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Efficacy Vs Tolerability in Bipolar Depression

Efficacy Vs Tolerability in Bipolar Depression

  • 1. Recall BP II and mid-spectrum bipolarity are 2-3 times more prevalent than BP I (depending on how you count)

    2. Thus, depression is the main target for most patients with bipolarity; a minority will require anti-manic prophylaxis as well

  • Efficacy

    Highest metabolic risk

    Metabolic risk substantial;
    side effects nearly universal
    (often somnogenic is helpful)

    Metabolic risk not zero; high cost


    Lowest long-term risks;
    no side effects for most

    Low-dose lithium
    Primarily adjunctive; see previous review for PT

    Sleep-regulating psychotherapy
    Bipolar-specific CBT-I adjunctive; IP/SRT under study as monotherapy*

    CBT-I, cognitive behavioral therapy for insomnia; IP/SRT, interpersonal and social rhythm therapy.

    *Efficacy equal to that of quetiapine in a pilot trial by Swartz et al[3] (neither was very good, unfortunately, but still, they were equal).


This analysis was very helpful to me. In our university health center, we have used lamotrigine as our first-line treatment for most of our patients with Bipolar II depression for years, usually with very good results. We have been concerned about how to treat a few with very severe depression and suicidality; we have usually started lamotrigine with lithium and/or quetiapine, but we have recently started submitting more prescriptions for lurasidone, most of which are denied by insurance. I have recently been struggling to try to figure out what to do with the 2016 CINP guidelines. Dr. Phelps' discussion elegantly provides very helpful perspective and guidance.
One problem: I can't print from this format to share this with my primary care colleagues. Is it available as an article or pdf format? I looked on psycheducation.org, but didn't find these points in a compact discussion.

Timothy @

Thank you for this eye-opening work. Atypical antipsychotics are rising in the treatment guidelines for mood disorders - including a new one by Stahl for unipolar mixed states.

It may be that the authors value efficacy at the expense of tolerability, or they over-estimate the safety of atypicals and the harm of lamotrigine. For example, these 2016 guidelines rank many atypicals as safer than lamotrigine:


In those guidelines it looks like the newer atypicals are viewed as less risky than the older ones - telling as most of their medical risks build up over time. I'll agree with Dr. Phelps on this one - it's the long term risks that matter in bipolar, and lamotrigine has the long-term data to support its safety over the lifespan. -Chris Aiken, MD

Chris @

I agree with Dr Phelps . Lamictal is safer ,effective with least side effects .

Chikkanayak @

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