Experts Are Divided on the Issue, but There’s One Thing Nearly All Agree on
Antidepressants are increasingly discouraged in bipolar I disorder but what about bipolar II? Here depression is the more prominent pole, and the risk of antidepressant-induced mania is smaller. On the other hand, most of what we know about treatment comes from studies on bipolar I. Research on anti-depressants in bipolar II is scant, but a new textbook gives a rare glimpse into how the experts approach them in their practice.
In Bipolar II Disorder: Modelling, Measuring and Managing, Gordon Parker surveyed 18 international experts on their treatment strategies with bipolar II disorder.1
I’ve clustered their responses about antidepressants into 4 categories:
1 Antidepressants are helpful in bipolar II and do not cause hypomania (endorsed by 1 out of 18 experts).
2 Antidepressants are helpful in bipolar II but are best used with a mood stabilizer to avoid hypomania (endorsed by 10 out of 18 experts).
3 Antidepressants are best avoided or used with a mood stabilizer as a last resort in bipolar II (endorsed by 6 out of 18 experts).
4 Antidepressants should almost always be avoided in bipolar II because of the risk of hypomania and cycling (endorsed by 1 out of 18 experts).
That’s quite a spread, but there is one thing nearly all agreed on: antidepressants can cause hypomania, mixed states, and worsen the overall course by triggering more frequent episodes and rapid cycling. This issue has long been debated, but studies over the past decade have largely put that debate to rest.2,3
On the other hand, nearly all experts saw a role for antidepressants in bipolar II disorder. Most saw bipolar II as a more varied group than bipolar I, and within that group are some who respond to antidepressants. Even those who tended to avoid antidepressants admitted that a small minority of bipolar II patients could do well with antidepressant monotherapy.
Which antidepressants are used?
SSRIs and bupropion were the favorites, as these have the lowest risk of inducing mania. The respondents were split on the SNRIs. There is evidence that these carry a higher risk of mania, but one of them—venlafaxine—also stood out for its efficacy and safety in a small, 12-week, controlled trial where it compared favorably with lithium in bipolar II depression.4 Nearly all agreed that the tricyclics and MAOIs carried the highest risk of mania, but several acknowledged that they had had success with these agents—particularly the MAOIs—when used as a last resort.
Dr Aiken 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.
Dr Aiken is Director of the Mood Treatment Center, Editor in Chief, The Carlat Psychiatry Report, and Instructor in Clinical Psychiatry, Wake Forest University School of Medicine. He is the Bipolar Disorder Section Co-Editor for Psychiatric Times.
1. Parker G, Ed. Bipolar II Disorder: Modelling, Measuring, and Managing, 3rd ed. Cambridge, UK: Cambridge University Press; 2019.
2. Viktorin A, Lichtenstein P, Thase ME, et al. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am J Psychiatry. 2014;171:1067-1073.
3. Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant-emergent mania in bipolar depression: a systematic review and meta-analysis. Bipolar Disord. 2018;20:195-227.
4. Amsterdam JD, Lorenzo-Luaces L, Soeller I, et al. Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate. Br J Psychiatry. 2016;208:359-365.
5. Bipolar Network News. Life Charting for Patients. www.bipolarnews.org/?page id=175. Accessed April 12, 2019.
6. Simon NM, Otto MW, Fischmann D, et al. Panic disorder and bipolar disorder: anxiety sensitivity as a potential mediator of panic during manic states. J Affect Disord. 2005;87:101-105.
7. Kotin J, Goodwin FK. Depression during mania: clinical observations and theoretical implications. Am J Psychiatry. 1972;129:679-786.