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

Abstract

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.

Pharmacotherapeutic trends in 2231 psychiatric inpatients with bipolar depression from the International AMSP Project between 1994 and 2009

“…Some of the observed discrepancies between expert recommendations and real-life pharmacotherapy may also be due to the limitations of current randomized clinical trials as suggested by a recent systematic review (Spanemberg et al, 2011). The authors concluded that several articles on the pharmacological treatment of bipolar depression have methodological errors, biases and statistical simplifications, which complicate the extrapolation of the data to real-life settings.…”

A systematic review of the evidence for the treatment of acute depression in bipolar I disorder

“…Given limited data on the efficacy of primary or adjunctive treatments (ie, there are no gold standard effective treatments), direct comparisons without placebo were not included, and there are only a handful of such studies in any case. 14,15 The discussion that follows organizes treatments by medication class. The evidence for the efficacy of each medication is then discussed.…”

Comprehensive comparison of monotherapies for psychiatric hospitalization risk in bipolar disorders

“…[0-1]*, 296. [4][5][6][7][8]*, F30* and F31*) or SCAD (295.7* and F25*) during the observation period 2003-2015, and were newly given one of 29 drugs of interest, including lithium, mood-stabilizing anticonvulsants (MSAs), first-generation antipsychotics (FGAs), secondgeneration antipsychotics (SGAs), and antidepressants (ADs) (Supporting Information Table S1). Each drug of interest had at least 250 observations that met study design criteria.…”

“…The evidence on drug‐dependent risk of hospitalization in BD is incomplete and contradictory. The majority of published comparative effectiveness studies of BD drugs have focused on symptom reduction and rates of remission achievement, relapses and recurrences, rather than on psychiatric hospitalization . Comparison is usually made for just a few agents (e.g.…”

“…The majority of published comparative effectiveness studies of BD drugs have focused on symptom reduction and rates of remission achievement, relapses and recurrences, rather than on psychiatric hospitalization. 5 Comparison is usually made for just a few agents (e.g. lithium, valproate, lamotrigine, quetiapine, imipramine and olanzapine), with relatively scarce data on other medications.…”