Long-Term SSRI Use Tied to Apathy Syndrome.

HOUSTON -- Depression is a highly cyclic disorder, but not every apparent return of symptoms represents a true recurrence of the disorder.

Late emerging adverse effects, discontinuation phenomena, or drug interacdons may be the true explanation, Dr. Lauren Marangell said at the Psychopharmacology Update 2000 sponsored by Baylor College of Medicine.

Medication adjustments or augmentation strategies can often rectify what seems like a loss of antidepressant effect, said Dr. Marangell, director of clinical psychopharmacology at the university.

When a patient reports that "the medicine isn't working anymore" after 6-18 months of successful therapy with a selective serotonin reuptake inhibitor (SSRI), the explanation may be the "asthenia/apathy syndrome" rather than a recurrence or simple loss of effect.

In such cases, closer examination will reveal that the symptoms are distinctly different than the patient's prior depression, with the prominent feature often being apathy without sadness, tearfulness, guilt, or hopelessness. "Flattening" of emotions and a loss of motivation are characteristic. In these cases, increasing the SSRI dosage will typically worsen, rather than improve symptoms, Dr. Marangell said.

Although the syndrome has not been studied systematically it appears to develop in 20%-50% of patients on long-term SSRI treatment, and to possibly involve attenuation of dopamine functioning in the frontal cortex, secondary to chronic stimulation of central serotonin neurons.

The addition of a psychostimulant or a switch to a different antidepressant is often effective, she noted.