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Atypical Antipsychotic Drugs in Dual Marín-Mayor et al. Int J Neurol Neurother 2015, 2:1 International Journal of DOI: 10.23937/2378-3001/2/1/1026 Volume 2 | Issue 1 Neurology and Neurotherapy ISSN: 2378-3001 Review Article : Open Access Atypical Antipsychotic Drugs in Dual Diagnosis Patients: A Review Marta Marín-Mayor1, Jorge López-Álvarez2, Francisco López-Muñoz3-5*, Francisco Arias-Horcajadas1,5 and Gabriel Rubio1,5,6 1Psychiatry Service, “Doce de Octubre” University Hospital, Spain 2Instituto de Formación y Tratamiento en Terapia Familiar Sistémica (ITAD), Spain 3Chair of Genomic Medicine and Faculty of Health Sciences, Camilo José Cela University, Spain 4Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Spain 5Neuropsychopharmacology Unit, “Hospital 12 de Octubre” Research Institute, Spain 6Department of Psychiatry, Complutense University, Spain *Corresponding author: Francisco López-Muñoz, Chair of Genomic Medicine and Faculty of Health Sciences, Camilo José Cela University, C/ Castillo de Alarcón, 49, Urb. Villafranca del Castillo, 28692 Villanueva de la Cañada, Madrid, Spain, Tel: +34 91 815 3131, Fax: +34 91 860 9343, E-mail: [email protected]/[email protected] Abstract Keywords Introduction: Dual Diagnosis (DD), defined as the co-occurrence Atypical antipsychotics, Dual diagnosis, Substance use disorder of a Substance Use Disorder (SUD) and a Severe Mental Illness (SMI), is associated with several negative outcomes. Typical antipsychotics (TAP) are not of great value for patients with DD as Introduction they are associated with poorer responses and can worsen SUD. Atypical antipsychotics (AAP) offer several advantages compared Dual diagnosis (DD) is traditionally defined as the co-occurrence to TAP. In DD, they have been found to be effective in treating both, of a Substance Use Disorder (SUD) and a Severe Mental Illness (SMI) psychiatric symptoms and substance use. The aim of this article is [1]. Although in recent years the concept of DD has been extended to review the use of AAP for treating DD patients. and it is being used to define the co-occurrence of any mental illness Methods: A search of MEDLINE, EMBASE and Pubmed was and a SUD, in this review we will consider Schizophrenia (SCH) and performed in order to identify publications that examined the use of related disorders, as well as Bipolar Disorder (BD) with concomitant AAP in the treatment of DD. SUD. Results: The largest number of studies focuse on clozapine, More than 50% of the patients with a psychiatric disorder with consistently positive data. Data regarding aripiprazole are meet DSM-IV criteria for alcohol and/or substance abuse and/ also consistent but less substantial. Olanzapine, risperidone or dependence [2]. The substances more commonly used by these and quetiapine have given inconclusive and inconsistent results. patients are alcohol, followed by cannabis and cocaine [3]. Several Finally, there is little use of amisulpride, ziprasidone, paliperidone and asenapine or it is has not been documented. complimentary hypotheses have been used to explain the comorbidity between SMI and SUD. Traditionally, the association between SUD Discussion: Today, there is a consensus on using AAT instead and SMI was explained with the “self-medication” theory, which of TAP for treating patients with DD. Patients with DD show a stated that patients use substances to relieve psychiatric symptoms poorer response to treatment with TAP, and TAP may even worsen or the side-effects of psychiatric medication [4]. However, in recent the addictive behaviour. AAP are as effective as TAP in treating psychiatric symptoms, but they are more effective in reducing years, the neurobiological theory proposed by Green et al. (1999) is substance use in DD patients. Because with the exception of CLO gaining importance in the field of DD. They suggest that there is a none of the AAP have shown to be superior to the others, when “reward deficiency syndrome” in people with SMI, so that they have choosing between the different AAP agents clinicians should take a dysfunction in their dopamine (DA)-mediated mesocorticolimbic into account other variables such as medical comorbidity, possible (MCL) reward pathways, and use alcohol and other drugs of abuse in pharmacological interactions of concomitant treatments and profile order to ameliorate this dysfunction in the brain reward system [5]. of side effects. Even though a growing body of evidence suggests the beneficial effects of AAP in DD patients, further randomized, Comorbid SUD among patients with SMI is associated with more blinded, controlled trials, with larger sample sizes and longer follow- negative outcomes such as more relapses [6], more admissions to ups are needed. hospital [7], poor response to treatments [8], non-compliance with Citation: Marín-Mayor M, López-Álvarez J, López-Muñoz F, Arias-Horcajadas F, Rubio G (2015) Atypical Antipsychotic Drugs in Dual Diagnosis Patients: A Review. Int J Neurol Neurother 2:026. doi.org/10.23937/2378-3001/2/1/1026 ClinMed Received: March 04, 2015: Accepted: March 27, 2015: Published: March 30, 2015 International Library Copyright: © 2015 Marín-Mayor M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.23937/2378-3001/2/1/1026 ISSN: 2378-3001 the treatment [9], increased rates of suicidal ideation [10], increased included: 25 studies on CLO (that have been described in detail in our rates of impulsive and violent behaviours [11], increased rates of previous work [24]), 20 studies on OLZ, 20 studies on RIS, 11 studies neurological and psychiatric symptoms [12], and higher incidence of on QUE, 6 studies on ARI, 2 studies on AMS and one study on ZIP. poverty, unemployment and social exclusion [13].The demographic correlates of substance use are well documented and DD patients tend Results to be younger males, with a lower educational level, a family history of Clozapine SUD, and a comorbid Antisocial Personality Disorder (ASPD) [14]. Clozapine (CLO) is the AAP with the greater body of research Typical antipsychotics (TAP), unfortunately, are often not regarding its use as a pharmacological agent for patients with DD. of great value for patients with a SMI and a SUD. In fact, a poorer Results regarding CLO have been published in a previous work of response to TAP has been described in patients with a past history our group [24]. To summarize, several case reports, case series, of SUD [15,16]. In addition, an increase in cigarettes smoked after retrospective and prospective studies, comparing CLO to TAP the initiation of haloperidol (HAL) treatment has also been reported or other AAP such as RIS, OLZ and ZIP have suggested that CLO [17]. Two main hypotheses have been proposed to explain this lack may decrease the use of nicotine, alcohol, or other drugs of abuse of efficacy of TAP in dual diagnosed patients: 1) TAP are associated among patients with DD, as well as craving for these drugs. It is with considerable side effects, such as extra pyramidal side effects also associated with an improvement of psychiatric symptoms and (EPS) and dysphoria, so that DD patients would “self-medicate” in social functioning. In addition, it has been found that a history of order to ameliorate these symptoms [18-20] and 2) they worsen the SUD does not influence the positive response to CLO. However, functioning of DA-mediated MCL brain reward circuits because of a clinicians are often hesitant to use CLO as a first-line treatment due potent D receptor blockade action [5,21]. 2 to its undesirable side effects such as the risk for agranulocytosis and Atypical antipsychotics (AAP) offer several advantages over seizures, and the need for frequent monitoring [24]. TAP: 1) they are effective in treating positive symptoms to the Olanzapine same extent as TAP; 2) they are as effective or superior to TAP in treating negative symptoms; 3) they exert antidepressant and mood For Olanzapine (OLZ), a search was performed combining all stabilization actions; 4) they are effective in treating aggression and possible major search terms: OLZ on one hand, and Dual Diagnosis or impulsivity; 5) they exhibit better tolerability, especially in terms of Psychosis, Schizophrenia, Schizoaffective Disorder, Bipolar Disorder decreased EPS, tardive dyskinesia and hyperprolactinemia; 6) they and Substance Use Disorder, on the other. Of the total of 411 articles diminish suicidality and 7) they are associated with an improvement identified, 16 were suitable for our review. Four further studies were in cognition. Furthermore, they have been reported to obtain some identified after reading through the full text of studies previously advantage in the treatment of SUD probably due to their mechanism found. At the end of our search 20 studies met our inclusion criteria of action, which includes less DA antagonism and pharmacological and were selected for our review. action on serotonin (5HT), histamine (HIS), and norepinephrine OLZ is an AAP with a mechanism of action similar to CLO (NE) pathways [22,23]. that has also shown some promising results when it comes to treat The aim of this article is to review the use of AAP for treating patients with a SMI and a comorbid SUD (Table 1).Two of the first DD, in order to critically discuss their effectiveness both in treating authors that pointed out the efficacy
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