Qom University of Medical Sciences Journal

In recent years, substance abuse has increased dramatically [1]. Substance abuse imposes high social and economic costs to the individuals, family members, and society due to its destructive physical and psychological effects [2]. Methadone as a maintenance and long-term treatment is one of the common treatments for substance abuse [3]. Considering that substance abuse is associated with mental health problems [4, 5], such as depression, anxiety [6, 7], and stress [8], lack of intervention for solving these mental problems can reduce the effects of methadone therapy and increase the risk of relapse [9]. Therefore, improving the mental health of drug addicts is very important. For this purpose, specialists use medication therapy, psychotherapy, or their combination [10].
Sertraline, as a selective serotonin reuptake inhibitor, is one of the medicines used for medication therapy [11]. Sertraline has an elimination half-life of about 26 hours, making it suitable for daily use [12]. The results of various studies have indicated the effect of sertraline on the components of mental health [13-16]. Compared to sertraline, venlafaxine is an inhibitor of the reuptake of serotonin, norepinephrine, and dopamine [17]. Venlafaxine has gastrointestinal absorption with a half-life of 3.5 hours for itself and 9 hours for its metabolites [18]. Venlafaxine can be more targeted than many other antidepressants because it does not affect muscarinic, nicotinic, histaminergic, or adrenergic receptors and the monoamine oxidase enzyme [17]. The results of various studies have indicated the effect of venlafaxine on several components of mental health [19-22]. However, few studies have focused on patients with substance abuse. There is no study that compares the effect of treatment with both sertraline and venlafaxine on the psychological distress of drug addicts under methadone therapy. Therefore, the present study aims to compare the effect of administration of methadone together with sertraline or venlafaxine on depression, anxiety, and stress of patients with substance abuse.
Method
The study population consists of all drug addicts under methadone maintenance treatment referred to addiction treatment clinics in Yazd city in 2020. Voluntary sampling method was used to select the samples. The inclusion criteria were a score above the average  in the depression, anxiety, stress scale (DASS-21), willingness to participate in the study, not taking other similar drugs that can influence the study variables, and not participating in other interventions. Exclusion criteria were the unwillingness to continue participation in the study, non-adherence to the group rules, occurrence of an unwanted reaction to the drug, and worsening of the patient conditions.
Forty addicts were selected based on the entry criteria and randomly assigned to two groups of 20 people. The first group received methadone (5-10 mg/day) plus sertraline (50 mg/day), and the second group received methadone (5-10 mg/day) plus venlafaxine (75 mg/day). Medication therapy by a psychiatrist was started 28 days before psychotherapy and continued until the end of psychotherapy. During the intervention, 2 people from the first group and 4 people from the second group withdrew from the study.
The participants were evaluated using the DASS-21 developed by Lovibond and Lovibond (1995) which has 21 items rated on a four-point Likert scale from 0 (not at all) to 3 (very much). The data were analyzed using paired t-test and analysis of covariance (ANCOVA). The significance level was set at 0.05.
Results
The mean age of participants was 34.9± 6.4 years in the venlafaxine group and 32.8±5.6 years in the sertraline group. In the venlafaxine group, 8 (4.4%) were single and 10 (55.6%) were married, and in the sertraline group, 5 (31.3%) were single, and 11 (68.8%) were married. In the venlafaxine group, 14 (77.8%) had lower than university education and 4 (22.2%) had a university education. In the sertraline group, 8 (50.0%) had lower than non-university education and 8 (50.0%) had a university education.
The independent t-test and chi-square test results showed no significant difference between the studied groups in demographic variables (P>0.05). In examining the assumptions of ANCOVA, the results of Shapiro-Wilk test, Box’s M test, and Levene’s test showed that all assumptions were met.
The paired t-test results showed that both venlafaxine and sertraline were significantly effective in reducing depression, anxiety, and stress of patients under methadone maintenance treatment (P<0.001). The results of ANCOVA showed a significant difference in the study groups between the depression, anxiety, and stress in the post-test phase (P<0.01). Although the combined use of methadone and sertraline had a greater effect on depression, anxiety, and stress of patients compared to the combined use of methadone and venlafaxine, this difference was not statistically significant.
Discussion
 The results showed that the use of methadone with sertraline or venlafaxine caused a significant reduction in depression, anxiety, and stress scores of patients with substance abuse. Although the results indicated the greater effects of the combined use of methadone and sertraline, the difference was not statistically significant. Both techniques can improve the efficacy of methadone therapy in drug addicts. The proper drug can be determined based on the psychiatrist’s opinion and the amount of drug side effects in patients.
Ethical Considerations
Compliance with ethical guidelines
This research was approved with the code of ethics IR.SSU.MEDICINE.REC.1399.170 in Shahid Sadougi University of Yazd. The researchers followed the ethical principles of clinical research such as (anonymity, confidentiality, etc.) in all stages
Funding
This article was carried out from the thesis of a research project approved and financially supported by Shahid Sadoughi University of Yazd.
Authors contributions
Writing of the article, statistical analysis and editing and finalization: Mehdi Shomali Ahmadabadi and Atefeh Barkhordari Ahmadabadi; Conducting the intervention: eyed Moazeddin Heidari Khormizi and Seyed Reza Ahmadi Mehrabadi; Scientific supervision of the research: Mohsen Zabihi, Ghasem Dastjerdi and Zahra Movahedian.
Conflicts of interest
The authors declared no conflict of interest.
Acknowledgements
Thanks are given to the addiction treatment clinics of Yazd city and all the people who helped the researcher in some way in conducting this research.