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Keywords:

  • cancer;
  • oncology;
  • depression;
  • combined therapy;
  • clinical trial

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objective: To compare narrative therapy (NT) plus escitalopram versus escitalopram plus usual care on quality of life and depressive symptomatology of depressed patients with oncologic disease.

Methods: A total of 72 subjects (mean age 54.6 years), predominantly female with non-metastatic breast, lung and colon cancer and depressive disorder (DSM-IV-TR) were randomized to receive treatment with NT plus escitalopram (n=39) or escitalopram (10–20 mg QD) plus usual care (n=33). Main endpoints were improvement in dimensions of quality of life measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and reduction of depressive symptoms using the Hospital Anxiety and Depression Scale at weeks 12 and 24.

Results: The combined therapy group showed significantly greater improvement in all the functioning dimensions (p<0.01), pain scale (p=0.02), global health (p=0.02), and global quality of life (p=0.007) at weeks 12 and 24. There were no statistically significant differences in depressive symptomatology between the groups. From week 12 to week 24 study retention was higher in the combined treatment group (p=0.01).

Conclusions: Brief NT in combination with escitalopram was superior to usual care and escitalopram in improving functioning dimensions of quality life. Copyright © 2010 John Wiley & Sons, Ltd.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The search for effective treatments for anxiety and depression remains one of the main goals of Psycho-oncology 1, 2. Depression is the most prevalent psychological disorder among cancer patients 3–5 and has a negative impact on quality of life, treatment adherence and the level of emotional burden on the caregivers 6.

Data suggest that the most effective treatment strategies for major depression include the combination of psychotherapeutic and pharmacologic interventions 7–11 and based on this, combined approaches to the treatment of depression in cancer patients may be the most effective 12, 13. To our knowledge, two clinical trials have examined the efficacy of combined care (antidepressant plus psychotherpeutic intervention) among cancer patients with major depression 14, 15.

In Newell's meta-analysis, it is concluded that the methodological quality of most of the RCT in the study of depression in oncology have been suboptimal due to small sample sizes and short follow-up periods 16. Furthermore, some studies fail to report the clinical characteristics of the sample, the expertise of the therapist and/or the number of sessions required for the intervention 17. Finally, they recommend testing the efficacy of other psychotherapy interventions apart from cognitive–behaviour therapy. Narrative Therapy (NT), an individually tailored, multi-component, integrative intervention, could be an appropriate one in the field of oncology due to its flexibility and its focus in fitting a person's particular and unique needs 18–20. In contrast to cognitive therapy, NT does not claim that there is one universal encompassing metanarrative to give account of reality. Also, in contrast to other making meaning interventions, NT is not limited to existential issues 21. The lack of studies using NT 22 could be related to its recent emergence as an empirical paradigm and its emphasis on a subjective and qualitative understanding of the problems. However, there are not any clinical trials of NT in depression in cancer, though there is a clinical trial for depressive disorders 19 and an RCT focused on pain in cancer patients 23.

In the present study we consider health related quality of life (HQoL), and not only symptomatic scores, an important endpoint. Previous studies recommend including HQoL as a result variable in the design of any psychosocial intervention 24–26, since assessing HQoL could contribute to improve outcome and may indicate the directions needed for more efficient treatments. Studies have shown that psychological factors predict subsequent quality of life and the treatment of mental disorder influences the HQoL 27–29.

In order to improve the quality of the evidence available we have carried out a randomized controlled trial following previous recommendations 16. The main objective of the study was to evaluate the effects of adding a psychotherapeutic intervention, NT, to escitalopram (combined therapy) on measures of quality of life and depressive symptoms compared with usual care plus escitalopram.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Design

This is a two-center, randomized, controlled trial comparing NT plus escitalopram versus escitalopram plus usual care. Randomization by a table of random numbers was centralized. The study was approved by the Ethical Committees of both hospitals. All eligible patients provided written informed consent to participate. The study was not registered in the public trials registry, as recommended by the International Commitee of Medical Journal Editors (ICMJE), because patients were enrolled before December 2006.

Participants

1026 patients with lung, breast and colorectal non-metastatic cancer, 18–75 years old, with a life expectancy≥1 year and a Karnofsky index≥70, receiving ambulatory care at La Paz Hospital and Principe de Asturias Hospital (Madrid, Spain) were screened for depression between March 2006 and June 2008 using the Hospital Anxiety and Depression Scale (HADS). Screening was performed 3 months after cancer diagnosis to avoid acute stress reactions, and no later than 2 years after diagnosis. Exclusion criteria were pregnancy or not using reliable contraception due to the use of antidepressant drugs; history of using escitalopram regardless of response; inability to give informed consent and/or comply with protocol requirements; history of hypersensitivity reaction to other selective serotonin reuptake inhibitors; acute suicide risk; and primary or secondary diagnosis of bipolar disorder, schizophrenia or any other psychotic disorder.

All subjects who scored≥8 in the HADS-D were interviewed by a member of the investigation team with experience in conducting structured interviews to generate DSM-IV-TR diagnoses. Diagnoses included were Major Depressive Disorder, single episode (DSM-IV-TR 296.2X) and Major recurrent Depressive Disorder (DSM-IV-TR 296.3X), adjustment disorder with a mixed anxiety and depressed mood (DSM-IV 309.28) and Adjustment disorder with depressed mood (DSM-IV 309.0). The diagnosis was confirmed by another member of the research team.

Figure 1 shows the flow of participants. A total of 150 subjects (14.7%) had a depressive disorder according to DSM-IV-TR criteria. Seventy-two subjects were enrolled and randomly assigned to receive either NT plus escitalopram or escitalopram plus usual care. Of the 72 subjects who completed the baseline assessment, 68 completed week 12, and 56 completed week 24. No differences were found for the HADS-D scores and sociodemographic variables, when patients who refused treatment were compared with patients who were included in the study.

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Figure 1. CONSORT diagram. HADS-D Hospital Anxiety and Depression Scale, depression subscale

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Interventions

Among the commonly prescribed antidepressants, escitalopram appears to be suitable as first-line treatment for moderate to severe major depression, showing clinically important differences for both efficacy and tolerability 30–32. It is being used in clinical trials in oncologic patients 33, 34.

Escitalopram was administered on a fixed-flexible schedule in both groups, beginning with 10 mg per day and adjusted up to 20 mg per day by week 8 if there was no complete response as per clinician evaluation. To monitor therapeutic compliance, patient's reports were used. We considered poor antidepressant adherence when patient's report was less than 80% of the prescribed doses. A pharmacologic treatment time of a minimum of 6 months was established in both groups.

NT focuses on specific patient's situations or existing concerns and includes interventions with other people significant to the patient and emotional regulation skills training. The essence of the NT approach is interpreting and giving meaning to experience 35–37. The therapist and the patient co-construct new meanings through the therapeutic conversation. In our study, we focused on grief, health-to-illness role transition, existential concerns and somatic symptoms without cognitive elaboration that required training in emotion regulation techniques (relaxation, mindfulness). The intervention was guided by a treatment manual designed by a member of the research team 38.

The therapy was carried out individually during 12 45-minute weekly sessions. Response to pharmacologic treatment and adverse events were also reviewed. Therapists were psychiatrists or psychologists with at least 2 years of experience, trained by the principal investigators (BRV, CBP and APT). The team met weekly to supervise sessions and to achieve clinical consensus. To assure adherence to the treatment manual, 10% of the sessions were randomly videotaped.

Usual care: The antidepressant was administered by oncologists who followed a depression didactic protocol designed by the study psychiatrists to minimize differences that could introduce bias. The protocol included the discussion about the effects and side-effects of medication, and the provision of practical support. In addition, consulting frequencies, and follow-ups were similar to the intervention group.

The pre-specified reasons to discontinue patients from the study were: suicidal ideation, intensification of depressive symptoms, patient's wish not to continue in the study, appearance of serious adverse effects or lack of response to treatment, progression of oncologic illness, not taking medication, and missing a third appointment.

Outcome assessments

The main outcome measures were changes in dimensions of quality of life measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) and depressive symptomatology measured by HADS-depression subscale at weeks 12 and 24. The evaluation was carried out by an independent evaluator who was blinded to the intervention. Subjects were specifically asked about severe life events (deaths, significant losses, concurrent illnesses) that had occurred during the follow-up.

The EORTC QLQ-C30 (version 1.0) is a self-rating scale that measures quality of life in cancer, and has been developed by the EORTC study group 39–41. This questionnaire is composed of a total of 30 items that evaluates five functioning domains, three symptom scales, five single items assessing common physical symptoms of cancer, and items of global health, global quality of life and the perceived financial impact of the disease and treatment. All scales range in a transformed score of 0 to 100. High functioning and global scale scores and low symptom scores reflect better functioning and lower symptom distress, respectively. This questionnaire has been validated in Spanish oncologic patients 42, 43.

The HADS is a 14-item self-rating scale that measures anxiety and depression, and is designed specifically for patients with physical illnesses. A score equal or greater than 11 indicates ‘probable’ psychological morbidity while a score of 8 to10 indicates ‘possible’ psychological morbidity. The scale has been validated in Spanish patients 44–46.

Statistical analysis

Analyses were performed with the use of SAS 9.1, Enterprise Guide 3.0 and SPSS (version 9.0; SPSS Inc Chicago, IL, USA) packages. Quantitative data were described as mean and standard deviation and categorical data as absolute frequencies and percentages.

The primary endpoint was to demonstrate that combined therapy group improves EORTC QLQ-C30 functioning scales more than usual care at 24 weeks and, on the other hand, demonstrate the non-inferiority of combined therapy compared with usual care with improved HADS-D at 24 weeks. Effect sizes were estimated through a pilot study using data from the first 23 enrolled patients. The analysis was done by an external unconnected study analyst. For EORTC QLQ-C30 social functioning dimension, a sample size of 27 in each group would have 80% power to detect a difference between means of −18.05 assuming that the common standard deviation is 23.0 using a two group t-test with a 0.05 two-side significance level. The other functioning subscales require fewer patients to achieve the same power. For HADS-D, when the sample size in each group is 32, a two-group 0.025 one-sided t-test would have 80% power to reject the null hypothesis of the difference in means 1.6 or further than zero, assuming that the expected difference is −0.5 and the common standard deviation is 1.5.

Baseline demographic and clinical characteristics at baseline were tested by the chi-square test and the Student t-test to assess comparability between the groups. The statistic analyses were considered bilateral and p<0.05 was considered significant.

We performed all analyses on an intention-to-treat basis to evaluate intervention effects. To analyse the average change of all the measures between the groups over time (12 and 24 week), a mixed linear regression model was conducted. The fixed effect of time and intervention condition and their interaction were evaluated. Time was included as repeated-effect covariate. Baseline scores on each scale were included in the model as covariate. A significant interaction effect indicated that the profiles of the groups had different shapes. A general covariance structure was used. Post-hoc least-squares tests were conducted at each assessment point to identify specific group differences significant. Ninety-five percent confidence intervals (CI) are shown for the main results.

To make a sensitivity analysis, we also conducted a mixed model with time as random effect, with the 72 cases included, and we found similar results.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

From week 12 to week 24 significantly more patients (p = 0.01) were discontinued from the study, due to poor adherence and missing appointments in the usual care group (n = 7, 21.9%) than in the combined treatment group (n = 1, 2.8%). At week 24, six patients (15.4%) randomized to combined therapy were lost to follow up with 10 (30.3%) in the usual care group (p = 0.129). Of 12 possible sessions of NT, the mean number of sessions completed was 8.4 in the combined therapy.

Table 1 presents baseline demographic variables and the mean scores for each scale of QLQ C-30 and HADS-D. Demographic variables did not differ significantly between the study groups. The mean age was 54.6 ± 10.4 years (range 35–75 years). The sample is unbalanced by the distribution of gender and age according to cancer type and the different prevalence of the cancer type. The distribution between genders is one man for every four women (19.4% compared with 80.6%). Mean HADS-D scores in both groups was 12.48 (:95% CI: 11.4–13.5) in usual care group, and 12.46 (95% CI: 11.4–13.4) in combined therapy group.

Table 1. Baseline characteristics of study participants
 Usual care N = 33Combined therapy N = 39Total N = 72p
  1. Data are number (%) or mean and SD, standard deviation; HADS-D, Hospital Anxiety and Depression Scale-depression subscale; QLQ-C30 (European organization for research and Treatment of Cancer quality of life questionnaire). *p value was calculated by the V Cramer test.

Age-yr. Mean (SD)56 (10.8)53.2 (9.5)54.6 (10.2)0.252
Female sex n(%)24 (72.7)34 (87.2)58 (80.6)0.145
Cancer n(%)
 Breast19 (57.6)29 (74.4)48 (66.7)0.263*
 Colo rectal8 (24.2)7 (17.9)15 (20.8) 
 Lung6 (18.2)3 (7.7)9 (12.5) 
Caregiver n(%)
 No6 (18.2)4 (10.3)10 (13.9)0.417
 Yes27 (81.8)35 (89.7)62 (86.1) 
Prior psychiatric history n(%)
 No27 (81.8)29 (74.4)56 (77.8)0.573
 Yes6 (18.2)10 (25.6)16 (22.2) 
History of cancer in the family n(%)
 No24 (72.7)19 (48.7)43 (59.7)0.581
 Yes9 (27.3)20 (51.3)29 (40.3) 
HADS- D12.5 ± 312.5 ± 3.112.5 ± 3.030.974
QLQ C-30 functioning dimensions
 Physical31.7 ± 15.230.8 ± 14.231.2 ± 14.60.786
 Social8 ± 121.7 ± 6.44.6 ± 9.80.005
 Emotional8.8 ± 10.24 ± 5.76.2 ± 8.40.015
 Cognitive13.6 ± 216.8 ± 9.99.9 ± 16.20.076
 Role14.6 ± 21.57.7 ± 15.210.9 ± 18.60.114
Symptoms
 Fatigue85.0 ± 1586 ± 18.785.8 ± 170.899
 Nausea64.1 ± 35.971.8 ± 36.568.3 ± 36.10.375
 Pain71.7 ± 33.775.6 ± 30.573.8 ± 31.90.606
 Dyspnea36.4 ± 35.735.9 ± 31.936.1 ± 33.40.953
 Insomnia78.8 ± 20.179.5 ± 24.979.2 ± 22.70.897
 Appetite loss66.7 ± 2556.4 ± 30.761.1 ± 28.50.129
 Constipation35.3 ± 31.124.8 ± 29.329.6 ± 30.40.143
 Diarrhea34.3 ± 30.726.5 ± 33.530.0 ± 32.20.306
 Financial difficulties9 ± 17.212.8 ± 23.711.1 ± 20.90.455
 Global health14.1 ± 17.213.7 ± 13.713.9 ± 15.30.899
 Global quality of life16.2 ± 15.319.7 ± 12.0118.1 ± 13.60.281

Clinical response

Depression scores measured by HADS-D were reduced over time in both treatment groups, but there were not statistically significant differences, (Figure 2). Depression scores for patients in the combined therapy group remained lower than scores in patients in the usual care group. Figure 3 shows functioning dimensions and pain scale scores of QLQ-C30 at each timepoint.

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Figure 2. HADS-Depression subscale at each timepoint. Boxes show the interquartile range (IQR) with continuous lines for mean scores. Whiskers indicate range. Circles and dots beyond the whiskers are outliers or extreme define as any points outside the IQR by anymore than 1.5 times the IQR

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Figure 3. Functioning dimensions and pain scale of QLQ-C30 at each timepoint. Panel A: Physical. Panel B: Cognitive. Panel C: Emotional. Panel D: Social. Panel E: Role. Panel F: Pain. Data are presented as box-plot that shows the mean and interquartile range

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Table 2 shows adjusted data by generalized linear model. Comparisons of adjusted mean scores between groups over time found that, at 12 weeks, combined treatment group had significantly higher scores on physical (p<0.001), social (p<0.001), emotional (p<0.001), cognitive (p<0.001), and role (p<0.001) in functioning dimensions on the QLQ-C30 questionnaire. The significant differences were maintained in favor of the combined therapy group at 24 weeks. The combined therapy intervention also showed significant pain reduction (p = 0.02) and better global health (p = 0.02), and global quality of life (p = 0.007) at 12 and 24 weeks.

Table 2. Adjusted data by generalized linear model
 Usual careCombined therapy 
 Mean (SE)Change from baseline95% CIMean (SE)Change from baseline95% CIp
  1. Combined therapy: n = 39. Usual care: n = 33. p = interaction term effect.

HADS-D
 Baseline12.48 (0.51)  12.46 (0.47)  0.463
 12 week7.42 (0.51)5.063.64 to 6.486.52 (0.47)5.954.64 to 7.25 
 24 week6.72 (0.51)5.74.33 to 7.185.54 (0.47)6.95.61 to 8.23 
QLQC-30 functioning dimensions
Physical
 Baseline31.49 (2.81)  30.96 (2.58)  <0.001
 12 week41.79 (2.81)−10.33−18.12 to −2.4756.60 (2.58)−25.6432.83 to −18.44 
 24 week39.77 (2.81)−8.28−16.1 to 0.466.52 (2.58)−35.55−35.55 to −28.3 
Social
 Baseline6.18 (3.62)  3.31 (3.32)  <0.001
 12 week29.42 (3.62)−23.23−33.22 to 13.2449.04 (3.32)−45.7354.92 to −36.54 
 24 week34.47 (3.62)−28.28−38.3 to 18.361.86 (3.32)−58.55−67.8 to −49.3 
Emotional
 Baseline7.21 (2.94)  5.44 (2.70)  <0.001
 12 week24.38 (2.94)−17.17−25.3 to −9.0346.04 (2.70)−40.5948.08 to −33.11 
 24 week29.68 (2.94)−22.47−30.6 to 14.356.72 (2.70)−51.28−58.8 to −43.8 
Cognitive
 Baseline10.70 (3.19)  9.32  <0.001
 12 week28.38 (3.19)−17.67−26.53 to −8.8253.34−44.0152.16 to −35.58 
 24 week33.93 (3.19)−23.23−32.1 to −8.868.29−58.97−67.1 to −6.8 
Role
 Baseline12.44 (3.12)  9.56 (2.87)  <0.001
 12 week27.59 (3.12)−15.15−23.83 to −6.4754.86 (2.87)−45.353.28 to −37.31 
 24 week34.16 (3.12)−21.71−30.4 to −13.0369.81 (2.87)−60.26−68.2 to −52.3 
QLQC-30 Symptoms
Pain
 Baseline73.23 (3.87)  74.36 (3.56)  0.002
 12 week57.07 (3.87)16.165.38 to 26.9446.58 (3.56)27.7717.86 to 37.69 
 24 week48.99 (3.87)24.2413.5 to 3529.49 (3.56)44.8734.9 to 54.8 
Insomnia
 Baseline79.03 (3.96)  79.29 (3.64)  NS
 12 week43.67 (3.96)35.3524.32 to 46.3941.68 (3.64)37.6127.46 to 47.76 
 24 week32.56 (3.96)46.4735.46 to 57.523.73 (3.64)55.5645.41 to 65.7 
Appetite loss
 Baseline63.54 (4.49)  59.05 (4.13)  NS
 12 week38.29 (4.49)25.2512.77 to 37.7331.7 (4.13)27.3515.87 to 38.83 
 24 week28.19 (4.49)35.3522.88 to 47.8322.3 (4.13)36.7525.27 to 48.23 
Nausea
 Baseline66.83 (4.4)  69.52 (4.05)  NS
 12 week61.38 (4.4)15.152.89 to 27.4151.57 (4.05)17.956.61 to 29.23 
 24 week43.6 (4.4)23.2310.97 to 35.4934.9 (4.05)34.6123.34 to 45.89 
Dyspnea
 Baseline36.24 (4.06)  36 (3.73)  NS
 12 week27.14 (4.06)9.09−2.22 to 20.418.05 (3.73)17.957.55 to 28.35 
 24 week19.07 (4.06)17.175.86 to 28.4815.49 (3.73)20.5110.11 to 30.92 
Fatigue
 Baseline85.71 (3.64)  85.97 (3.35)  NS
 12 week70.9 (3.64)14.814.66-24.9661.37 (3.35)24.515.17 to 33.84 
 24 week61.81 (3.64)32.3222.57 to 42.0753.39 (3.35)32.4823.14 to 41.81 
Global health
 Baseline13.96 (2.77)  13.83 (2.55)  0.02
 12 week24.06 (2.77)−11.61−19.96 to −3.2733.92 (2.55)−19.32−26.9 to −11.55 
 24 week27.09 (2.77)−15.15−23.5 to −6.843.74 (2.55)−30.77−38.4 to −23.1 
Quality of life
 Baseline17.68 (2.99)  18.37 (2.76)  0.007
 12 week29.30 (2.99)−10.1−17.82 to −2.3737.6 (2.76)−20.0827.19 to −12.9 
 24 week32.84 (2.99)−13.13−20.8 to −5.449.14 (2.76)−29.91−37 to −22.8 

Post-hoc analysis of all the functioning dimensions of QLQ C-30 revealed a greater improvement in combined therapy group at 12 weeks. Pain scale was reduced in combined therapy while global quality of life and global health were improved at 12 weeks. The treatment effect for all the mentioned variables was sustained at 24 weeks, though the differences were lesser.

With respect to HADS-D, mean change from baseline to 12 weeks was 5.06 (95% CI: 3.64–6.48) and 5.7 (95% CI: 4.33–7.18) at 24 weeks for usual care group. For combined therapy group, mean change from baseline at 12 weeks was 5.95 (95% CI: 4.64–7.25), and 6.9 (95% CI: 5.61–8.23) at 24 weeks. Adjusted mean differences between both groups was 0.89 (95% CI: −0.99–2.77).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Our study suggests that using combined therapy for major depression in oncologic patients results in significant improvements in functioning dimensions, global health and global quality of life as well as reduction of pain at 12 weeks. These gains are sustained at the 6-month follow-up. We have also found a non-significant trend towards a reduction in depressive symptoms in the combined therapy group compared with the usual care group. Globally these results support the notion that combined treatment compared with usual care improves significantly overall patient's quality of life but does not reduce significantly depressive symptoms in oncologic patients. An explanation for the negative result in depressive symptomatology could be that HADS may not be a sensitive measure to evaluate therapeutic efficacy 47, 48.

HQoL seems really useful as a result variable when two treatments give the same level of symptoms reduction, since we can expect differences respect to HqoL 49. It is possible that HQoL scores are more sensitive to inherent changes to the adaptation process to illness or ‘response change phenomenon’ 50, than the measures of depressive symptoms 51. Combined intervention, which adds psychotherapy, could be more useful to impulse the adaptation process to the multiple challenges that the patient must face.

To our knowledge, this study represents the first randomized, controlled clinical trial to assess the effectiveness of NT plus escitalopram compared with escitalopram delivered by oncologists on measures of quality of life and depressive symptomatology among Spanish patients with non-metastatic cancer who met depression diagnostic criteria according to DSM-IV-TR. In addition, this study represents the first one in which an adaptation of NT for depression has been used. NT is an integrative intervention designed to address components that are of critical importance in depressed patients. In the oncological field, we have found that using somatosensorial interventions that modulate emotion arousal and mind–body interactions, as well as interventions directed to family and other important caregivers whose attitudes might influence psychological distress is crucial 18, 19.

Following the recommendations of Sellick, Newell and the Revised Consort Statement 5, 16, 52 about clinical trials, we have clearly detailed randomization procedure, have made blind outcome assessments and have accounted for all patient's disposition and clinical characteristics of the treatment population. In addition, we have included up to 30 patients per treatment arm, with a longer follow-up period than in previous studies. The type of intervention and the number of sessions have been described. The intervention was carried out by well-trained clinicians (psychiatrists and psychologists) with ample experience in the field of psychotherapy. Another advantage of our clinical trial is that the population of patients is homogeneous in terms of their illness status (non-metastatic), and the study includes data in cancer types that are less well studied than breast cancer, such as colon and lung cancer. Moreover, all the subjects met depression diagnostic criteria using clinical interviews conducted by trained clinicians.

The proportion of patients who discontinued from the trial was different between the two interventions with an overall better compliance for patients randomized to the combined therapy group. The reasons given by patients to stop medication were mainly the belief that they did not need antidepressants and the fear of a possible pharmacological interaction with cancer medications. NT with its emphasis in working with patient's narrative and with an acceptation stance might have a positive impact in patient's fears and worries about medication interactions and side effects.

Our study has several limitations. First, the sample size in each arm is less than 50, a number advised in Newell's review. However, most of previous clinical trials comparing psychosocial interventions had less than 30 per treatment group 18. This fact reflects the difficulties in recruiting patients with strict inclusion criteria and high refusal rates to participate. In our study, before randomization, approximately half of the sample (78 subjects) refused to participate in the study though they met all inclusion criteria. A substantial number of patients communicated their fear of worsening or collapsing if they talked about their feelings with a therapist. This refusal rate number is similar to other trials of depressed patients 14, 15, 21. Second, the combined therapy group had a higher percentage of patients with breast cancer and lower percentage of lung cancer patiens compared with the usual care group. Third, we have used an interim analysis to estimate statistical power and sample size. However, the analysis was done by an external unconnected study analyst, blind to the randomization. Finally, the administration of the drug was done by a different specialist. We have tried to be closer to natural conditions and in our setting, oncologists may use antidepressants in some patients without derivation to psychiatry service. In addition, due to the design of the study and with the objective of reducing comparison bias, combined therapy has been compared with a highly intensified usual care regimen that is not commonly used in our setting. The fact that the study has been developed in a real clinical context with patients that present well-diagnosed depression adds effectiveness value to this study. The applicability of our results might be compromised by the feasibility in the ‘real world’ and its cost-effectiveness, since intervention was delivered by well-trained therapists. The implementation of our approach might require further adaptation that could imply group interventions. One thing in favour of our intervention is that it proved to be acceptable to patients, shows good potential for dissemination, is relatively easy to implement, and improved the compliance.

As a conclusion we could say that NT used in combination with antidepressants appears to be a potentially beneficial intervention in depression in oncologic non-metastatic illness. Combined therapy does not seem superior to pharmacological approach to reduce depressive symptoms, but it improves much more quality of life. Further research, with larger samples, is clearly needed to better understand the psychological mechanisms provided by NT.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The authors thank the contribution of patients, oncologists and the Statistics and Epidemiology department of La Paz University Hospital for his valuable help.

Special thanks to Jose R Arribas, M.D for his helpful suggestions.

The work was supported with unrestricted grants from Lundbeck, FIS PI 050737 and FIS PI 052062. The funding source had no role in the study design, data collection, analysis and interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication.

Author contributions: Conception and design: Beatríz Rodríguez Vega, Carmen Bayón, Ángela Palao.

Provision of patients and application of interventions: Angela Palao, Ana Hospital, María Dieguez, Beatríz Castelo.

Collection and assembly of data: Guadalupe Torres, Guillermo Benito.

Data Analysis and interpretations: Carmen Bayón, Beatriz Rodríguez Vega, Angela Palao, Guadalupe Torres, Elia Pérez.

Manuscript writing: Beatríz Rodriguez Vega, Carmen Bayón.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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