Low-Dose Buprenorphine May Be First Treatment Step

Short-term use of very low doses of buprenorphine may help to decrease severe suicidal ideation in some patients, but that finding should be interpreted cautiously, Yoram Yovell, M.D., Ph.D., co-director of the Institute for the Study of Affective Neuroscience at the University of Haifa, Israel, and colleagues wrote in a study published December 18 in AJP in Advance.

In fact, the work should be considered preliminary, said the researchers, noting that despite buprenorphine’s “favorable safety profile, [the medication] is potentially addictive and possibly lethal.”

The study was carried out in four medical or psychiatric facilities in Israel between 2010 and 2013. A total of 88 patients (aged 18 to 65) who reported clinically significant suicidal ideation (a score of greater than or equal to 11 on the self-report Beck Scale for Suicide Ideation for at least one week) were randomly assigned to receive sublingual buprenorphine lozenges, starting at 0.1 mg once or twice a day (n=57) or placebo (n=31) for four weeks. Once a week, at the decision of the study psychiatrists, the daily dose could be raised in 0.1 to 0.2 mg increments, to a maximal daily dose of 0.8 mg.

At two weeks and four weeks, scores on the Beck Scale for Suicide Ideation dropped significantly for the patients who received the low-dose buprenorphine (mean final dosage=0.44 mg/day) compared with those taking placebo. For ethical reasons, more than 70 percent of the patients were also using antidepressants, but the effects of buprenorphine on suicidal ideation did not differ between patients who were treated and those who were not.

There was no difference in response between patients with and without borderline personality.

“This finding, if replicated, raises the possibility that ultra-low-dose buprenorphine treatment addresses a subset of affective symptoms—those associated with painful feelings of rejection and abandonment, and that in this dosage range, it is less active against neurovegetative and other symptoms that are more related to reduced hedonic tone,” wrote Yovell et al.

Replication trials should add clinician determination of suicidality and depression, they wrote. About 30 percent of patients dropped out in the first week, making unclear whether the results could be extended to “more stable, less suicidal patients.”

Yovell also cautioned, “This is a single, time-limited trial of an experimental treatment for suicidal ideation rather than suicidal behavior, and its results do not support the widespread, long-term, or nonexperimental use of buprenorphine for suicidality.”

The study was funded by the Hope for Depression Research Foundation of New York, the Neuropsychoanalysis Foundation, and the Institute for the Study of Affective Neuroscience at the University of Haifa.

In an accompanying editorial, former APA President Alan Schatzberg, M.D., a leading psychopharmacology researcher and professor of psychiatry at Stanford University School of Medicine, also noted the risks of addiction or diversion of buprenorphine. He drew an analogy about “the abuse liability, long-term risks, and social cost” in the swift adoption by some practitioners of off-label use of ketamine to quickly alleviate symptoms of depression.

“The potential gain of some patients versus the overall societal cost needs to be addressed, and guidelines need to be promulgated for any such use [of buprenorphine],” wrote Schatzberg. “The time has come for the specialty and regulators to begin to formally address the issues associated with the potential off-label use of drugs of potential abuse for severely ill and refractory patients.” ■

“Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized, Controlled Trial” can be accessed here. The accompanying editorial, “Opioids in Psychiatric Disorders: Back to the Future?,” is available here.