CRD summary

The review found that it was unclear whether switching antidepressants was effective as a strategy for management of treatment-resistant depression. Other than suboptimal reporting of review processes, the review was well conducted and the authors’ conclusions appear reliable.

Authors' objectives

To assess the effectiveness of managing treatment-resistant depression by switching antidepressants.

Searching

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to May 2007. Search terms were reported. Reference lists of eligible studies, recent reviews and textbooks were checked. Citations of eligible studies were searched in SciSearch.

Study selection

Double-blinded randomised controlled trials (RCTs) of adults who were non-responsive to antidepressant monotherapy (at a standard or higher dose ) and that compared switching antidepressants to continuing the initial antidepressant were eligible for inclusion. Studies were required to focus on treatment of depressive disorders diagnosed by established criteria (defined in the review) and to use established rating scales to confirm non-response and measure outcomes. It was required that the initial antidepressant and the trial interventions were administered for at least four weeks each, with or without benzodiazepines or antipsychotics.

Participants in the included studies had major depression and had not responded to six or seven weeks’ treatment with fluoxetine (20mg/day), nortriptyline (75 to 175mg/day) or venlafaxine (75 to 375mg/day). Non-response was evaluated prior to randomisation in two of the studies. The antidepressants received by the switch groups were mianserine (60mg/day) and fluoxetine (25 to 50mg/day). The included studies used the Hamilton or Montgomery-Asberg Depression Rating Scales to measure rates of response (defined as at least 50% decrease in total score) and remission (defined as total score or mean of two scores of 8 points or fewer). Duration of the switch/continuation phase of studies ranged from six to 12 weeks. None of the studies was designed to assess switching strategies, but evaluated study arms of monotherapy with a different antidepressant against another that continued the initial antidepressant.

Two reviewers independently selected the studies. Disagreements were resolved by consensus.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Odds ratios (ORs) were extracted or calculated from event rates in the primary studies, with 95% confidence intervals (CIs). Intention-to-treat analysis was used.

The authors did not state how many reviewers performed data extraction

Methods of synthesis

Studies were combined to calculate pooled odds ratios and 95% confidence intervals using a fixed-effect model. All switch groups were compared with all continuation groups. Heterogeneity was assessed using Χ² and I² tests. The effect of using a random-effects model was examined.

Results of the review

Three RCTs were included in the review (n=395 participants analysed in the review).

There was no statistically significant difference in either response or remission rates between the switch group and the continuation group for response rate. Heterogeneity was in the medium range (I²=42.9% and I²=47.9%). Confidence intervals were wide. Results did not differ substantially when a random-effects model was used.

Authors' conclusions

It was unclear whether switching antidepressants was effective as a strategy for management of treatment-resistant depression.

CRD commentary

The objectives and inclusion criteria of the review were clear and relevant sources were searched for studies. It was unclear whether the search was restricted by language and publication status. Steps were taken to minimise the risk of reviewer bias and error by having more than one reviewer independently select studies; it was unclear whether this also applied to data extraction. No systematic assessment of study validity was reported, although the restriction to double-blinded RCTs and the use of intention-to-treat analysis in the review provided some assurance of data quality. Appropriate statistical techniques were used to combine the studies and to assess heterogeneity. The authors noted other potential sources of bias in the review, such as the effect of patients dropping out after non-response to the initial antidepressant and before randomisation. Other than suboptimal reporting of review processes, the review was well conducted and the authors’ conclusions appear reliable.

Implications of the review for practice and research

Practice: The authors stated that physicians should not use switching of antidepressants as their preferred strategy for management of non-responders to an initial antidepressant; alternative strategies should at least be considered (electroconvulsive therapy, lithium augmentation).

Research: The authors stated that more controlled studies were needed on antidepressant switching strategies.

Funding

Not stated.

Bibliographic details

Bschor T, Baethge C. No evidence for switching the antidepressant: systematic review and meta-analysis of RCTs of a common therapeutic strategy. Acta Psychiatrica Scandinavica 2010; 121(3): 174-179. [PubMed: 19703121]

Original Paper URL

http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0447.2009.01458.x/abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Antidepressive Agents /therapeutic use; Depression /drug therapy; Depressive Disorder /drug therapy; Double-Blind Method; Drug Administration Schedule; Drug Resistance /drug effects; Humans; MEDLINE; Randomized Controlled Trials as Topic; Registries; Treatment Outcome

AccessionNumber

12010001772

Database entry date

15/09/2010

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.