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Journal of Addiction Medicine:
doi: 10.1097/ADM.0000000000000024
Original Research

Observational Study on Medications Prescribed to Dual-Diagnosis Outpatients

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

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Author Information

From the Outpatient drug clinic (CAS) Vall d'Hebron (LGL, CR, CD, LM, CB, BG), Department of Psychiatry, Vall Hebron University Hospital, Public Health Agency of Barcelona (ASPB), Barcelona, Spain; Department of Psychiatry (LGL, CR, LM, CB, FC, MC), Vall Hebron University Hospital, Autonomous University of Barcelona, CIBERSAM, Barcelona, Spain; and Department of Psychiatry and Forensic Medicine (LGL, CD, CR, FC, MC), Autonomous University of Barcelona, Barcelona, Spain.

Send correspondence and reprint requests to Lara Grau-López, MD, Department of Psychiatry, Vall Hebron University Hospital, Paseo de Vall Hebron 119-129, 08035. Barcelona. Spain. E-mail: lgrau@vhebron.net.

The authors declare that they have no competing interests.

Received November 12, 2012

Accepted January 04, 2014

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Abstract

Objectives: To quantify the number of medications used for treating psychiatric and addictive disorders in a cohort of dual diagnosis with substance dependence outpatients and report the most frequent pharmacological groups used.

Methods: A descriptive, cross-sectional study was conducted. Demographic data, Axis I comorbidity diagnosis with substance dependence, and the medications prescribed were recorded. Diagnosis was assessed by the Structured Clinical Interview for DSM-IV (SCID).

Results: One hundred seven patients (mean age 37.7 years; SD = 10.2 years) were evaluated (76.6% men). On average, patients took 4.0 (SD = 1.8) medications. The pharmacological groups prescribed were antipsychotics (69.2%) followed by antidepressants (65.4%), antiepileptics (58.9%), anxiolytics (37.4%), alcohol-aversive drugs (15.9%), methadone (15.9%), lithium (3.7%), and naltrexone (2.8%). Older patients (>45 years old) were found to have a higher number of prescribed medications. Patients diagnosed with a dual psychotic disorder were prescribed a larger number of pharmacological agents (mean = 4.4; SD = 2.1) than patients with a mood disorder (mean = 3.7; SD = 1.3) or an anxiety disorder (mean = 2.9; SD = 1.2), K = 10.5, P = 0.005.

Conclusions: Because polypharmacy is frequent in patients with mental illness and a co-occurring substance use disorder, specialized approaches need to be developed.

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.

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METHODS

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.

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RESULTS

Sample Characteristics

One hundred seven patients were evaluated. Sociodemographic, clinical, and therapeutic characteristics of patients are shown in Table 1

Table 1
Table 1
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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.

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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).

Figure 1
Figure 1
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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).

Table 2
Table 2
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DISCUSSION

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.

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CONCLUSIONS

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.

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ACKNOWLEDGMENTS

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.

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addiction; drug dependence; dual diagnosis; outpatient drug clinic; polypharmacy

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