Bipolar Disorder

The Conundrum of Bipolar II Depression: Q and A

Should it be treated the same way as Bipolar I depression?

Posted Apr 29, 2019

Question: What’s the best treatment for Bipolar II depression?

Answer: If only we knew! First a little background: Bipolar II disorder is characterized by episodes of ‘hypomania’ as opposed to the full-blown manic states seen in Bipolar I. In hypomania, a person can feel euphoric or unpleasantly agitated, along with increased energy, rapid speech, a decreased need for sleep, and at times poor judgment including impulsive decision-making and overspending. In contrast to full-blown mania, though, there’s no loss of ‘reality testing,’ no overt psychosis. So Bipolar II is generally a milder disorder than Bipolar I, in that the hypomanic phase is less dangerous than mania—but the depressive phase can be very disabling.

Q: Is bipolar depression different than unipolar depression?

A: The depressive episodes of Bipolar I and II are pretty much the same, symptom-wise, as those seen in plain old unipolar major depression. Symptoms such as low mood, pessimism, sleep disturbance, fatigue, anxiety, and so on, are common in bipolar and unipolar major depressive episodes. Importantly, for both Bipolar I and II, while mania and hypomania may be dramatic and require emergency treatment, people with bipolar disorder actually tend to spend a lot more time in depressed states. Mania generally lasts days or weeks, whereas depression can last months to years. Which can lead to problems in daily functioning, in holding jobs and maintaining relationships. Therefore it’s crucial to find good treatments for bipolar depression.

Q: Should Bipolar II depression be treated differently than unipolar depression?

A: Yes. There’s one important difference between unipolar and bipolar depression: traditional antidepressants if used alone can be dangerous for people with Bipolar II depression (though exactly how dangerous is not clearly known). Research has suggested that for some people with Bipolar II, antidepressants may cause flips from depressive to hypomanic states, and may also increase the frequency of cycling between lows and highs.

Q: So should antidepressants be completely avoided in Bipolar II disorder? 

A: That’s the big question. Many experts say they should be entirely avoided in Bipolar I disorder. Unfortunately, there’s a lack of definitive data for Bipolar II. In fact, a recent compilation of opinions of expert bipolar psychopharmacologists in a new book on Bipolar II disorder edited by Gordon Parker, as summarized by Dr. Chris Aiken, found a wide range of recommendations for antidepressant use.

Out of 18 experts, 10 felt that antidepressants are helpful in Bipolar II but are best used with a mood stabilizer to avoid hypomania. Another 6 felt that antidepressants are best avoided entirely or only used as a last resort in combination with a mood stabilizer. Only 1 expert felt antidepressants did not cause hypomania in Bipolar II, and 1 believed they should never be used. So overall the consensus is that antidepressants may be helpful in Bipolar II, but should generally be used in combination with mood stabilizers. There was also a consensus that certain antidepressants are best avoided (the tricyclics) in comparison to SSRIs and bupropion, but obviously, that has to be discussed with one’s doctor.

Q: What are other new treatment approaches for Bipolar II depression?

A: Most of these treatments involve behavioral components. For instance, social rhythms therapy has been shown to have a significant effect on bipolar disorder. Bright light therapy (delivered in the middle of the day) has been shown to help for bipolar depression. Both of these approaches may help to maintain healthy sleep patterns, which can stabilize biological rhythms in bipolar disorder. Exercise (moderate levels of activity such as walking 45 minutes every other day) has been shown to help depression, possibly by stimulating the brain’s neurotrophic factors, though we are lacking good studies in bipolar depression.

Q: What about new medication treatments for bipolar depression?

A: There is interesting work on the use of supplements such as N-acetylcysteine (NAC), a modified amino acid that has anti-inflammatory properties. Also, the Parkinson’s disease medication pramipexole, which increases levels of dopamine in the brain, has shown promise for treating bipolar depression. Most of the new treatments for bipolar depression are augmentation treatments; with a mood stabilizer used as a primary medication, with other medicines being added. Lamotrigine is an exception: as a mood stabilizer (originally used for seizure disorders) lamotrigine also has antidepressant effects, and can thus be used as a single medication. Augmenting medicines include an increasing number of atypical antipsychotic medicines, such as Seroquel, Abilify, Latuda, Brexpiprazole, and Vraylar. There are other medications under study for bipolar depression, and ongoing clinical trials can be found by doing a search for ‘bipolar depression’ at www.clinicaltrials.gov.

Q: So what’s the long-term outlook?

A: For people with Bipolar II disorder, there are numerous existing treatments that can be explored to find combinations of treatments, including medications, complementary treatments, and behavioral approaches that can make a significant difference and increase one’s ability to feel well and be productive in life.

That said, I wish that the National Institute of Mental Health would put more resources into research on the treatment of the depressive phases of Bipolar I and II disorders. For that matter, pharmaceutical manufacturers have also backed away from treatment studies of bipolar disorder, with some recent exceptions, which is shameful. Since depression is the most common and persistent state affecting people with Bipolar Disorder (approximately 1 to 4 percent of the American population), and is poorly understood, this neglect has huge public health and economic costs.  There will be a huge potential benefit once better treatments are identified. Overall we are making progress, but it is essential to have funding for large studies to investigate how depression damages the brain in bipolar depression and to develop effective new treatments to repair and prevent that damage.

References

1. Aiken C. Antidepressants in bipolar II disorder. Psychiatric Times, April 16, 2019

https://www.psychiatrictimes.com/bipolar-disorder/antidepressants-bipolar-ii-disorder

2. Parker G. Bipolar II disorder: Modelling, Measuring and Managing. 3rd edition. Cambridge University Press, 2019

3. Dean OM, Gliddon E, Van Rheenen TE, et al. An update on adjunctive treatment options for bipolar disorder [published online January 25, 2018]. Bipolar Disord. doi:10.1111/bdi.12601

4. Haelle T. Adjunctive Therapies for Bipolar Disorder Show Promise, Need More Evidence, Psychiatry Advisor March 15, 2018

https://www.psychiatryadvisor.com/home/bipolar-disorder-advisor/adjunctive-therapies-for-bipolar-disorder-show-promise-need-more-evidence/

5. Fawcett, Jan, et al. Clinical experience with high-dosage pramipexole in patients with treatment-resistant depressive episodes in unipolar and bipolar depression. American Journal of Psychiatry 173.2 (2016): 107-111.

6. Sit, Dorothy K., et al. "Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial." American Journal of Psychiatry 175.2 (2017): 131-139.

7. Crowe, M., B. Beaglehole, and M. Inder. "Social rhythm interventions for bipolar disorder: a systematic review and rationale for practice." Journal of psychiatric and mental health nursing 23.1 (2016): 3-11.

8. Minarini, Alessandro, et al. "N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects." Expert opinion on drug metabolism & toxicology 13.3 (2017): 279-292.