Depression predominates across the lifespan in patients with bipolar disorder. Here: A discussion about (and beyond) the four FDA-approved drugs to treat symptoms.
Depression predominates across the lifespan in patients with bipolar disorder. Here: A discussion about (and beyond) the four FDA-approved drugs to treat symptoms. Listen to the podcast.
The atypical antipsychotics are complex drugs. No two have the same profile, and the line between their receptor profile and clinical effects is a hard one to follow. Only four are FDA-approved in bipolar depression: Cariprazine (Vraylar), lurasidone (Latuda), olanzapine-fluoxetine combo (Symbyax), and quetiapine (Seroquel). Most of the others have tried and failed in this condition, including a few that work in unipolar depression: aripiprazole, ziprasidone, and risperidone. Asenapine (Saphris®), brexpiprazole (Rexulti®), and illoperidone (Invega®) are untested.
For patients, bipolar is a disorder of depression. It is here that they spend the majority of their days, so an atypical antipsychotic that with benefits in depression is usually the best choice.
To minimize akathisia, start with 1.5 mg every other day. Cariprazine's long half-life (2-5 days) allows this kind of dosing.
We don’t know the ideal dose of lurasidone because it was dosed flexibly in the bipolar depression trials. Higher doses may work better, with a linear dose-response relationship between 20 mg and 120 mg.
Although OFC has the highest effect size in bipolar depression, its efficacy ranks near the bottom among the atypicals in unipolar depression. Some patients save on copays with the combo pill, but for others, OFC is more affordable as two separate scripts. It depends on the insurance plan.
Both the XR and instant release (IR) versions of quetiapine are FDA-approved in bipolar depression. For reasons that have more to do with its patent than its pharmacology only the XR is approved in unipolar depression. Quetiapine IR can be dosed all-at-night, and this strategy usually results in less fatigue than the XR version. Hypotension, however, is lessened with the smoother peaks of quetiapine XR, particularly in doses above 300mg.
None of the atypical antipsychotics stands out as the best choice for bipolar depression. Both of the generic options are low on tolerability, but OFC is the most likely to work and quetiapine has additional benefits in sleep and anxiety. Cariprazine and lurasidone are better tolerated overall, unless the problem is akathisia or out-of-pocket expense.
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Dr Aiken is Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine and the Director of the Mood Treatment Center in Winston-Salem, NC. He is Editor in Chief of The Carlat Psychiatry Reportand Bipolar Disorder Section Co-Editor for Psychiatric Times.
Dr Aiken does not accept honoraria from pharmaceutical companies but receives royalties from W.W. Norton & Co. for a book he co-authored with James Phelps, MD, Bipolar, Not So Much.