Antidepressant Debate May Miss the Mark
Suicide fears overshadow misuse in bipolar disorder

by Brenda Patoine

May, 2008

The question of whether some prescription medications, particularly antidepressants, increase the risk of suicide has stirred great debate, but some experts in psychiatry lament that the continued emphasis on this extremely rare event has deflected attention from matters of greater clinical relevance. Of particular concern are side effects such as agitation and mania that are often the result of inappropriate use of antidepressants in people with bipolar disorder.

The current debate with respect to suicide risk erupted in 2004, when the Food and Drug Administration required drug makers to place a “blackbox” warning on the pills’ labels to reflect data suggesting increased rates of suicidal thinking among adolescents.

In the wake of the action there has been both outrage and applause, and opinions on the subject from mental health experts tend to be strong. Fred Goodwin, a former director of the National Institute of Mental Health who is now director of a research center at George Washington University, called the 2004 black-box warning “the worst example of regulatory overreach” he has seen.

Tom Insel, current director of the National Institute of Mental Health, is more cautious: “Has the black box done more harm? The jury is still out,” he says, citing conflicting research findings.

Robert Post, former chief and 36-year veteran of the National Institute of Mental Health’s Biological Psychiatry Branch, says that the publicity after the FDA decision largely ignored the complexities of the issue and left many people with the false idea that antidepressants cause suicide. “The suicide issue has been totally blown out of proportion,” he says.

Bipolar Mistreatment a Bigger Problem

Post, Goodwin and other mental health experts say a far greater concern centers on the use of antidepressants in bipolar disorder. Bipolar is characterized by mood swings from depression to states of mania or hypomania (literally, “below” mania), in which the person may feel a range of possible symptoms including heightened energy, racing thoughts and less need for sleep. The manic phase differentiates bipolar illness from “unipolar” depression, which is also known as major depression or recurrent depression.

Bipolar is often misdiagnosed and treated as unipolar depression, particularly in general practices but even among psychiatric specialists. One reason, Goodwin says, is because people with the disorder are far more likely to seek medical help during a depressed period than during a manic period, and clinicians do not always uncover a history of manic symptoms.

“The biggest issue is the problem of improper diagnosis,” says Post. “There are more than a half-dozen studies around the world indicating that if you do careful diagnostic assessments of people diagnosed with recurrent unipolar depression, you find that about 30 to 40 percent of the people who are being treated as depressives actually have bipolar disorder. These people are at extraordinarily greater risk for switching into mania.”

Post says it is clear from research that antidepressants can induce agitated states or outright mania in someone who has an underlying vulnerability to bipolarity, such as a previous manic episode or a family history of manic or hypomanic behavior. But these histories are notoriously difficult to nail down in the real world of time-constrained general-medicine practices.

“If the clinician doesn’t insist on talking with a relative, then half the diagnoses for bipolar are going to be missed,” says Goodwin, who coauthored the definitive medical textbook on bipolar disorder with Kay Redfield Jamison. Studies suggest that even among people who have been hospitalized for mania, up to 60 percent do not report the episodes to their clinicians.

“If clinicians don’t recognize a patient is bipolar and they think they’re treating a unipolar patient, often they only find out they’re treating a bipolar when the treatment [with an antidepressant] brings out the bipolarity,” Goodwin says. “They may have actually created bipolarity. It’s a step you can’t take back, because once a person has had a manic episode they’re likely to have more, even without the antidepressant.”

Changing Standards of Care

Goodwin is not willing to see a depressed Patient for evaluation or treatment unless a family member is present in the interview process, which he says is quickly becoming the standard of care at mood disorder clinics affiliated with major academic hospitals.

Even among people who are correctly diagnosed as bipolar, research indicates that close to half are being treated with antidepressants without a mood-stabilizing drug such as lithium or newer antipsychotic drugs, a situation that “everyone agrees is inappropriate and is going to lead to problems with switching,” Post says.

The most recent expert consensus report designed to guide the treatment of bipolar disorder, dubbed the Texas Algorithm, recommends using antidepressants only as a last resort if other combinations of mood stabilizers don’t work. “In the eyes of the experts, antidepressants have been demoted [in bipolar treatment],” says Goodwin. “But still, in clinical practice, the most likely thing to happen when the patient is depressed is that they will end up on an antidepressant.”

There are signs that the inappropriate use of antidepressants in bipolar disorder is actually changing the characteristics of the disease. “We know that bipolar illness has gotten worse since the explosion in the use of antidepressants,” Goodwin says. His hunch is that the trend is related to how many bipolar patients are on antidepressants, since the drugs are known to induce switching to manic states or to induce more rapid “cycling” between depression and mania.

“I think the advice is, pay attention to antidepressants for the real reasons, like the increased agitation and mania that can occur. If these drugs had a label that said: ‘Before using an antidepressant, you must screen for bipolarity and include a family member in the screening process,’ that would be a really helpful label.”

He adds: “Unfortunately, we got distracted by this suicidality silliness.”