Depression in male patients on methadone maintenance therapy

Authors

  • Azlin Baharudin MD (UKM) MMedPsych (UKM),

    Corresponding author
    • Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
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  • Noormazita Mislan MBBChBAO (Ireland) MMed Psych (UKM),

    1. Department of Psychiatry, Batu Pahat Hospital, Johor, Malaysia
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  • Normala Ibrahim MBBChBAO (Ireland) MMed Psych (UKM),

    1. Department of Psychiatry, Faculty of Medicine, Putra University Malaysia, Selangor, Malaysia
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  • Hatta Sidi MBBS MMed Psych (UKM),

    1. Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
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  • Nik Ruzyanei Nik Jaafar MBBChBAO( Ireland) MMed Psych (UKM)

    1. Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
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Correspondence

Azlin Baharudin MD (UKM) MMedPsych (UKM), Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia.

Tel: +603 9145 6152/6142

Fax: +603 9173 7841

Email: jelin72@hotmail.com

Abstract

Introduction

Depression is one of the most common psychiatric conditions in men. The aim of the study was to determine the depressive symptoms and associated factors among men on methadone maintenance therapy (MMT).

Methods

A cross-sectional study was conducted involving 108 subjects who attended the Drug Clinic at Hospital Kuala Lumpur. The instruments used include the Structured Clinical Interview for Diagnostic and Statistical Manual, Fourth Edition Axis-I Disorder, Beck Depression Inventory and the 15-item International Index of Erectile Function.

Results

The rate of depression was 44.4%. There were significant associations between Malay ethnicity, secondary education level and concurrent illicit cannabis use with depression (P < 0.05). However, there was no significant associations between depression and erectile dysfunction (P = 0.379).

Discussion

Even though depression is common among men on MMT, it is often missed by the treating doctors. It is important to make the treating doctors aware that depression is a serious clinical condition that has a profound impact on the individual and compliance to treatment.

Introduction

Opiate dependence is a serious problem worldwide. It leads to increasing burden, especially in health, economics and social problems. The United Nations Office on Drugs and Crime (UNODC) estimates the global prevalence of opioid use in 2010 to have been 0.6–0.8% of the population aged 15–64 years (i.e. 26.4–36 million opioid users). North America (3.8–4.2%), Oceania (2.3–3.4%) and Eastern and South-Eastern Europe (1.2–1.3%) are the regions with a higher than global average prevalence of opioid users. In 2010, an increase in heroin users was observed mainly in Armenia, Azerbaijan and Georgia in Central Asia and Transcaucasia, and in Indonesia, Singapore and Sri Lanka in South Asia and South-East Asia (UNODC, 2012). In 2001, the estimated number of drug users in Malaysia was 400,000–800,000 and was estimated to increase to 1 million in the next few years (Jesjeet et al., 2007). In Malaysia, the AIDS epidemic is driven by injection-drug use, mainly opiates. In 2007, of the 80,938 HIV infection cases in the country, 58,135 were injecting drug users (Ministry of Health Malaysia, 2006). In 2005, the Malaysian government had approved opiate maintenance therapies as part of harm reduction strategies in the management of heroin addiction. Methadone and buprenorphine are used to treat the opiate dependence. The Ministry of Health Malaysia has directed that methadone be a heavily regulated medicine to prevent potential negative implications (National Methadone Maintenance Therapy Guidelines, 2005). Statistics from the Agensi Anti-Dadah Kebangsaan (AADK, the national antidrug agency) revealed that between January to September 2008, an average of 17 new addicts and 20 relapse cases were identified every day in Malaysia. Remaining in treatment for an adequate period of time is critical for treatment effectiveness. Programs need strategies to engage and keep patients in treatment. It is important also to study factors that can influence treatment programs.

Depression is a common medical condition among former heroin addicts in methadone maintenance therapy (MMT) but often goes unrecognized and hence untreated. Approximately one-third of narcotic addicts maintained on methadone in the community were moderately to severely depressed (Weissman et al., 1976). Fifty percent of those on MMT were found to be suffering from depression (Peles et al., 2007). Depression was found in nearly a third (32.9%) of older adults on MMT (Rosen et al., 2008). Applebaum et al. (2010) found that substantial proportions of participants (55.6%) met criteria for major depressive disorder. Lifetime prevalence rates for depression in opiate-dependant patients enrolled in treatment programs ranged 20–50% and current prevalence rates in the 10–20% range (Nunes et al. 1994). Depressive symptoms require early detection and treatment as the combination of depression and drug dependence creates a high risk for suicide. Few studies revealed that depressive disorders or syndromes among opiate addicts are associated with worse treatment outcome (Kosten et al., 1986; Rounsaville et al., 1982). It is also important for the doctors to diagnose depression as it may interfere with therapeutic compliance with MMT. Interestingly, there is also evidence that depression is associated with increased retention in methadone treatment (Joe et al., 1999). The prevalence of depression is lower in out-of-treatment addicts than in those who are seeking treatment (Rounsaville and Kleber, 1985). Thus, depression may interfere with treatment effectiveness and at the same time be a driving force in motivating opiate-dependent individuals toward treatment. Depression is commonly a psychological problem related to erectile dysfunction; the relationship between depression and erectile dysfunction is unclear and they may form a vicious cycle. Spring et al. (1992) suggested that methadone patients presenting with sexual dysfunction should receive psychiatric evaluation after he found a significant association between lower Global Sexual Satisfaction Index scores with low Hamilton Rating Scale for Depression scores. Hallinan et al. 2008) and Brown et al. 2005) used the Beck Depression Inventory (BDI) to measure the presence of depression in methadone patients and reported significant association with erectile dysfunction. Contrary to Bliesener et al. (2005), who used a two-question self-rating scale for sexual function, depression as measured by BDI was not associated with erectile dysfunction in neither methadone nor buprenorphine groups. This present study aimed to examine the factors associated with depressive symptoms among men on MMT. Findings from the study may have implications for researchers and clinicians in MMT seeking to identify aspects of substance abuse treatment that can be targeted to improve treatment engagement, retention and outcome.

Methods

This was a cross-sectional study conducted at the Drug Clinic of Hospital Kuala Lumpur (HKL) between October and December 2008. Patients on the MMT program need to come daily to the clinic as the methadone is given under direct observed treatment, in which the methadone dose is not allowed to be taken away for the first 4–6 weeks. The inclusion criteria were subjects who were male, aged 18–65 years, fulfilled the diagnosis of opiate dependence based on the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV), had been treated for 2 months or more with a maintenance dose of methadone, had been in a stable heterosexual relationship for the past 6 months, were able to read and understand the national language (Bahasa Malaysia) or English and consented to the study. Being in a stable heterosexual relationship was defined as “having a person you consider an intimate and primary sexual partner”. This was important in the assessment of male sexual function as one of the variables as described in the method below. Subjects who were in withdrawal or intoxication were excluded.

Instruments

Instruments used in this study were a demographic and clinical data questionnaire, Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I), BDI and 15-item International Index of Erectile Function (IIEF-15).

The demographic questionnaire collected data on age, race, marital status, educational level, employment status, type of occupation, age of partner and monthly family income. Clinical data on the comorbid medical history, history of other substance use in the previous month, and duration and dose of methadone were also included in the questionnaire.

The SCID-I (Spitzer et al., 1992), a semistructured interviewer-rated questionnaire, was used to confirm the diagnosis of heroin dependence according to DSM-IV Axis-I diagnosis.

The BDI is a self-administered measure of the severity of depression. In this study, the 21-item BDI version that had been translated by two groups was used. The first group consisted of a trainee psychiatrist and the second group consisted of a family medicine trainee and a final year medical student who helped to translate the BDI to Bahasa Malaysia and back-translated independently. The two sets of translation and back-translation were then compared by a psychiatrist and trainee clinical psychologist. A pretest was conducted and it showed an internal reliability coefficient (Cronbach's α) of 0.956.

The IIEF-15 is a multidimensional self-report questionnaire for the evaluation of male sexual function (Lukasc, 2001; Rosen et al., 2002). The Malay version of the IIEF-15 was used. It is a reliable and valid instrument with high internal consistency for five domains (α ≥ 0.74), with a high test–retest correlation of coefficient and intraclass correlation of coefficient (ICC ≥ 0.59) for 15 items and five domains (Quek et al., 2002). Effect size was evaluated and it showed a high degree of sensitivity and specificity.

Data collection

Written informed consent was obtained from subjects who were willing to participate in the study. They were assured of their anonymity and the confidentiality of the data obtained. A coding system was used to identify the subject. The SCID-I was administered to confirm the diagnosis of heroin dependence. The subjects were also required to complete the sociodemographic form, IIEF-15 and BDI.

Statistical analysis

The data was analyzed using the Statistical Package for Social Science ver. 12. The relationships between the study parameters were analyzed using appropriate statistical tests. The statistical tests used include Student's independent t-test, Mann–Whitney U-test, χ2-test, Kolmogorov–Smirnov test and multiple logistic regressions. P < 0.05 was considered statistically significant.

Ethical consideration

This study was approved by the Research and Ethics Committee, National University of Malaysia Medical Center. Permission to carry out the study was obtained from the Hospital Director of General Hospital Kuala Lumpur. The purpose of the study was explained to the participants and written informed consent was obtained from them.

Results

Of the 254 male patients who attended the Drug Clinic of HKL for MMT, only 135 were in a stable heterosexual relationship. The inclusion of only those in a stable partnership is essential in this study which also assessed male erectile function because the IIEF is not useful for men without partners. However, 23 patients did not consent while four patients did not complete the IIEF-15 or BDI questionnaires. The overall response rate was 80% with a final total of 108 respondents recruited for the study (Table 1).

Table 1. Sociodemographic characteristics and clinical variables of the patients
VariableFrequency (n)Percent (%)
Age (years)  
21–3098.3
31–402321.3
41–504844.4
>502825.9
Ethnicity  
Malay8275.9
Chinese1110.2
Indian1413.0
Others10.9
Marital status  
Married8578.7
Single2321.3
Employment  
Present9487.0
Absent1413.0
Education level  
Primary1917.6
Lower secondary4138.0
Upper secondary3835.2
Malaysian Higher School Certificate/Diploma109.2
Comorbid medical illness  
Present4642.6
Absent6257.4
Erectile dysfunction  
Present7468.5
Absent3431.5

The majority of respondents were within the age group of 41–50 years (44.4%), Malay (75.9%) and still married (78.7%). Most of them had at least secondary education (73.2%), were employed (87.0%) and had family income of more than 2,000 Malaysian ringgit/month (60.0%).

The majority of patients had no comorbid medical illness (57.4%). Among respondents with a history of comorbid medical illness, more than half had positive history of substance-related medical illness. Of these, 47.8% were hepatitis C positive, 25.3% hepatitis B positive and 7.0% HIV positive. In this study, patients on MMT also had histories of concurrent abuse of other substance such as heroin (45.37%), alcohol (14.81%), cannabis (11.11%), amphetamine (8.33%) and benzodiazepine (2.78%).

The mean duration of the patients on MMT was 24.26 months (SD ± 6.99; range, 4–36). The mean methadone dose was 62.41 mg (SD ± 17.51; range, 30–150).

Of the respondents, 44.4% (n = 48) had depressive symptoms with BDI scores of 10 or more. The percentage of erectile dysfunction was 68.5% (n = 74). Table 2 shows that ethnic, education level and cannabis use had significant association with depressive symptoms. No significant association was found between depressive symptoms and marital status, occupation, comorbid medical history and erectile dysfunction.

Table 2. Sociodemographic characteristics and clinical variables of patients with depressive symptom among patients on methadone maintenance therapy
 Depressed n (%)Not depressed n (%)d.f.χ2P
  1. Bolded text indicates significance at P < 0.05.
Ethnicity     
Malay43 (52.4)39 (47.6)18.8170.003
Non-Malay5 (19.2)21 (80.8)   
Marital status     
Married39 (45.9)46 (54.1)10.3340.563
Unmarried9 (39.1)14 (60.9)   
Education     
Primary2 (10.5)17 (89.5)210.7550.005
Secondary41 (51.9)38 (48.1)   
Tertiary5 (50.0)5 (50.0)   
Employment status     
Employed44 (46.8)50 (53.2)11.6410.200
Unemployed4 (28.6)10 (71.4)   
Medical history     
Yes19 (48.7)20 (51.3)10.4520.502
No29 (42.0)40 (58.0)   
Erectile dysfunction     
Yes35 (47.3)39 (52.7)10.7750.379
No13 (38.2)21 (61.8)   
Concurrent substance use     
Yes30 (46.9)34 (53.1)1  
No18 (40.9)26 (59.1) 0.3760.540
Cannabis use     
Yes9 (75.0)3 (25.0)15.1050.024
No39 (40.6)57 (59.4)   

Discussion

Depression is prevalent in opiate-dependent patients and the presence of psychiatric comorbidity in opiate-dependent patients is usually described as a dual diagnosis. Emotional disorders likes depression and anxiety present much more prominently in this group of patients (Rounsaville et al., 1982). Their etiology and relationship to opiate dependence is complex. The presence of depressive symptoms in this study was 44.4%, and this is comparable with previous studies which showed a slightly higher prevalence of depressive disorder (Ahmad Rasidi and Chin, 1996; Lotfi, 2008). Brooner et al. 1997) reported that the prevalence of mood disorder was 19% using the Structured Clinical Interview for DSM, Third Edition, Revised. Brienza et al. (2000) found that 42% of those on MMT met criteria for major depression. Lotfi (2008) conducted a study among those seeking treatment for opiate dependence in 10 urban community centers in Kuala Lumpur; he found that prevalence of depressive disorder was 58.4% using the SCID-I. In this study, the author had used BDI as a screening tool on the respondents. As a self-rated scale, the BDI suffers from the same problems as other self-report inventories. There is a possibility that the scores can be easily maximized or minimized by the person completing it.

Factors contributing to depression are important considerations in the administration of MMT in any treatment setting to ensure good compliance, maintaining in the treatment program and best outcome. In this study, we found that Malay ethnicity, secondary education level and concurrent illicit cannabis use were significantly associated with depression. As of 2006, Malaysia has a population of almost 27 million, and ethnic Malays make up approximately half this number (Department of Statistics, 2006). Overall, the majority of the respondents were Malay (75.9%), followed by Indian (13%), then Chinese (10.2%) and finally others. According to the AADK 2008 yearly report, a large number of those with drug dependencies are Malay (76.45%), followed by Chinese then Indian. The high percentage of Malays involved in drug addiction was mainly due to the Malay ethnicity being largest of constituent of the Malaysian population. Many local studies (Ahmad Rasidi and Chin, 1996; Mohamed and Kasa, 2007) showed that heroin addiction was more popular among Malays as compared to other races. It was observed in this study that the majority of respondents (70.2%) had secondary education, followed by primary education (17.6%) and tertiary education (9.2%). Lotfi (2008) also reported the same finding among patients receiving opiate-substitute treatment in community-based centers. It has been shown that most delinquent behavior begins in adolescence, which later can lead to school dropout (Lotfi, 2008). This may be the underlying reason for the low percentage of tertiary education among those seeking treatment for opiate dependence.

The comorbidity of major depression and cannabis use was high, particularly among adolescent inpatients (Grilo et al., 1997). In this study we found that 75% of patients who use cannabis had history of depression as compared to non-users. Gregory (2001) found that those patients who abuse cannabis were four-times more likely to have depressive symptoms than those with no diagnosis of cannabis abuse. Data from the Australian National Survey of Mental Health and Well-Being, a representative survey of Australians aged 18 years and over, showed that 14% of those who had history of cannabis abuse or dependence met the criteria for an affective disorder, compared to 6% of non-users (Degenhardt et al., 2001). Cannabis use is very high in clinically depressed adolescents, and use increases depressive symptoms in this population (Rey et al., 2002). Cannabis and depression is comorbid in a unique way, suggested by a study that found the prevalence of clinical depression is higher in patients who use cannabis alone compared to those who use cannabis and harder drugs such as cocaine (Arendt and Munk-Jørgensen, 2004). A longitudinal survey concluded that there is a causal relationship between increasing cannabis use in the population with increased prevalence of depression of 9% (Harder et al., 2006).

In the present study, we found that there was no significant association between depression and erectile dysfunction. The causal relationship between depression and erectile dysfunction is probably bidirectional. The depression may be a consequence of erectile dysfunction or depression may cause erectile dysfunction (Seidman and Roose, 2000; Quaglio et al., 2008). Past studies showed that data regarding depression and erectile dysfunction are inconsistent. Spring (1992) found that patients on MMT with a lower Derogratis Sexual Functioning Inventory score had a higher level of depression on the Hamilton Rating Scale. They concluded that the sexual dysfunction may have been due to the psychiatric problems rather than to the opiates. Hallinan (2008) also reported that depression was found to be associated with global sexual dysfunction in groups of patient on MMT or buprenorphine. Our study results revealed that the presence of depressive symptoms was not associated with respondents with erectile dysfunction; this is consistent with the findings of Niclaas et al. (2005) and Brown et al. (2005). Though not significant, it is worth noting that a higher percentage of respondents with depressive symptoms had erectile dysfunction compared to those without. The explanation for non-significant finding between depressive symptoms and erectile dysfunction in the present study was most likely due to the self-rated questionnaire that had been used to detect the respondents with depressive symptoms. In order to make an accurate finding, a structured interview instrument and clinical evaluation would be the most effective measurement. We were using the IIEF-15 to assess erectile dysfunction. Excluding males without stable partners is important as IIEF is known to not be useful in men without partners. Moreover, in our culture, asking an unmarried person questions related to homosexuality and sexual function is sensitive (Sidi et al., 2006). However, we acknowledge that this could be a study limitation as there is the possibility that men without stable partners may be prone to both depression and sexual dysfunction.

There is a possibility that the high prevalence of erectile dysfunction in the present study is a cry for help for depression. Puri and Hall (2004) reported that – in masked depression – depressed mood is not always complained of, but rather somatic or other complaints. This is more common in the less developed world, especially in those who are unable to articulate their emotions and in elderly patients.

A few limitations were noted in this study. It was confined to one particular urban center as part of cross-sectional survey, thus narrowing the generalizability of the study findings. The sample size in this study was not large enough to obtain a definitive conclusion. This small sample size is partly due to only one center being selected. Probably, we should have conducted the study in multiple, community-based centers, to increase the sample size by recruiting more patients and to achieving better heterogeneity of the social background of the study population. Another possible limitation concerns the use of a self-report questionnaire for assessing depressive symptoms and erectile dysfunction. This introduces a potential for response bias, as respondents may exaggerate or inaccurately report their symptoms. In the absence of clinical evaluation and objective assessment, this possibility cannot be excluded. Then again, the questionnaire that was used essentially has good sensitivity and specificity; thus, it is a suitable, reliable, valid and sensitive instrument to measure erectile dysfunction and depressive symptoms in this group.

In conclusion, all opiate-dependent patients in treatment should be screened for depression, given its prevalence and prognostic implications. Diagnosing and monitoring depression of opiate addicts could help in prevention of opiate relapse.

Conflicts of interest

Assoc Prof Nik Ruzyanei received honorarium speaker fees for the 13th Johor Mental health convention 2011 (Servier Malaysia Sdn Bhd) and the Wellness Pre conference workshop at Malaysia Psychiatry conference 2011 (Eli Lily Malaysia Sdn Bhd). All other authors have no conflicts of interests to declare.

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