.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomised" - no further details.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"The mean postal response rate of ESM questionnaires [...] is 83%". No further details provided.

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasUnclear riskSmall sample size. Protocol not available.

Turkington 2006

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 1 year.

Design: parallel.
Setting: secondary care.
Country: UK.


ParticipantsDiagnosis: schizophrenia (ICD-10).

N = 422.
Age: Average ˜40 years.
Sex: M 325, F 97.
History: ongoing positive and/or negative symptoms or at risk of relapse.


Interventions1. Psychoeducation + TAU: community psychiatric nurse delivered 6 hour-long sessions over 2-3 months, carers offered 3 sessions. CBT including symptom management and relapse prevention (N = 257).

2. TAU: care of community mental health teams (N = 165).


OutcomesTime to first relapse*.

Unable to use -

Mental state: Comprehensive psychopathological rating scale; Schizophrenia change scale, Montgomery and Asberg rating scale (no SD).
Insight: Insight rating scale (no SD).

Burden of care: Burden of care questionnaire (no SD).


Notes*Time to relapse was imputed using method 3 from Tierney 2007 (report presents HR and CIs).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation conducted by computer-generated blocks of 6 random numbers and stratified by site.

Allocation concealment (selection bias)Low riskResults of the randomisation placed in sealed envelopes and only opened at the time of treatment allocation.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskRaters were independent. Patients were "asked not to reveal or even hint at their treatment allocation to the raters. Raters were informed that some study material would be left with TAU patients to help preserve the blindness of the ratings".

Incomplete outcome data (attrition bias)
All outcomes
Low riskData analysed on an intention-to-treat basis.

Selective reporting (reporting bias)High riskNot all expected outcomes reported.

Other biasHigh riskProtocol not available. Trial funded by a research grant from Pfizer.

Van Meijel 2006

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 1 year.

Design: parallel.
Setting: secondary care.
Country: Netherlands.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 95.
Age: average ˜35 years.
Sex: M 65, F 30**.
History: mean number of previous episodes: treatment group 4.4, control group 3.8.


Interventions1. Psychoeducation + TAU: Relapse prevention plan with patient and carers, early signs are systematically inventoried and recognition assisted, followed by an action plan (pure early warning signs work). 4 phases: preparatory phase, listing of early warning signs, monitoring of the early signs, preparation of an action plan (N = 51).

2. TAU: care as usual (N = 44).


OutcomesRelapse*: relapse rate, time to relapse.

Unable to use -
Mental state: PANSS (no SD); CGI (no data).
Knowledge: Insight scale (no mean and SD).

Satisfaction with care: Working Alliance Inventory (no mean and SD).


Notes*Relapse defined as a significant increase in i) delusions, ii) hallucinations, iii) disorganisation of thinking, iv) chaotic or aggressive behaviour; 6 or higher on CGI; symptoms had to be present for at least 7 days. Time to relapse was imputed using method 7 from Tierney 2007 (report presents P value and events on each arm and randomisation ratio is 1:1).

**Demographic data only reported for participants completing the study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation of nurses (therapists) and patients, nurses were divided at random per department between experimental and treatment conditions. A researcher determined at random the order in which the patients would be approached for participation.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"11 patients dropped out from the experimental group and 2 from the control group. The reasons for dropping out of the experimental group were: premature discharge (n = 1); stress caused by preparing the relapse prevention plan (n = 2); psychotic relapse (n = 1); lack of motivation to prepare the relapse prevention plan (n = 5); and lack of time of the nurses (n = 2). The reason for dropping out of the control group was completion of the treatment (n = 2).

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasHigh riskProtocol not available. Financial support in part from Eli Lilly The Netherlands.

Vreeland 2006

MethodsAllocation: randomised.
Blinding: single-blind.
Duration: 24 weeks.

Design: parallel.
Setting: secondary care.
Country: USA.


ParticipantsDiagnosis: schizophrenia (DSM-IV).

N = 74.
Age: average not reported, range 35 to 64 years.
Sex: M 33, F 41.
History: not reported.


Interventions1. Psychoeducation + TAU: (Team Solutions Program): groups met twice a day, two days per week, for 24 weeks including education and management of illness, one session covering preventing relapse and crisis resolution (N = 40).

2. TAU + other: Day treatment: prevocational work areas, recreational groups, social skills training, psychoeducational groups (N = 34).


OutcomesMental state: PANSS positive and PANSS negative.
Social functioning: GAF-DIS (Global Assessment of Functioning-Disability Scale).

Satisfaction with care: IAPSRS (International association of psychosocial rehabilitation services).

Knowledge: KASQ.

Unable to use -

Mental state: CGI (no overall scores).

Quality of life: PGWB (Psychological general well-being scale) (no overall scores).

Knowledge: TSCKAS (not validated scale).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation of participants based on a table of random numbers.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Trained raters who were blind to the study group assignment conducted interviews with participants to complete outcome measures at baseline, eight weeks and 24 weeks".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThree participants were not included in the final analysis "because of missing data for the primary outcomes at time 1".

Selective reporting (reporting bias)High riskNot all expected outcomes were reported.

Other biasHigh riskProtocol not available. Funded in part by Eli Lily and Company.

Weng 2005

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 2 months.

Design: parallel.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).

N = 124.
Age: not reported.
Sex: not reported.
History: not reported.


Interventions1. Psychoeducation + TAU: Multimodal rehabilitation program including medication management and symptom management delivered in groups of 8-10 patients over 2 months (N = 62).

2. TAU: standard inpatient services (N = 62).


OutcomesRelapse: number.

Service use: re-hospitalisation number.

Social functioning: employment.
Unable to use -

Mental state: BPRS (mean change from discharge to follow-up).
Social functioning: SDSS (Social disability screening scale); NOSIE-30 (Nurses' observation scale for inpatient evaluation) (mean change from discharge to follow-up).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomly assigned" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"Double-blind assessments", no further details provided.

Incomplete outcome data (attrition bias)
All outcomes
Low risk"61 patients in each group were successfully followed up one year after discharge", no further details about participants lost to follow-up.

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskNone obvious.

Xiang 2001

MethodsAllocation: randomised.
Duration: 20 weeks, follow-up 1 year.

Design: parallel.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R/ ICD-10).

N = 133.
Age: average ˜38 years (SD 21).

Sex: male and female.
History: patients in remission, average length of illness: median˜10.5 years


Interventions1. Psychoeducation + TAU: With reference to "Social and independent living skills" by Liberman: 1) medication self-management, including information on antipsychotic medication, how to self-manage medication, assess the effect of medication, recognise adverse effect of medication, communicate the effect and adverse effect of medication to medical staff. 2) early warning sign training, including training on how to recognise and monitor signs of relapse, deal with symptoms of relapse, resist intake of alcohol and narcotics. Training was provided by a psychiatrist and a psychologist. Frequency 90˜120 minutes per session, 3 sessions a week for 20 weeks. (N = 66).

2. TAU: standard psychological intervention (N = 67).


OutcomesRelapse: Relapse rate, time to relapse*.

Service use: re-hospitalisation rate, time to re-hospitalisation*.
Mental state: BPRS.

Adverse events: leaving the study early.

Unable to use-

Number of missed doses (skewed data).

Score of patient compliance with medication (not a validated scale).


NotesIn Chinese.

*Time to relapse and time to re-hospitalisation were imputed using method 7 from Tierney 2007 (report presents P value and events on each arm and randomisation ratio is 1:1).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number table.

Allocation concealment (selection bias)Unclear riskNot stated.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssessor blind.

Incomplete outcome data (attrition bias)
All outcomes
Low risk2 people in the intervention group left the study early and 3 in the control group. Incomplete outcome data was excluded from the final analysis.

Selective reporting (reporting bias)Unclear riskInsufficient information to permit judgement.

Other biasLow riskNone obvious.

Xiong 1994

MethodsAllocation: randomised.
Blinding: unclear.
Duration: 18 months.

Design: parallel.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: schizophrenia (DSM III R).

N = 63*.
Age: average ˜ 31 years (SD 10).
Sex: M 43, F 20.
History: mean duration of illness 7.5 years (SD 6.8); mean number of hospitalisations 4 (SD 5.1).


Interventions1. Psychoeducation + TAU: Family-based intervention, included discussion about detecting relapse. Introduction: two to three 45-minute sessions- family +/- patient; then monthly 45-minute counselling with patient (average 8.1 contacts per year) and family, and 90-minute family group; finally maintenance: families seen once in 2-3 months and monthly group meetings up to 18 months (N = 34).

2. TAU: prescription for antipsychotic medication given at discharge, sporadic renewals (N = 29).


OutcomesRelapse**: relapse rate.

Service use: re-hospitalisation rate.
Adverse events: deaths***.

Employment: mean number of months of employment.

Unable to use -

Mental state: SAPS; SANS; BPRS (no mean and SD).

Social functioning: SDSS; GAF (no mean and SD).

Burden of care: overall burden on a 4 point scale (not validated scale).


Notes*The number of patients in the groups at different time periods varies because the length of follow-up after hospitalisation differed.

**Relapse: hospitalisation or serious suicide attempt or deterioration on SAPS as marked or severe, symptoms on SANS marked or severe, BPRS items 4,7,11,12,and 15 rated severe; overall GAF score 40 or less; greater than 80% disability on SDSS.

***Suicides treated as relapses in the data, not entered as relapse on our analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomly assigned" - no further details.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"As in all family intervention studies, there was some difficulty in maintaining blinding [...] this problem by instructing families not to state who had provided treatment and by ensuring that the evaluators were unaware of the purpose of the study".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOne patient from the experimental group and one patient in the control group committed suicide. One patient form the experimental group died from complications of inadequately treated diabetes. "These deaths were treated as relapses in the analysis". "Non-compliance does not confound the results because all subjects are included in the analysis".

Selective reporting (reporting bias)Low riskAll stated outcomes were reported.

Other biasUnclear riskProtocol not available.

Zhan 2003

MethodsAllocation: randomised.
Duration: 1 year.

Design: parallel.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: first episode or relapsing schizophrenia (CCMD-2-R).

N = 146.

Age: 37. 87 ± 10.12 years for intervention group and 36. 59 ± 11.12 years for control group.
History: average length of illness: 3. 45 ± 1.58 years for intervention group and 3. 57 ±1. 78 years for control group.


Interventions1. Psychoeducation + TAU: pharmacotherapy, with reference to "social and independent living skills" by Liberman, intervention group received the following: 1) medication self-management, including information on antipsychotic medication, how to self-manage medication, assess the effect of medication, recognise adverse effect of medication, communicate the effect and adverse effect of medication to medical staff. 2) symptom self-monitoring, including training on how to recognise and monitor signs of relapse, learn to communicate with medical staff and prevent relapse, deal with persisting symptoms and develop good living habits. Training was provided by psychiatrists and psychologists. Frequency: 60˜90 minutes per session, 1 session a week for 12 weeks. (N = 74).

2. TAU: pharmacotherapy + standard psychological intervention (N = 72).


OutcomesRelapse: relapse rate (occurrence of overt psychiatric symptoms, BPRS score ≥28).
Mental state: BPRS.

Social functioning: NOSIE.

Medication compliance.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised by a tossing a coin.

Allocation concealment (selection bias)Unclear riskNot stated.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssessor blind.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data.

Selective reporting (reporting bias)Low riskAll measured outcomes were reported.

Other biasLow riskNone obvious.

Zhang 2004

MethodsAllocation: randomisation.
Duration: 1 year.
Setting: secondary care.
Country: China.


ParticipantsDiagnosis: schizophrenia (CCMD-III) and their families.

N = 120.
Age: 26 ± 8 years for intervention group and 28 ± 7 years for control group.
Sex: male and female.
History: not reported.


Interventions1. Psychoeducation + TAU: With reference to "social and independent living skills" by Liberman, intervention group received the following: 1) independent community living skill , 2) medication self-management, 3) symptom self-monitoring skills, including recognise early warning signs of relapse, symptom coping strategy, apply these strategy in a community setting. 16 sessions of group work by health professional, social and independent living skills training with elements of early warning signs training. Class learning (90˜120 minutes per session, 2 sessions a week for 8 weeks) Plus community follow-up and home-based intervention. (N = 60).

2. TAU: Conventional rehabilitation service (outpatient follow-up every 3 months, or telephone counselling as needed)
(N = 60).


OutcomesRelapse: relapse rate.

Service use: re-hospitalisation rate.
Mental state: SAPS; SANS; BPRS.
Social functioning: SDSS (Social dysfunction screening scale).

Knowledge: ITAQ (Insight and treatment attitude questionnaire).

Compliance with medication.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number table.

Allocation concealment (selection bias)Unclear riskNot stated.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding of participants and personnel was not possible due to the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssessor blind.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk16 people left the study early, 6 from the intervention group and 10 from the control group. Incomplete outcome data were excluded from the final analysis.

Selective reporting (reporting bias)Low riskAll measured outcomes were reported.

Other biasLow riskNone obvious.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Armstrong 1991Allocation: randomised.
Participants: 50% schizophrenia.
Interventions: does not include education to increase awareness of early signs of recurrence.

Beebe 2004Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Birchwood 2003Allocation: randomised.

Participants: schizophrenia.

Interventions: early warning signs intervention is used for both control and experimental groups.

Buchkremer 1991Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups; mainly evaluated therapeutic relatives' group.

Carra 2007Allocation: randomised.

Participants: relatives of people with schizophrenia.

Interventions: multiple group family treatment, does not include education to increase awareness of early signs of recurrence.

Cerniglia 1978Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Collins 2007Allocation: randomised.

Participants: schizophrenia.

Interventions: cognitive behavioural social skills training.

Craig Thomas 2000Allocation: randomised.
Participants: population includes early psychosis.

Deng 2007Allocation: randomised.

Participants: chronic schizophrenia (CCMD-3)

Intervention: social skills training vs routine care.

Dong 2008Allocation: randomised. 

Participants: schizophrenia (CCMD-3), in remission.

Intervention: rehabilitation therapy (mainly social skills training and psycho-education) vs routine care.

Druss 2010Allocation: randomised.

Participants: <5 0% schizophrenic, mostly bipolar disorder.

Interventions: Health and Recovery Program (HARP), no early warning signs training.

Falloon 1996Allocation: randomised.
Participants: schizophrenia.

Interventions: early warning signs intervention is used for both control and experimental groups.

Foster 2008Allocation: quasi-randomised.

Participants: serious and enduring mental illness, mostly depressive illness, < 50% schizophrenia.

Gaebel 2002Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Gleeson 2009Allocation: randomised.

Participants: first episode of a DSM-IV psychotic disorder.

Interventions: early warning signs training versus TAU, which includes some early warning signs training.

Glick 1989Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Glick 1990Allocation: randomised.
Participants: schizophrenia

Interventions: does not include education to increase awareness of early signs of recurrence.

Glynn 2002Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Goldberg 1977Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Gong 2007Allocation: Quasi-randomisation (randomised using hospital admission number: odds = intervention group, even = control group).

Participants: schizophrenia (CCMD-3).
Intervention: Family intervention vs routine care.

Grawe 1998Allocation: randomised.
Participants: population includes early psychosis and this is an exclusion criterion.

Gray 2004Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Guohui 2003Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Hahlweg 1999Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Haut 2007Allocation: randomised.

Participants: schizophrenia.

Interventions: cognitive remediation versus control group skills training (includes relapse prevention skills).

Outcomes: working memory tasks, fMRI.

Hayward 1995Allocation: randomised.
Participants: schizophrenia.

Interventions: do not include education to increase awareness of early signs of recurrence.

Herz 1989Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Herz 1991Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Hogarty 1988Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Horan 2011Allocation: randomised

Participants: schizophrenia, schizoaffective, delusional, disorder or psychosis

Interventions: Social Cognitive Skills Training, does not include education to increase awareness of early signs of recurrence.

Hou 2007Allocation: Patients were randomly assigned according to hospital admission number.

Participants: first onset schizophrenia (CCMD-3) 

Intervention: insight and confidence training vs routine care.

Jolley 1990Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Jumnoodoo 2008Allocation: randomised.
Participants: ICD-10 criteria were not used for diagnoses and less than 50% of patients had a diagnosis of schizophrenia.

Kallert 2004aClarification from authors not available, no published papers relevant to the abstract from a conference.

Klosterkötter 2007Allocation: randomised.

Participants: exclusion criteria was schizophrenia.

Interventions: clinical management and aripiprazole combined versus clinical management and placebo; CBT versus clinical management and placebo.

Kopelowicz 1998bAllocation: randomised.
Participants: schizophrenia.

Interventions: do not include education to increase awareness of early signs of recurrence.

Leavey 2004Allocation: randomised.
Participants: population includes early psychosis.

Leclerc 2000Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Leff 1984Allocation: randomised.

Participants: schizophrenia.

Interventions:do not include education to increase awareness of early signs of recurrence.

Leff 2001Allocation: randomised.
Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Lenior 2001Allocation: randomised.
Participants: schizophrenia.
Interventions: Early warning signs intervention is used for both control and experimental groups.

Liang 2002Allocation: randomised.

Patients: schizophrenia (CCMD-2-R).

Intervention: Psychoeducation vs routine care. 

Liberman 1986Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Liberman 1988Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Linden 2001Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Linszen 1994Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Linszen 1998Allocation: randomised.

Participants: schizophrenia, recent onset.

Interventions: Early warning signs intervention is used for both control and experimental groups.

Linszen 1998aAllocation: randomised.

Participants: schizophrenia, recent onset.

Interventions: Early warning signs intervention is used for both control and experimental groups.

Lopez-Luengo 2003Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Malm 2003Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Marder 1994Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Marder 2003Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Mausbach 2008Allocation: randomised.
Participants: schizophrenia.
Interventions: does not include education to increase awareness of early signs of recurrence.

McFarlane 1995Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

McGill 1983Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Merson 1992Allocation: randomised.

Participants: not schizophrenia.

Monking 1994Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Montero 2001Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Moxon 2008Allocation: Randomised

Participants: Schizophrenia & family members

Interventions: Psychoeductaion, does not include education to increase awareness of early signs of recurrence.

Munroe-Blum 1993Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Newton 2005Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Nordentoft 1998Allocation: randomised.
Participants: population includes early psychosis.

Owens 2001Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Papageorgiou 2002Allocation: randomised.

Participants: sample not specifically schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Pietzcker 1993Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Power 2003Allocation: randomised.
Participants: population includes early psychosis.

Rogers 2003Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Rossotto 2003Allocation: randomised.
Participants: schizophrenia.
Interventions: early warning signs intervention is used for both control and experimental groups.

Rotondi 2005Allocation: randomised.

Participants: Schizophrenia and family members.

Interventions: web-based tele-health psycho education, includes early warning signs training, but no face-to-face contact.

Salzer 2004Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Saren 2003Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Schonell 1995Allocation: randomised.

Participants: schizophrenia.

Interventions: Clarification from authors not available regarding whether early warning signs of recurrence was the focus of intervention.

Schooler 1997Allocation: randomised.
Participants: schizophrenia.
Interventions: Early warning signs intervention is used for both control and experimental groups.

Smith 1999Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

So 2006Allocation: randomised.

Participants: carers of people with first episode psychoses (schizophrenia, schizoaffective or schizophreniform disorder).

Interventions: family psycho-education, relapse prevention only included as one third of a 1.5 hour session.

Tamaras 2000Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Tsang 2001Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Van Der Krieke 2010Allocation: not randomised.

Velligan 2002Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Wallace 1985Allocation: randomised.

Participants: schizophrenia.

Interventions: does not include education to increase awareness of early signs of recurrence.

Wei 2007Allocation: Quasi-randomisation. Randomised according to hospital admission order.

Woods 2002Allocation: randomised.
Participants: population includes early psychosis.

杜芳 2010Allocation: quasi-randomisation. Randomised according to hospital admission order.

王莉 2010Allocation: randomised.

Patients: schizophrenia (CCMD-3), male patients only.

Intervention: self-management education vs routine care.

许玉芳 2008Allocation: randomised.

Patients: schizophrenia (CCMD-3)

Intervention: comprehensive skills training vs routine care.

许玉芳 2008aAllocation: randomised.

Patients: Schizophrenia.

Intervention: comprehensive skills training vs routine care.

 
Characteristics of ongoing studies [ordered by study ID]
Farhall 2001

Trial name or titleApplicability of Cognitive Behavior Therapy to Unselected Mental Health Service Clients With Psychotic Disorders

MethodsAllocation: Randomised.

Duration: 12 to 24 sessions over a maximum of 12 month period.

Setting: Community mental health services - unspecified.

Country: Australia

ParticipantsDiagnosis: A preliminary DSM-IV diagnosis of schizophrenia, schizoaffective disorder, mood disorder with psychotic features, or delusional disorder.

N = target 94.

Age: not stated.

History: A recovery "need" in one of the areas addressed by the therapy elements (below)

Interventions1. Recovery therapy: A variant of CBT. Implementation, as needed by the client, of one or more of the following elements: i) introduction or enhancement of techniques for better coping with persisting positive symptoms ii) adoption of a more adaptive explanatory model of their disorder by clients iii) strengthening of positive beliefs of self within a reality framework iv) implementation of practical strategies for relapse prevention, v) progress in resolution of personal/emotional issues impeding adaptation.

2. Standard case management.

OutcomesMental state: PANSS

Readmissions,

Insight,

Depression.

Uptake and effectiveness of Recovery therapy- dropout rates,

Starting date1/06/2001

Contact informationMr John Farhall
Address: Academic Unit Whittlesea Community Mental Health
Service c/o The Northern Hospital 185 Cooper Street
Epping VIC 3076
Country: Australia
Tel: +61 3 94098779
Fax: +61 3 94089508
Email: john.farhall@mh.org.au

Notes

Jones 2012

Trial name or titleInvestigation into the efficacy of cognitive training on cognition in adults with schizophrenia.

MethodsAllocation: not reported.

Duration: not reported.

Setting: Multi-centre.

Country: England

ParticipantsDiagnosis: Schizophrenia DSM-IV

N = 75

Age: not reported.

History: not reported.

InterventionsCognitive training

OutcomesCognition

Starting dateNot reported.

Contact informationMs Jennifer Cook
University of Cambridge
Psychiatry
Herchel Smith Building
Robinson Way
Cambridge
Cambridgeshire

CB2 0SZ
UNITED KINGDOM
Tel: 07793386431
jc746@cam.ac.uk

Notes

NCT00046085

Trial name or titleOnline Family Support and Education for Schizophrenia.

MethodsAllocation: Randomised.

Duration: 18 months

Setting: not reported.

Country: United States, California

ParticipantsRelatives of patients with schizophrenia.

Diagnosis: DSM-IV diagnosis of schizophrenia or schizoaffective disorder.

N = 72.

Age: 18-60.

History: Stable antipsychotic medication regimen for at least 1 month.

InterventionsFamily Psychoeducational Program: Relatives of patients with schizophrenia receive 18 months of customary care with access to the educational website for the first year. Families are provided with private, secure access to the website, which features family-to-family chat capabilities, video lectures on the management of schizophrenia, written materials on important issues in schizophrenia management, professionally facilitated online discussions of the material, and additional resource links.

OutcomesRelatives:

Perception of the patient's symptoms

Knowledge of the illness

Illness's impact on the family member

Perception of the website intervention

Patients with schizophrenia or schizoaffective disorder:
Symptoms

Medication compliance
Side effects

Hospitalisations

Social functioning

Starting dateMarch 2001

Contact informationNational Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00046085

Notes

NCT00069433

Trial name or titleEnhancing the Outcome of Skills Training for People With Schizophrenia

MethodsAllocation: Randomised.

Duration: 12 months.

Setting: not reported.

Country: United States.

ParticipantsDiagnosis: schizophrenia or schizoaffective disorder for > 5 years.

N = 60.

Age: 18 = 55.

History: Use of stable dose risperidone, olanzapine, or quetiapine for at least 1 month with no planned medication changes; social Behavior Scale (SBS) score > 45

InterventionsSocial skills and symptom management training

OutcomesNot reported.

Starting dateNot reported.

Contact informationNCT00069433

NotesTrial suspended. http://clinicaltrials.gov/ct2/show/NCT00069433

NCT00169052

Trial name or titleHealth Care Management and Rehabilitation Skills Training for Treating Serious Mental Illness in Older People

MethodsAllocation: randomised.

Duration: not reported.

Setting: community.

Country: USA.

ParticipantsDiagnosis: schizophrenia,schizoaffective disorder,bipolar disorder, major depression with functional impairment.

N = 180.

Age: over 50 years.

History: older persons with serious mental illness.

Sex: female.

InterventionsHealth management (HM) and supported rehabilitation (SR) intervention (by nurses who monitor and facilitate routine preventive and acute health care) versus usual care.

OutcomesIndependent living skills.

Social skills.

Health behaviour skills.
Preventive health care.

Acute emergency, hospitalisation and long-term institution-based care.

Starting dateSeptember 2001

Contact informationPrincipal Investigator: Stephen J Bartels, MD Dartmouth.

NotesClinicalTrials.gov identifier: NCT00169052

NCT00435721

Trial name or titleThe Families Coping With Mental Illness Program.

MethodsAllocation: randomised.

Duration: not reported.

Setting: not reported.

Country: USA.

ParticipantsDiagnosis: Self identified family members of individuals with schizophrenia or schizoaffective disorder or psychosis NOS

N = 50.

Age: 18 years and over.

History: not reported.

InterventionsPractical, short-term support and education program for relatives of individuals with schizophrenia.

OutcomesFamily knowledge.

Family Burden.

Expressed emotion.

Social Support.
Coping Strategies.
Confidence in knowledge.
Use of community resources.

Starting dateJune 2002

Contact informationPrincipal Investigator: Michelle S. Friedman-Yakoobian, Ph.D, Massachusetts General Hospital, Beth Israel Deaconess Medical Center.

NotesProtocol
Allocation: randomised.

Participants: relatives of individuals with schizophrenia or schizoaffective disorder.

Interventions: behavioural psycho-education, does not include education to increase awareness of early signs of recurrence.

NCT00515671

Trial name or titleIllness Management and Recovery for Veterans With Severe Mental Illness

MethodsAllocation: Randomised.

Duration:18 months (nine months course, follow-up at 18 months).

Setting: Day Treatment Program of Roudebush Veterans affairs.

Country: USA.

ParticipantsDiagnosis: SCID-confirmed diagnosis of schizophrenia or schizoaffective disorder.

N = 200.

Age: 18 and older.

History: Currently receiving (or newly admitted to) mental health services from the Day Treatment Program of Roudebush Veterans affairs.

InterventionsIllness Management and Recovery Training

OutcomesIllness Management Ratings

Patient Activation

Functioning Level,
Perceived Recovery
Psychiatric symptoms

Substance abuse

Hope

Employment
Independent living

Starting dateMay 2008

Contact informationClinicalTrials.gov identifier: NCT00515671

Contact: Michelle P Salyers, MS PhD
(317) 988-4419
mpsalyer@iupui.edu
Contact: Gretchen Ricketts
(317) 988-2802
grickett@iupui.edu

Notes

 
Comparison 1. EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Relapse: 1. Relapse151502Risk Ratio (M-H, Random, 95% CI)0.53 [0.36, 0.79]

    1.1 training delivered to patient only
8933Risk Ratio (M-H, Random, 95% CI)0.43 [0.20, 0.92]

    1.2 training delivered to carer/health professional only
278Risk Ratio (M-H, Random, 95% CI)0.58 [0.24, 1.37]

    1.3 training delivered to both patient and carer/health professional
6491Risk Ratio (M-H, Random, 95% CI)0.68 [0.46, 1.02]

 2 Relapse: 2. Time to first relapse6550hazards ratio (Random, 95% CI)0.53 [0.27, 1.06]

    2.1 training delivered to patient only
3372hazards ratio (Random, 95% CI)0.26 [0.13, 0.53]

    2.2 training delivered to both patient and carer/health professional
3178hazards ratio (Random, 95% CI)1.00 [0.59, 1.68]

 3 Service use: 1a. Re-hospitalisation151457Risk Ratio (M-H, Random, 95% CI)0.48 [0.35, 0.66]

    3.1 training delivered to patient only
7791Risk Ratio (M-H, Random, 95% CI)0.30 [0.14, 0.66]

    3.2 training delivered to carer/health professional only
141Risk Ratio (M-H, Random, 95% CI)0.53 [0.15, 1.82]

    3.3 training delivered to both patient and carer/health professional
7625Risk Ratio (M-H, Random, 95% CI)0.64 [0.51, 0.79]

 4 Service use: 1b. Re-hospitalisation (5-7 year follow-up)2156Risk Ratio (M-H, Random, 95% CI)0.82 [0.49, 1.36]

    4.1 training delivered to patient only
1108Risk Ratio (M-H, Random, 95% CI)1.04 [0.79, 1.36]

    4.2 training delivered to both patient and carer/health professional
148Risk Ratio (M-H, Random, 95% CI)0.62 [0.42, 0.92]

 5 Service use: 2. Time to re-hospitalisation61149hazards ratio (Random, 95% CI)0.58 [0.33, 1.04]

    5.1 training delivered to patient only
3409hazards ratio (Random, 95% CI)0.37 [0.07, 1.95]

    5.2 training delivered to both patient and carer/health professional
3740hazards ratio (Random, 95% CI)0.62 [0.46, 0.83]

 6 Mental state: general 1a. Average score (BPRS, high = bad)10Mean Difference (Random, 95% CI)-4.55 [-8.21, -0.90]

 7 Mental state: general 1b. Average score (PANSS, high = bad)3385Mean Difference (IV, Random, 95% CI)-5.89 [-15.86, 4.09]

 8 Mental state: general 1c. Average score (KGV, high = bad)1Mean Difference (Fixed, 95% CI)-2.6 [-4.07, -1.13]

 9 Mental state: specific 2. Average score in positive symptoms (various scales)6Mean Difference (IV, Random, 95% CI)Subtotals only

    9.1 BPRS (high = bad)
164Mean Difference (IV, Random, 95% CI)-0.90 [-3.52, 1.72]

    9.2 PANSS positive (high = bad)
4508Mean Difference (IV, Random, 95% CI)-0.41 [-2.70, 1.87]

    9.3 SAPS (high = bad)
1104Mean Difference (IV, Random, 95% CI)-2.04 [-3.22, -0.86]

 10 Mental state: specific 3. Average score in negative symptoms (various scales)7Mean Difference (IV, Random, 95% CI)Subtotals only

    10.1 PANSS negative (high = bad)
4508Mean Difference (IV, Random, 95% CI)-0.74 [-3.13, 1.64]

    10.2 SANS (high = bad)
3194Mean Difference (IV, Random, 95% CI)-3.95 [-15.25, 7.35]

 11 Social functioning: 1a. Not employed2185Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.57, 0.82]

 12 Social functioning: 2a. Average scores (various scales)7Mean Difference (IV, Fixed, 95% CI)Subtotals only

    12.1 GAF (high = good)
288Mean Difference (IV, Fixed, 95% CI)2.51 [-3.84, 8.85]

    12.2 GAF-DIS (high = good)
161Mean Difference (IV, Fixed, 95% CI)-6.10 [-12.34, 0.14]

    12.3 ILSS (high = good)
184Mean Difference (IV, Fixed, 95% CI)0.35 [-0.70, 1.40]

    12.4 Time budget interview (high = good)
1224Mean Difference (IV, Fixed, 95% CI)1.61 [-4.04, 7.25]

    12.5 SOFAS (high = good)
1236Mean Difference (IV, Fixed, 95% CI)1.21 [-2.71, 5.13]

    12.6 SLOF (high = good)
164Mean Difference (IV, Fixed, 95% CI)27.5 [17.03, 37.97]

    12.7 SAS (high = good)
180Mean Difference (IV, Fixed, 95% CI)-0.43 [-2.20, 1.34]

 13 Social functioning: 2b. Average scores (various scales)6Mean Difference (Random, 95% CI)Subtotals only

    13.1 SFS (high = good)
1Mean Difference (Random, 95% CI)4.4 [-3.16, 11.96]

    13.2 GAS (high = good)
3Mean Difference (Random, 95% CI)1.92 [-0.54, 4.38]

    13.3 NOSIE (high = good)
3Mean Difference (Random, 95% CI)25.12 [5.75, 44.48]

 14 Quality of life: Average scores (various scales)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    14.1 QLS (high = good)
146Mean Difference (IV, Fixed, 95% CI)-5.05 [-16.12, 6.02]

    14.2 LQLP (high = good)
148Mean Difference (IV, Fixed, 95% CI)-0.40 [-1.30, 0.50]

    14.3 EuroQoL (high = good)
1206Mean Difference (IV, Fixed, 95% CI)-4.80 [-10.79, 1.19]

    14.4 LQoLS (high = good)
180Mean Difference (IV, Fixed, 95% CI)0.09 [-0.24, 0.42]

 15 Satisfaction with care: 1a. Average endpoint scores (various scales)2Mean Difference (Fixed, 95% CI)Subtotals only

    15.1 CALPAS (high = good)
1Mean Difference (Fixed, 95% CI)0.3 [0.12, 0.48]

    15.2 IAPSRS (high = good)
1Mean Difference (Fixed, 95% CI)0.1 [-0.11, 0.31]

 16 Satisfaction with care: 1b. Average change scores (various scales)1Mean Difference (Fixed, 95% CI)2.15 [-9.66, 13.96]

    16.1 VSSS (high = good)
1Mean Difference (Fixed, 95% CI)2.15 [-9.66, 13.96]

 17 Adverse events: 1. Lost to follow-up171495Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.72, 1.28]

 18 Adverse events: 2. Death4462Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.29, 2.89]

 19 Knowledge: 1a. Average scores (various scales)4Mean Difference (IV, Random, 95% CI)Subtotals only

    19.1 KASQ (patients, high = good)
161Mean Difference (IV, Random, 95% CI)1.60 [-0.84, 4.04]

    19.2 IS (patients, high = good)
140Mean Difference (IV, Random, 95% CI)0.96 [-0.48, 2.40]

    19.3 ITAQ (patients, high = good)
2166Mean Difference (IV, Random, 95% CI)7.21 [0.94, 13.48]

 20 Knowledge: 1b. Average scores (various scales)1Mean Difference (IV, Random, 95% CI)Subtotals only

    20.1 SUMD (patients, high = bad)
181Mean Difference (IV, Random, 95% CI)-1.18 [-2.46, 0.10]

 21 Knowledge: 1c. Average scores (various scales)2Mean Difference (Fixed, 95% CI)Subtotals only

    21.1 DAI (patients, high = good)
1Mean Difference (Fixed, 95% CI)1.4 [-0.97, 3.77]

    21.2 KASI (relatives, high = good)
1Mean Difference (Fixed, 95% CI)2.83 [0.93, 4.73]

 22 Burden of care: 1. Average scores (FBIS, high = bad)164Mean Difference (IV, Random, 95% CI)-2.40 [-7.10, 2.30]

 23 Medication compliance: Not compliant to medication4374Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.42, 0.77]

 
Summary of findings for the main comparison. Early warning signs training and treatment as usual compared to treatment as usual for schizophrenia

Early warning signs training and treatment as usual compared to treatment as usual for schizophrenia

Patient or population: patients with schizophrenia
Settings: secondary care
Intervention: Early warning signs training and treatment as usual
Comparison: treatment as usual

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Treatment as usualEarly warning signs training and treatment as usual

Relapse: Rate of relapse
Follow-up: 3 to 36 months
432 per 1000229 per 1000
(155 to 341)
RR 0.53
(0.36 to 0.79)
1502
(15 studies)
⊕⊝⊝⊝
very low1, 2,3

Relapse: Time to relapse
Follow-up: 12 to 18 months
See commentSee commentHR 0.53
(0.27 to 1.06)
550
(6 studies)
⊕⊝⊝⊝

very low2, 3, 4
The data were added to the meta-analysis as generic inverse variance.

Service use: Rate of re-hospitalisation
Follow-up: 2 to 36 months
385 per 1000185 per 1000
(135 to 254)
RR 0.48
(0.35 to 0.66)
1457
(15 studies)
⊕⊝⊝⊝
very low2, 6, 7

Service use: Time to re-hospitalisation
Follow-up: 12 to 24 months
See commentSee commentHR 0.58
(0.33 to 1.04)
1149
(6 studies)
⊕⊝⊝⊝
very low2, 3, 5
The data were added to the meta-analysis as generic inverse variance.

Satisfaction with care
Follow-up: 24 weeks to 12 months
See commentSee commentNot estimableSee comment
(3 studies)
⊕⊝⊝⊝
very low8, 9
2 RCTs (92 participants) and 1 cluster RCT (56 clusters) report on satisfaction with care.10

Adverse events: Lost to follow-up
Follow-up: 10 weeks to 24 months
105 per 1000101 per 1000
(76 to 134)
RR 0.96
(0.72 to 1.28)
1495
(17 studies)
⊕⊝⊝⊝
very low3, 7, 11 ,16

Economic burden (cost of care)See commentSee commentNot estimable129
(2 studies)
⊕⊝⊝⊝
very low12, 13, 14
Two studies report on costs of care, but data could not be pooled.15

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Eight studies had an unclear risk of bias for sequence generation and 13 for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. Eight studies had an unclear risk of bias for attrition and two studies had received funding from industry.
2There was high heterogeneity in the pooled results.
3The 95% confidence intervals are wide and include both significant benefit and harm of the intervention.
4The data were not provided for most studies and had to be imputed. Three studies had an unclear risk of bias for random sequence generation and all studies had an unclear risk for allocation concealment. In one study the assessors were not blinded and in another the risk of bias for blinding was unclear. In three studies there was an unclear risk of bias for attrition.
5The data were not provided for most studies and had to be imputed. Two studies had an unclear risk of bias for random sequence generation and two were unclear for allocation concealment. One study did not have assessors that were blinded and in another it was unclear. Three studies had an unclear risk of attrition bias. One study was funded by industry.
6Nine studies had an unclear risk of bias for sequence generation and 12 for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. One study had a high risk of attrition bias and eight studies had an unclear risk of bias for attrition. One study had received funding from industry.
7The funnel plot indicates that there may be the equivalent number of ’negative’ trials that have not been included in this analysis.
8Two studies had an unclear risk of bias for sequence generation and three for allocation concealment. One study did not use blind assessors and one study had an unclear risk of bias for attrition. Two studies were part funded by industry.
9Only three studies reported this outcome.
10The two RCTs found no significant difference in satisfaction with care between early warning signs training and treatment as usual, although the data may be skewed for one trial. The cluster RCT did find a significant difference in favour of early warning signs training.
11Ten studies had an unclear risk of bias for sequence generation and fifteen for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. One study had a high risk of attrition bias and eight studies had an unclear risk of bias for attrition. Two studies had received funding from industry.
12One study had skewed data and the other did not report SDs.
13The two studies found very different results.
14This outcome included relatively few participants.
15Kuipers 1997 showed no significant difference between the mean cost of care for the early warning signs training group and standard care group, but the data was skewed. McDonell 2006 found that the mean costs of care were less in the early warning signs group ($1641) than the standard psychiatric group ($5199), no SDs were reported.
16 Some indication of publication bias from funnel plot.
 
Table 1. Skewed and incomplete data

OutcomeStudyResults

Mental state: average score in positive symptoms (PAS positive, high = bad)Drury 1996The early warning signs group (N = 20) had a mean of 2.06 (SD 2.57) and the control group (N = 20) had a mean of 4.59 (SD 2.72).

Mental state: average score in positive symptoms (PAS negative, high = bad)Drury 1996The early warning signs group (N = 20) had a mean of 1.33 (SD 1.8) and the control group (N = 20) had a mean of 1.71 (SD 2.2).

Social functioning: average score (REHAB scale, high = bad)Anzai 2002The early warning signs group (N = 14) had a mean of 18.2 (SD 13) and the control group (N = 15) had a mean of 32.5 (SD 22.7).

Social functioning: average score (HoNOS scale, high = bad)Bradley 2006The early warning signs group (N = 25) had a mean of 9.26 (SD 4.63) and the control group (N = 24) had a mean of 7.66 (SD 4.85).

Social functioning: average score (SDSS, high = bad)Chen 2003The early warning signs group (N = 31) had a mean of 4.04 (SD 3.89) and the control group (N = 31) had a mean of 7.63 (SD 4.27).

Social functioning: average score (SDSS, high = bad)Zhang 2004The early warning signs group (N = 54) had a mean of 4.8 (SD 3) and the control group (N = 50) had a mean of 9.8 (SD 3.9).

Social functioning: average months of employmentXiong 1994The early warning signs group (N = 30) had a mean of 7.83 (SD 3) and the control group (N = 28) had a mean of 4.64 (SD 7.39).

Burden of care: average score (FBIS, high = bad)Bradley 2006The early warning signs group (N= 24) had a mean of 18.95 (SD 15.39) and the control group (N = 22) had a mean of 9.38 (SD 8.1).

Burden of care: average score (FAS, high = good)Li 2003The early warning signs group (N = 46) had a mean of 21 (SD 14.54) and the control group (N = 55) had a mean of 25.15 (SD 20).

Mean number of missed dosesXiang 2001The early warning signs group had a mean of 0.2 missed doses (SD 0.6) and the control group had a mean of 4.7 missed doses (SD 2.2).

Economic burden (cost of care)Kuipers 1997The early warning signs training group had a mean care package cost of £1220 (SD 736) and the standard treatment group had a mean care package cost of £1403 (SD 887) after 18 months follow-up. There was no significant difference between the costs.

Economic burden (cost of care)McDonell 2006The mean cost of inpatient service utilisation was $5199 for the standard psychiatric care group and $1641 for the early warning signs training group at 3 years post-randomisation.

 FAS: Family Attitude Scale
FIBS: Family Burden Interview Schedule
HoNOS: Health of the Nation Outcome Scale
PAS: Psychiatric Assessment Scale
REHAB: Rehabilitation Evaluation Hall and Baker
SD: standard deviation
SDSS: Social disability screening scale
 
Table 2. Comparison of nature of intervention of studies that reported primary outcome as relapse/ re-hospitalisation

Study IDEWS as primary focusEWS delivered to patient onlyEWS delivered to patient and carer/ health workerEWS delivered to carer/ health worker onlyEWS delivered individuallyEWS delivered in groupsEWS promoting only help seeking from othersEWS promoting additional self-directed coping

Anzai 2002

Bauml 2007

Bradley 2006  

Buchkremer 1997  

Chan 2007not reported not reported 

Chen 2003not reportednot reported

Chien 2004

Drury 1996  

✗ 
not reported 

Garety 2008✓ (CBT)✓ (family intervention)✓ (CBT)✓ (family intervention)no (CBT)

yes (family intervention)
✓ (CBT)

no (family intervention) 

Granholm 2005

Gumley 2003  

Harris 2009

Herz 2000

Hogarty 1997a

Horan 2009

Kopelowicz 1998b

Kopelowicz 2003  

Kuipers 1997

Li 2003optional

Liberman 1998

McDonell 2006  

Merinder 1999  

Norman 2002  

Shin 2002✗ optional 

Shon 2002unclear

Tait 2002  ✓ includes cognitive therapy

Turkington 2006  

Van Meijel 2006  

Vreeland 2006

Weng 2005  

Xiang 2001

Xiong 1994

Zhan 2003not reportednot reported

Zhang 2004

 CBT: cognitive behavioural therapy
EWS: early warning signs
 
Table 3. Comparison of description of intervention of studies that reported primary outcome as relapse/ re-hospitalisation

Study IDFocus of interventionAt least one hour/ session focus on EWSEWS intervention delivered byNo. of sessionsControl group

Anzai 2002Community re-entry programyesWard Nurses18 one-hour sessionsOccupational rehabilitation

Bauml 2007Psychoeducation of patients and relatives (reduce re-hospitalisation and improve compliance)yesPsychiatrist or clinical psychologist8 one-hour groups, 4 sessions weekly and 4 monthly

8 bi-weekly 90-minute sessions for relatives
Outpatient treatment, antipsychotic medication

Bradley 2006  Multiple family group treatmentyesPsychoeducation:Psychiatrist, psychologists, social workers, occupational therapists

Family groups: Therapists
3 single family joining sessions.

2 half-day psychoeducation sessions.

Multiple family group fortnightly for 12 months
Appointments with case manager and doctor for medication and individual psychosocial rehabilitation. Family contact as required

Buchkremer 1997  Psychoeducational medication training and key person counsellingyesProject staff10 sessions, first 5 at weekly intervals and 5 at fortnightly intervals1.Cognitive psychotherapy: 7 sessions weekly and 8 sessions fortnightly

2. Leisure time group activities led by students of psychology or educational sociology

Chan 2007Psychoeducation & relapse preventionnoOccupational therapistTen 50-minute sessions over two weeks for patientsTraditional ward occupational therapy including work, rest, leisure activities

Chen 2003Medication & symptom management training programmenot reportedNot reportedNot reportedAntipsychotic therapy

Chien 2004PsychoeducationyesTrained psychiatric nurses12 bi-weekly 2-hour sessions over 6 months for patients and families together1. Mutual support group for families only

2. Standard outpatient care

Drury 1996 Cognitive TherapyNoNot reported8 hours a week – four individual and four group sessions, 2 sessions with family engagementRecreation therapy,  leisure and social activities outside the ward

Garety 2008CBT or family interventionNoEach session with 2 therapists - mix of doctoral clinical psychologists and nurses all trained in CBT9 months (intended minimum 12 months, max 20 months) – 1-hour sessions with a mean number of 14.3 sessionTAU- standard of care delivered according to national and local service protocols including antipsychotic medication.

Granholm 2005Cognitive behavioural skills trainingYesEach session led by 2 therapists - mix of doctoral or senior graduate level psychologists24 two-hour weekly group sessionsTAU – continuation of prior treatment

Gumley 2003  Targeted CBT for relapseyesClinical psychologist5 session engagement phase between 0-12 weeks; intensive targeted phase (2-3 sessions per week) after for 12 monthsOngoing medication, regular psychiatric review, follow-up from a key worker, access to multidisciplinary community mental health team

Harris 2009Medication management training programmeyesNot reportedCommunity mental health professionals (CMHPs; nurses, occupational therapists, social workers) received a 10-day programme: 3 days assessment training, followed by seven fortnightly study days. These were followed by 1-hour individual supervision sessions, at the CMHP’s workplace, every month for 6 months, giving a total educational input of 9 months.Waiting list

Herz 2000Relapse preventionyesMaster's level nurse clinician or certified social workerOne-hour weekly supportive group therapy OR 30-45-minute individual supportive therapy

90-minute multifamily psychoeducation groups bi-weekly for 6 months and monthly after
Individual supportive therapy and medication management biweekly for 15-30 minutes

Hogarty 1997aPersonal therapy (relapse prevention) and/or family therapy (psychoeducation/ management)yesPersonal and family therapy: master's level psychiatric nurse clinical specialists and doctoral- level clinical psychologists30-45-minute weekly for about 3 years

1.9 additional monthly medication management sessions
Supportive therapy

Horan 2009Symptom managementyesNot reported12 one-hour groups that met twice weeklySocial cognitive intervention

Kopelowicz 1998bCommunity re-entry programyes2 trainers per session – from a multi-disciplinary staff of 10Eight 45-minute group sessions, twice a day for 4 days in a week.Occupational therapy

Kopelowicz 2003  Family assisted skills training programyesNurses, psychologists and social workers90-minute sessions four times per week for 3 months.

Weekly group sessions with families included
Case management by social workers and monthly 20-minute psychiatric visits to see a psychiatrist

Kuipers 1997CBTYesTherapistWeekly sessions that become fortnightly- up to one hour and up to nine monthsStandard care- case management and medication

Li 2003Comprehensive patient/ family education guide (CP/FEG)yesWard NursesIn hospital- Patient 8 hours; family member 36 hours. Post-discharge- patient and family member 2 hours per month for 3 months.Not reported

Liberman 1998Social and Independent Living Skills Program consisting of basic conversation, recreation for leisure, medication management, and symptom managementyesOccupational therapist and paraprofessionals6 months of intensive, clinic-based treatment 3 hours a day, 4 days per week.Psychosocial occupational therapy

McDonell 2006  Multiple family group treatmentyesclinicians24 sessions in year 1 and 12 sessions in year 2Outpatient services: medication management, case management, phone consultation, crisis services, group psychotherapy, occupational therapy, individual psychotherapy

Merinder 1999  Patient and relative psychoeducationyesnot stated8 weekly sessions separately for patients and relativesPsychopharmacological treatment, psychosocial rehabilitation efforts, some supportive psychotherapy

Norman 2002  Stress management programyesNurse case managers12 weeks of group sessions, and 12 individual sessionsSocial activities program similar in frequency and length to treatment group

Shin 2002Psychoeducational group  program with individual supportive therapyyesGroup sessions – psychiatric social worker

Individual sessions – Master’s degree student
10 weekly group sessions (90 minutes each) & individual sessions (45 minutes each)Individual supportive therapy

Shon 2002Self management educational groupYes2 psychiatric nurses & 2 social workers12 group sessions (70 minutes each)Non-equivalent control group - undefined

Tait 2002  EWS recognition and targeted cognitive therapyyesTherapist5 one-hour sessions on initial engagement and formulation

Early signs monitoring questionnaire dispatched fortnightly for an average of 10 months

Targeted cognitive therapy, intensive for a brief period, about 2-3 sessions per week
Routine appointments with psychiatrist and key worker (community psychiatric worker, social worker or occupational therapist)

Turkington 2006  Modify patient's condition and family approachyesTrained Community Psychiatric Nurseup to 6 hour-long sessions of CBT and/or 3 sessions with carerCare of community mental health teams

Van Meijel 2006  Relapse prevention plan using EWS monitoringyesTrained nursesTherapy for a total of mean (SD) 155 (94) daysCare as usual

Weng 2005  Psychiatric rehabilitationyesInterdisciplinary teams2 months, possibly weekly sessionsStandard inpatient services and activities

Xiang 2001Medication & symptom management training programmeyesPsychiatrist and a psychologist90 to 120-minute sessions, 3 sessions per week for 20 weeksAntipsychotic medication and standard psychological intervention

Xiong 1994Family based interventionyesClinicians1. Introduction- two to three 45-minute sessions- family +/- patient

2. Monthly 45-minute counselling with patient (average 8.1 contacts per year) and family and 90 minute family group

3. Maintenance- families seen once in 2-3 months and monthly group meetings up to 18 months
2-3 months of medication post discharge +/- out patient follow-up

Zhan 2003Medication & symptom management training programmeyesPsychiatrist and a psychologist60 to 90 minutes per session, 1 session per week for 12 weeksPharmacotherapy and standard psychological intervention

Zhang 2004Life skills, medication & symptom management training programmeyesPsychiatrist and psychiatric nurseGroup training for 90 to 120 minutes, 2 times a week. Then community follow-up by nurses, number of sessions not reportedConventional rehabilitation service (outpatient follow-up every 3 months, or telephone counselling as needed)