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IN THIS ISSUE:
September 2009

Prenatal Valproate Lowers IQ
Valproate may adversely affect fetal cognitive development throughout pregnancy.

Stimulant Augmentation for Treatment-Resistant OCD?
In one study, amphetamine was not superior to caffeine as an augmentation strategy for patients with obsessive compulsive disorder.

Antipsychotics in Alzheimer's Patients: New Evidence on Metabolic Effects
Second-generation antipsychotic drugs increase the risk of weight gain and metabolic effects in patients with Alzheimer’s disease.

In Brief
Contraception Use in Female Bipolar Patients Suboptimal; CBT Available over Internet for Insomnia

SSRIs and Gestational Hypertension
Use of a serotonin selective reuptake inhibitor beyond the first trimester of pregnancy is associated with an increased risk of hypertension and preeclampsia.

Stimulant Augmentation for Treatment-Resistant OCD?

September 2009

Obsessive compulsive disorder (OCD) is a common and disabling condition. The mainstays of current treatment are serotonergic antidepressants and behavioral therapy. But even with best practices, the most fortunate patients achieve only partial improvement. There is considerable "unmet need."

A handful of small studies dating back to the early 1980s suggests that amphetamines may help to combat the symptoms of OCD.1 To follow up on these clues, Koran and coauthors studied amphetamine as an augmentation agent in 24 patients with OCD who had responded incompletely to antidepressant therapy.1 All subjects continued to have substantial symptom burden (≥ 20 score on the Yale Brown Obsessive Compulsive Scale [Y-BOCS]) after 12 weeks of treatment with an established effective dose of a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI). These 11 women and 13 men ranged in age from 19 to 62 years.

Twelve subjects were randomly assigned to take d-amphetamine, 30 mg, each morning, in addition to their SSRI or SNRI and other medications. In an attempt to maintain the study's "blindness" in the face of stimulant side effects, the investigators employed caffeine augmentation rather than placebo as the control condition. Therefore, the other 12 subjects took 300 mg of caffeine each morning (the equivalent of roughly three cups of coffee). Subjects were to have refrained from drinking caffeine-containing beverages for a week before starting the study medication.

At the end of the first week of treatment, 50% of the d-amphetamine group and 58% of caffeine-treated patients met the Y-BOCS response criterion (decrease ≥ 20%). "Full response" (Y-BOCS score decrease of ≥ 35% and Clinical Global Impression Improvement [CGI-I] score of very much or much improved) was attained by 33% of d-amphetamine and 42% of caffeine subjects. Subjects in both treatment groups who were deemed responders after 1 week were continued into a 4-week double-blind extension phase. Twelve of the 13 maintained or increased their OCD improvement. At the 5th week of treatment, d-amphetamine subjects showed a mean 48% decrease in Y-BOCS score, and caffeine subjects, a mean 55% decrease. Thirty-three percent of d-amphetamine patients and 50% in the caffeine group met the criterion of "full response."

Side effects were mild to moderate. In the d-amphetamine group, the most common effects were transient insomnia, dry mouth, and decreased appetite. The most common side effects among caffeine-treated subjects were nausea and intermittent jitteriness. Blood pressure and pulse increased slightly with caffeine and more substantially with d-amphetamine. No subject discontinued treatment due to adverse effects, but 25% of all subjects had to have the dosage reduced due to increased pulse or blood pressure, irritability, or nausea and abdominal pain. Neither study drug was associated with a subjective drug "high" or a sense of "liking" the treatment.

Contrary to the scientists' hypothesis, amphetamine was not superior to caffeine as an augmentation strategy for these treatment-resistant OCD patients. Both stimulants were associated with substantial and continuing improvement. In the absence of a placebo control, one cannot draw conclusions about the efficacy of either of these agents. They may have been equally effective or equally ineffective. The authors argue that the continuing clinical improvement in treatment-resistant OCD patients suggests that both stimulants were in fact efficacious. They suggest the benefit may have been related to increased release of dopamine and resulting increased D1-receptor stimulation in the prefrontal cortex. The obvious next step is for additional research comparing amphetamine and/or caffeine to placebo in a similar design.

1Koran LM, Aboujaoude E, Gamel NN: Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry, in press.