Pramipexole is noteworthy because it has a large effect size (0.77 - 1.1) and lacks detrimental effects on weight, sexuality, and cognition.8 Modafinil and armodafinil also share that side-effect profile, although the research on these agents is not as clearly positive as it is for pramipexole.1 In my experience, these novel stimulants rarely break through severe depression but often improve residual symptoms such as cognition and fatigue. For patients, however, that can make the difference between staying in bed and returning to work.
Thyroid augmentation is particularly useful in lithium-treated patients, in whom keeping the thyroid-stimulating hormone level close to 2.6 mIU/L lowers the risk of depressive relapse.9
Among devices, ECT has long been known to surpass pharmacologic options for unipolar depression, and a recent study confirmed that effect in bipolar depression.1 Transcranial magnetic stimulation has a smaller effect size than ECT, but it appears to work equally well in unipolar and bipolar depression.10
Light therapy has promising open-label studies and a positive controlled trial (when paired with wake therapy) in bipolar depression. Although morning light has been associated with mania, the problem can be reduced by using the lightbox at noon and reducing its duration.11
Therapy and lifestyle
My top choices in this category are Social Rhythm Therapy (SRT), Cognitive Behavioral Therapy for Insomnia-Bipolar (CBT-ib), and moderate aerobic exercise.
The benefits of exercise compare favorably with those of antidepressants, and in one study exercise surpassed antidepressants in maintaining remission.12 The dose is relatively low: brisk walking, 45 minutes every other day. Though research is lacking in bipolar depression, from what we know about its mechanism (exercise raises levels of brain-derived neurotrophic factor [BDNF]), it is likely to work.
That raises a question: Can exercise trigger mania? I think not, unless the patient is exercising in place of sleep. BDNF levels are low in depression and mania.13 Exercise also deepens sleep quality, which could improve manic states. If done at regular times, exercise might stabilize mood by setting the biological clock, which is the mechanism behind the next 2 therapies.
Regular rhythms of sleep and daytime activity are the focus of the 2 therapies I’ve highlighted: SRT and CBT-ib. These approaches are better at preventing relapses than resolving acute episodes.14 For example, patients saw little change in their mood after a 2-month course of CBT-ib, but 4 months after completing the therapy, they had an 8-fold improvement in days well.15 That’s a remarkable benefit, and the delay is just as important to emphasize. People are less likely to give up prematurely when they know what to expect.
The most important expectation to clarify for people with bipolar depression is this one: they should expect, and do deserve, a full recovery. Bipolar disorder may be chronic, but its episodes need not be.
This article was originally posted 5/10/17 and has since been updated.
Dr. Aiken is the Director of the Mood Treatment Center and an Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine. He does not accept honoraria from pharmaceutical companies but receives honoraria from W.W. Norton & Co. for Bipolar, Not So Much, which he coauthored with Jim Phelps, MD.
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