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Pharmacological interventions for people with depression and chronic physical health problems: systematic review and meta-analyses of safety and efficacy |
Taylor D, Meader N, Bird V, Pilling S, Creed F, Goldberg D |
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CRD summary The authors concluded that antidepressants were efficacious and safe in the treatment of depression occurring in the context of chronic physical health problems. The conclusions appear reliable, but inadequate handling of heterogeneity in some analyses suggest a need for caution. Authors' objectives To assess the efficacy, tolerability and safety of antidepressants in adults with depression and chronic physical health problems. Searching MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PsyclNFO were searched from their inceptions to March 2009). The search was repeated in December 2009. Search terms were reported. Reference lists of identified articles, key journals, previous systematic reviews and meta-analyses were handsearched. Experts in the field were contacted. Study selection Randomised controlled trials (RCTs) that compared antidepressants (selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, duloxetine, mirtazapine, mianserin, trazodone and others licensed since 1958) to placebo or other antidepressants in participants with depression and chronic physical illnesses (such asthma, cancer, cardiovascular disease, chronic obstructive pulmonary disease, diabetes) were eligible for inclusion. Outcome measures were: remission, response, discontinuation for any reason, discontinuation due to adverse events, mean score on a validated depression scale, mean score on quality of life measure and physical health outcomes.
Studies were conducted in USA, UK, China, Ireland, Germany, Belgium, Italy, Austria, The Netherlands, Canada, Finland, Turkey, Denmark, France and Sweden (where reported). A large proportion of the studies were conducted in USA. Study settings were varied (hospitals, outpatient clinics, oncology clinics, coronary care clinics; further details reported in paper). The mean age of participants (where reported) ranged between 34 to 82 years. Diagnoses of included patients were varied (asthma, cancer, arthritis, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, epilepsy, general medical conditions, HIV, multiple sclerosis, stroke, myocardial infarction, Parkinson’s disease, renal dialysis). Study durations ranged from one to 52 weeks (where reported).
The authors did not state how many reviewers assessed studies for inclusion. Assessment of study quality Study quality was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) checklist for RCTs. Key criteria assessed included method of randomisation, allocation concealment, masking, completion of treatment and differences between groups other than treatment. Overall quality of evidence was rated (as high, moderate, low, very low) using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.
Study quality was assessed by one reviewer and double-checked by another for accuracy; disagreements were resolved by discussion. Data extraction Data to enable calculation of risk ratios (RRs) and mean differences, and 95% confidence intervals (CIs), were extracted by one reviewer and double-checked by another; disagreements were resolved by discussion. Intention-to-treat data with last observation carried forward was preferred over observed case data. Methods of synthesis Pooled standardised mean differences (SMDs), effect sizes and risk ratios, with 95% CIs, were calculated using a random-effects model. Heterogeneity was assessed using I2. Publication bias was assessed using funnel plots and Egger’s tests. Results of the review Sixty-three studies (5,794 participants, range 12 to 596) were included. The GRADE quality of included studies ranged from low to moderate. Most studies were double-blinded.
SSRIs versus placebo (35 RCTs): SSRIs were associated with higher levels of remission and response in all studies (remission, RR 0.81, 95% CI 0.73 to 0.91; response, RR 0.83, 95% CI 0.71 to 0.97).
SSRIs were associated with a positive effect on mean change in depression rating scale score (effect size) in all studies (patient-rated scales, SMD -0.19, 95% CI -0.36 to -0.02; observer rated scales, SMD -0.34, 95% CI -0.47 to -0.20).
Mixed results were reported on tolerability of SSRIs compared to placebo: no differences were found between groups for leaving the study for any reason, but participants who received SSRIs were more likely to leave the study early because of adverse events (RR 1.80, 95% CI 1.16 to 2.78).
SSRIs were associated with significantly higher quality of life (SMD -0.27, 95% CI -0.44 to -0.10)
TCAs versus placebo (nine RCTs): TCAs were associated with medium-to-large benefits on most depression outcomes (observer-rated depression scales SMD -0.70, 95% CI -0.97 to -0.43; patient-rated scales SMD –0.58, 95% CI -1.14 to -0.02). Participants who received TCAs were more likely to respond to treatment (RR 0.55, 95% CI 0.43 to 0.70). No effect on remission was found.
There was evidence of a trend for TCAs being less well tolerated. There were no significant differences between TCAs and placebo with regard to number of participants leaving the study for any reason or because of adverse events.
SSRIs versus TCAs (14 studies): No significant differences were found on efficacy between the two types of drugs.
Results for additional comparisons were reported in the paper. There was no evidence of publication bias
Other drugs versus placebo (six studies): Mixed results were reported in studies comparing other drugs (trazodone, mirtazapine, duloxetine, mianserin, psychostimulants) to placebo.
Other head-to-head comparisons (four studies) were fluoxetine versus paroxetine, citalopram versus venlafaxine, TCAs versus nomifensine and maprotiline versus mianserin. Overall, there was little if any evidence of benefit of one drug or drug class over another; further details were reported in the paper. Authors' conclusions Antidepressants were efficacious and safe in the treatment of depression occurring in the context of chronic physical health problems. CRD commentary The review question was clearly stated. Four major databases were searched. Efforts were made to search for unpublished papers, which minimised potential publication bias. Appropriate steps were taken to minimise potential reviewer error and bias in data extraction and validity assessment; it was unclear whether similar processes were used in study selection and this raised the possibility of error and bias. Study quality was assessed using appropriate criteria and results reported. Statistical heterogeneity was inadequately addressed in a number of analyses.
The authors’ conclusions appear reliable, but inadequate handling of heterogeneity in some analyses suggest a need for caution. Implications of the review for practice and research
Practice: The authors stated that overall no particular drug could be recommended in any particular situation based on data reviewed; however, SSRIs may be seen as drugs of choice in people with chronic physical health problems assuming interactions and contraindications do not preclude their use.
Research: The authors did not state any implications for further research. Bibliographic details Taylor D, Meader N, Bird V, Pilling S, Creed F, Goldberg D. Pharmacological interventions for people with depression and chronic physical health problems: systematic review and meta-analyses of safety and efficacy. British Journal of Psychiatry 2011; 198(3): 179-188 Indexing Status Subject indexing assigned by NLM MeSH Adult; Antidepressive Agents /classification /therapeutic use; Attitude to Health; Chronic Disease /drug therapy; Depression /drug therapy; Humans; Myocardial Infarction /drug therapy; Placebos; Psychiatric Status Rating Scales; Quality of Life; Randomized Controlled Trials as Topic; Remission Induction; Serotonin Uptake Inhibitors /therapeutic use; Treatment Outcome AccessionNumber 12011002000 Date bibliographic record published 03/08/2011 Date abstract record published 29/01/2012 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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