Pharmacological Treatment of Bipolar Depression: Qualitative Systematic Review of Double-Blind Randomized Clinical Trials

Randomized clinical trial (RCT) is the best study design for treatment-related issues, yet these studies may present a number
of biases and limitations. The objective of this study is to carry out a qualitative analysis of RCT methodology in the treatment
of bipolar depression (BD). A systematic review covering the last 20 years was performed on PubMed selecting double-blind
RCTs for BD. The identification items of the articles, their design, methodology, outcome and grant-related issues were all
analyzed. Thirty articles were included, all of which had been published in journals with an impact factor >3. While almost
half studies (46.7%) used less than 50 patients as a sample, 70% did not describe or did not perform sample size calculation.
The Last Observation Carried Forward (LOCF) method was used in 2/3 of the articles and 53.4% of the studies had high sample
losses (>20%). Almost half the items were sponsored by the pharmaceutical industry and 33.3% were sponsored by institutions
or research foundations. Articles on the pharmacological treatment of BD have several limitations which hinder the extrapolation
of the data to clinical practice. Methodological errors and biases are common and statistical simplifications compromise the
consistency of the findings.