Amitriptyline Versus Placebo for Major Depressive Disorder.
Amitriptyline versus placebo for major depressive disorder.
Filed under: Depression Treatment
Cochrane Database Syst Rev. 2012; 12: CD009138
Leucht C, Huhn M, Leucht S
Amitriptyline is a tricyclic antidepressant that was synthesised in 1960 and introduced as early as 1961 in the USA, but is still regularly used. It has also been frequently used as an active comparator in trials on newer antidepressants and can therefore be called a ‘benchmark’ antidepressant. However, its efficacy and safety compared to placebo in the treatment of major depression has not been assessed in a systematic review and meta-analysis.To assess the effects of amitriptyline compared to placebo or no treatment for major depressive disorder in adults.We searched the Cochrane Depression, Anxiety and Neurosis Group’s Specialised Register (CCDANCTR-Studies and CCDANCTR-References) to August 2012. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). The reference lists of reports of all included studies were screened and manufacturers of amitriptyline contacted for details of additional studies.All randomised controlled trials (RCTs) comparing amitriptyline with placebo or no treatment in patients with major depressive disorder as diagnosed by operationalised criteria.Two review authors independently extracted data. For dichotomous data, we calculated the odds ratio (OR) with 95% confidence intervals (CI). We analysed continuous data using standardised mean differences (with 95% CI). We used a random-effects model throughout.The review includes 39 trials with a total of 3509 participants. Study duration ranged between three and 12 weeks. Amitriptyline was significantly more effective than placebo in achieving acute response (18 RCTs, n = 1987, OR 2.67, 95% CI 2.21 to 3.23). Significantly fewer participants allocated to amitriptyline than to placebo withdrew from trials due to inefficacy of treatment (19 RCTs, n = 2017, OR 0.20, 95% CI 0.14 to 0.28), but more amitriptyline-treated participants withdrew due to side effects (19 RCTs, n = 2174, OR 4.15, 95% CI 2.71 to 6.35). Amitriptyline also caused more anticholinergic side effects, tachycardia, dizziness, nervousness, sedation, tremor, dyspepsia, sedation, sexual dysfunction and weight gain. In subgroup and meta-regression analyses the results of the primary outcome were robust towards publication year (1971 to 1997), mean participant age at baseline, mean amitriptyline dose, study duration in weeks, pharmaceutical sponsor, inpatient versus outpatient setting and two-arm versus three-arm design. However, higher severity at baseline was associated with higher superiority of amitriptyline (P = 0.02), while higher responder rates in the placebo groups were associated with lower superiority of amitriptyline (P = 0.05). The results of the primary outcome were rather homogeneous, reflecting comparability of the trials. However, methods of randomisation, allocation concealment and blinding were usually poorly reported. Not all studies used intention-to-treat analyses and in many of them standard deviations were not reported and often had to be imputed. Funnel plots suggested a possible publication bias, but the trim and fill method did not change the overall effect size much (seven adjusted studies, OR 2.64, 95% CI 2.24 to 3.10).Amitriptyline is an efficacious antidepressant drug. It is, however, also associated with a number of side effects. Degree of placebo response and severity of depression at baseline may moderate drug-placebo efficacy differences.
HubMed – depression
Psychological therapies for the treatment of post-traumatic stress disorder in children and adolescents.
Filed under: Depression Treatment
Cochrane Database Syst Rev. 2012; 12: CD006726
Gillies D, Taylor F, Gray C, O’Brien L, D’Abrew N
Post-traumatic stress disorder (PTSD) is highly prevalent in children and adolescents who have experienced trauma and has high personal and health costs. Although a wide range of psychological therapies have been used in the treatment of PTSD there are no systematic reviews of these therapies in children and adolescents.To examine the effectiveness of psychological therapies in treating children and adolescents who have been diagnosed with PTSD.We searched the Cochrane Depression, Anxiety and Neurosis Review Group’s Specialised Register (CCDANCTR) to December 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We also checked reference lists of relevant studies and reviews. We applied no date or language restrictions.All randomised controlled trials of psychological therapies compared to a control, pharmacological therapy or other treatments in children or adolescents exposed to a traumatic event or diagnosed with PTSD.Two members of the review group independently extracted data. If differences were identified, they were resolved by consensus, or referral to the review team.We calculated the odds ratio (OR) for binary outcomes, the standardised mean difference (SMD) for continuous outcomes, and 95% confidence intervals (CI) for both, using a fixed-effect model. If heterogeneity was found we used a random-effects model.Fourteen studies including 758 participants were included in this review. The types of trauma participants had been exposed to included sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service.The psychological therapies used in these studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most compared a psychological therapy to a control group. No study compared psychological therapies to pharmacological therapies alone or as an adjunct to a psychological therapy.Across all psychological therapies, improvement was significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42), anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly lower within a month of completing psychological therapy compared to a control group.The psychological therapy for which there was the best evidence of effectiveness was CBT. Improvement was significantly better for up to a year following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01 to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD symptom scores were also significantly lower for up to one year (up to one month: three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13) in the CBT group compared to a control. No adverse effects were identified.No study was rated as a high risk for selection or detection bias but a minority were rated as a high risk for attrition, reporting and other bias. Most included studies were rated as an unclear risk for selection, detection and attrition bias.There is evidence for the effectiveness of psychological therapies, particularly CBT, for treating PTSD in children and adolescents for up to a month following treatment. At this stage, there is no clear evidence for the effectiveness of one psychological therapy compared to others. There is also not enough evidence to conclude that children and adolescents with particular types of trauma are more or less likely to respond to psychological therapies than others.The findings of this review are limited by the potential for methodological biases, and the small number and generally small size of identified studies. In addition, there was evidence of substantial heterogeneity in some analyses which could not be explained by subgroup or sensitivity analyses.More evidence is required for the effectiveness of all psychological therapies more than one month after treatment. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies or the effectiveness of psychological therapies compared to other treatments. More details are required in future trials in regards to the types of trauma that preceded the diagnosis of PTSD and whether the traumas are single event or ongoing. Future studies should also aim to identify the most valid and reliable measures of PTSD symptoms and ensure that all scores, total and sub-scores, are consistently reported.
HubMed – depression
Interventions to facilitate return to work in adults with adjustment disorders.
Filed under: Depression Treatment
Cochrane Database Syst Rev. 2012; 12: CD006389
Arends I, Bruinvels DJ, Rebergen DS, Nieuwenhuijsen K, Madan I, Neumeyer-Gromen A, Bültmann U, Verbeek JH
Adjustment disorders are a frequent cause of sick leave and various interventions have been developed to expedite the return to work (RTW) of individuals on sick leave due to adjustment disorders.To assess the effects of interventions facilitating RTW for workers with acute or chronic adjustment disorders.We searched the Cochrane Depression, Anxiety and Neurosis Review Group’s Specialised Register (CCDANCTR) to October 2011; the Cochrane Central Register of Controlled Trials (CENTRAL) to Issue 4, 2011; MEDLINE, EMBASE, PsycINFO and ISI Web of Science, all years to February 2011; the WHO trials portal (ICTRP) and ClinicalTrials.gov in March 2011. We also screened reference lists of included studies and relevant reviews.We selected randomised controlled trials (RCTs) evaluating the effectiveness of interventions to facilitate RTW of workers with adjustment disorders compared to no or other treatment. Eligible interventions were pharmacological interventions, psychological interventions (such as cognitive behavioural therapy (CBT) and problem solving therapy), relaxation techniques, exercise programmes, employee assistance programmes or combinations of these interventions. The primary outcomes were time to partial and time to full RTW, and secondary outcomes were severity of symptoms of adjustment disorder, work functioning, generic functional status (i.e. the overall functional capabilities of an individual, such as physical functioning, social function, general mental health) and quality of life.Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently clinically homogeneous in different comparison groups, and assessed the overall quality of the evidence using the GRADE approach.We included nine studies reporting on 10 psychological interventions and one combined intervention. The studies included 1546 participants. No RCTs were found of pharmacological interventions, exercise programmes or employee assistance programmes. We assessed seven studies as having low risk of bias and the studies that were pooled together were comparable. For those who received no treatment, compared with CBT, the assumed time to partial and full RTW was 88 and 252 days respectively. Based on two studies with a total of 159 participants, moderate-quality evidence showed that CBT had similar results for time (measured in days) until partial RTW compared to no treatment at one-year follow-up (mean difference (MD) -8.78, 95% confidence interval (CI) -23.26 to 5.71). We found low-quality evidence of similar results for CBT and no treatment on the reduction of days until full RTW at one-year follow-up (MD -35.73, 95% CI -113.15 to 41.69) (one study with 105 participants included in the analysis). Based on moderate-quality evidence, problem solving therapy (PST) significantly reduced time until partial RTW at one-year follow-up compared to non-guideline based care (MD -17.00, 95% CI -26.48 to -7.52) (one study with 192 participants clustered among 33 treatment providers included in the analysis), but we found moderate-quality evidence of no significant effect on reducing days until full RTW at one-year follow-up (MD -17.73, 95% CI -37.35 to 1.90) (two studies with 342 participants included in the analysis).We found moderate-quality evidence that CBT did not significantly reduce time until partial RTW and low-quality evidence that it did not significantly reduce time to full RTW compared with no treatment. Moderate-quality evidence showed that PST significantly enhanced partial RTW at one-year follow-up compared to non-guideline based care but did not significantly enhance time to full RTW at one-year follow-up. An important limitation was the small number of studies included in the meta-analyses and the small number of participants, which lowered the power of the analyses.
HubMed – depression
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