Psychopharmacology and Psychiatry Updates Beyond Monotherapy: Mixed Episode Management
Nov 2, 2025
Dr. David Osser, Associate Professor of Psychiatry at Harvard Medical School, shares his expertise on managing mixed manic episodes. He discusses the critical timing for adding lithium or valproate to antipsychotics, emphasizing patience and evidence-based strategies. Osser cautions against rushing into combination therapies due to managed care pressures and advocates for temporary use of benzodiazepines to stabilize patients. He weighs the pros and cons of lithium versus valproate and considers carbamazepine as a viable third-line option.
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Give The First Drug A Proper Trial
- Give the first antimanic drug a full trial before adding another agent.
- Wait up to two weeks when possible to avoid unnecessary polypharmacy and extra side effects.
Add-On Studies Require A Two-Week Fail
- Randomized add-on studies required an unsatisfactory two-week trial on the first drug before adding a second.
- No robust trials compare starting with combination therapy versus monotherapy first.
Choose Valproate First; Lithium If Needed
- When mixed mania needs combination therapy, prefer valproate as the add-on given the strongest evidence.
- Consider lithium if valproate is contraindicated or for its anti-suicide benefits despite less robust mixed-episode efficacy.