Session number: 1112
Abstract title: Evidence-Based Review of Mood Stabilizers for Manic-Depressive Disorder
Author(s):
L Mitchner - Residency Training Program, Brown University
MS Bauer - Providence VA Medical Center
Objectives: A plethora of medications are used for the various phases of manic-depressive (bipolar) disorder, including lithium, certain anticonvulsants, calcium channel blockers, benzodiazepines, neuroleptics, and antidepressants. We are aware of no systematic review that has investigatated available clinical trial evidence with particular attention to which specific medications have empirical support for which phases of the disorder (mania/depression, acute/prophylaxis). Clinical practice has evolved without sufficient attention to its evidence basis and many medications are used in various phases despite having little or no emprical support for that use.
Methods: This review sought to locate all studies on somatotherapy (pharmacotherapy + devices) for bipolar disorder that filled the following criteria: (a) published in peer-reviewed journals, (b) investigated an intervention in a sample of patients with bipolar disorder, or reported separately results for bipolar subsamples from a diagnostically heterogeneous group, (c) outcome reported in quantitative terms, (d) written in English. Literature databases including MedLine, PsychLit and the Cochrane Collaboration were searched. Articles were reviewed by title, abstract, and text as relevant. Authors known to be actively working in the field in the US and Europe were contacted regarding further work in print or in press. Review of the bibliography of each located article was scanned for additional articles. This step was repeated iteratively until no further references were found. The search covered studies published or in press through September, 2001. Studies were then catetorized according to the AHCPR/AHRQ evidence-rating scheme as Class A, B, or C. Studies classified A or B were included in this analysis.
Results: Over 500 studies were reviewed. To date 101 Class A or Class B studies investigating agents in monotherapy studies were identified, and 45 Class A or Class B studies combination therapy trials were identified. Kappa statistic for inter-rater reliability in classifying studies was 0.85. A 2x2 system was used to categorize efficacy evidence: Acute/Prophylaxis and Manic/Depressive Symtpoms. The only agent with Class A/B efficacy evidence for roles in all four phases of treatment is lithium. Anticonvulsants and atypical neuroleptics, widely used for long-term treatment have much more limited support, with carbamazepine and lamotrigine having the most promising prophylactic evidence to date among anticonvulsants. Acute mania has far and away the greatest number of agents with proven efficacy, while many fewer agents have efficacy in acute depression, prophylaxis of mania, and prophylaxis of depression.
Conclusions: Using AHCPR/AHRQ criteria and the 2x2 approach to categorizing efficacy data, it is clear that with the exception of lithium no agent can be considered efficacious for all phases of manic-depressive disorder, and therefore this agent is the only one that can truly be considered a mood stabilizer in the fullest sense of the term. Moreover, clinical usage far outstrips its evidence basis.
Impact statement: These data help us recognize the need in particular for more studies of agents for acute depressive symptoms and for prophylaxis. Moreover, this study indicates that lithium remains the "gold standard" against which to compare other putative mood stabilizers.