To the Editor: We read the study by Dr. Suppes et al. (1) with a great deal of interest and wish to raise concerns about the methodology. The authors evaluated the efficacy and safety of the combination of quetiapine with lithium or divalproex relative to monotherapy with lithium or semisodium valproate in maintenance treatment for patients with bipolar I disorder.
Randomized controlled trials are usually cited as the gold standard for detecting the efficacy of results. However, they often can be flawed in design and are not immune to bias.
First, in this study, 1,953 patients received open-label quetiapine. However, only 628 patients were randomly allocated for maintenance treatment. This indicates that only one-third of the patients were selected for maintenance therapy, which raises the possibility of selection bias. In this regard, Healy (2) stated that company sponsored clinical trials invariably recruit samples of convenience, which by definition do not actually sustain extrapolation to normal clinical practice.
Second, the authors used a wide range of exclusion and restricted inclusion criteria, which minimized the generalizability of the results.
Finally, although both arms received active treatment, the authors failed to perform power calculation, and they did not justify the sample size, which is also a requirement of the Consolidated Standards of Reporting Trials guidelines (3).
We would appreciate clarification of these issues raised.
Suppes T, Vieta E, Liu S, Brecher M, Paulsson B: Maintenance treatment for patients with bipolar I disorder: results from a North American study of quetiapine in combination with lithium or divalproex (trial 127). Am J Psychiatry 2009; 166:476–488
Healy D: Evidence biased psychiatry? Psychiatr Bull 2001; 25:290–291
Begg C, Cho M, Eastwood S: Improving the quality of reporting of randomized controlled trials: the CONSORT statement. JAMA 1996; 276:637–639
The authors report no competing interests.
This letter (doi: 10.1176/appi.ajp.2009.09050700) was accepted for publication in July 2009.