Proceed with caution when considering antidepressants for bipolar depression

SAN ANTONIO — Despite a lacking research base for efficacy of antidepressants for bipolar depression, they are the most commonly used medication class in bipolar illness, according to a presenter here the U.S. Psychiatric and Mental Health Congress.

“As you know, antidepressants are the most commonly used class medications in bipolar disorder. They are more commonly used than mood stabilizers,” S. Nassir Ghaemi, MD, MPH, of Tufts University School of Medicine, said. “None of them are FDA indicated for anything in this condition, which tells you something. There’s been a lot of data about whether these drugs cause mania and rapid cycling.”

Within the last 20 years, expert guidelines have increasingly recommended against antidepressants as a first-line treatment for bipolar depression, according to Ghaemi.

However, there is some debate about their role in later illness trajectories.

“Research evidence is much more limited than in so-called major depressive disorder,” Ghaemi said. “There are hundreds and hundreds of randomized clinical trials in antidepressants and MDD.”

To indicate the paucity of evidence for efficacy and safety of antidepressants for bipolar disorder, Ghaemi reviewed all available randomized literature on safety and efficacy of antidepressants for bipolar depression.

Many studies had conflicting results, were underpowered or had flawed study designs.

“Maybe antidepressants don’t work because many of these bipolar depressed patients have mixed states,” he suggested to the audience. “They’re not even really depressed, they’re mixed. It doesn’t matter if you’re bipolar or unipolar, those patients don’t seem to get much better and can actually get worse.”

He recommended clinicians change their way of thinking regarding bipolar depression, and “think of it as mixed states too and then take a different approach.”

Clinicians should consider that randomized studies provide the average effect on the average patient. Because patients can be so individualized, randomized findings may not indicate a hard and fast rule.

“The point here is it’s not all or nothing. I’m not telling you to never use the drug ever. I’m not telling you that these drugs never work or that they are always harmful. What I am telling you is these randomized data tell you that there’s generally not much benefit, if any,” Ghaemi said. “That means in most people they’re not going to have much benefit. That should be your clinical practice: don’t give them to most people. But that doesn’t mean you might not give them to 3% of people. It means you should pay attention to a minority who might do really badly and that doesn’t mean you should never give it to everybody.”

To address the lack of data on antidepressants for bipolar depression, Ghaemi and colleagues are publishing an updated comprehensive meta-analysis in Lancet Psychiatry in the near future. – by Amanda Oldt

Reference:

Ghaemi N. Antidepressants in bipolar depression: An update. Presented at: U.S. Psychiatric and Mental Health Congress; Oct. 21-24, 2016; San Antonio.

Disclosure: Ghaemi reports consulting for Sunovion.