Send Orders for Reprints to reprints@benthamscience.net Current Psychopharmacology, 2013, 2, 000-000 1 2211-5560/13 $58.00+.00 © 2013 Bentham Science Publishers Antipsychotics Management in Addictive Disorders Pierre Alexis Geoffroy *,1,2,3 , Benjamin Rolland 3,4,5 , Vincent Laprevote 6,7 and Olivier Cottencin 3,4,8 1 Inserm, U955, Psychiatrie génétique, Créteil, 94000, France 2 AP-HP, Hôpital H. Mondor - A. Chenevier, Pôle de Psychiatrie, Créteil, 94000, France 3 Univ Lille Nord de France, F-59000 Lille, France 4 Department of Addiction Medicine, CHU Lille, F-59000 Lille, France 5 Department of Pharmacology, EA 1046, F-59000 Lille, France 6 CHU Nancy, Centre d’Investigation Clinique Pierre-Drouin CIC-Inserm 9501, Nancy F-54 000, France 7 INSERM, Centre d’Investigation Clinique 9501, Vandoeuvre-les-Nancy, F-54500, France 8 UDSL, LNFP, EA4559, F-59000 Lille, France Abstract: Several authors have hypothesized that antipsychotics could down-regulate the activation of dopamine receptors in the mesolimbic pathway, thus decreasing the occurrence and the intensity of addiction-related symptoms. We conducted a critical review of the theoretical arguments that have been published on this subject and evaluated how they compare to the published clinical data. Despite interesting findings, the effects of antipsychotics may not be as compelling as what would be theoretically expected. Thus far, antipsychotics have shown no efficacy in treating addictive disorders alone. Nevertheless, effective strategies for the use of antipsychotics against addictions are available and discussed. To treat individual vulnerability factors to addictions, such as psychiatric comorbidities (schizophrenia or bipolar disorder) that share vulnerability factors with addictive disorders and contribute to triggering addictive behaviors are among the strategies. The evidence for using antipsychotics is still the best in subjects with comorbid schizophrenia and alcohol or substance use disorder. Additionally, in some clinical situations of major impulsivity, the off-label prescription of atypical antipsychotics is worth exploring, but should be further investigated in a clinical setting. Keywords: Antipsychotics, addiction, comorbidity, impulsivity, reward system, substance use disorder. 1. INTRODUCTION Addictive behavior is currently considered to have a strong neurobiological basis. The reward system, regulated by the activation of the mesolimbic dopaminergic pathway, is presumed to play a central role in addictive behavior. Indeed, drug use induces an increased release of dopamine in the nucleus accumbens assuming that this dopamine release has a relation to the reward effect of addictive drugs. Because antipsychotics are dopamine receptor antagonists, they could possibly down-regulate the activation of these receptors in the mesolimbic pathway, thus, decreasing the occurrence and intensity of addiction-related symptoms [1,2]. According to this reasoning it could be discussed whether the administration of anti-psychotic drugs could have a positive effect as a measure of prevention in the early course of the development or could even be indicated in case of a manifest addictive disorder. Thus far, however, few clinical studies have tested the relevance of this hypothesis in practice. In this review, we summarize the theoretical arguments that have been *Address correspondence to this author at the Pôle de Psychiatrie, Centre Expert Bipolaire, Hôpital Albert Chenevier, pavillon Hartman, 40, rue de Mesly, 94000 Créteil Cedex, France; Tel: + 33 1 49 81 32 90; Fax: + 33 1 49 81 30 99; E-mail: pierre.a.geoffroy@gmail.com published on this subject and evaluate how they compare to the clinical data in published literature. 2. THEORETICAL INTEREST OF ANTIPSYCHOTICS IN ADDICTION Reward, emotion processing and attention are fundamental cognitive functions involved in addictive behaviors, and they are closely related to the dopaminergic transmission in the limbic striatum [3-5]. Nearly all addictive drugs target the reward-system either directly, notably with psychostimulant drugs, or more often, indirectly with other types of drugs [6]. Moreover, striatal dopamine rates of firing decrease during withdrawal, regardless of which addictive drug was discontinued [6,7]. Dopamine is, therefore, the central neurotransmitter of addiction, which is overexpressed during reward-inducing drug intake and underexpressed during frustration-inducing drug withdrawal. All antipsychotics share the feature of being dopamine D2 receptor (D2R) antagonists, a pharmacological property that is considered to be the therapeutic mode of action of antipsychotics [8,9]. The sole exception is aripiprazole, which is not a D2R antagonist, but rather a partial agonist [10]. Antipsychotics’ action on D2R is particularly sustained in the striatum [11]. Furthermore, antipsychotics share an antagonism action with other monoamine receptors, in particular, the D3 dopamine receptor (D3R) [12]. D3R could