What are the VA/DoD guidelines for combination therapies in the treatment of bipolar affective disorder (manic-depressive illness)?

Updated: May 30, 2019
  • Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD  more...
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In patients whose bipolar depression is unresponsive to monotherapy, consider the combination of lithium with lamotrigine. [3] Alternatively, consider short-term augmentation of antidepressant agents with a selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), bupropion, and monoamine oxidase inhibitor (MAOI); patients using this treatment strategy must be closely monitored for triggering of manic symptoms. [3]

As in severe mania or severe mixed episodes, consider adding clozapine for augmentation, and closely monitor the patient for metabolic or other adverse effects. [3] Because of the known complications involved with clozapine, it is recommended that a psychiatric consultation be initiated.

The VA/DoD found insufficient evidence for or against the use of augmentation with aripiprazole, olanzapine, risperidone, haloperidol, oxcarbazepine, topiramate, ziprasidone, valproate, or carbamazepine in bipolar depression. [3] However, the VA/DoD advised against the use of gabapentin and tricyclic antidepressant agents (TCAs) for monotherapy or augmentation in patients with acute bipolar depression, except in cases in which there was [3] : (1) a previous good response during depression without a switch to mania or (2) a history of treatment of refractory depression.

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