Five of the 20 patients dropped out of the study, 3 because of side effects, which included diarrhea, constipation, and nausea. Two patients developed tachycardia, which resolved in one with a reduction in the duloxetine dose from 60 to 30 mg/day. The other tachycardic patient dropped out of the study (Psychopharmacol. Bull. 2010;43:26-34).
The other recent duloxetine study was a Yale University naturalistic study involving 21 men with combat-related, refractory PTSD and comorbid major depressive disorder who were placed on duloxetine at 60-120 mg/day. Twenty patients completed the 8-week trial. They showed significant improvement both in PTSD symptoms, including nightmares, and in major depression symptoms (Pharmacopsychiatry 2010;43:45-9).
Summing up recent results with other classes of medications, Dr. Villarreal said the findings with anticonvulsants have been disappointing save for one small promising randomized trial of lamotrigine in veterans, which yielded a 50% response rate, twice that of placebo. Studies of propranolol for the prevention of PTSD in individuals at high risk also have been generally disappointing.
The antiadrenergic agent prazosin is gaining increasing use in PTSD on the strength of several positive studies, including one that showed efficacy comparable to that of quetiapine but with far fewer side effects. Dr. Villarreal is an investigator in an ongoing clinical trial in which male veterans are titrated fairly quickly to 20 mg/day of prazosin with regular blood pressure monitoring for possible hypotension.
Four years ago the Department of Veterans Affairs did a survey and found 60% of prescribing of atypical antipsychotic agents were off label –and 42% were for PTSD. The pendulum has swung away since then in response to increased appreciation of the drugs’ metabolic and other side effects.
Yet Dr. Villarreal was a coinvestigator in an as-yet unpublished multicenter, randomized, placebo-controlled trial of quetiapine monotherapy for PTSD that he said yielded "very impressive findings."
The study included 80 veterans. Those randomized to quetiapine received a mean daily dosage of 258 mg, with a range of 50-800 mg. They experienced a threefold greater decrease in CAPS scores than placebo-treated controls as well as a significant improvement on the Positive and Negative Syndrome Scale.
"It was a very remarkable finding. I’ve continued to follow these patients, and some of them have continued on quetiapine after the study. In fact, in some patients it has been difficult to try to get them off of it," according to the psychiatrist.
Asked by an audience member how long to treat patients for PTSD, Dr. Villarreal replied that the number of long-term studies has been few, so the minimum duration of an effective course of therapy really isn’t known. But PTSD is a chronic condition, and his severely affected patients essentially are on medications for life. He said he strongly encourages his patients to get into a program of exposure-based therapy, which he has found to be quite helpful in reducing polypharmacy.
Dr. Villarreal said he had no relevant financial disclosures.