Grau-López, Lara MD; Roncero, Carlos PhD; Daigre, Constanza MS; Miquel, Laia MD; Barral, Carmen MD; Gonzalvo, Begoña MD; Collazos, Francisco MD; Casas, Miquel PhD
Dual diagnosis/disorders are defined as the coexistence of a substance use disorder (SUD) and another mental disorder (Lehman et al., 1989; Szerman et al., 2013). It has been reported that up to 80% of patients with an SUD have another psychiatric disorder, and that 30% to 50% of patients with a psychiatric disorder have an SUD (Kosten and Kleber 1988; Regier et al. 1990; Roncero et al., 2011b; Szerman et al., 2011). Dual diagnosis with substance dependence has been related to earlier onset of psychopathological alterations, suicidal behavior, violent behavior, greater family instability, and social marginalization, as well as poor treatment adherence, worse prognosis, higher medical comorbidity, and an increase in health care costs (Regier et al., 1984).
The therapeutic approach to patients with a mental illness and a co-occurring SUD is complex (Roncero et al. 2011a), because specific therapies should be used for both the addiction and the other mental disorder (Havassy et al., 2004; Cleary et al., 2009). These patients receive not only standard medications used in general psychiatry (antidepressants, antipsychotics, mood stabilizers, antiepileptics, and benzodiazepines) but also specific medications for the treatment of substance dependence (eg, alcohol-aversive drugs, opioid agonists, and naltrexone) (Hilton, 2007). As a result, it can be expected that polypharmacy is common among these patients.
Polypharmacy is not exclusive to dual-diagnosis patients and is common in singly occurring mental disorders (Preskorn and Lacey, 2007; Mojtabai and Olfson, 2010) such as those with substance abuse disorders (particularly alcohol and opioids) (Welsh and Liberto, 2001), and patients with psychotic disorders such as schizophrenia (Freudenreich and Goff, 2002; Botts et al., 2003; Ganguly et al., 2004), schizoaffective disorder (Clark et al., 2002), or affective disorders (Frye et al., 2000) such as major depression (Glezer et al., 2009) or bipolar disorder (Bauer et al., 2010).
Recent studies reviewed the efficacy of pharmacotherapy and psychotherapy with patients with SUDs comorbid with mental illness (Kelly et al., 2012; Murthy and Chand, 2012). However, to our knowledge, the medications used in these patients have not been quantified.
The polypharmacy frequency is not known in patients with SUD comorbid with mental illness. On the contrary, naturalistic studies conducted with patients with 1 psychiatric diagnosis show that it is frequent for 2 or more medications to be prescribed despite the recommendations for using monotherapy. If we consider this, it can be expected that patients with dual diagnosis would be prescribed a higher number of medications.
We hypothesized that patients with mental illness and a co-occurring SUD will probably have more than 3 medications prescribed as 2 illnesses are being treated.
The aims of this study were to quantify the number of medications prescribed for treating psychiatric and addictive disorders in a group of patients with a mental illness and substance dependence followed in an outpatient drug treatment setting, and compare these aspects by age, sex, and type of diagnosis. The study also aimed to describe the pharmacological groups prescribed.
An observational, retrospective study was conducted in a specialized program for outpatients with mental illness and a co-occurring SUD treated in a drug treatment setting.
Inclusion criteria required that participants were older than 18 years and have 2 diagnoses on Axis I (DSM-IV-TR criteria), one of which was substance use dependence (opioids, cocaine, alcohol, cannabis, benzodiazepines, and designer drugs). The other disorders on Axis I were grouped as follows: psychotic disorders (schizophrenia, schizoaffective disorder), affective disorders (bipolar disorder, major depressive disorder), and anxiety disorders (obsessive-compulsive disorder and other anxiety disorders). Patients received no financial compensation for their participation and all gave their written informed consent; the study was approved by the hospital ethics committee. Exclusion criteria was having only an Axis II disorder and having an acute psychotic episode or other condition that impaired the decision capacity.
Participants with a preliminary dual diagnosis with substance dependence were recruited consecutively when they were admitted to our drug treatment setting from general practitioners, general psychiatric settings, and other drug treatment programs of the outpatient drug clinic. Axis I mental disorder and SUD were confirmed by trained clinical psychologists using SCID-I and SCID-II interviews (Structured Clinical Interview for the DSM-IV Axis I Disorders) (First et al., 1996, 2003). A retrospective chart review was performed between November and December 2011. Data gathered retrospectively included sociodemographic data (age, sex, nationality, marital status, domicile, educational level, and occupational status), clinical characteristics (family history, medical history, main drug dependence, and main psychiatric diagnosis in Axis I other than SUD), and therapeutic data (admissions).
Medications prescribed, including psychotropics, and medications for medical conditions were collected at 3 months after admission to our dual-diagnosis program.
To determine the number of medications per patient, we added all of the drugs included in clinical history. Psychotropic medications were prescribed in outpatient drug clinic to treat mental disorders, and medications for medical conditions were prescribed by general practitioners and other specialists.
Our study focused on the following psychotropic medications for adults: antidepressants, antipsychotics, anticonvulsants, benzodiazepines, and mood stabilizers such as lithium. The use of other psychotropic medications, particularly for addictive disorders, such as methadone, naltrexone, and disulfiram, were also assessed. Medications for medical conditions included antihypertensives, antiretrovirals, antidiabetics, and others.
Descriptive statistics of the primary variables included sociodemographic characteristics, primary diagnoses of substance-dependence disorders, other Axis I psychiatric disorders, and prescribed medications. Subsequently, bivariate analyses were conducted. Nonparametric tests were used owing to the small sample size. Statistical tests used were the Mann-Whitney U and Kruskal-Wallis tests to analyze differences among means. All statistical tests were 2-sided, and a P < 0.05 was considered statistically significant. Data were collected and analyzed using the statistical package SPSS, version 18.0.
One hundred seven patients were evaluated. Sociodemographic, clinical, and therapeutic characteristics of patients are shown in Table 1
When patients were evaluated according to diagnosis other than SUD, 52.3% were found to have a dual psychotic disorder, of which 50% used cocaine, 21.4% opioids, 12.5% alcohol, 10.7% cannabis, 3.6% designer drugs, and 1.8% benzodiazepines. Dual affective disorder was present in 31.8%; of these, 38.2% used cocaine, 26.5% cannabis, 20.6% alcohol, 11.8% opioids, and 2.9% benzodiazepines. Finally, 15.9% of the sample had a diagnosis of dual anxiety disorder; of these, 41.2% used cocaine, 29.4% cannabis, 23.5% alcohol, and 5.9% opioids.
Number of Medications Prescribed
The mean number of total medications prescribed per patient was 4.0 (SD = 1.8), including psychotropic (mean = 3.2; SD = 1.1) and medications for medical conditions (mean = 0.7; SD = 1.2).
Patient age groups were categorized as follows: 18 to 25, 26 to 45, and >45 years. The oldest group of patients had more drugs prescribed: 4.4 (SD = 2.1) in the >45 years versus 4.0 (SD = 1.7) in the 26- to 45-year group and 3 (SD = 1.2) in the 18- to 25-year group (K = 5.9, P = 0.05). No sex-related differences were found regarding the average number of medicines (mean = 3.9; SD = 1.8) in men versus 4.3 (SD = 1.4) in women (U = 802, P = 0.09).
The mean number of medications prescribed to patients was analyzed according to the dual-diagnosis with substance dependence condition. Patients diagnosed with a dual-psychotic disorder had a higher number of medications prescribed compared with those with dual-mood disorders or dual-anxiety disorders, with these differences being statistically significant (K = 10.52, P = 0.005). When the mean of psychotropics prescribed to patients according to type of diagnosis other than SUD was obtained, dual-psychotic disorders accounted for a higher number of medications than dual-mood disorders or dual-anxiety disorders (P = 0.0001) (Fig. 1).
Description of Pharmacological Groups Prescribed
Antipsychotics were prescribed in 69.2% of the total sample (n = 74), followed by antidepressants (65.4%; n = 70), antiepileptics (58.9%; n = 63), anxiolytics (37.4%; n = 40), alcohol-aversive drugs (15.9%; n = 17), methadone (15.9%; n = 17), lithium (3.7%; n = 4), and naltrexone (2.8%; n = 3).
The pharmacological group prescribed was based on the type of Axis I diagnosis other than SUD. All patients diagnosed with dual-psychotic disorders and dual-anxiety disorders, regardless of drug dependence, were prescribed antipsychotic drugs and antidepressants, respectively; 85.3% of dual-affective patients had been prescribed an antidepressant, regardless of drug dependence. Moreover, all patients diagnosed with a heroin addictive disorder had a prescribed opioid agonist.
When we analyzed the nonpsychotropic medications, we found that 55.6% of dual-psychotic, 33.3% of dual-mood patients, and 11.1% of dual-anxiety patients have been prescribed these medications (Table 2).
This study shows that polypharmacy is widely present in patients with mental illness and a co-occurring SUD treated in a specialized program in an outpatient drug setting (mean = 4.0, SD = 1.8). Our results concur with our hypothesis. Dually diagnosed patients are often treated with specific medications, such as methadone and interdictors, for the addictive disorder, and specific medications for the other Axis I psychiatric disorders. Despite is infrequent to prescribe a medication to treat patients with cocaine and cannabis addiction, patients with a dual diagnosis receive medication for treating not only the addiction but also the concomitant mental illness.
The quantification of medications prescribed in patients with SUD comorbid with mental illness cannot be compared directly with those used in other patient populations with similar diagnoses because, to our knowledge, very few such studies have been conducted (Kelly et al., 2012; Murthy and Chand, 2012). However, we can compare our results with mental illness patients without substance dependence (Kreyenbuhl et al., 2007; Lerma-Carrillo et al., 2008; Pandurangi and Dalkilic, 2008; Bauer et al., 2010). In our study, dual-psychotic patients were prescribed 3.6 (SD = 1.1) medications. In 2007, Kreyenbuhl et al. reported the amount of antipsychotic medications consumed by psychotic patients and they found that 12.8% of psychotic patients took 2 or more antipsychotics. In another study, Pandurangi and Dalkilic (2008) described in a meta-analysis that 5% to 39% of psychotic patients consumed 2 or more medications. Furthermore, in a retrospective study, Lerma-Carrillo et al. (2008) reviewed all the psychotropic drugs dispensed to 209 inpatients diagnosed with schizophrenia or schizoaffective disorder of a brief hospitalization psychiatric unit. They found that only 45.5% received monotherapy, and the most frequent number of antipsychotic medications prescribed was 2 (range: 1–9) (Lerma-Carrillo et al., 2008). In the sample, dual-affective patients consumed 3 (SD = 0.9). However, a high level of polypharmacy was also found in patients with bipolar disorders, with a mean number of medications used of 3.1 (SD = 1.6), very close to our mean (Bauer et al., 2010).
This study also showed relationships between certain demographic factors and the consumption of medications in dual-diagnosis patients. Patients older than 45 years were found to be prescribed a larger number of medications than younger patients. The increase in medication consumption with age may be due to the fact that the course of the diseases progressively worsens with age (Tsutsumi et al., 2011).
No differences were observed regarding sex. This contrasts with studies conducted in the general population that found a higher use of medications in women (Sans et al., 2002) or studies carried out in primary care settings that found that women take a greater number of medications, mainly analgesics and benzodiazepines (Fernández-Liz et al., 2008). It should be taken into account that more men than women are treated in the addiction unit (Green et al., 2002; Miquel et al., 2013).
When the number of prescriptions according to psychiatric diagnosis was compared, we found that patients with dual-psychotic disorder were prescribed more medications than individuals with other dual psychiatric diagnoses. This coincides with the conclusion published by Welsh and Liberto (2001), who established that patients with schizophrenia comorbid with SUD had a higher probability of receiving more antipsychotics than patients with schizophrenia alone (Welsh and Liberto, 2001).
In this study, the most prescribed pharmacological group was that of antipsychotic agents, which may be explained by the predominance of patients with psychotic disorders (52.3%) in the study sample. Atypical antipsychotics are commonly used for comorbid schizophrenia and addictive disorders and could be more effective for the treatment of schizophrenia and comorbid substance abuse than conventional antipsychotics. Current evidence suggests that clozapine, olanzapine, and risperidone are among the best, and quetiapine is also beneficial in duapsychotic patients, particularly those using alcohol, cocaine, and amphetamines (Kelly et al., 2012; Murthy and Chand, 2012); however, the evidence for any of these medications has yet to be well established (Roncero et al., 2011a).
The second most prescribed pharmacological group in this study was antidepressants. This may be due to the efficacy of antidepressants in patients with depression and comorbid SUD (Torrens et al., 2005); however, Kelly et al. (2012) found that antidepressants used to improve substance-related symptoms among patients with mood and anxiety disorders either are not highly effective or involve risk due to high side-effect profiles or toxicity (Kelly et al., 2012). Moreover, antidepressants and antipsychotics are used as hypnotics and anxiolytics to minimize the risk of benzodiazepine-dependence disorder (Robert et al., 2005; Terán et al., 2008). Some patients with dual affective disorder did not receive antidepressant agents because they had bipolar disorders, for which the use of antidepressants is not generally recommended (Casas et al., 2008).
Antiepileptics were also another group often used in drug abusers in this study (58.9%). However, the percentage of patients with bipolar disorder or schizoaffective disorder was low (22.5%). This difference can be explained by the fact that antiepileptics are used in addicted patients owing to their potential anti-impulsive or anticraving effects (Johnson et al., 2004).
It should be emphasized that in this study, benzodiazepines were not prescribed with the same frequency as that described in other studies (Gual, 2007). In the present study, benzodiazepines were prescribed to a lesser extent because alcoholic patients were underrepresented in the sample and because the doctors from the treatment center follow expert international recommendations and national consensus to prevent benzodiazepine abuse (Consensus of the Spanish Society of Psychiatry on the diagnosis and treatment of alcoholism and other addictions, 2003; Consensus on Dual Pathology, 2004; Rijswijk et al., 2005).
Methadone was prescribed to all opioid-dependent patients. Heroin addicts are known to have a greater probability of relapse than other addictive patients (Grau-López et al., 2012a). Furthermore, in psychotic patients, methadone use has been suggested because of its antipsychotic effect (Brizer et al., 1985; Ros-Cucurull et al., 2012).
In this study, alcoholic aversives such as disulfiram were prescribed for the most part in alcoholics and, in a minor percentage, in cocaine addiction because it has been reported that disulfiram can exert an anticocaine craving effect (Shorter and Kosten, 2011). However, it is recommended to use disulfiram with caution in dual psychotic patients because it can produce psychotic symptoms (Murthy, 1997; Grau-López et al., 2012b).
Nonpsychotropic medications were mainly prescribed in dual-psychotic patients, mainly opioid and alcohol addicts, because these patients have more comorbid medical conditions than others with mental illness and a co-occurring SUD. It is possible that patients with medical illness had less treatment compliance due to the greater number of drugs that they need. Moreover, patients with comorbid medical conditions increase the administration and cost burden of health care systems.
This study has several limitations. The design of this research was cross-sectional and retrospective, and we know only the medications prescribed by psychiatrists but not the medications taken by patients. We did not control for possible mediator role of medical illnesses between age and the number of medications. Moreover, in this study patients with cocaine and cannabis addiction outnumbered those with other addictive disorders. On these grounds, caution should be taken when extrapolating the results. Patients included in this study were admitted to a specialized program of co-occurring diagnosis and do not represent all patients with a dual diagnosis; therefore, the generalizability of the results is limited.
Despite these limitations, to our knowledge, this is the first study to quantify the number of medications prescribed per patient with a dual diagnosis with substance dependence. Moreover, the description reveals the daily clinical practice in a specialized program for dual-diagnosis outpatients. In addition, the validity of the diagnoses obtained was supported by the use of semistructured interviews according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria.
Although a combination of medications is recommended for patients with SUD comorbid with mental illness (Kelly et al., 2012; Murthy and Chand, 2012), polypharmacy has been associated with worse treatment compliance, higher occurrence of side effects and pharmacological interactions, and an increase in financial costs (Claxton et al., 2001). Thus, the description of how medicines are prescribed in these patients is important because it represents the first step in optimizing pharmacological treatment and analyzing possible factors associated with polypharmacy.
Patients treated in a dual-diagnosis program received 3.6 (SD = 1.1) psychopharmacological drugs for treatment of their conditions. Based in our study that supports the high rates of polypharmacy, we can hypothesize that it can be important to use medications that can treat several symptoms simultaneously to diminish the total number of medication used.
The authors thank the psychologists who performed the diagnostic interviews: Ms Laia Rodriguez-Cintas, Ms Susana Gómez-Baeza, and Ms Diana Bachiller and nurse Oriol Esteve, who collected the data. The authors also thank the Agencia de Salut Publica de Barcelona for supporting the outpatient drug clinic Vall Hebron. The authors thank Adil Qureshi, PhD, for the revision of the manuscript.
Bauer M, Glenn T, Grof P, et al. The association between concurrent psychotropic medications and self-reported adherence with taking a mood stabilizer in bipolar disorder. Hum Psychopharmacol 2010;25(1):47–54.
Botts S, Hines H, Littrell R. Antipsychotic polypharmacy in the ambulatory care setting. 1993–2000. Psychiatr Serv 2003;54(8):1086.
Brizer D, Hartman N, Sweeney J, et al. Effect of methadone plus neuroleptics on treatment resistant chronic paranoid schizophrenia. Am J Psychiatry 1985;142:1106–1107.
Casas M, Franco MD, Goikolea JM, et al. Spanish Working Group on bipolar disorders in dual diagnosis. Bipolar disorder associated to substance use disorders (dual diagnosis). Systematic review of the scientific evidence and expert consensus. Actas Esp Psiquiatr 2008;36(6):350–361.
Clark RE, Bartels SJ, Mellman TA, et al. Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy. Schizophr Bull 2002;28(1):75–84.
Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23(8):1296–1310.
Cleary M, Hunt GE, Matheson S, et al. Psychosocial treatments for people with co-occurring severe mental illness and substance misuse: systematic review. J Adv Nurs 2009;65(2):238–258.
Consensus on Dual Pathology. Fundación Española de Psiquiatría y Salud Mental. Sociedad Española de Psiquiatría. Barcelona. Ars Médica, 2004.
Consensus of the Spanish Society of Psychiatry on the Diagnosis and Treatment of Alcoholism and Other Addictions. Barcelona, Spain: Euromedine, 2003.
Fernández-Liz E, Modamio P, Catalán A, et al. Identifying how age and gender influence prescription drug use in a primary health care environment in Catalonia, Spain. Br J Clin Pharmacol 2008;65:407–417.
First MB, Gibbon M, Spitzer R. Structured Clinical Interview for the DSM-IV Axis II Disorders, Research Version, Patient Edition. (SCID-II/P). New York: Biometrics Research, New York State Psychiatric Institute, 2003.
First MB, Spitzer RL, Gibbon M, et al. Structured Clinical Interview for the DSM-IV Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute, 1996.
Freudenreich O, Goff DC. Antipsychotic combination therapy in schizophrenia: a review of efficacy and risks of current combinations. Acta Psychiatr Scand 2002;106(5):323–330.
Frye MA, Ketter TA, Leverich GS, et al. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000;61(1):9–15.
Ganguly R, Kotzan JA, Miller S, et al. Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998–2000. J Clin Psychiatry 2004;65:1377–1388.
Glezer A, Byatt N, Cook R Jr, et al. Polypharmacy prevalence rates in the treatment of unipolar depression in an outpatient clinic. J Affect Disord 2009;117(1/2):18–23.
Grau-López L, Roncero C, Daigre C, et al. Risk factors of relapse in drug dependent patients after hospital detoxification. Adicciones 2012a;24(2):115–122.
Grau-López L, Roncero C, Navarro C, et al. Psychosis induced by the interaction between disulfiram and methylphenidate may be dose dependent. Substance Abuse 2012b;33(2):186–188.
Green CA, Polen MR, Dickinson DM, et al. Gender differences in predictors of initiation, retention, and completion in an HMO-based substance abuse treatment program. J Subst Abuse Treat 2002;23(4):285–295.
Gual A. Dual diagnosis in Spain. Drug Alcohol Rev 2007;26:65–71.
Havassy BE, Alvidrez J, Owen KK. Comparisons of patients with comorbid psychiatric and substance use disorders: implications for treatment and service delivery. Am J Psychiatry 2004;161:139–145.
Hilton T. Pharmacological issues in the management of people with mental illness and problems with alcohol and illicit drug misuse. Crim Behav Ment Health 2007;17:215–224.
Johnson BA, Swift RM, Ait-Daoud N, et al. Development of novel pharmacotherapies for the treatment of alcohol dependence: focus on antiepileptics. Alcohol Clin Exp Res 2004;28(2):295–301.
Kelly TM, Daley DC, Douaihy AB. Treatment of substance abusing patients with comorbid psychiatric disorders. Addict Behav 2012;37(1):11–24.
Kosten TR, Kleber HD. Differential diagnosis of psychiatric comorbidity in substance abusers. J Subst Abuse Treat 1988;5:201–206.
Kreyenbuhl JA, Valenstein M, McCarthy JF, et al. Long-term antipsychotic polypharmacy in the VA health system: patient characteristics and treatment patterns. Psychiatr Serv 2007;58(4):489–495.
Lehman AF, Myers CP, Corty E. Assessment and classification of patients with psychiatric and substance abuse syndromes. Hosp Community Psychiatry 1989;40:1019–1025.
Lerma-Carrillo I, de Pablo Brühlmann S, del Pozo ML, et al. Antipsychotic polypharmacy in patients with schizophrenia in a brief hospitalization unit. Clin Neuropharmacol 2008;31(6):319–332.
Miquel L, Roncero C, García-García G, et al. Gender differences in dually-diagnosed outpatients. Subst Abuse 2013;34(1):78–80.
Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry 2010;67(1):26–36.
Murthy KK. Psychosis during disulfiram therapy for alcoholism. J Indian Med Assoc 1997;95(3):80–81.
Murthy P, Chand P. Treatment of dual diagnosis disorders. Curr Opin Psychiatry 2012;25(3):194–200.
Pandurangi AK, Dalkilic AJ. Polypharmacy with second-generation antipsychotics: a review of evidence. Psychiatr Pract 2008;14(6):345–367.
Preskorn SH, Lacey RL. Polypharmacy: when is it rational? J Psychiatr Pract 2007;13(2):97–105.
Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug use: results from the Epidemiologic Catchment Area (ECA). JAMA 1990;264:2511–2518.
Regier DA, Myers JK, Kramer M, et al. The NIMH Epidemiologic Catchment Area program: historical context, major objectives, and study population characteristics. Arch Gen Psychiatry 1984;41:934–941.
Rijswijk E, Zandstra SM, Lisdonk EH, et al. Appropriateness of benzodiazepine prescribing in general practice. Int J Clin Pharmacol Ther 2005;43:411–412.
Robert S, Hamner MB, Kose S, et al. Quetiapine improves sleep disturbances in combat veterans with PTSD: sleep data from a prospective, open-label study. J Clin Psychopharmacol 2005;25(4):387–388.
Roncero C, Barral C, Grau-López L, et al. Protocols of dual diagnosis intervention in schizophrenia. Addict Disord Their Treat 2011a;10(3):131–154.
Roncero C, Fuste G, Barral C, et al. Therapeutic management and comorbidities in opiate-dependent patients undergoing a replacement therapy programme in Spain: the PROTEUS study. Heroin Addict Relat Clin Probl 2011b;13:5–16.
Ros-Cucurull E, Miquel L, Quesada Franco M, et al. Reduction of psychotic symptoms during the use of exogenous opiates. Heroin Addict Relat Clin Probl 2012;14(2):57–58.
Sans S, Paluzie G, Puig T, et al. Prevalence of drug utilization in the adult population of Catalonia, Spain. Gac Sanit 2002;16(2):121–130.
Shorter D, Kosten TR. Novel pharmacotherapeutic treatments for cocaine addiction. BMC Med 2011;3(9):119.
Szerman N, Arias F, Vega P, et al. [Pilot study on the prevalence of dual pathology in community mental health and substance misuse services in Madrid]. Adicciones 2011;23(3):249–255.
Szerman N, Martinez-Raga J, Peris L, et al. Rethinking dual disorders/pathology. Addict Disord Their Treat 2013;12(1):1–10.
Terán A, Majadas S, Galan J. Quetiapine in the treatment of sleep disturbances associated with addictive conditions: a retrospective study. Subst Use Misuse 2008;43(14):2169–2171.
Torrens M, Fonseca F, Mateu G, et al. Efficacy of antidepressants in substance use disorders with and without comorbid depression. A systematic review and meta-analysis. Drug Alcohol Depend 2005;78(1):1–22.
Tsutsumi C, Uchida H, Suzuki T, et al. The evolution of antipsychotic switch and polypharmacy in natural practice—a longitudinal perspective. Schizophr Res 2011;130:40–46.
Welsh C, Liberto J. The use of medication for relapse prevention in substance dependence disorders. J Psychiatr Pract 2001;7(1):15–31.
addiction; drug dependence; dual diagnosis; outpatient drug clinic; polypharmacy