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A Study of the Sexual Function, Sleep, and Weight Status of Patients after 6 Months of Methadone Maintenance Treatment.

Background Methadone is a synthetic opioid and receptor agonist morphine; thus, its consumption has the effects and side effects of opioid. Methadone maintenance treatment (MMT) is used as an alternative treatment for people who are suffering from substance abuse and do not have the ability to withdraw. Despite its benefits, this drug also has side effects. The purpose of this study was to investigate the effects of methadone treatment on sexual function, sleep, and weight after 6 months. Methods The study subjects consisted of 200 patients who had referred to the Methadone Clinic of Shahid Beheshti Training Hospital, Kerman, Iran, during a 6-month period and were treated using MMT. Data collection tools consisted of the demographic questionnaire, Pittsburgh sleep quality index (PSQI), and Arizona sexual experience scale (ASEX). The questionnaires were completed by the participants before and 6 months after the treatment. Findings The results of this study showed that methadone consumption has significant effects on sexual dysfunction, sleep disorders, and weight gain. Conclusion The consideration of the side effects of MMT can result in consumers’ commitment to the treatment.


Introduction
Methadone is a synthetic narcotic substance and a mu receptor agonist. Its intake causes satisfaction and has an analgesic effect and other effects of morphine-like substances. 1 Due to its 2 features of long half-life and high oral absorption, methadone is used as an alternative treatment to prevent or reduce withdrawal symptoms in the treatment of drug abuse. 2 Methadone maintenance treatment (MMT) is used in addicts who are not able to maintain a constant abstinence from drugs. Using this method of treatment the craving for drugs is resolved in these patients. However, psychological dependence to heroin can be gradually overcome. 3 Refusal of injection and the prevention of risky behaviors, and returning to work, community, and family is a major goal of public health and is expected with MMT. 4 The purpose of this study was to investigate the effects of methadone treatment on sexual function, sleep, and weight after 6 months of use.
MMT is a continuity of a kind of addiction, and despite its proven success in many countries, its careless and irresponsible prescription can cause serious danger. Methadone has a low therapeutic index, meaning that the medication dose required for treatment is very close to the toxic dose. In particular, its use in combination with other drugs has potential risks. 5 In addition, MMT can have some side effects. Drowsiness, opioid craving, constipation, dental problems, weight gain, sleep disturbance, decreased libido, nausea and vomiting, irregular menstruation, excessive sweating, dizziness, blurred consciousness, rash, loss of appetite, irritability, and weakness are some side effects of methadone. 3 Some of these side effects, like nausea and drowsiness, abate within the first weeks of treatment, but some side effects, such as constipation, excessive sweating, and reduced libido or sexual dysfunction, persist for months. 6 Sexual disorders are major barriers to commitment to continuing maintenance treatment with opioid pharmaceutical compounds especially in patients who are treated with high doses or for prolonged periods. 7 In his research, Kreek concluded that in patients undergoing MMT, the side effects of sweating, constipation, sexual dysfunction, and sleep and appetite disorders may emerge or persist from 6 months to 3 years after treatment. 8 Babakhanian et al., in their study on men under MMT, found that after 6 months of treatment patients showed moderate improvement in erectile function, complete improvement regarding sexual intercourse, and partial improvement regarding sexual desire, but no improvement in orgasmic function. 9 The results of the study by Ramazanzadeh et al. in Sanandaj, Iran, showed a significant improvement in patients' marital satisfaction after 7 months of treatment with methadone. 10 The study by Sadeghpour et al. on patients undergoing MMT in Tehran, Iran, showed that patients who had been treated for more than 6 months had more satisfactory quality of life and sleep compared to those who were new to the treatment, or had been previously treated and had relapsed. 11 The study by Peles et al. conducted on 23 patients undergoing MMT showed no significant change regarding sleep during 6-12 months of follow-up, but weight gain in a small group of patients increased sleep apnea. 12 Mysels et al. Performed a comparative study on methadone and naltrexone. Methadone is a mu receptor agonist which causes weight gain and naltrexone is a mu receptor agonist which causes weight loss; however, no significant differences were observed between the two and in comparison to the baseline condition. 13 Due to the expansion of MMT centers, the consideration of the complications of MMT can be effective in the increasing or continuation of MMT in order to achieve benefits. In the present study, the prevalence of sexual dysfunction, and sleep and appetite disorders were investigated on patients who referred to the Methadone Clinic of Shahid Beheshti Training Hospital, Kerman, Iran. The results of this study, in addition to clarifying the aspects or effects of this treatment, could be a prelude to future interventions to reduce morbidity and increase patients' continuation of treatment, and thus, the improvement of their quality of life and public health. Kerman. The subjects were selected via convenience sampling method. During admission, the demographic questionnaire, Pittsburgh sleep quality index (PSQI), and Arizona sexual experience scale (ASEX) were completed for all participants. Moreover, the patients were weighed at the beginning of treatment. The study was explained to them and they were reassured regarding the confidentiality of their information. After 6 months, the questionnaires were completed again by the patients. They were also asked about night sweats and lack of appetite.

Methods
Exclusion criteria included inability to understand the questions, history of hospitalization at a psychiatric hospital except for withdrawal, diabetes, epilepsy, high blood pressure and use of anti-hypertensive drugs, and use of antidepressants, tranquilizers, anticholinergic drugs, and antipsychotics. The Persian version of the PSQI had a 0.77 Cronbach's alpha coefficient, score range of 0-21 and cut-off point of 5. 11,14 The Persian translation of the ASEX had a Cronbach's alpha of 9%, a good reliability, and a correlation coefficient of 0.80. 15 Data analysis was performed using SPSS software (version 20, SPSS Inc., Chicago, IL, USA) and after determining the descriptive measures of central tendency and dispersion. Repeated measure was used to investigate the effects of methadone on sexual function, sleep, and weight over time and the impact of the gender factor.
Night sweating was mentioned by 29 patients (14.6%) and lack of appetite in 26 cases (13.1%). The results showed that methadone had a significant effect on sexual function of the consumers (P < 0.001). Therefore, methadone caused sexual dysfunction in the patients and this effect was not significantly different in males and females (P = 0.100) ( Table 1). Table 2 illustrates the effect of methadone on each sexual stage.

Discussion
This study was conducted on 199 patients who underwent MMT. The incidence of sexual dysfunction and sleep disorders had significantly increased with methadone (P < 0.001). Their weight had also significantly increased after receiving MMT (P < 0.001). These changes were not associated with the gender of the patients. The complications of the medications were due to lack of commitment to the treatment. Sexual dysfunction was a barrier to commitment to continuing maintenance therapy with opioid componds. 7 Some side effects abate within the first weeks of treatment which is a sign of physiological adaptations to the effects of the medication. Some of the side effects, such as constipation, excessive sweating, and sexual dysfunction, persisted for months during MMT. 6 The results of the present study were consistent with that of other studies on MMT. In the study by Kreek, the rate of sexual dysfunction in the participants was similar to that in the general population, but the rate of orgasmic disorders was higher which may respond to the reduction of dose. 8 In the study by Kheirabadi et al., the majority of the subjects in the study (94.8%) had sexual dysfunction, ranging from mild to severe, and this had a significant relationship with prolactin blood levels. 16 In the study by Roshanpajhu et al. 17 in Tehran a reduction in sexual desire was also observed which was consistent with the present study. Nevertheless, the results of this study were inconsistent with some previous studies. Including the study by Babakhanian et al. which showed a moderate improvement in erectile function and sexual function after maintenance treatment. 9 Furthermore, the results of this study were inconsistent with that of Ramazanzadeh et al. regarding improvement in marital satisfaction after treatment, which could be related to differences in study methods. 10 The results of this study were in consistent with that of Peles et al. regarding sleep quality of patients treated with methadone maintenance. 12 The strength of the present study was its larger sample size compared to the mentioned study. Weight gain was observed in a small number of patients in the study by Peles et al. 6 The present study results regarding weight changes were also different from Mysels et al. study. 13 That study had a smaller sample size compared to the present study. The social life improvement of the patients was possibly the reason for their weight gain as a positive factor during MMT in the present study. 13 The side effects of MMT, in comparison to its public health benefits and focus on reduction of harm, are justifiable. Furthermore, the disagreement between the results of the present study and other studies may be due to the different variables addressed in different studies, including quality of life and improving family relationships, which may affect the outcome of the research.
Addiction has different aspects, and thus, extensive research is necessary regarding various factors and comparative methods in the normal population and people who continue substance abuse. Lack of available studies on the effects of methadone, its growing use, and MMT justify the need for further studies in this field.

Conclusion
This study showed that, despite the benefits of methadone in reducing damage, and hence, promoting health, it can have complications such as sleep disorders, sexual dysfunction, and weight gain which can create obstacles for its use. Paying attention to these side effects and trying to control them can be effective in the consumers' commitment to the treatment.