International prescribing patterns for mood illness: the International Mood Network (IMN).

OBJECTIVE: To show the feasibility of creating an international network that will build a common database for mood disorders research, and to present initial data on prescribing patterns worldwide. METHODS: An international research database was organized with clinicians and researchers actively treating mood disorders. Participating sites were asked to provide data on 10-50 subjects initially. This work was conducted under the auspices of a committee with representatives from North and South America, Europe, and Asia. Data was pooled from multiple sites using a centralized online system and then analyzed. Each site received IRB approval for its participation in the IMN and the Tufts Medical Center IRB provided approval for the entire project. LIMITATIONS: More than half of the population came from one country (United States) and there is the possibility of cultural bias. RESULTS: Among the 186 subjects enrolled in the IMN, a majority of subjects were prescribed mood stabilizers including lithium (64%), lamotrigine (37%), valproate (31%), and carbamazepine (3%). 79% had a diagnosis of bipolar disorder type I, II or NOS and 21% had a diagnosis of MDD. 81% of subjects used antidepressants at some point. 25% experienced antidepressant-induced mania and 26% had antidepressant-related rapid cycling. Mood stabilizers were prescribed more in Europe (86%), neuroleptics in South America (70%), and antidepressants in Asia (58%). CONCLUSIONS: The results confirm the diversity and feasibility of an international mood disorders database. Important regional differences in psychotropic drug treatment of mood illnesses were observed, with more mood stabilizer use in Europe and South America, and more antidepressant use in non-European populations.

Solving the antidepressant efficacy question: effect sizes in major depressive disorder.

BACKGROUND: Numerous reviews and meta-analyses of the antidepressant literature in major depressive disorders (MDD), both acute and maintenance, have been published, some claiming that antidepressants are mostly ineffective and others that they are mostly effective, in either acute or maintenance treatment. OBJECTIVE: The aims of this study were to review and critique the latest and most notable antidepressant MDD studies and to conduct our own reanalysis of the US Food and Drug Administration database studies specifically analyzed by Kirsch et al. METHODS: We gathered effect estimates of each MDD study. In our reanalysis of the acute depression studies, we corrected analyses for a statistical floor effect so that relative (instead of absolute) effect size differences were calculated. We also critiqued a recent meta-analysis of the maintenance treatment literature. RESULTS: Our reanalysis showed that antidepressant benefit is seen not only in severe depression but also in moderate depression and confirmed a lack of benefit for antidepressants over placebo in mild depression. Relative antidepressant versus placebo benefit increased linearly from 5% in mild depression to 12% in moderate depression to 16% in severe depression. The claim that antidepressants are completely ineffective, or even harmful, in maintenance treatment studies involves unawareness of the enriched design effect, which, in that analysis, was used to analyze placebo efficacy. The same problem exists for the standard interpretation of those studies, although they do not prove antidepressant efficacy either, since they are biased in favor of antidepressants. CONCLUSIONS: In sum, we conclude that antidepressants are effective in acute depressive episodes that are moderate to severe but are not effective in mild depression. Except for the mildest depressive episodes, correction for the statistical floor effect proves that antidepressants are effective acutely. These considerations only apply to acute depression, however. For maintenance, the long-term efficacy of antidepressants is unproven, but the data do not support the conclusion that they are harmful.

Long-term worsening of bipolar disorder related with frequency of antidepressant exposure.

BACKGROUND: The aim of this study of 53 persons with bipolar disorder (BD) was to evaluate the relationship between history of exposure to antidepressants (AD) and mood stabilizers (MS) and the percentage of time spent ill. METHODS: BD outpatients with more than 12 months of prospective follow-up were included. Outcome was documented using a life charting technique. Current and previous exposure to AD and MS were assessed using a scale that provides a quantitative measure of exposure to psychotropic medications. Regression models were used to correct for possible confounders. RESULTS: Previous treatment with AD was an independent predictor of polarity changes (P < .001) and mixed symptoms (P = .01). In contrast, "years of exposure to MS" was an independent predictor of time spent asymptomatic (P = .019). The ratio between exposure to AD vs MS was associated with less weeks asymptomatic (P = .03), more mixed symptomatology (P = .019), and more polarity changes (P = .001). CONCLUSIONS: Antidepressant exposure was a major predictor of mood instability in the long-term outcome of BD. The ratio used of previous exposure to AD vs MS was associated with poor outcomes, suggesting that the harmful effect of AD may be additive and related to how much they are used.

The pharmacogenetics of antidepressant-induced mania: a systematic review and meta-analysis.

OBJECTIVE: Antidepressant-induced mania (AIM) has been associated with the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism in some studies but not in others. We conducted a meta-analysis of those studies and other studies of genetic predictors of AIM. METHODS: MEDLINE-based searches of genetic studies of AIM were conducted, and a meta-analysis of six studies of 5-HTTLPR was performed. Other polymorphisms were insufficiently studied to allow for meta-analysis. RESULTS: There was an association of the short (s) variant of 5-HTTLPR and AIM [risk ratio (RR) = 1.35, 95% confidence interval (CI): 1.04-1.76, p=0.02]. There was a higher frequency of s carriers (sl and ss genotypes) in those who developed AIM [RR = 1.38, 95% CI: 0.98-1.93), p=0.06]. CONCLUSION: The 5-HTTLPR polymorphism appears to have a moderate effect size association with AIM in patients with bipolar disorder.