Deciding Which Bipolar Patients Need Antidepressants Remains Challenging


The limited number of FDA approved medications indicated for bipolar depression makes treatment challenging, said Terence A. Ketter, MD. Several drugs that have been tested could not meet standards to receive an indication.

An estimated 1 in 7 patients with bipolar disorder would likely benefit from long-term treatment with an antidepressant, but deciding who those patients are—and selecting the right drug—remains challenging and controversial, said Terence A. Ketter, MD, professor of psychiatry and behavioral sciences at Stanford University School of Medicine.

Ketter’s talk, “To Use or Not to Use Antidepressants in Bipolar Disorder?” came Saturday during the 28th US Psychiatric and Mental Health Congress, held in San Diego, California.

Most psychiatrists would not say to “never” treat patients with bipolar disorder with an antidepressant or to “always” do so, Ketter said. “A lot of the controversy is, ‘Where do you put the cut point?’ “

There are only 3 FDA approved medications specifically for acute bipolar depression. Several others have been tested and may work for some patients but could not get an FDA indication, representing a huge unmet need. The problem, as Ketter demonstrated in a review of various studies, is that too few patients benefited relative to the number who experienced adverse events. “The things that are more potent for the good are probably more potent for the bad,” he said.

Thus, clinicians are faced with limited options and many choices in weighing risks and benefits for individual patients. The second-generation antipsychotics may be more effective, but they offer risks of developing hyperglycemia or diabetes, as well as cognitive impairment. Using an antidepressant as an adjunct therapy might be better tolerated, but for many patients, “the biggest problem is they don’t get the job done.”

Mood stabilizers, the best-known of which is lithium, are “considered foundational treatment for bipolar disorder,” said Ketter. It would be helpful, he said, if this class carried the same weight for bipolar depression. And many mood stabilizers have highly unpleasant side effects, including acne, psoriasis and hair loss (lithium), rashes (carbamazepine and lamotrigine) and weight gain (lithium, valproate).

The issue is so challenging that the current consensus report of the International Society of Bipolar Disorders features more recommendations on what to avoid than what actions are permissible, Ketter noted in highlighting 6 basic recommendations.

He took the audience through 2 very different case studies, the first involving a 35-year-old Asian woman with bipolar I and multiple social problems, and an apparent family history of bipolar disorder. Treatment for this patient’s depression and irritability proved difficult, since she refused some promising options due to potential side effects. At an outpatient visit, the less powerful antidepressant she agreed to take did not appear to be working for her, and she had started an affair with a married co-worker.

In the second case, a 26-year-old graduate assistant with bipolar II was having extreme anxiety about teaching, and came for treatment with a suggestion that he take sertraline—not only were the indications positive, but it had worked for his mother, who suffered social anxiety. “If patient comes in with an idea that is not completely unreasonable, it might be worth pursuing,” Ketter said. The young man did very well with the medication.

In general, Ketter said, antidepressants may be problematic in patients with bipolar I, who have more switch risk, mixed depression, and rapid cycling. They may be beneficial in bipolar II patients, who have less switch, more pure depression, and non-rapid cycling.

The most important thing to remember, he said, is “there is no one size fits all.”

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