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Carbamazepine for schizophrenia

  1. Stefan Leucht1,*,
  2. Bartosz Helfer2,
  3. Markus Dold3,
  4. Werner Kissling3,
  5. John McGrath4

Editorial Group: Cochrane Schizophrenia Group

Published Online: 2 MAY 2014

Assessed as up-to-date: 6 JUL 2012

DOI: 10.1002/14651858.CD001258.pub3


How to Cite

Leucht S, Helfer B, Dold M, Kissling W, McGrath J. Carbamazepine for schizophrenia. Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD001258. DOI: 10.1002/14651858.CD001258.pub3.

Author Information

  1. 1

    Technische Universität München, Department of Psychiatry and Psychotherapy, München, Germany

  2. 2

    Technische Universität München, Klinik für Psychiatrie und Psychotherapie, München, Bayern, Germany

  3. 3

    Technische Universität München Klinikum rechts der Isar, Klinik und Poliklinik für Psychiatrie und Psychotherapie, München, Germany

  4. 4

    The University of Queensland, Epidemiology and Developmental Neurobiology, Brisbane, Queensland, Australia

*Stefan Leucht, Department of Psychiatry and Psychotherapy, Technische Universität München, Ismaningerstrasse 22, München, 81675, Germany. Stefan.Leucht@lrz.tum.de.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 2 MAY 2014

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Characteristics of included studies [ordered by study ID]
Carpenter 1991

MethodsAllocation: randomised - no further details.
Blinding: double - no further information.
Design: cross-over.
Duration: 95 days each phase.
Setting: outpatient department.


ParticipantsDiagnosis: schizophrenia (DSM-III & RDC).
N = 34.*
Sex: 18 M, 9 F.*
Age: mean ˜ 33 years.
History: stabilised on neuroleptic maintenance, hospitalised ˜3 times, ill ˜10 years.


Interventions1. Carbamazepine: dose 800-1200 mg/day. N˜15.*
2. Placebo (neuroleptics withdrawn over 1-5 days when study medication dose was reached). N˜16.*


Outcomes1. Leaving the study early.
2. Relapse.*
3. Mental state: BPRS (mean and number with 20% reduction).*
4. Side effects - allergic reactions, blood dyscrasia.*


NotesData analysed on 31 patients, no information about treatment status of 3 people.
Interim analyses showed high relapse rates in both arms of study - study stopped.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Patients were randomly assigned, within prognostic strata", no further details (p.69).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Double-blind", "identical placebo tablets" (p.69), "number of carbamazepine tablets was adjusted by a nonblind psychiatrist" (p.70).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Double-blind", "identical placebo tablets" (p.69), "number of carbamazepine tablets was adjusted by a nonblind psychiatrist" (p.70).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Double-blind", "identical placebo tablets" (p.69).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Low risk"Blind rater" (p.69).

Incomplete outcome data (attrition bias)
All outcomes
Low riskSame dropout rate in each group.

Selective reporting (reporting bias)Low riskNo selective reporting.

Other biasLow riskNo other bias.

Dose 1987

MethodsAllocation: randomised - no further details.
Blinding: double - no further information.
Design: parallel.
Duration: 5 weeks (at week 4 interventions withdrawn).
Setting: in hospital.


ParticipantsDiagnosis: acute schizophrenia (ICD-9 & DSM-III).
N = 41.
Sex: not reported.
Age: not reported.
History: hospitalised ˜1.2 times, ill ˜6 years.


Interventions1. Adjunctive carbamazepine: dose 200 mg, increased to 600-1200 mg/day (target plasma level 8-12 micrograms/dL) + haloperidol 6 mg/day then titrated to clinical judgement. N = 18.
2. Placebo additional treatment + haloperidol 6 mg/day then titrated to clinical judgement. N = 23.


Outcomes1. Leaving the study early.
2. Mental state: (BPRS 20%, 35%, 50% reduction, mean at endpoint; mean IMPS at endpoint).
3. Side effects: allergic reactions, substantial white blood cell decline, increase of liver enzymes, worsening of EEG.

Unable to use:.
Medication use (mean haloperidol dose - no SD, biperiden, chlorprothixene - data skewed).
Movement disorder (SAS - data skewed).
Haloperidol plasma-levels - data skewed.


Notes** Two people taking carbamazepine had falls in white cell counts, but not below usual reference range.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomized", "randomly assigned" (p.304) - no further details.

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Double-blind" - no further details (p.304).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Double-blind" - no further details (p.304).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Double-blind" - no further details (p.304).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear risk"Double-blind" - no further details (p.304).

Incomplete outcome data (attrition bias)
All outcomes
Low risk"[All patients] survived for the end-of-treatment-analysis without any dropouts" (p.304).

"No patients dropped out because of side effects or adverse reactions" (p.306).

Selective reporting (reporting bias)High riskCGI results not reported.

Other biasUnclear risk"Dosages of haloperidol, chlorprothixene and biperiden, as well as the occurrence of side effects, differed significantly (...) between the carbamazepine and placebo group" (p.307-8).

Heßlinger 1998

MethodsAllocation: randomised - sealed envelopes.
Blinding: single.
Design: parallel.
Duration: 4 weeks.
Setting: in hospital.


ParticipantsDiagnosis: schizophrenia (n = 16) or schizoaffective (n = 2) psychosis (ICD-10).
N = 18.
Sex: 12 M, 6F.


Interventions1. Adjunctive carbamazepine: dose mean 567mg/day, titrated in week 1 to plasma-level of 6-12 mg/mL + constant haloperidol dose: dose mean ˜ 15 mg/day, higher in this group to maintain effective plasma levels. N = 9.
2. No additional treatment + constant haloperidol dose. N = 9.


Outcomes1. Leaving the study early.
2. Mental state (BPRS 20%, 35%, 50% reduction and mean at endpoint, PANSS positive score at endpoint).

Unable to use:.
Haloperidol plasma levels - data skewed.
Mean biperiden and chlorprothixen dose - data skewed.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomly assigned" (p.311).

Allocation concealment (selection bias)Low risk"Sealed envelopes".

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Psychiatrist (...) was blind to medication and drug levels. However, he had access to the nursing charts" (p.311). Patients were not aware of the treatment (information received by letter).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Psychiatrist (...) was blind to medication and drug levels. However, he had access to the nursing charts" (p.311) Patients were not aware of the treatment (information received by letter).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Psychiatrist (...) was blind to medication and drug levels. However, he had access to the nursing charts" (p.311). Patients were not aware of the treatment (information received by letter).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear risk"Psychiatrist (...) was blind to medication and drug levels. However, he had access to the nursing charts" (p.311). Patients were not aware of the treatment (information received by letter).

Incomplete outcome data (attrition bias)
All outcomes
Low risk"25 out of 27 patients completed the study protocol", 2 CBZ dropouts, ITT analysis (p.311).

Selective reporting (reporting bias)Low riskNo selective outcome reporting.

Other biasLow riskNo other bias.

Llorca 1993

MethodsAllocation: randomised - Latin square procedure.
Blindness: double - identical capsules.
Design: cross-over, no wash-out.
Duration: 4 X 5 week cross-over (preceded by 5 weeks no adjunctive treatment).
Setting: in hospital.


ParticipantsDiagnosis: treatment-resistant schizophrenia patients (DSM-III-R, Kane criteria).
N = 24.
Sex: 18 M, 6 F.
Age: mean ˜44 years.


Interventions1. Adjunctive carbamazepine: dose 2 weeks 200 mg/day, 3 weeks 400 mg/day + constant haloperidol (15-65 mg/day). N = 6.
2. Adjunctive bromocriptine: dose 2.5 mg/day + constant haloperidol (15-65 mg/day). N = 6.*
3. Adjunctive cyproheptadine: 12-24 mg/day + constant haloperidol (15-65 mg/day). N = 6.*
4. Placebo additional treatment + constant haloperidol (15-65 mg/day). N = 6.


Outcomes1. Leaving the study early.

Unable to use: .
Mental state (BPRS, SAPS, SANS - P values only).
Movement disorder (SAS, AIMS - P values only).


Notes* Data from groups 2 & 3 not used in this review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomized succession using a latin square procedure" (p.565).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Tout au long de l'étude, les patients sont à l'insu du traitement recu. Durant les 4 phase de l'expérimentation, patients et investigateurs sont à l'insu de la médication adjuvante recue". "Afin de maintenir les conditions de double aveugle, les résultats des dosages pratiqués sont collectés au fur et à mesure de l'étude par un médecin différent du cotateur (M.A.W.)". "capsules identiques".

Blinding of participants and personnel (performance bias)
Subjective outcomes
Low risk"Tout au long de l'étude, les patients sont à l'insu du traitement recu. Durant les 4 phase de l'expérimentation, patients et investigateurs sont à l'insu de la médication adjuvante recue". "Afin de maintenir les conditions de double aveugle, les résultats des dosages pratiqués sont collectés au fur et à mesure de l'étude par un médecin différent du cotateur (M.A.W.)" "capsules identiques".

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Tout au long de l'étude, les patients sont à l'insu du traitement recu. Durant les 4 phase de l'expérimentation, patients et investigateurs sont à l'insu de la médication adjuvante recue". "Afin de maintenir les conditions de double aveugle, les résultats des dosages pratiqués sont collectés au fur et à mesure de l'étude par un médecin différent du cotateur (M.A.W.)". "capsules identiques".

Blinding of outcome assessment (detection bias)
Subjective outcomes
Low risk"Tout au long de l'étude, les patients sont à l'insu du traitement recu. Durant les 4 phase de l'expérimentation, patients et investigateurs sont à l'insu de la médication adjuvante recue". "Afin de maintenir les conditions de double aveugle, les résultats des dosages pratiqués sont collectés au fur et à mesure de l'étude par un médecin différent du cotateur (M.A.W.)". "capsules identiques".

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo participant left the study early.

Selective reporting (reporting bias)High riskNo SDs reported.

Other biasLow riskNo clear evidence for other bias.

Mair 1990

MethodsAllocation: randomised - no further details.
Blinding: open.
Design: parallel.
Duration: 5 weeks.
Setting: in hospital.


ParticipantsDiagnosis: schizophrenia & schizophrenia-like psychoses (ICD-9).
N = 23.
Age: range 31-44 years.
History: "acutely ill", unresponsive to 5 days clozapine or haloperidol, admitted 4-9 times.


Interventions1. Adjunctive carbamazepine: dose 600 mg/day + titrated dose of haloperidol or clozapine. N = 13.
2. No additional treatment + titrated dose of haloperidol or clozapine. N = 10.


Outcomes1. Leaving the study early.

Unable to use:.
General functioning (CGI - no SD).
Mental state (BPRS - no SD).
Extrapyramidal side effects (Webster scale - no data).
Other side effects (FSUCL - no data).
Mean haloperidol/clozapine dose - no SD.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"random number list" (p.79).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low riskBlinding not described (an open study) (p.79).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear riskBlinding not described (an open study) (p.79).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low riskBlinding not described (an open study) (p.79).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear riskBlinding not described (an open study) (p.79).

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskIt was not mentioned whether there were dropouts or not.

Selective reporting (reporting bias)High riskNo SDs reported for CGI and BPRS, no data reported for FSUCL and Webster Scale.

Other biasLow riskNo other bias.

Martin-Munoz 1989

MethodsAllocation: randomised - no further information.
Blinding: not stated.
Design: parallel.
Duration: 18 days.
Setting: in hospital.


ParticipantsDiagnosis: paranoid schizophrenia (RDC).
N = 20.
Age: mean ˜29 years.
Sex: 18 M, 2 F.


Interventions1. Adjunctive carbamazepine: dose initially 600 mg/day, adjusted to plasma levels of 8-12 ng/mL + haloperidol, 30 mg/day, fixed dose. N = 10.
2. No additional treatment + haloperidol, 30 mg/day, fixed dose. N = 10.


Outcomes1. Leaving the study early.
2. Mental state (20%, 35%, 50% BPRS reduction).
3. Movement disorder.

Unable to use:.
Side effects (UKU-scale - no data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Allocated (...) randomly using a coin toss method" (letter).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Doble ciego", no further details.

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Doble ciego", no further details.

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Doble ciego", no further details.

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear risk"Doble ciego", no further details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts (according to the letter).

Selective reporting (reporting bias)High riskNo SD's in BPRS, UKU-scale results not reported.

Other biasLow riskNo clear evidence for other bias.

Nachshoni 1994

MethodsAllocation: randomised - random allocation list.
Blinding: double - identical capsules.
Design: parallel.
Duration: 5 weeks.
Setting: in hospital.


ParticipantsDiagnosis: residual schizophrenia (DSM-III-R).
N = 30.*
Age: mean ˜46 years.
Sex: 15 M, 13 F.
History: predominant negative symptoms, ill mean ˜19 years.


Interventions1. Adjunctive carbamazepine: dose increased to 600 mg/day during week 1, then adjustment to plasma levels of 4-12 ng/mL + 300-800 chlorpromazine equivalent antipsychotic treatment. N = 15.
2. Placebo adjunctive treatment + 300-800 chlorpromazine equivalent antipsychotic treatment. N = 15.


Outcomes1. Leaving the study early.
2. Mental state (20%, 35%, 50% BPRS reduction, HRSD, SANS at endpoint).

Unable to use:.
EPS (SAS - no data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Random allocation list" (p.24).

Allocation concealment (selection bias)Low risk"Dr. Joseph Levin was the control psychiatrist who knew what the patients were receiving, according to a random allocation list" (letter from the authors). It appears that other members of the team were blind to allocation.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Double-blind design" (p.24), patients and personal were blind, tablets were identical (letter).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Low risk"Double-blind design" (p.24), patients and personal were blind, tablets were identical (letter).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Double-blind design" (p.24), patients and personal were blind, tablets were identical (letter).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Low risk"Ratings were done by psychiatrist, who was blind to whether the patients were receiving placebo or carbamazepine" (p.23).

Incomplete outcome data (attrition bias)
All outcomes
Low risk"Two patients were withdrawn, one from each group" (p.24).

Selective reporting (reporting bias)Low riskNo selective reporting.

Other biasLow riskNo other bias.

Neppe 1983

MethodsAllocation: randomised - no further information.
Blinding: double - no further information.
Design: cross-over.
Duration: 2 X 6 weeks (preceded by 3-week baseline).
Setting: in hospital.


ParticipantsDiagnosis: schizophrenia (10), non-progressive dementia (2), rapid cycling (1) (diagnostic criteria unclear).
N = 13.*
Age: mean ˜34 years.
Sex: 8 M, 5 F.
History: chronic, "poor-responders", EEG abnormalities.


Interventions1. Adjunctive carbamazepine: dose 600 mg/day + various antipsychotics (constant dose). N = 3.
2. Placebo adjunctive treatment + various antipsychotics (constant dose). N = 6.


Outcomes1. Leaving the study early.
2. Global impression (CGI).
3. Mental state (20%, 35%, 50% BPRS reduction).

Unable to use: .
General improvement (Global Assessment, OCR unpublished scales).


Notes*Data extracted for 9 participants with schizophrenia from published data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomized" (p.326), "random number list" (letter).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Double blind" (p.326).

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Double blind" (p.326).

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Double blind" (p.326).

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear risk"Double blind" (p.326).

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk"Two out of six patients in the control group compared to zero out of three in the intervention group dropped out [out of 13]" (p.327).

Selective reporting (reporting bias)High riskNo SDs for BPRS.

Other biasLow riskNo other bias ("one [subject had] a history of contaminating cannabis use", p.327).

Simhandl 1996

MethodsAllocation: randomised - no further details.
Blindness: double.
Design: parallel.
Duration: 8 weeks (intervention withdrawn at week 6).
Setting: no information available.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).
N = 42.
Age: mean ˜35 years.
Sex: 30 M, 12 F.
History: "chronic", non-response to > 3 neuroleptics (2 different chemical classes) in last 2 years, duration ill ˜ 10 years.


Interventions1. Adjunctive carbamazepine: dose increased week 1-2 until plasma levels = 15-42 micromol/L + constant dose of antipsychotics. N = 15.
2. Lithium*: dose increased week 1-2 until plasma level = 0.6-1.2 mml/L) + constant dose of antipsychotics. N = 13.
3. Placebo + constant dose of antipsychotics. N = 14.


Outcomes1. Leaving the study early.
2. Global impression (CGI).
3. Mental state (20%, 35%, 50% BPRS reduction, SANS at endpoint).

Unable to use: .
Plasma levels of antipsychotics - skewed data.


NotesJadad = 4.
*This group was not used in the analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Low risk"Double-blind", no further details.

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear risk"Double-blind", no further details.

Blinding of outcome assessment (detection bias)
Objective outcomes
Low risk"Double-blind", no further details.

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

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo patients in each group dropped out, both because of non-compliance.

Selective reporting (reporting bias)Unclear riskThe study is only available as an abstract.

Other biasLow riskNo clear other bias.

Svestka 1989

MethodsAllocation: randomised - no further details.
Blindness: single (raters).
Design: cross-over.
Duration: 6 weeks (2 weeks placebo - 3 weeks carbamazepine/perphenazine - 1 week placebo - 3 weeks carbamazepine/perphenazine).
Setting: hospital.


ParticipantsDiagnosis: ICD-9 schizophrenia (n = 28) or schizoaffective disorder (n = 10).
History: "acutely ill", duration ill ˜9 years.
N = 38.
Age: mean ˜38 years.
Sex: 30 M, 8 F (the gender of 2 people who left early is unknown).


Interventions1. Carbamazepine, flexible dose, mean = 1374 SD = 334, N = 22.
2. Perphenazine, flexible dose, mean = 53, SD = 12. N = 18.
Then 1 week placebo and 3 weeks cross-over to other treatment.


Outcomes1. Leaving the study early.
2. Mental state (20%, 35%, 50% BPRS reduction and BPRS at endpoint).
3. Various side effects.


NotesJadad = 4.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomised" - no further details ("intraindividual comparison", p.276).

Allocation concealment (selection bias)Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Objective outcomes
Unclear riskNo information available.

Blinding of participants and personnel (performance bias)
Subjective outcomes
Unclear riskNo information available.

Blinding of outcome assessment (detection bias)
Objective outcomes
Unclear riskNo information available.

Blinding of outcome assessment (detection bias)
Subjective outcomes
Unclear riskNo information available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo out of 20 participants in the intervention group dropped out compared to zero out of 18 in the control group.

Selective reporting (reporting bias)High riskNo SDs and global scores reported for BPRS.

Other biasLow riskNo other bias.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Arana 1986Allocation: not randomised, A-B design.

Azorin 1986Allocation: not randomised, A-B design.

Ballenger 1984Allocation: not randomised, case series.

Barnes 1996Allocation: not randomised, review.

Bellaire 1990Allocation: randomised.
Participants: people with schizoaffective disorders or bipolar illness.
Interventions: lithium versus carbamazepine, no placebo group.

Birkheimer 1985Allocation: not randomised, review.

Borison 1991Allocation: randomised.
Participants: people with schizophrenia.
Interventions: rimcazole, no carbamazepine.

Botte 1988Allocation: not randomised, A-B design.

Cabrera 1987Allocation: randomised.
Participants: people with schizoaffective disorders and bipolar illness.
Interventions: oxcarbazepine versus lithium, no placebo group.

Cegalis 1984Allocation: not randomised, case report.

Chouinard 1990Allocation: not randomised, case series.

Costa 1986Allocation: not randomised, case report.

Covell 2004Allocation: randomised.
Participants: people with schizophrenia.
Interventions: clozapine versus typical antipsychotics, no carbamazepine group.

Dalby 1971Allocation: not randomised, A-B design.

de Vogelaer 1981Allocation: randomised.
Participants: very heterogeneous group of patients, some with "behavioral disorders", some with "psychotic" disorders. No clear diagnoses, study focuses on character disorders.
Interventions: not entirely clear, but probably carbamazepine or placebo were added to antipsychotic drugs .
Outcomes: impossible to extract data just for people with serious mental illness. As yet, no response from the author to a letter.

Dehing 1968Allocation: randomised (random number list).
Participants: mixed group, no data on people with schizophrenia, the focus of the study was on 'character disorders'.
Interventions: Carbamazepine or placebo added to ongoing treatment.
Outcomes: according to the authors no original data are available and therefore no single outcome parameter can be used for this review.

Denicoff 1994Allocation: not randomised, clinical practice survey/audit.

Elphick 1985Allocation: not randomised, A-B-A design.

Frankenburg 1988Allocation: not randomised, case series.

Gadow 1992Allocation: not randomised, review.

Galletly 1997Allocation: not randomised, case series.

Ginestet 1996Allocation: not randomised, review.

Goncalves 1985Allocation: randomised.
Participants: manic people, seven with bipolar disorder, five with schizoaffective disorder.
Interventions: carbamazepine versus placebo, but most participants also received haloperidol. The trial could therefore not be classified according to the three comparisons analysed in this review and no data could be extracted.

Greil 1997Allocation: randomised.
Participants: people with schizoaffective disorder.
Interventions: carbamazepine versus lithium, no placebo group.

Hakola 1982Allocation: not randomised, A-B design.

Hermle 1993Allocation: not randomised, case report.

Herrera 1987Allocation: not randomised, A-B-A design.

Ivkovi 2004Allocation: not randomised, controlled clinical trial.

Iwahashi 1995Allocation: not randomised, case-control study.

Iwahashi 1996Allocation: not randomised, case series.

Jann 1985Allocation: not randomised, A-B design.

Johns 1995Allocation: not randomised, review.

Kahn 1990Allocation: randomised.
Participants: people with schizophrenia.
Intervention: carbamazepine plus neuroleptics versus lithium plus neuroleptics, no placebo group.

Karper 1992Allocation: not randomised, case report.

Keck 1996Allocation: not randomised, review.

Kessler 1989Allocation: not randomised, case series.

Kidron 1985Allocation: randomised, cross-over.
Participants: people with schizophrenia or schizoaffective disorders and excited states.
Interventions: haloperidol + carbamazepine versus haloperidol + placebo.
Outcomes: no usable data.

Klein 1984Allocation: randomised, parallel (participants with poor response were crossed-over at the end).
Participants: those with schizophrenia or schizoaffective disorders and excited states.
Interventions: haloperidol + carbamazepine versus haloperidol + placebo.
Outcomes: no usable data.

Kraft 1984Allocation: not randomised, case report.

Lambert 1987Allocation: review.

Lapensee 1992Allocation: not randomised, review.

Lenzi 1986Allocation: randomised.
Participants: mixed affective and nonaffective psychoses.
Interventions: carbamazepine + chlorpromazine versus lithium + chlorpromazine, no placebo group.

Llorca 1992Allocation: not randomised, review.

Luchins 1983Allocation: not randomised, case series.

Luchins 1984Allocation: not randomised, case report.

Makaric 2000Allocation: controlled clinical trial, but not randomised.

McAllister 1985Allocation: not randomised, case series.

McKee 1989Allocation: not randomised, case report.

Meltzer 1992Allocation: not randomised, review.

Meshel 1967Allocation: randomised.
Participants: people with psychosis.
Interventions: tybamate versus placebo, no carbamazepine group.

Meshel 1968Allocation: randomised.
Participants: people with schizophrenia.
Interventions: tybamate versus placebo, no carbamazepine group.

Miceli 2000Allocation: randomised.
Participants: healthy volunteers.

Miller 1965Allocation: unclear.
Participants: people with schizophrenia.
Interventions: hydroxyphenamate, no carbamazepine group.

Miodownik 2003Allocation: unclear, but probably randomised.
Participants: people with schizophrenia.
Interventions: vitamin B6, no carbamazepine group.

Mokrusch 1987Allocation: not randomised, review.

Morinigo 1992Allocation: randomised.
Participants: people with mania.

Mosca 1998Allocation: randomised.
Participants: people with violent behaviour or impulsivity.
Interventions: carbamazepine versus valproate, no placebo.

Munetz 1989Allocation: randomised.
Participants: people with schizophrenia.
Interventions: rimcazole, no carbamazepine group.

Möller 1989Allocation: randomised, cross-over.
Participants: people with schizophrenia or schizoaffective disorders and excited states.
Interventions: haloperidol + carbamazepine versus haloperidol + placebo.
Outcomes: no usable data.

Möller 1996Allocation: not randomised, review.

Nasser 1990Allocation: not randomised, case series.

Nelson 1993Allocation: not randomised, review.

Neppe 1988aAllocation: not randomised, review.

Neppe 1988bAllocation: not randomised, review.

Neppe 1988cAllocation: not randomised, case report.

Neppe 1991Allocation: not randomised, case series.

Nijdam 1992Allocation: unclear.
Participants: people with mental retardation and psychoses.
Interventions: comparison of two different formulations of carbamazepine, no placebo.

Ohlmeier 2007Allocation: randomised.

Participants: people with schizophrenia.

Interventions: carbamazepine plus perazine versus olanzapine, i.e. not the same antipsychotic in both groups.

Okuma 1989aAllocation: alternate allocation, category C, inadequate randomisation.

Okuma 1989bAllocation: not randomised, A-B design.

Ortega 1991Allocation: randomised (aleatory numbers list generated with a computer program).
Participants: inhalant-induced psychotic disorders, not schizophrenia.
Interventions: carbamazepine as a sole treatment versus haloperidol as a sole treatment.

Otani 1997Allocation: not randomised, A-B design.

Pantelis 1996Allocation: not randomised, review.

Panu 1984Allocation: not randomised, case series.

Placidi 1986Allocation: randomised.
Participants: mixed affective and nonaffective psychoses.
Intervention: carbamazepine versus lithium, no placebo.

Raitasuo 1994Allocation: not randomised, case report.

Rankel 1988Allocation: not randomised, case series.

Rittmannsberger 1990Allocation: not randomised, review.

Scher 1983Allocation: not randomised, case series.

Schulz 1990Allocation: randomised.
Participants: people with schizophrenia.
Interventions: antipsychotics + carbamazepine versus antipsychotics versus lithium, no placebo.

Simhandl 1992Allocation: not randomised, review.

Siris 1993Allocation: not randomised, review.

Sramek 1988Allocation: not randomised, A-B design.

Sugerman 1970Allocation: unclear, probably randomised.
Participants: people with schizophrenia.
Interventions: adrenochrome semicarbazone, no carbamazepine group.

Svestka 1985Allocation: not randomised, A-B design.

Svestka 1988Allocation: not randomised, A-B design.

Tohen 1994Allocation: not randomised, case series.

Walden 1996Allocation: not randomised, review.

Wetterling 1987Allocation: not randomised, A-B-A design.

Wunderlich 1983Allocation: not randomised, A-B design.

Yassa 1983Allocation: not randomised, case report.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Kamisada 1988

MethodsUnclear whether study was randomised.

ParticipantsSchizophrenia.

InterventionsProbably either lithium or carbamazepine added to antipsychotic drugs.

OutcomesSymptoms, side effects.

NotesWe wrote a letter but have not received an answer, we can not be sure whether the address was still correct.

Lee 1996

MethodsUnclear whether study was randomised.

ParticipantsPeople with schizophrenia and negative symptoms.

InterventionsProbably carbamazepine and valproate added to antipsychotic drugs.

OutcomesProbably symptoms, side effects.

NotesWe wrote a letter but have not received an answer, we can not be sure whether the address was still correct.

 
Comparison 1. CARBAMAZEPINE AS SOLE TREATMENT vs PLACEBO AS SOLE TREATMENT

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

 1 Leaving the study early131Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.17, 6.64]

 2 Relapse (by 3 months)131Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.78, 1.45]

 3 Mental state: 1. Less than 20% BPRS reduction131Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.75, 1.30]

 4 Mental state: 2. Average endpoint score of the BPRS at 3 months127Mean Difference (IV, Fixed, 95% CI)-0.07 [-0.46, 0.32]

 5 Adverse effects1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 allergic reactions
131Risk Ratio (M-H, Fixed, 95% CI)7.44 [0.42, 132.95]

    5.2 blood dyscrasia
131Risk Ratio (M-H, Fixed, 95% CI)3.19 [0.14, 72.69]

 
Comparison 2. CARBAMAZEPINE AS SOLE TREATMENT vs ANTIPSYCHOTICS AS SOLE TREATMENT

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

 1 Leaving the study early138Risk Ratio (M-H, Fixed, 95% CI)4.52 [0.23, 88.38]

 2 Mental state: 1. Categories of reduction on BPRS scores1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 less than 20% reduction
138Risk Ratio (M-H, Fixed, 95% CI)1.29 [0.62, 2.66]

    2.2 less than 35% reduction
138Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.86, 3.24]

    2.3 less than 50% reduction
138Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.78, 1.92]

 3 Mental state: 2. Mean BPRS at endpoint138Mean Difference (IV, Fixed, 95% CI)2.30 [-3.84, 8.44]

 4 Adverse effects: 1. Movement disorders1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 akathisia
138Risk Ratio (M-H, Fixed, 95% CI)0.13 [0.01, 2.34]

    4.2 parkinsonism
138Risk Ratio (M-H, Fixed, 95% CI)0.03 [0.00, 0.43]

    4.3 tremor
138Risk Ratio (M-H, Fixed, 95% CI)0.30 [0.01, 6.97]

    4.4 use of anticholinergic drugs
138Risk Ratio (M-H, Fixed, 95% CI)0.23 [0.09, 0.55]

 5 Adverse effects: 2. Others1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 blurred vision
138Risk Ratio (M-H, Fixed, 95% CI)0.45 [0.04, 4.55]

    5.2 collapse
138Risk Ratio (M-H, Fixed, 95% CI)0.3 [0.03, 2.63]

    5.3 constipation
138Risk Ratio (M-H, Fixed, 95% CI)0.45 [0.04, 4.55]

    5.4 dizziness
138Risk Ratio (M-H, Fixed, 95% CI)4.52 [0.23, 88.38]

    5.5 dry mouth
138Risk Ratio (M-H, Fixed, 95% CI)0.45 [0.04, 4.55]

    5.6 fatigue
138Risk Ratio (M-H, Fixed, 95% CI)5.4 [0.72, 40.66]

    5.7 nausia
138Risk Ratio (M-H, Fixed, 95% CI)2.71 [0.12, 62.70]

    5.8 salivation
138Risk Ratio (M-H, Fixed, 95% CI)2.71 [0.12, 62.70]

    5.9 tachycardia
138Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 2.04]

 6 Subgroup analysis - schizoaffective disorder excluded - Mental state: Categories of reduction on BPRS score1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 less than 20% reduction
128Risk Ratio (M-H, Fixed, 95% CI)3.09 [1.22, 7.84]

    6.2 less than 35% reduction
128Risk Ratio (M-H, Fixed, 95% CI)2.32 [1.15, 4.67]

    6.3 less than 50% reduction
128Risk Ratio (M-H, Fixed, 95% CI)1.40 [0.94, 2.09]

 
Comparison 3. ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS

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

 1 Leaving the study early8182Risk Ratio (M-H, Fixed, 95% CI)0.47 [0.16, 1.35]

 2 Global state: No improvement238Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.37, 0.88]

 3 Mental state: 1a. General - categories of reduction on BPRS scores6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 less than 20% reduction
6147Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.44, 1.07]

    3.2 less than 35% reduction
6147Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.57, 1.05]

    3.3 less than 50% reduction
6147Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.67, 1.12]

 4 Mental state: 1b. General - average BPRS endpoint score (high = poor)379Mean Difference (IV, Fixed, 95% CI)-3.21 [-7.82, 1.40]

 5 Mental state: 1c. General - average BPRS endpoint score (high = poor, skewed data)Other dataNo numeric data

 6 Mental state: 1d. General - average IMPS endpoint score (high = poor)250Mean Difference (IV, Fixed, 95% CI)4.61 [1.30, 7.91]

 7 Mental state: 2a. Specific - positive symptoms (PANSS subscale at endpoint, high = poor)118Mean Difference (IV, Fixed, 95% CI)4.22 [0.75, 7.69]

 8 Mental state: 2b. Specific - positive symptoms (IMPS score at endpoint, high = poor)Other dataNo numeric data

 9 Mental state: 2c. Specific - negative symptoms (SANS at endpoint, high = poor)253Mean Difference (IV, Fixed, 95% CI)-2.75 [-6.71, 1.22]

 10 Mental state: 2d. Specific - depression (Hamilton scale at endpoint, high = poor)126Mean Difference (IV, Fixed, 95% CI)-0.35 [-2.20, 1.50]

 11 Behaviour: Average dose of medication used for agitation (chlorprothixene, skewed data)Other dataNo numeric data

 12 Adverse effects: 1a Movement disorders - at least one movement disorder120Risk Ratio (M-H, Fixed, 95% CI)0.38 [0.14, 1.02]

 13 Adverse effects: 1b. Movement disorders - average dose of antiparkinsonism drugs (biperiden, skewed data)Other dataNo numeric data

 14 Adverse effects: 1c. Movement disorders - average endpoint score (SAS, high = poor, skewed data)Other dataNo numeric data

 15 Adverse effects: 1d. Movement disorders - average endpoint TD rating (high = poor, skewed data)Other dataNo numeric data

 16 Adverse effects: 2. Others1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    16.1 allergic reaction
141Risk Ratio (M-H, Fixed, 95% CI)3.79 [0.16, 87.86]

    16.2 EEG deterioration
141Risk Ratio (M-H, Fixed, 95% CI)2.13 [0.59, 7.75]

    16.3 liver enzyme elevation
141Risk Ratio (M-H, Fixed, 95% CI)2.56 [0.53, 12.42]

    16.4 white blood cell decline (substantial)
141Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.09, 19.06]

 17 Physiological effect: Haloperidol plasma levelsOther dataNo numeric data

 18 Subgroup analysis - treatment-resistant participants6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    18.1 treatment-resistant
129Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.51, 1.18]

    18.2 not treatment-resistant
5118Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.65, 1.23]

 19 Subgroup analysis - EEG abnormalities6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    19.1 with EEG abnormalities
19Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.65, 1.90]

    19.2 without EEG abnormalities
5138Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.63, 1.11]

 20 Subgroup analysis - negative symptoms6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    20.1 predominant negative symptoms
130Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.83, 1.21]

    20.2 no predominant negative symptoms
5117Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.55, 1.17]

 21 Sensitivity analysis: random effects model - less than 50% BPRS reduction6147Risk Ratio (M-H, Random, 95% CI)0.93 [0.60, 1.45]

 
Analysis 3.5 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 5 Mental state: 1c. General - average BPRS endpoint score (high = poor, skewed data).
Mental state: 1c. General - average BPRS endpoint score (high = poor, skewed data)

Study

Martin-Munoz 19891. Carbamazepine + antipsychotics: mean 8.6, SD 9.6, N = 10.
2. Placebo + antipsychotics: mean 7.4, SD 4.7, N = 10.

Nachshoni 19941. Carbamazepine + antipsychotics: mean 5.0, SD 2.70, N = 15.
2. Placebo + antipsychotics: mean 5.1, SD 1.6, N = 15.

Neppe 19831. Carbamazepine + antipsychotics: mean 14.7, SD 5.8, N = 3.
2. Placebo + antipsychotics: mean 22.0, SD 13.4, N = 4.

 
Analysis 3.8 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 8 Mental state: 2b. Specific - positive symptoms (IMPS score at endpoint, high = poor).
Mental state: 2b. Specific - positive symptoms (IMPS score at endpoint, high = poor)

Study

Dose 19871. Carbamazepine + antipsychotics: mean 4.9, SD 6.4, N = 16.
2. Placebo + antipsychotics: mean 7.5, SD 8.1, N = 16.

 
Analysis 3.11 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 11 Behaviour: Average dose of medication used for agitation (chlorprothixene, skewed data).
Behaviour: Average dose of medication used for agitation (chlorprothixene, skewed data)

Study

Dose 19871. Carbamazepine + antipsychotics: mean dose 40 mg/day, SD 36. N = 17.
2. Placebo + antipsychotics: mean dose 63 mg/day, SD 49. N = 17.

Heßlinger 19981. Carbamazepine + haloperidol: mean chlorprothixene dose 182 mg/day, SD 30.1. N = 9.
2. Placebo + haloperidol: mean dose 21.6 mg/day, SD 5.8. N = 9.

 
Analysis 3.13 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 13 Adverse effects: 1b. Movement disorders - average dose of antiparkinsonism drugs (biperiden, skewed data).
Adverse effects: 1b. Movement disorders - average dose of antiparkinsonism drugs (biperiden, skewed data)

Study

Dose 19871. Carbamazepine + antipsychotics: mean dose 1.3 mg/day, SD 1.6. N = 17.
2. Placebo + antipsychotics: mean dose 3.8 mg/day, SD 2.3. N = 17.

Heßlinger 19981. Carbamazepine + haloperidol: mean dose 3.9 mg/day, SD 0.8. N = 9.
2. Placebo + haloperidol: mean dose 2.9 mg/day, SD 1.0 N = 9.

Simhandl 19961. Carbamazepine + antipsychotics: mean dose 2.67 mg/day, SD 2.89. N = 15.
2. Placebo + antipsychotics: mean dose 2.67 mg/day, SD 4.62. N = 12.

 
Analysis 3.14 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 14 Adverse effects: 1c. Movement disorders - average endpoint score (SAS, high = poor, skewed data).
Adverse effects: 1c. Movement disorders - average endpoint score (SAS, high = poor, skewed data)

Study

Dose 19871. Carbamazepine + antipsychotics: mean 1.03, SD 0.86. N = 17.
2. Placebo + antipsychotics: mean 2.84, SD 2.18. N = 17.

Nachshoni 19941. Carbamazepine + antipsychotics: mean 0.9, SD 0.9. N = 13.
2. Placebo + antipsychotics: mean 0.4, SD 0.5. N = 13.

Simhandl 19961. Carbamazepine + antipsychotics: mean 0.27, SD 0.19. N = 15.
2. Placebo + antipsychotics: mean 0.31, SD 0.35. N = 12.

 
Analysis 3.15 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 15 Adverse effects: 1d. Movement disorders - average endpoint TD rating (high = poor, skewed data).
Adverse effects: 1d. Movement disorders - average endpoint TD rating (high = poor, skewed data)

Study

Simhandl 19961. Carbamazepine + antipsychotics: mean 7.1, SD 0.2. N = 15.
2. Placebo + antipsychotics: mean 13.1, SD 14.2. N = 12.

 
Analysis 3.17 Comparison 3 ADJUNCTIVE CARBAMAZEPINE + ANTIPSYCHOTICS vs PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 17 Physiological effect: Haloperidol plasma levels.
Physiological effect: Haloperidol plasma levels

Study

Dose 19871. Carbamazepine + antipsychotics: mean level 5.8 (mg haloperidol/d)/(microgms/L haloperidol), SEM 3.3. N = 17.
2. Placebo + antipsychotics: mean level 3.1 (mg haloperidol/d)/(microgms/L haloperidol), SEM 1.65. N = 17.

Heßlinger 19981. Carbamazepine + haloperidol: mean haloperidol level change -3.8 ng/mL, SD 3.0. N = 9 (˜45% decrease).
2. Placebo + haloperidol: mean haloperidol level change 1.9 ng/mL, SD 2.3. N = 9 (˜51% increase).

 
Summary of findings for the main comparison. Adjunctive carbamazepine + antipsychotics compared with placebo/no adjunctive treatment + antipsychotics for schizophrenia

adjunctive Carbamazepine + antipsychotics compared to placebo/no adjunctive treatment + antipsychotics for schizophrenia

Patient or population: People with schizophrenia
Settings: Outpatients/ inpatients
Intervention: Adjunctive Carbamazepine + antipsychotics
Comparison: Placebo/no adjunctive treatment + antipsychotics

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

Assumed riskCorresponding risk

Placebo/no adjunctive treatment + antipsychoticsAdjunctive Carbamazepine + antipsychotics

Acceptability of treatment
Leaving the study early due to any reason
Follow-up: mean 7.7 weeks
108 per 100051 per 1000
(17 to 145)
RR 0.47
(0.16 to 1.35)
182
(8 studies)
⊕⊝⊝⊝
very low1,2,3

No clinically important change in general mental state
Scale used: less than 50% BPRS reduction
Follow-up: mean 6.1 weeks
623 per 1000536 per 1000
(418 to 698)
RR 0.86
(0.67 to 1.12)
147
(6 studies)
⊕⊕⊝⊝
low1,4

Average endpoint general mental state score
Scale used: Average BPRS endpoint score. Scale from: 0 to 108.
Follow-up: mean 5.7 weeks
The mean global mental state in the control groups was
BPRS total score points
The mean global mental state in the intervention groups was
0.3 higher
(12.49 lower to 13.09 higher)
79
(3 studies)
⊕⊕⊝⊝
low5,6

Average endpoint positive symptom score

Scale used: Mean PANSS positive subscore at endpoint. Scale from: 7 to 49.
Follow-up: mean 4 weeks
The mean positive symptoms in the control groups was
PANSS positive subscore
The mean positive symptoms in the intervention groups was
4.22 higher
(0.75 to 7.69 higher)
18
(1 study)
⊕⊕⊕⊝
moderate6

Average endpoint depressive symptom score
Scale used: Hamilton scale at endpoint. Scale from: 0 to 54.
Follow-up: mean 5 weeks
The mean depression in the control groups was
Hamilton scale at endpoint
The mean depression in the intervention groups was
0.35 lower
(2.2 lower to 1.5 higher)
26
(1 study)
⊕⊕⊝⊝
low6

AggressionSee commentSee commentNot estimable0
(0)
See comment

*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;

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.

 1 Risk of bias: reporting bias is especially prevalent in this study pool with high risk being a problem in a majority of reports.
2 Inconsistency: differences between studies (number of events, effects size sometimes in favour of carbamazepine sometimes in favour of no treatment).
3 Indirectness: acceptability was measured by the number of participants leaving the studies for any reason which is an indirect measure of acceptability.
4 Imprecision: 95% confidence interval includes both benefit and harm. Moreover, the number of events was small.
5 Inconsistency: high heterogeneity of trial results
6 Imprecision: very small population size.
 
Table 1. Reviews or additional comparisons

CategoryTitleExcluded study

Additional comparisonCarbamazepine (+/- antipsychotics) versus lithium (+/- antipsychotics)Bellaire 1990, Greil 1997, Kahn 1990, Lenzi 1986, Placidi 1986, Schulz 1990

Carbamazepine plus one antipsychotic versus another antipsychoticOhlmeier 2007

Carbamazepine versus valproateMosca 1998

Different formulations of carbamazepineNijdam 1992

Oxcarbazepine versus lithiumCabrera 1987

Existing review*Clozapine versus typical antipsychoticsCovell 2004

New reviewAdrenochrome semicarbazone for schizophreniaSugerman 1970

Hydroxyphenamate for schizophreniaMiller 1965

Rimcazole for schizophreniaBorison 1991, Munetz 1989

Tybamate for schizophreniaMeshel 1967, Meshel 1968

Vitamin B6 for schizophreniaMiodownik 2003

 
Table 2. Suggested design for future study

MethodsAllocation: random.
Blinding: blind or independent raters.
Duration: minimum one year follow-up.

ParticipantsDiagnosis: people with schizophrenia whose illness is resistant to treatment; people with psychoses and EEG abnormalities; people with psychoses and aggressive behaviour; and people with schizoaffective disorders.
Age: Sex: male and female.
N = 750.

Interventions1. Carbamazepine/oxcarbazepine alone: any dose.
2. Placebo (or no intervention).
3. Carbamazepine/oxcarbazepine in combination with any antipsychotic treatment: any dose.
4. Placebo (or no intervention) in combination with any antipsychotic treatment.
5. Antipsychotics alone: any dose.

OutcomesLeaving the study early.

Service utilisation.

Global state - no clinically important change.*

Relapse.

Mental state - no clinically important change.

Behaviour - no clinically important change.

Social functioning - no clinically important change.
Adverse effects - clinically important general adverse effects*; sudden and unexpected death.

Economic outcomes.

Satisfaction with treatment.

Quality of life.

Pharmacokinetic interactions.

All outcomes by time - short term (up to 12 weeks), medium term (13 to 26 weeks) and long term (over 26 weeks).

Notes*Primary outcomes of interest.