Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence

Thomas Beresford, Jennifer Buchanan, Elizabeth Brie Thumm, Chad Emrick, David Weitzenkamp, Patrick J. Ronan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients. Methods In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable. Results Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 ± 0.43 (P < 0.0005) points, craving frequency by 1.4 ± 0.40 (P > 0.0004) points, and craving duration by 1.76 ± 0.44 (P > 0.0001) points. Conclusions A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse.

Original languageEnglish (US)
Pages (from-to)657-663
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume37
Issue number6
DOIs
StatePublished - Dec 1 2017

Fingerprint

Perphenazine
Cocaine-Related Disorders
Cocaine
Schizophrenia
Dopamine
Urine
Dual (Psychiatry) Diagnosis
Dopamine Agents
Acclimatization
Dopamine Receptors
International Classification of Diseases
Aripiprazole
Craving
Pharmaceutical Preparations
Antipsychotic Agents
Therapeutics
Recurrence
Brain

Keywords

  • aripiprazole
  • cocaine
  • craving
  • dependence
  • dopamine
  • partial agonist/antagonist
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence. / Beresford, Thomas; Buchanan, Jennifer; Thumm, Elizabeth Brie; Emrick, Chad; Weitzenkamp, David; Ronan, Patrick J.

In: Journal of Clinical Psychopharmacology, Vol. 37, No. 6, 01.12.2017, p. 657-663.

Research output: Contribution to journalArticle

Beresford, Thomas ; Buchanan, Jennifer ; Thumm, Elizabeth Brie ; Emrick, Chad ; Weitzenkamp, David ; Ronan, Patrick J. / Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence. In: Journal of Clinical Psychopharmacology. 2017 ; Vol. 37, No. 6. pp. 657-663.
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AU - Emrick, Chad

AU - Weitzenkamp, David

AU - Ronan, Patrick J.

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AB - Purpose Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients. Methods In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable. Results Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 ± 0.43 (P < 0.0005) points, craving frequency by 1.4 ± 0.40 (P > 0.0004) points, and craving duration by 1.76 ± 0.44 (P > 0.0001) points. Conclusions A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse.

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