NEW YORK (Reuters Health) – In people with schizophrenia, the dopamine modulator aripiprazole appears to reduce cocaine cravings better than the dopamine blocker perphenazine after an acclimation period, according to a small, double-blind randomized trial.
“The results were unexpected. Aripiprazole appears to have a late effect in reducing cocaine cravings, defined as an urge to use between use episodes. We did not see this effect until after 5 weeks of exposure to aripiprazole,” lead author and principal investigator Dr. Thomas P. Beresford of the University of Colorado School of Medicine at the Anschutz Medical Campus, in Aurora, told Reuters Health.
“Because both schizophrenia and cocaine use raise dopamine in the brain, we wanted to look for a specific treatment where the two dopamine conditions exist concurrently. Clinically, this sample represents a ‘dual-diagnosis’ group of patients who are often very ill from both causes,” he said in an email.
Dr. Beresford and colleagues randomized 44 cocaine-dependent active users with schizophrenia (ages 18 to 65) to receive either daily aripiprazole or perphenazine for 8 weeks. Aripiprazole was started at 15 mg/day and up- or down-titrated in 5-mg increments (to a 30-mg maximum or 10-mg minimum); perphenazine dosing was three times daily (4 to 8 mg; maximum, 24 mg/day).
The findings were published online October 3 in the Journal of Clinical Psychopharmacology.
The proportion of negative urine-test results for cocaine during the 8-week study did not differ significantly between the groups (32.4% with aripiprazole and 44.0% with perphenazine).
Frequency of cocaine cravings declined modestly but significantly with aripiprazole, as assessed by the change from weeks 3-5 to weeks 6-8. The same was true for craving intensity and duration. Craving parameters did not change significantly in the perphenazine group.
Dr. Drew D. Kiraly, of the Icahn School of Medicine at Mount Sinai in New York City, told Reuters Health by email that finding a successful medication regimen for patients with a major mental illness, such as schizophrenia, as well as a substance use disorder, is difficult.
“The thought process of the authors was sound,” said Dr. Kiraly, who was not involved in the study. “And it seems that they found a small effect using aripiprazole to reduce cravings.”
“They suggest that using aripiprazole may be moderately more effective than another antipsychotic for reducing cocaine craving, but this needs to be interpreted with caution due to the relatively small number of patients and effect size,” he added.
Dr. Thomas Kosten of Baylor College of Medicine in Houston, Texas, told Reuters Health by email, “Some troubling findings were that even if craving decreased, the cocaine use was higher, rather than lower, with aripiprazole (although not a significant difference). We consider craving reduction as an indication of wanting and using less of the abused drug, not more of the abused drug.”
“Furthermore, the statistical analyses for this type of post-hoc study would need to be somewhat more stringent for comparing the craving change over time,” added Dr. Kosten, who also was not involved in the study. “A more appropriate statistical approach would include both treatment groups in the analyses and test for an interaction term. Instead, they used two paired t-tests and did not use the whole period of data collection.”
“Comparing an early to a later period would require a clearer rationale, such as that a period of medication dosage escalation for the first 2 to 3 weeks was required to reach a therapeutic dose, which was not evident in this study. Thus, it appears to generate a hypothesis that is relatively weak and may capitalize on a chance difference between the two treatment groups over time,” Dr. Kosten said.
Dr. Beresford said, “It is too early to say for certain, but the results suggest that a clinical trial should proceed for about two months or more to establish whether there is an effect in specific cases,” he noted. “There may be a similar effect in cocaine dependent-only cases that should be investigated since this is a far larger group.”
“Although ours was a randomized, double blind comparison study, it must be replicated by other similarly controlled studies and with larger samples,” he advised.
SOURCE: http://bit.ly/2iafVLs
J Clin Psychopharmacol 2017.
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