Long-Term Side Effects Surface With SSRIs

Physicians are seeing long-term side effects with selective serotonin reuptake inhibitors far in excess of what was expected from clinical trial data, Dr. Norman Sussman said at a psychopharmacology update sponsored by New York University.

If these particular side effects - sleep disturbances, sexual dysfunction, and weight gain - are problematic for patients, one of the newer non-SSRI antidepressants may be a better choice, he said. Of course, these drugs have their own particular side effect profiles.

When SSRIs first appeared a decade ago, their favorable side effect profile was a key selling point. They were clearly safer and easier to use than tricyclics and monoamine oxidase inhibitors and, above all, better tolerated by patients.

But experience has shown that some side effects are more common and problematic than initially expected, said Dr. Sussman, director of the psychopharmacology research and consultation service at Bellevue Hospital Center in New York.

Depression is a chronic, recurrent disorder, so long-term side effects actually may be more important than acute ones in terms of patient compliance and quality of life, and this has come to guide Dr. Sussman's choice of antidepressants.

Early-onset side effects may be responsible for rapid withdrawals from treatment, but some of the most troubling of these - nausea, diarrhea, headache, and agitation - will remit in 2-3 weeks.

A knottier problem is adverse effects that persist as long as the patient takes the medication, such as sexual dysfunction and sleep disturbances. Also particularly troubling are those, like weight gain, that don't even develop until late in treatment. "These are the ones that are not in the insert, which is based on short-term studies," Dr. Sussman said.

Significant insomnia affects 15%-20% of patients taking SSRIs, twice the rate with placebo. Polysomnography has consistently found that these drugs cause activation during the night: In addition to insomnia, bruxism, sweating, and periodic limb movement are common. Vivid dreams and nightmares also occur. With ongoing treatment, increasing numbers of patients report lethargy and fatigue, he said.

"There are a lot of data showing that people who sleep poorly are more likely to relapse and that suicide risk is higher," he said.

Sleep problems often require concurrent medication: 22%-34% of patients taking SSRIs also are prescribed sedatives or hypnotics, Dr. Sussman said.

Sexual dysfunctions are among the most distressing SSRI side effects. Decreased libido and delayed or absent orgasm are the best known, but there are others, such as the "yawning-excitement syndrome." Patients experience sexual arousal when they yawn, often progressing to orgasm. "This is probably underreported. Patients often say, 'If you hadn't asked me, I wouldn't have mentioned it,'" he said.