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S075-1

Balancing Benefits and Harms of Treatments for Acute Bipolar Depression

Terence A. Ketter

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

Background/Objective: Bipolar depression is more pervasive than mania, but has fewer
evidence-based treatments.

Method: Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-
analyses, we assessed the number needed to treat (NNT) for response and the number needed to
harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.

Result: The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine
combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC,
NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP
sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and
adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this
advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for
antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response
NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability
(NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive
armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently
demonstrated in randomized controlled trials.

Conclusion: Limitations: NNT and NNH are categorical metrics; only selected NNHs were assessed;
limited generalizability of efficacy (versus effectiveness) studies.

Conclusions: For acute bipolar depression, older approved treatments may have utility in
high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency
situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug
development needs to focus on not only efficacy but also on tolerability.