|Year : 2020 | Volume
| Issue : 6 | Page : 657-662
Gender differences on methadone maintenance treatment outcome among patients with opioid use disorder: A systematic review
Mohemmad Redzuan Mohemmad Rizal1, Amer Hayat Khan2, Sabariah Noor Harun2, Zaiton Saleh3
1 Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; Health District Pontian, Ministry of Health, Johor, Malaysia
2 Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
3 Health District Pontian, Ministry of Health, Johor, Malaysia
|Date of Submission||03-Nov-2019|
|Date of Decision||09-Mar-2020|
|Date of Acceptance||04-Apr-2020|
|Date of Web Publication||05-Nov-2020|
Mohemmad Redzuan Mohemmad Rizal
Pharmacist, Department of Clinical Pharmacy, School of Pharmaceutical Sciences, University Science Malaysia, Penang.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objectives: The objective of this study was to review the significant differences of MMT outcomes related to drug use behavior, health status, and social behavioral functioning between genders. Materials and Methods: A search of publication was conducted in PubMed/MEDLINE, Embase, CINAHL, PsycINFO, and Scopus database. Two reviewers independently screened the titles, abstracts, and keyword use for the search. Inclusion of studies was based on randomized controlled trials (RCTs) or observational studies that report the difference of opioid addiction treatment outcomes between genders. Any conflict between the two reviewers was resolved through discussion and consensus. The systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO with a registration number CRD42019116261. Results: A total of 25 studies were evaluated as part of qualitative synthesis. The review resulted in three main themes, which are (1) improving well-being and methadone-related outcome (five subthemes), (2) impact on social and behavioral (four subthemes), and (3) illicit drug use pattern–related behavior (four subthemes). Conclusion: This review will highlight how men and women differ in methadone treatment outcomes for further application and improvement in the clinical setting.
Keywords: Gender difference, methadone treatment outcome, systematic review
|How to cite this article:|
Mohemmad Rizal M, Hayat Khan A, Noor Harun S, Saleh Z. Gender differences on methadone maintenance treatment outcome among patients with opioid use disorder: A systematic review. J Pharm Bioall Sci 2020;12, Suppl S2:657-62
|How to cite this URL:|
Mohemmad Rizal M, Hayat Khan A, Noor Harun S, Saleh Z. Gender differences on methadone maintenance treatment outcome among patients with opioid use disorder: A systematic review. J Pharm Bioall Sci [serial online] 2020 [cited 2021 May 12];12, Suppl S2:657-62. Available from: https://www.jpbsonline.org/text.asp?2020/12/6/657/299981
| Introduction|| |
Opioid abuse leading worldwide death. A significant increase is observed in rates of opioid use and the risk of its addiction. This risk of addiction includes medical, psychiatric comorbidity, infection, use of polysubstance, and criminal behavior. The increasing pattern of opioid abuse and illicit substance use will approximately double from 2.8 million, which is annual average in 2002–2006, to 5.7 million in the year 2020.
Women are typically of younger age, married, unemployed, and have earlier onset age of heroin use. Whereas for men, it is usually for pleasure and recreational purpose, and they have slower disease progression than women. Moreover, women have shown late treatment entry compared to men, less frequent utilization of substance abuse treatment, and more psychological and medical problems at treatment admission compared to men. This shows that the gender difference between men and women is not the same in methadone maintenance therapy (MMT), which requires attention in treatment strategies.
There were studies on factors associated with gender differences in MMT outcome including drug use pattern, opioid use, psychiatric comorbidity, prescription opioid use, smoking outcomes, and quality of life. However, the difference of MMT outcomes between genders reported in previous studies is inconclusive and needs to be compared. Besides, there were studies that investigated gender differences in terms of MMT remission, adverse events, health status, retention rate, criminal activity, social relation, and mortality, nevertheless they showed inconsistent result. Thus, a systematic review was performed to determine the significant differences of MMT outcomes related to drug use behavior, health status, and social behavioral functioning between genders.
| Study Design|| |
Literature search strategy
Data for this review were identified by structured review of publications listed in PubMed/MEDLINE, Embase, CINAHL, PsycINFO, and Scopus database. Keywords used to find database studies were as follows: “drug addicts’ treatment,” “opioid addiction,” “opiate substitution treatment,” “methadone maintenance treatment,” “sex differences/characteristic,” “gender differences methadone outcome,” “male,” “female,” “men,” and “women. No language barrier and time constraints were applied. The search was limited to publications in English language that were published after January 1988 to January 2018. Additional publications were identified by reviewing study reference lists and consulting expert review.
Inclusion and exclusion criteria
Inclusion of studies was based on randomized controlled trials (RCTs) or observational studies that described/reported the differences of opioid addiction therapy outcomes between genders. Systematic reviews or studies that investigated patient subpopulations or studies that involved the use of methadone for other than opioid addiction, such as for chronic pain treatment, were also excluded. Studies that involved population that may be influenced by their environment, which lead to a high potential for confounding and bias in the outcome, were also excluded. Weak and irrelevant articles, such as patient on a substitute opioid treatment other than methadone (naltrexone and buprenorphine/naloxone) or using methadone other than maintenance treatment, were excluded.
Two reviewers independently screened the titles and abstracts and recruited the original studies, which fulfill the inclusion criteria. Any conflict between the two reviewers was resolved through discussion, and consensus was developed. Author of the article was contacted directly if data clarification was needed.
Preferred reporting items for systematic reviews and meta-analyses
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [Figure 1]. The systematic review was registered in “International prospective register of systematic reviews (PROSPERO)” with a registration number CRD42019116261.
|Figure 1: Data extraction of article by using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines|
Click here to view
Data analytical strategy
The two reviewers independently assessed the risk of bias by using Newcastle–Ottawa Scale (NOS) for observational studies, and the Cochrane Collaboration tool for assessing the risk of bias in RCTs. Risk of bias was measured on a scale of 0 (high risk of bias) to 3 (low risk of bias), and specific description with example was provided. Items regarding selecting participant and ascertainment of outcome were retained, whereas other items relating to the comparability of groups and adequate follow-up for Cohort and case–control studies were removed as these were not directly applicable to this review. There were categories introduced to emphasize on cofounding effect and statistical analysis to minimize bias on methodology. Besides, seven domains on Cochrane’s tool to assess risk of bias in RCTs were used, that is, random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Each domain was evaluated and assessed on a per study or a per domain basis accordingly based on high or low risk of bias.
| Results|| |
The identification of articles through the searching and information strategy revealed a total of 1747 articles. Examination of these records through abstract and full-text review against the inclusion criteria resulted in a total of 25 studies. Therefore, a total of 25 studies were evaluated as part of qualitative synthesis. The review consists of three main themes: improving well-being and methadone-related outcome (five subthemes), impact on social and behavior (four subthemes), and illicit drug use pattern–related behavior (four subthemes) [Table 1].
| Discussion|| |
From this review will be focused on generate ideas during methadone intervention and enhance health-care, especially among opioid use disorders. Opioid addiction is a crucial concern with limited treatment community. Gender difference, especially men or women, are difference in their susceptibility to opioid addiction and response to methadone treatment.
Improving well-being and methadone-related outcome
The effectiveness of methadone treatment helps by improving well-being outcome toward patient in many aspects, such as psychological status, health status, reduce mortality, adverse drug reaction, and methadone-related dose issues. Concerning the psychological status of the patient, both women and men are different in their mental and psychological aspect. However, in terms of psychological status, women showed greater medical, family-social, and psychiatric illness compare to men.,,
Besides, a significant difference between men and women is found in family support, the proposition than women tend to be more concerned with interpersonal issues than men., Women tend to have conflict with family members and felt greater need for treatment for family problems compared to men. Men showed likely to have lifetime diagnose cannabis and alcohol compare to women. Besides, women are likely to have lifetime diagnoses of major depression, bipolar, generalize anxiety, and simple phobia.
Physical and health status is main concern towards opioid use disorder during methadone treatment. Women have overall poorer health status, more chronic health problems, and poorer functioning particularly related to mental health., The older age and physical limitation are a greater risk factor for developing chronic illness and comorbidities.
Although death from methadone have been reported over the past 30 years, and methadone treatment is likely to reduce mortality risk among men, concurrent opioid and methamphetamine/cocaine use increase the mortality risk among women.,, This is the reason that most of the death related to methadone is due to the respiratory depression and more likely if it is used in combination with other illicit drugs, which include opioid and alcohol.
While, methadone related dose in the differences physiological function between men and women showed no significance differences between gender.
Impact on social and behavioral function
Methadone treatment gives a positive impact on social and behavioral function toward the patient by reducing opiate use. By reducing opiates use related behavior. This resulted on decreasing negative behavior such as committed crimes to obtain money for purchase illegal drugs. There are three studies showed that methadone effectiveness in reducing negative behavior and crime related drug use.,,
As a response to this, women show more engaging weekly and daily illegal activities, and they had committed more serious crimes in the past year compared to men. Women were significantly more likely than men to have arrested for prostitution and forgery, whereas men compared to women were arrested for burglary. Arrest for theft significantly decreased for women but remained constant for men. Besides, methadone helps to reduce expenditure on drug-injecting behavior and high-risk behavior, involving the sharing of syringes and needles. There are three studies, which reported that women differ from men in their patterns of obtaining drugs, drug use, and in equipment-sharing behavior.,, Besides, Women showed have a higher risk to be infected with human immunodeficiency virus (HIV) because of unprotected sex by partner and injection practices., The difference is in their unsafe sexual intercourse, drug injection, and prison.
While, for employment status showed that men were more likely to be employed compared to women for the past six months on methadone treatment.,, Men are easily employed due to the job demand or sociocultural.
Illicit drug use pattern–related behavior
The higher methadone dose may reflect patient with polysubstance use, which led to poor sleep quality and chronic pain., This may affect patient behavior, psychological, and physical health., Patient taking methadone and other polysubstance drugs may develop several side effects including dizziness, drowsiness, constipation, nausea, and vomiting. Overdose may occur due to increased dosage and build up concentration in plasma of substance abuse overtime.
There are no differences between women and men in response to the treatment and they have a similar retention rate during methadone treatment., However, methadone client rarely refused to terminate drug abuse unless they refused to have their methadone dose raised or if they refused to address chronic addiction to a secondary drug such as cocaine or alcohol.,
| Strength and Limitation of the Review|| |
The review on methadone treatment outcome focuses on gender difference between men and women during receiving methadone, and allows us to generate information, which can be applied to methadone treatment. Gender difference in this review may be a representation of the general population and may not be specific to methadone client. We were additionally unable to determine any relation in outcomes because the data were cross-sectional. Thus, we cannot conclude if there were any significant improvements and outcomes between induction treatment until completion.
| Conclusion|| |
The systematic review performed will highlight the difference between men and women in methadone treatment outcome and will help us to understand methadone treatment. This review helps us to provide essential information to physicians and pharmacists during patient monitoring and to perform an intervention on methadone dose adjustment and management of sign and symptom withdrawal and intoxication effect.
Future review direction
This review suggests several recommendations for future studies. First, more studies are needed as it requires to have specific and standard systematic review method for guide research synthesis in the context of methadone treatment outcome, and second, further examination into sex differences in methadone treatment prognosis for individual’s treatment is needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bawor M, Dennis BB, Anglin R, Steiner M, Thabane L, Samaan Z Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol. Syst Rev 2014;3:45.
Han B, Gfroerer JC, Colliver JD, Penne MA Substance use disorder among older adults in the United States in 2020. Addiction 2009;104:88-96.
Acharyya S, Zhang H Assessing sex differences on treatment effectiveness from the drug abuse treatment outcome study (DATOS). Am J Drug Alcohol Abuse 2003;29:415-44.
Back SE, Lawson KM, Singleton LM, Brady KT Characteristics and correlates of men and women with prescription opioid dependence. Addict Behav 2011;36:829-34.
Bawor M, Dennis BB, Varenbut M, Daiter J, Marsh DC, Plater C, et al
. Sex differences in substance use, health, and social functioning among opioid users receiving methadone treatment: a multicenter cohort study. Biol Sex Differ 2015;6:21.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyss: the PRISMA statement. PLoS Med 2009;6:e100097.
Brown LS Jr, Alterman AI, Rutherford MJ, Cacciola JS, Zaballero AR Addiction severity index scores of four racial/ethnic and gender groups of methadone maintenance patients. J Subst Abuse 1993;5:269-79.
Chatham LR, Hiller ML, Rowan-Szal GA, Joe GW, Simpson DD Gender differences at admission and follow-up in a sample of methadone maintenance clients. Subst Use Misuse 1999;34:1137-65.
Steer RA, Kotzker E Affective changes in male and female methadone patients. Drug Alcohol Depend 1980;5:115-22.
Magura S, Kang SY, Rosenblum A, Handelsman L, Foote J Gender difference in psychiatric comorbidity among cocaine using opiate addicts. J Addict Dis Dis1998;17:49-61.
Icick R, Vorspan F, Karsinti E, Ksouda K, Lépine JP, Brousse G, et al
. Gender-specific study of recurrent suicide attempts in outpatients with multiple substance use disorders. J Affect Disord 2018;241:546-53.
Grella CE, Lovinger K Gender differences in physical and mental health outcomes among an aging cohort of individuals with a history of heroin dependence. Addict Behav 2012;37:306-12.
Jimenez-Treviño L, Saiz PA, García-Portilla MP, Díaz-Mesa EM, Sánchez-Lasheras F, Burón P, et al
. A 25-year follow-up of patients admitted to methadone treatment for the first time: mortality and gender differences. Addict Behav 2011;36:1184-90.
Schiff M, Levit S, Moreno RC Retention and illicit drug use among methadone patients in Israel: a gender comparison. Addict Behav 2007;32:2108-19.
Evans E, Kelleghan A, Li L, Min J, Huang D, Urada D, et al
. Gender differences in mortality among treated opioid dependent patients. Drug Alcohol Depend 2015;155:228-35.
Graziani M, Nisticò R Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy. Front Pharmacol 2015;6:122.
Wells EA, Calsyn DA, Clark LL, Saxon AJ, Jackson TR Retention in methadone maintenance is associated with reductions in different HIV risk behaviors for women and men. Am J Drug Alcohol Abuse 1996;22:509-21.
Camacho LM, Bartholomew NG, Joe GW, Cloud MA, Simpson DD Gender, cocaine and during-treatment HIV risk reduction among injection opioid users in methadone maintenance. Drug Alcohol Depend 1996;41:1-7.
Rezaei M, Hatami SE, Hojjat SK, Rahimi A, Ein Beigi E Demographic background and dangerous behaviors of heroin-addicted patients under maintenance treatment in the North East of Iran (North Khorasan province). J Subst Use2018;23:181-6.
Marsch LA The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis. Addiction 1998;93:515-32.
Savage LJ, Simpson DD Posttreatment outcomes of sex and ethnic groups treated in methadone maintenance during 1969–1972. J Psychoactive Drugs 1980;12:55-64.
Peles E, Schreiber S, Adelson M 15-year survival and retention of patients in a general hospital-affiliated methadone maintenance treatment (MMT) center in Israel. Drug Alcohol Depend 2010;107:141-8.
Jones HE, Fitzgerald H, Johnson RE Males and females differ in response to opioid agonist medications. Am J Addict 2005;14:223-33.
Marchand K, Palis H, Peng D, Fikowski J, Harrison S, Spittal P, et al
. The role of gender in factors associated with addiction treatment satisfaction among long-term opioid users. J Addict Med 2015;9:391-8.
Levine AR, Lundahl LH, Ledgerwood DM, Lisieski M, Rhodes GL, Greenwald MK Gender-specific predictors of retention and opioid abstinence during methadone maintenance treatment. J Subst Abuse Treat 2015;54:37-43.
Adelson M, Linzy S, Peles E Characteristics and outcome of male and female methadone maintenance patients: MMT in Tel Aviv and Las Vegas. Subst Use Misuse 2018;53: 230-8.
Mulvaney FD, Brown LS Jr, Alterman AI, Sage RE, Cnaan A, Cacciola J, et al
. Methadone-maintenance outcomes for hispanic and African-American men and women. Drug Alcohol Depend 1999;54:11-8.
Preston KL, Schroeder JR, Kowalczyk WJ, Phillips KA, Jobes ML, Dwyer M, et al
. End-of-day reports of daily hassles and stress in men and women with opioid-use disorder: relationship to momentary reports of opioid and cocaine use and stress. Drug Alcohol Depend 2018;193: 21-8.