NICE advises against using antipsychotic agents for treatment of GAD in primary care, because the evidence of clinical efficacy is weak and the risk of serious side effects is well established.
Dr. Alan J. Gelenberg
In psychiatrists’ hands, however, Dr. Gelenberg considers second-generation antipsychotic agents a reasonable next step in treatment nonresponders. The evidence of efficacy for quetiapine (Seroquel) in GAD is "quite impressive," he said, citing a recent Cochrane analysis of four placebo-controlled clinical trials of quetiapine monotherapy for GAD totaling 2,265 patients. The Cochrane report concluded that quetiapine’s efficacy is comparable to that of antidepressants, although the dropout rate attributable to side effects – mostly sedation and weight gain – is higher (Cochrane Database Syst. Rev.;12:CD008120).
The NICE guidelines do not address the question of how long effective therapy should be continued. Dr. Gelenberg pointed to a recent enlightening study on this score by Dr. Karl E. Rickels and his colleagues at the University of Pennsylvania, Philadelphia, which concluded that treatment should continue for at least 12 months.
The study involved 268 GAD patients treated for 6 months with open-label extended-release venlafaxine. The 51% who were significantly improved at that point were then randomized double-blind to an additional 6 months of extended-release venlafaxine or placebo. Among patients still in the study at the 12-month mark, those on placebo were placed on another 6 months of placebo, while those on venlafaxine XR were randomized to a double-blind test for an additional 6 months of the drug or placebo.
During months 6-12, patients still on venlafaxine XR had a 10% relapse rate, compared with 54% in those switched to placebo. Among patients who’d been on venlafaxine XR during the first 12 months, those assigned to the antidepressant in months 12-18 had a 7% relapse rate during that final period, compared with 32% for those switched to placebo. Reassuringly, most patients who relapsed when taken off the antidepressant responded to a second course of therapy. The take-home message, according to the investigators, is that successful treatment should be maintained for at least a year (Arch. Gen. Psychiatry 2010;67:1274-81).
"GAD is a chronic disorder, and probably most patients need much longer therapy, but I don’t get as upset when a patient wants to stop as I do when it’s someone with severe major depressive disorder or bipolar disorder. I’m more inclined to say, ‘Try it. We’ll work together, and if you feel the anxiety start to return we’ll put you back on therapy,’ " Dr. Gelenberg said.
He disclosed that he serves as a consultant to Eli Lilly, Best Practice, AstraZeneca, Wyeth, GlaxoSmithKline, ZARS Pharma, Jazz Pharmaceuticals, H. Lundbeck A/S, Takeda, eResearch Technology, Dey Pharma, PGxHealth, and Myriad Genetics.