Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Chau, David T.; Khokhar, Jibran Y.; Gulick, Danielle; Dawson, Ree; Green, Alan I.

doi:10.1016/j.jpsychires.2015.07.010

Cited by 5 publications

(9 citation statements)

References 38 publications

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“…1 AUD usually occurs in patients with schizophrenia, contributes greatly to their morbidity 2 and drastically increased their course. 3 There are few data available on pharmacological approaches in this population, but among antipsychotics, clozapine shows positive evidence in the literature, 4 it has been associated with a decrease in alcohol consumption in patients with schizophrenia, but its toxicity reduces its use. 3 In addition, this group of patients often show poor adherence to medication.…”

Section: Discussionmentioning

confidence: 99%

“…3 There are few data available on pharmacological approaches in this population, but among antipsychotics, clozapine shows positive evidence in the literature, 4 it has been associated with a decrease in alcohol consumption in patients with schizophrenia, but its toxicity reduces its use. 3 In addition, this group of patients often show poor adherence to medication. To improve substance consumption and adherence to treatment in schizophrenic patients with SUD, direct and indirect evidence tends to favor the use of second generation antipsychotics (SGA), particularly those with less metabolic effects, cardiovascular and extra pyramidal, as well as those with their depot formulation.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these studies have been carried out with risperidone, aripiprazole, paliperidone and iloperidone. 1,3,[7][8][9][10] Chau et al 8 propose the unique and broad pharmacology of clozapine profile, including its weak dopamine D 2 receptor blockade, its potent antagonism of the noradrenergic receptor alpha-2, and its ability to elevate chronically and highly. Norepinephrine may have the property of reducing alcohol abuse.…”

Section: Discussionmentioning

confidence: 99%

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Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

T¹

2018

PPIJ

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Alcohol use disorder (AUD) worsens the course of schizophrenia. Its treatment is with antipsychotics, mainly clozapine. However, long-acting injectable (LAI) antipsychosis second generation (ASG) also shows improvement in the reduction of alcohol consumption in patients with schizophrenia. We have two clinical cases, a woman and a man, both with schizophrenia and AUD that after treatment with paliperidone palmitate depot monthly. The psychopathology improved and reduction of alcohol consumption was observed in one of the cases, by monotherapy with paliperidone palmitate monthly and, complete abstinence in the other case, by polytherapy with clozapine and paliperidone palmitate monthly.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

T¹

2018

PPIJ

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“…Furthermore, remoxipride decreases the number of alcohol presentations per session in rats by inducing an early termination of the alcohol-drinking bout during the self-administration session [132] and repeated systemic administration of paliperidone decreased the acquisition of alcohol consumption in high-alcohol-preferring P rats [156]. In addition, a recent study, comparing the effect of the atypical antipsychotic drug clozapine to that of the traditional dopamine D2 receptor antagonist haloperidol, showed that clozapine but not haloperidol attenuated the initiation of alcohol drinking and development of alcohol preference in highalcohol-preferring rats [157].…”

Section: Preclinical Evidence For the Use Of Atypical Dopamine D2 Recmentioning

confidence: 99%

Dopamine and Alcohol Dependence: From Bench to Clinic

Jayaram‐Lindström¹,

Ericson²,

Steensland³

et al. 2016

Recent Advances in Drug Addiction Research and Clinical Applications

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Alcohol dependence, a chronic relapsing psychiatric disorder, is a major cause of mortality and morbidity. The role of dopamine in alcohol-induced reward as well in the development of alcohol dependence is reviewed herein. Both preclinical and clinical studies have suggested that alcohol activates the mesolimbic dopamine system (defined as a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc, i.e. ventral striatum)) leading to a euphoric sensation. Alcohol dependence is characterized by a disruption in the reward-related brain areas including fewer dopamine D2 receptors in ventral striatum. Investigations of the underlying dopaminergic mechanisms involved during the development and maintenance of alcohol dependence could identify novel targets. Human and rodent experimental studies show that dopamine receptor antagonists, agonists and partial agonists as well as dopamine stabilizers influencing dopamine transmission, alter alcohol-mediated behaviours and thus may be potential treatment targets for alcohol dependence. Although there exists promising preclinical results, the majority of placebo-controlled randomized clinical trials with traditional dopamine antagonists and agonists have so far have been discouraging. Furthermore, the severe side-effect profiles of many of these compounds may limit their clinical use. Newer dopamine agents, such as partial agonists and dopamine stabilizers, attenuate alcohol-mediated behaviours in rodents as well as humans. Preclinical as well as clinical studies have shown that substances indirectly targeting the mesolimbic dopamine system may be potential targets for attenuation of alcohol reward. Collectively, the data reviewed herein may contribute to further understanding the complex mechanisms involved in development of alcohol dependence and we suggest that the newer dopamine agents as well as indirect modulators of dopamine signalling deserve to be further evaluated for treatment of alcohol dependence.

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“…We have used the hamster model in previous studies to test the effects of antipsychotic drugs (e.g., risperidone, paliperidone), alone or in combination with a NE reuptake inhibitor, on alcohol drinking (Chau et al, 2015; Gulick et al, 2014; Khokhar et al, 2015). While results from our studies are not in agreement with rat studies assessing the effects of antipsychotics on alcohol withdrawal symptoms (Celikyurt et al, 2011; Uzbay, 2012), possibly due to the lack of demonstrable withdrawal in the hamster (Kulkosky and Cornell, 1979), our findings in the hamster are consistent with reports from human studies (Green et al, 2003; Green et al, 2007), further supporting our use of the hamster model.…”

Section: Introductionmentioning

confidence: 99%

Effects of iloperidone, combined with desipramine, on alcohol drinking in the Syrian golden hamster

Khokhar

Green

2016

Neuropharmacology

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Alcohol use disorder in patients with schizophrenia dramatically worsens their clinical course, and few treatment options are available. Clozapine appears to reduce alcohol use in these patients, but its toxicity limits its use. To create a safer clozapine-like drug, we tested whether the antipsychotic iloperidone, a drug that combines a weak dopamine D2 receptor blockade and a potent norepinephrine alpha-2 receptor blockade would reduce alcohol drinking, and whether its effect on alcohol drinking could be increased if combined with an agent to facilitate norepinephrine activity. Syrian golden hamsters (useful animal model for screening drugs that reduce alcohol drinking in patients with schizophrenia) were given free access to water and alcohol (15% v/v) until stable drinking was established. Animals (n=6-7/group), matched according to alcohol intake, were treated daily with each drug (iloperidone; clozapine; haloperidol; desipramine [norepinephrine reuptake inhibitor]; with idazoxan [norepinephrine alpha-2 receptor antagonist]) or with a two-drug (iloperidone+desipramine; iloperidone+idazoxan) combination for 14 days. Moderate doses of iloperidone (1-5mg/kg) significantly reduced alcohol drinking (p<0.05) in the hamster, whereas higher doses (10-20mg/kg) did not. In addition, 5 mg/kg of iloperidone reduced alcohol drinking to the same extent as clozapine (8mg/kg), whereas haloperidol (0.2mg/kg) did not. Moreover, iloperidone's effects were enhanced via the addition of desipramine (3mg/kg), but not idazoxan (1.5/3mg/kg). In this animal model, iloperidone decreases alcohol drinking as effectively as clozapine, and desipramine appears to amplify this effect. The data suggest that iloperidone, alone or in combination with desipramine, should be tested in patients with schizophrenia and alcohol use disorder.

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Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Cited by 5 publications

References 38 publications

Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

Dopamine and Alcohol Dependence: From Bench to Clinic

Effects of iloperidone, combined with desipramine, on alcohol drinking in the Syrian golden hamster

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