Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D (2002) Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence

Department of Veterans Affairs, VISN 3 Mental Illness, Research, Education and Clinical Center, Lyons, New Jersey, USA.
Canadian journal of psychiatry. Revue canadienne de psychiatrie (Impact Factor: 2.55). 10/2002; 47(7):671-5.
Source: PubMed


To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapses during protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence.
We conducted a 6-week, open-label pilot study comparing risperidone with typical neuroleptics in a sample of withdrawn cocaine-dependent schizophrenia patients.
Preliminary results suggest that individuals treated with risperidone had significantly less cue-elicited craving and substance abuse relapses at study completion. Further, they showed a trend toward a greater reduction in negative and global symptoms of schizophrenia.
Atypical neuroleptics may help reduce craving and relapses in this population. Future research should include more rigorous double-blind placebo-controlled studies with this class of medications.

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Available from: David A Smelson, Jan 08, 2015
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    • "Risperidone, however, may differ from clozapine in regard to norepinephrine reuptake, since it does not appear to elevate norepinephrine levels in patients with schizophrenia to the same extent as clozapine (Elman et al., 2002; See et al., 1999). We suggest that this difference between the clozapine and risperidone may explain why risperidone does not appear to limit alcohol drinking in patients with schizophrenia (Green et al., 2008; Smelson et al., 2002). In support of this suggestion, we have shown that while risperidone itself has little effect on alcohol drinking in the Syrian golden hamster, its co-administration with the norepinephrine reuptake inhibitor desipramine chronically suppresses alcohol drinking (Gulick et al., 2014). "
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    ABSTRACT: Alcohol use disorder commonly occurs in patients with schizophrenia and dramatically worsens their course. The atypical antipsychotic clozapine has been associated with reduced drinking in these patients, but its toxicity reduces its use. We have attempted to create a clozapine-like drug by combining agents that capture components of clozapine's pharmacologic action, including its weak dopamine D2 blockade and noradrenergic modulation. The current study assessed whether paliperidone, a dopamine D2 receptor and adrenergic alpha-2 receptor antagonist like clozapine, would attenuate alcohol drinking in the alcohol-preferring P rat and the Syrian golden hamster, and whether desipramine, a norepinephrine reuptake inhibitor, would potentiate the ability of paliperidone to attenuate alcohol drinking in the P rat and the Syrian golden hamster. Daily subcutaneous injections of paliperidone (5 mg/kg for the rat; 1 mg/kg for the hamster) over 20 days slightly and transiently attenuated initiation of alcohol consumption in both animals. Desipramine (3 mg/kg) or lower doses of paliperidone alone did not affect alcohol drinking. However, the combination of desipramine (3 mg/kg) and paliperidone essentially prevented initiation of alcohol drinking and acquisition of alcohol preference in the P rat (2.5 or 5 mg/kg), and almost as dramatically suppressed chronic alcohol intake and alcohol preference in the hamster (2.5 mg/kg). Taken together, the current data suggest that (1) the desipramine and paliperidone combination attenuates alcohol drinking in a synergistic manner, and (2) desipramine and paliperidone may serve as an effective new treatment for alcohol use disorder in patients with schizophrenia.
    Journal of Psychiatric Research 09/2015; 69:9-18. DOI:10.1016/j.jpsychires.2015.07.010 · 3.96 Impact Factor
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    • "Substance abuse among patients with schizophrenia has been found to be associated with a number of serious impacts and higher risks for poor outcome and poor overall response to pharmacologic treatment (Dixon, 1999; Goff et al., 2005; Keltner and Grant, 2006; Kerfoot et al., 2011; McCloughen, 2003; Steinberg et al., 2004). Unlike the present study, a number of case studies or observational studies that relied on small samples or used retrospective designs have reported benefits for SGAs compared with first-generation agents in the treatment of comorbid substance abuse (Green, 2005; Swanson et al., 2007); however, most of the published reports were limited to examination of a single drug (Rubio et al., 2006; Smelson et al., 2002, 2004; Tsuang et al., 2002), with limited information on quetiapine or aripiprazole (Brown et al., 2002; Potvin et al., 2008; Zhornitsky et al., 2011). Most importantly, no large randomized trial has been published on substance abuse outcomes with all SGAs compared with FGAs. "
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    ABSTRACT: No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.
    The Journal of nervous and mental disease 06/2015; 203(7). DOI:10.1097/NMD.0000000000000317 · 1.69 Impact Factor
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    • "Compared to schizophrenic individuals treated with olanzapine, haloperidol-treated patients score significantly higher on the energy subcomponent of cue-evoked craving for cocaine (Smelson et al., 2006). Finally, amongst cocaine-addicted schizophrenia patients, those treated with haloperidol, fluphenazine or chlorpromazine versus risperidone score higher on the intensity and depression dimensions of cue-elicited craving, and are also markedly more likely to relapse to cocaine use following abstinence [70% of patients on typicals versus 12.5% on risperidone (Smelson et al., 2002)]. "
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    ABSTRACT: Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain's dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2013; 52. DOI:10.1016/j.pnpbp.2013.06.008 · 3.69 Impact Factor
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