Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder

A randomized trial

Alan I. Green, Mary F. Brunette, Ree Dawson, Peter F Buckley, Amy E. Wallace, Hisham Hafez, Marvin Herz, Meera Narasimhan, Douglas L. Noordsy, Christopher O'Keefe, Roger W. Sommi, Richard M. Steinbook, Marjorie Weeks

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective: Alcohol use disorders worsen the course of schizophrenia. Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia, risperidone does not. We have proposed that risperidone's relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use. Since long-acting injectable (LAI) risperidone both results in lower average steady-state plasma concentrations than oral risperidone (with lower D2 receptor occupancy) and encourages adherence, it may be more likely to decrease heavy alcohol use (days per week of drinking 5 or more drinks per day) than oral risperidone. Method: Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were randomized to 6 months of oral or LAI risperidone between 2005 and 2008. Explanatory (efficacy) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions (in contrast to real-world settings), with intent-to-treat analyses being secondary. Results: Explanatory analyses showed that heavy drinking in the oral group worsened over time (P = .024) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups (P = .054). Furthermore, the 2 groups differed in the mean number of drinking days per week (P = .035). The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses (P = .018). Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale. The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI (P < .05), despite their significantly (overall) better treatment adherence (P < .005). Conclusion: For the population considered here, schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone. Nonetheless, our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients.

Original languageEnglish (US)
Pages (from-to)1359-1365
Number of pages7
JournalJournal of Clinical Psychiatry
Volume76
Issue number10
DOIs
StatePublished - Oct 1 2015

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Risperidone
Schizophrenia
Alcohols
Drinking
Injections
Dual (Psychiatry) Diagnosis
Dopamine D2 Receptors
Clozapine
Diagnostic and Statistical Manual of Mental Disorders
Alcohol Drinking
Antipsychotic Agents

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Green, A. I., Brunette, M. F., Dawson, R., Buckley, P. F., Wallace, A. E., Hafez, H., ... Weeks, M. (2015). Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: A randomized trial. Journal of Clinical Psychiatry, 76(10), 1359-1365. https://doi.org/10.4088/JCP.13m08838

Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder : A randomized trial. / Green, Alan I.; Brunette, Mary F.; Dawson, Ree; Buckley, Peter F; Wallace, Amy E.; Hafez, Hisham; Herz, Marvin; Narasimhan, Meera; Noordsy, Douglas L.; O'Keefe, Christopher; Sommi, Roger W.; Steinbook, Richard M.; Weeks, Marjorie.

In: Journal of Clinical Psychiatry, Vol. 76, No. 10, 01.10.2015, p. 1359-1365.

Research output: Contribution to journalArticle

Green, AI, Brunette, MF, Dawson, R, Buckley, PF, Wallace, AE, Hafez, H, Herz, M, Narasimhan, M, Noordsy, DL, O'Keefe, C, Sommi, RW, Steinbook, RM & Weeks, M 2015, 'Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: A randomized trial', Journal of Clinical Psychiatry, vol. 76, no. 10, pp. 1359-1365. https://doi.org/10.4088/JCP.13m08838
Green, Alan I. ; Brunette, Mary F. ; Dawson, Ree ; Buckley, Peter F ; Wallace, Amy E. ; Hafez, Hisham ; Herz, Marvin ; Narasimhan, Meera ; Noordsy, Douglas L. ; O'Keefe, Christopher ; Sommi, Roger W. ; Steinbook, Richard M. ; Weeks, Marjorie. / Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder : A randomized trial. In: Journal of Clinical Psychiatry. 2015 ; Vol. 76, No. 10. pp. 1359-1365.
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AU - Buckley, Peter F

AU - Wallace, Amy E.

AU - Hafez, Hisham

AU - Herz, Marvin

AU - Narasimhan, Meera

AU - Noordsy, Douglas L.

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N2 - Objective: Alcohol use disorders worsen the course of schizophrenia. Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia, risperidone does not. We have proposed that risperidone's relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use. Since long-acting injectable (LAI) risperidone both results in lower average steady-state plasma concentrations than oral risperidone (with lower D2 receptor occupancy) and encourages adherence, it may be more likely to decrease heavy alcohol use (days per week of drinking 5 or more drinks per day) than oral risperidone. Method: Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were randomized to 6 months of oral or LAI risperidone between 2005 and 2008. Explanatory (efficacy) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions (in contrast to real-world settings), with intent-to-treat analyses being secondary. Results: Explanatory analyses showed that heavy drinking in the oral group worsened over time (P = .024) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups (P = .054). Furthermore, the 2 groups differed in the mean number of drinking days per week (P = .035). The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses (P = .018). Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale. The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI (P < .05), despite their significantly (overall) better treatment adherence (P < .005). Conclusion: For the population considered here, schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone. Nonetheless, our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients.

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