Should Antidepressants Be Used in Bipolar Depression? A Pro-Con Debate

At Psych Congress 2018, 2 experts in the field of psychiatry squared off in a session called “The Great Debate in Contemporary Psychiatry: The Use of Antidepressants in Bipolar Disorder," about whether antidepressants should be used to treat patients with bipolar depression.

Nassir Ghaemi, MD, MPH, professor of psychiatry at Tufts University, presented the “con” side of the argument, while Joseph F. Goldberg, MD, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai, presented the arguments “for” using antidepressants.

The Con Side

Ghaemi said he had 20 years of data to show that antidepressants don’t work, and that he wasn’t out to change anyone in the audience who had already made up their mind on the issue. But he said he hoped to influence a younger generation of clinicians.

He reviewed a meta-analysis of 6 studies looking at antidepressants in bipolar depression, which showed an overall effect size of 0.16, which he said was “very small.” He added that the effect size of antidepressants in major depressive disorder is 0.3.

The same analysis showed a lack of response rate as well as a lack of efficacy at 1 year, even when mood stabilizers were added.

“You might conclude then that these drugs are safe but useless,” he said. "There’s no point in using them.”

Citing 2 of his own studies, he also said antidepressants could worsen bipolar depression in people with rapid cycling and cause long-term manic episodes in people with bipolar depression.

The Pro Side

Goldberg said he didn’t think the issue about antidepressants and bipolar disorder was so black and white.

“Under what circumstances might antidepressants be more likely to be helpful or to be harmful, rather than to speak of the entirety of bipolar depression?” he asked, comparing the issue to discussions about the best way to treat cancer, hypertension, or infectious diseases.

For a subgroup of patients with bipolar depression, there may be value in antidepressant treatment. However, most antidepressants have not been studied in bipolar depression, and it is difficult to make generalizations with limited information, he said.

Goldberg said certain factors need to be considered when using antidepressants in patients with bipolar depression. These include:

• Bipolar type 2
• No rapid cycling
• No recent mania or hypomania
• No comorbid alcohol or substance use disorders
• History of favorable antidepressant response
• No history of antidepressant-induced mania
• The SLC6A4 l/l genotype

However, there are many other factors that are linked with poor antidepressant response, he said, including severity, comorbidity, anxious features, psychosis, nonadherence, and more. These moderating factors have to be considered before deciding that antidepressants are the reason treatment is not working, he said.

“We really have to think about not just the diagnosis, but of the patient that has it,” he said.

In the end, the audience voted on their smartphones about who had the winning argument. Goldberg received 132 votes (50.6%), edging out Ghaemi by 3 votes (49.4%).