Conference Coverage

Refractory OCD? Consider opioids, amphetamines, caffeine



– An expert in obsessive-compulsive disease had some surprising advice at the American Psychiatric Association annual meeting for treatment of adults with refractory illness. He endorsed amphetamines, caffeine, and once-weekly opioids in carefully selected patients.

Dr. Lorrin M. Koran, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University M. Alexander Otto/MDedge News

Dr. Lorrin M. Koran

“These are not things that will be taught to you in your residency,” said Lorrin M. Koran, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, and past director of the university’s OCD clinic and research program. “These are pharmacological pearls that have come to my attention over many years. I hope at the end of this talk you’ll be more comfortable, especially [with] stimulants, because [they are] very simple and very quick.”

Opioids are a last resort but can prove effective for some patients. “I had a woman who wrote me just last week who said her son’s been on an opioid for 9 years once a week,” Dr. Koran said. “He does very well, and if he stops, he relapses within a few days. He has not become dependent or abusive. You have to screen who you give these to.

“You and I are dedicated to helping people not suffer, so we might want to take a little risk” for people who are struggling, he said.

Bolus caffeine, not a casual cup

Inspired by findings from the 1980s-90s, Dr. Koran and his colleagues randomized 12 treatment-resistant adults at Stanford’s OCD clinic to dextroamphetamine (Dexedrine) 30 mg/day and 12 others to caffeine (NoDoz pills) 300 mg/day, both in pink capsules so patients couldn’t tell them apart. “They were really sick” at baseline, Dr. Koran said, with a mean Yale Brown OCD Scale (YBOCS) score of 28 points (J Clin Psychiatry. 2009 Nov;70[11]:1530-5).

Subjects remained on their antidepressants during the study. Patients with histories of substance abuse, heart disease, schizophrenia, bipolar disorder, or panic attacks were among those excluded.

Caffeine was supposed to be the placebo. But a curious thing happened: About half of patients in both groups did remarkably well after 1 week, with a mean YBOCS drop of 41% among the six amphetamine responders and 45% among seven caffeine responders – with more improvement after 5 weeks.

“I was shocked. In clinical trials, anything 25% or more is considered a response. What patients said was, ‘Gee doc, I still get my obsessions, but I can shift my attention. I can get away from them, so I don’t have to do my compulsions, anymore,’ ” Dr. Koran said.

There were a few dose reductions for insomnia and anxiety. However, overall, YBOCS improvement did not correlate with depression and anxiety scores, so responses appeared to be independent. There were no differences between the groups in liking their treatment or how high people felt.

“I encourage you to try this” – amphetamine or caffeine bolus – “for people who have not responded to say two [treatment] trials. It’s simple. It’s safe. It’s quick. You know within 3 days, 5 days, and it lasts.” Meanwhile, “the data for methylphenidate are less convincing,” Dr. Koran said.

He’s wondered why caffeine helps. After all, no one has ever come into the OCD clinic and said they felt better after their morning coffee. The hypothesis is that 300 mg of caffeine all at once triggers a spike of methylxanthines in the brain, which, much like amphetamines, promotes dopamine and serotonin release. Casually sipping coffee does not have the same effect.


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