Journal of Addiction & Addictive Disorders Category: Clinical Type: Case Report

Current Evidence-Based Treatment for Stimulant Use Disorder. Do we arrive at Definite Conclusion? Case Report- “Methadone Maintained Patient with Attention Deficit Hyperactivity Syndrome, Stimulant Use Disorder (Amphetamine) and Treatment Dilemma”

Usman Riaz1* and Ehinor Isidahome1
1 Montefiore Medical center, Division of Substance Abuse, Albert Einstein College of Medicine, 1510 Waters Place Bronx, NY 10461, United states

*Corresponding Author(s):
Usman Riaz
Montefiore Medical Center, Division Of Substance Abuse, Albert Einstein College Of Medicine, 1510 Waters Place Bronx, NY 10461, United States
Tel:+1 7188293440, 8517
Fax:+1 718824899
Email:usriaz@montefiore.org

Received Date: Jan 10, 2025
Accepted Date: Jan 22, 2025
Published Date: Jan 29, 2025

Abstract

Stimulants including cocaine, methamphetamine, and other amphetamine-type substances are among the most common illicit psychoactive substances used around the world. Stimulant use disorder contributes to a substantial worldwide burden of disease, although evidence-based treatment options are limited. Stimulant Use Disorder (SUD) is a public health problem in the United States that is associated with increased morbidity and mortality. The psychosocial interventions, such as cognitive behavioral therapy and contingency management, are the main treatment modality for SUDs and no pharmacotherapy is currently yet FDA approved for this indication. Although some medications show promising data for the treatment of SUD, the evidence remains inconsistent, and the clinical application is limited due to the heterogenicity of the population and the lack of studies in patients with various comorbidities. Stimulant Use Disorders (SUDs) include the use of cocaine, amphetamine-type substances, and other stimulants with similar effects, such as methylphenidate and khat. Amphetamines refer to both amphetamine and the structurally similar methamphetamine. Methamphetamine is a more potent derivative of amphetamine with a longer duration of action and increased ability to cross the blood- brain barrier. Although prescription stimulants, such as amphetamines, are FDA approved for the treatment of attention-deficit hyperactivity disorder and narcolepsy, patients with SUD misuse prescription and illicit stimulants to produce effects of euphoria, increased energy, confidence, wakefulness, and reduced hunger. It is estimated that the global prevalence of cocaine and amphetamine use disorders was 0.4% and 0.7%, respectively. According to the 2018 National Survey on Drug Use and Health, the misuse of stimulants has significantly increased since 2015, and overdose deaths linked to stimulants have increased more than 3-fold over the past 5 years. The presence of fentanyl in methamphetamine and cocaine increases polysubstance use and could contribute to accidental overdose and death as opioids are involved in more than 50% of all stimulant-related overdose deaths. 

This case study/literature review suggested interventions identified include contingency management, cognitive behavioral therapy, antidepressants, dopamine agonists, antipsychotics, anticonvulsants, disulfiram, opioid agonists, N-Acetylcysteine, and psychostimulants for treatment of stimulant use disorder. There was sufficient evidence to support the efficacy of contingency management programs for treatment of stimulant use disorder. Psychostimulants, n-acetylcysteine, opioid agonist therapy, disulfiram and antidepressant pharmacological interventions were found to have insufficient evidence to support or discount their use. The literature does not support the use of other treatment options.

Keywords

ADHD (Attention deficit hyperactivity syndrome); CM (Contingency management); OUD (Opioid use Disorder); SUD (Stimulant use disorder)

Introduction

Stimulant use and stimulant use disorder are associated with a range of health and social harms, including psychiatric and cardiovascular morbidity, infectious disease transmission (i.e. HIV and hepatitis C), drug associated crime, and homelessness [1-5]. The global prevalence of stimulant use has increased over the past decade, and there has been an alarming rise in the use of amphetamine-type stimulants in many jurisdictions. Recent estimates indicate there are approximately 18.1 million cocaine users worldwide, with the highest rates in North America (2.1 percent). From 2007 to 2017 there was an eightfold rise in methamphetamine seizures in East and South-East Asia, which has continued to increase [6]. North America however maintains the highest prevalence of methamphetamine use worldwide, at 2.1 percent of the population aged 15-64 [6]. 

The growing problem of stimulant use globally has emphasized a pressing need to expand access to evidence-based treatment for stimulant use disorder. Of those accessing publicly funded treatment for substance use disorder in the United States, less than one in five individuals (17.8%) are doing so for cocaine or other stimulant treatment [7]. The pursuit of evidence-based interventions for treatment of stimulant use disorder has resulted in extensive investigation into a wide range of both behavioral and pharmacological therapies with mixed outcomes. While there is still no FDA approved medication on the market, some psychosocial interventions have shown promising results. There are many systematic reviews and meta- analyses that have now been conducted on various treatment options for stimulant use disorder. Though several studies have assessed the efficacy for a range of interventions, there is little literature available that consolidates the current evidence. 

This case report/literature review aims to: (i) synthesize the available evidence on both psychosocial and pharmacological interventions for the treatment of stimulant use disorder; (ii) identify the most effective therapies to guide clinical practice, and (iii) highlight gaps for future study.

Case Report

A 38 y/o Caucasian male with Opioid use disorder, Stimulant use disorder (Amphetamine), ADHD referred to the writer for establishing psychiatric care (restart his ADHD medications). As per patient, his previous psychiatrist stopped prescribing Amphetamines, and he was seeking a new provider for continuity of care. He blamed his mother for creating distrust between his previous psychiatrist and him that led to the discontinuation of Amphetamine by his previous psychiatrist. The I-stop registry for controlled substance was checked to confirm the prescribed controlled substance history of patient and the writer was able to check his previous inpatient admission records from another facility that indicated that he has had stimulant use disorder that led to his couple of brief inpatient psych hospitalizations in the past. The writer started treating him with Bupropion and Atomoxetine, but he repeatedly reported focusing issues even while on maximum dose of those two medications. Later Mirtazapine (15 mg-45mg) was tried but other than addressing his sleep issues as per patient it didn’t help much. Since his toxicology results were readily available at the facility, writer put him on Methylphenidate with the treatment plan agreement that he couldn’t use stimulants from streets while on prescribed controlled substance and regular random urine toxicology tests and pill counting were part of treatment plan and he agreed to the treatment plan [8]. 

For brief period, he did well, but later started abusing his prescription of Methylphenidate and admitted to psychiatry emergency room for 2-3 days. When he was asked for pill counting at that time, he blamed his brother to steal all his meds (including prescribed stimulants while he was in ER). His methylphenidate was discontinued and kept him on non-stimulants for a while, but he repeatedly requested to put him back on stimulants and reassured that he will be complaint with the writers’ recommendations. His stimulant use from streets continued in the meantime with hypomanic/manic like presentations at the clinic on multiple occasions. Later, to help him better his mother wanted to be a part of care and agreed to give him medications under her supervision on daily basis and he agreed and fixated to restart Amphetamines, otherwise as per patient he had strong desire to use Amphetamines/Methamphetamine from the streets [9]. The writer started him on Amphetamines 20 mg XR and gradually increased the dose to 40 mg XR and he did well on it for 3-4 months. He was drug free at that time but relapsed again on street stimulants and started abusing his prescribed Amphetamines. He had to go to Emergency room for 2-3 days and again failed his pill counting when returned to the clinic and blamed his brother for stealing his meds while he was in the emergency room and denied abusing the controlled substance (which was contrary to collateral information from his mother and ER reports). His urine drug testing results at that time were positive for Methamphetamines and Amphetamines besides being on prescribed Amphetamines, even had toxic levels of Methamphetamine. 

Latest random confirmatory urine drug toxicology (GCMS) results at the clinic: 

Amphetamines urine ng/ml

240 Positive

Methamphetamine urine ng/ml

2200 Positive

Ecstasy 3,4-methylenedioxy-N- methylamphetamine (MDMA) urine

Negative

3,4 methylenedioxyamphetamine (MDA), urine

Negative

3,4 methylenedioxy-N-ethylamphetamine (MDEA), urine

Negative

At that time his stimulants were discontinued, and he was advised to go to inpatient drug rehab to address his stimulant use disorder which he refused and started seeking another provider for ADHD meds. 

Note - His TOVA test was positive for ADHD which was confirmed by the writer before staring prescribed stimulants. He was doing well regarding his Opioid addiction, was on (Methadone Maintenance treatment) MMT and had regular therapy sessions by assigned counselors at the clinic, which included cognitive behavioral therapy and supportive therapy. The clinic had limited resources to provide CM and he was advised to go to inpatient drug rehab which he repeatedly refused.

Discussion

Stimulant use remains a prominent issue worldwide/nationwide, this review suggests that evidence-based treatment options are limited. It has been observed that the strongest evidence exists for contingency management. The pharmacological intervention that shows the most promise is psychostimulant agonist therapy. Some positive results have also been reported for (Opioid agonist treatment) OAT, (N acetylcysteine) NAC, Disulfiram, and antidepressants for methamphetamine use. All other interventions reviewed here, including dopamine agonists, antipsychotics, anticonvulsants, have found predominantly negative results. For Contingency Management (CM) programs, it has been found consistently positive results across systematic reviews demonstrating their effectiveness compared to treatment as usual, as well as other interventions, including community reinforcement (CRA), pharmacotherapy and CBT. Furthermore, CM may be supplemented with CBT or CRA to ensure both short- and long-term success, given the demonstrated delayed benefit of CBT, and additive effects of CM with CRA [10]. 

Despite the encouraging results, CM programs are rarely implemented, and questions remain about the long-term benefits associated with CM interventions. Barriers that have been identified in the literature include treatment providers viewing programs as too costly, difficult to implement, or not aligning with political or philosophical values [11]. A qualitative assessment of treatment providers’ opinion on barriers to incentive-based programs found many view the intervention positively, but that cost, and training of providers was a significant barrier. Randomized controlled trials, however, have demonstrated the cost effectiveness of contingency management programs [12]. In a trial by Peirce et al., the intervention was successful at just $1.46 per participant per day, rather than an average cost of $120 per day that has been previously reported. Given strong evidence for its effectiveness, and in the absence of other similarly efficacious interventions, efforts to expand access to contingency management programs for stimulant use are warranted [13]. 

Psychostimulant treatment has a similar pharmacological rationale as other evidence-based substance treatments like nicotine replacement and opioid agonist therapies [14]. The core review by Castells and colleagues found significant positive results for sustained cocaine abstinence and found positive, but insignificant results for reduction in use [15]. These results were reiterated in the core review by Chan et al., [16]. Therefore, though the writer’s assessed the available evidence to date as insufficient to support or discount the use of psychostimulants for treatment of cocaine use disorder, this class of medication warrants further investigation. Chan et al., also reported positive results in the outcome of reduction in use for the use of methylphenidate for treatment of methamphetamine use disorder, and this area warrants further investigation [17]. Further evaluation of the outcomes of reduction in use as well as sustained abstinence would allow for better pooling of results and increase the quality of evidence available to recommend clinical practice. Evaluation of the effectiveness of psychostimulants should also include trials of longer duration, as the average length of trial in the review by Castells et al., [15] was 12.6 weeks (range 6 -24) which may be insufficient to achieve abstinence. Furthermore, subgroup analyses addressing optimal dosing, as well as trials that evaluate combination pharmacotherapy may provide further insight into the effectiveness of the intervention. 

Positive results have also been noted for CBT, OAT, NAC, disulfiram, and Antidepressants, though data is not sufficient to recommend their use due to limitations in data quality and sample size. The available data for OAT focuses on dual opioid-cocaine use disorders, which may be an important area of future study given the concurrent rise in opioid and cocaine use in recent years [6]. Castells et al. found a significant superiority of methadone when compared to buprenorphine in reduction of cocaine use, however it is important to note that OAT was not compared to a control group, and no dose response was observed for the methadone group [18]. Further characterization of this finding as well as evaluation of other OAT medications may help guide clinical practice in this area. 

CBT has been studied both alone and in combination with other psychotherapy interventions for treatment of stimulant use disorder, with some positive results. De Crescenzo et al., found a reduction in participant dropout with CBT alone, however when combined with CM, CBT was found to have a more pronounced effect, including in the outcome of participant abstinence [10]. The available data for CBT in the treatment of stimulant disorder is limited, and more research is warranted to determine its clinical utility, focusing on a potentially more sustained effect when employed complementarily to contingency management psychosocial interventions, or pharmacologic treatment options. The available data for the possible benefits of NAC is quite limited, with only six human trials included in the review by Nocito Echevarria et al., and further investigation is necessary to evaluate its clinical utility. Similarly, for disulfiram, data supporting its clinical utility in treatment of stimulant use disorder is limited. The review by Pani et al., found positive results in reduction in use for one of four included RCTs [19]. However, concerns regarding the safety of Disulfiram, particularly in concurrent alcohol users may limit its potential for future research [20]. 

Current data does not support the use of antidepressants for treatment of cocaine use disorder, although with regards to amphetamine use there is insufficient evidence to discount its use. Due to predominantly negative results for the use of antidepressants for treatment of cocaine use disorder, it may be possible to extrapolate from this data for the treatment of amphetamine use disorder [21]. However, due to the unique mechanisms of action on presynaptic monoamine reuptake transporters, further research focused on the utility of antidepressants for amphetamine-type stimulants may be warranted. 

It is important to note that the available literature in treatment for stimulant use disorder is primarily focused on cocaine use disorder, rather than amphetamine or methamphetamine, for which data is extremely limited. Although the mechanism of action of these substances are similar, there are important distinctions that should be addressed moving forward to expand research in this area, and when applying the evidence to clinical practice. Both cocaine and methamphetamine act to increase the availability of monoamines in the synapse, however cocaine acts as a reuptake inhibitor, whereas methamphetamine binds transporters at the presynaptic membrane and is exchanged to release more monoamine neurotransmitter into the synapse [22]. Methamphetamine use has been increasing in the United States since 2011 and is the most identified substance associated with violent crime [6]. Given the rising rates of methamphetamine use, its associated harms, and the differences in mechanism of action between stimulants, it is critical that future studies evaluate outcomes for both substances. Limitation of meta-analyses to date is the lack of standardized outcomes, making pooling of data difficult. Without evidence-based, standardized clinical trial outcomes for the treatment of stimulant use disorder, it will remain difficult to pool data and provide strong clinical recommendations. Long-term cessation of use has traditionally been the primary goal of substance use treatment and abstinence measures have been the most implemented standard outcomes in randomized controlled trials [13]. However, the definition of recovery may vary based on individual patient goals, by feasibility within the study time period, and may not always include abstinence [23]. 

In 2015, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) group made recommendations for meaningful indicators of treatment success in future clinical trials on stimulant use, including a focus on the validation of patient reported outcome measures of functioning and the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits [12]. Future study may benefit from patient-oriented outcome measures, including psychosocial parameters such as improved social functioning, employment and acquisition of adequate housing. It is important to note that the variability in treatment response among population subgroups is poorly addressed in the literature. Given the extensive variability in individual response to treatment, it is possible that an intervention appraised as ‘sufficient evidence to discount the effectiveness’ or ‘insufficient evidence to support or discount its effectiveness’ may have significant benefits for some patients or patient subgroups. In studies that performed subgroup analyses, including but not limited to: age, sex, severity of substance use disorder and comorbid substance use disorders, meaningful results were limited. Future research would benefit from identifying those subgroups that may be more likely to benefit from certain interventions. 

Subgroup analyses by Bhatt et al. demonstrated increased retention in treatments of longer duration at 12 weeks [24]. Stratification by treatment duration moving forward may aid in identifying optimal and minimum effective treatment durations. Castells et al., [15] found that psychostimulants increased abstinence and reduced cocaine use in those studies in which Attention Deficit Hyperactivity Disorder (ADHD) was not an inclusion criteria, which may be an important replicate moving forward [15] and finally, polysubstance use is common in majority of studies [25]. Recent data demonstrates a rise in concurrent amphetamine and opioid use, and the role of stimulant use in the overdose epidemic remains poorly defined [1,26-28]. Several of the included reviews identified that many participants suffered from polysubstance use disorder, however the effect of polysubstance use on treatment efficacy was rarely addressed. Future research would benefit from identifying the efficacy of interventions for stimulant use disorder specifically in the context of polysubstance use. Alternate pharmacotherapy for stimulant use disorder has been proposed in the literature, with limited RCTs available and no systematic review to date. These include naltrexone, for which several RCTs have been conducted with some positive results [29] and buspirone [30]. 

Furthermore, novel therapies have been evaluated in pre-clinical studies including ibogaine, lobeline, TV-1380, and vaccines to combat substance use disorder. These alternative therapies are beyond the scope of this review, although may warrant further investigation [31]. This review has several limitations. Notably, attrition bias was common across several studies, reducing the power of results in intention to treat analysis. Several factors may contribute to participant drop-out including heavy substance use, financial and transportation barriers, and ambivalence toward abstinence [32]. This search was limited to English language literature and as a result we may not have included some important data. Finally, the assessment of quality of evidence was based on the methods of each review, which may not be adequate.

Conclusion

This case report/review synthesized the evidence to date for treatment of stimulant use disorder, including both pharmacological and psychosocial interventions. Despite the extensive amount of research in this area, little clinical application has resulted thus far. The strongest evidence-based approach for the treatment of stimulant use disorder currently remains contingency management interventions. While treating stimulant use disorder with psychostimulants has shown some favorable results, high quality clinical trials and meta- analyses are needed to determine the clinical utility of psychostimulants and other pharmacotherapies to address the growing need for stimulant treatments. The result of literature review supports the use of contingency management interventions for the treatment of stimulant use disorder. Although evidence to date is insufficient to support the clinical use of psychostimulants, the literature search demonstrates potential for future research in this area. The case here presented is further complex as this patient had ADHD disorder along with his drug addiction which made things really challenging and the writer’s treatment approach aligns with literature review that none of medication tried had definite role in addressing stimulant use disorder. Thus, first line recommendations will be cognitive and behavioral approaches to address stimulant use disorder.

Role of the Funding Source

Authors state that this study was financed with internal funds.

Conflict of Interest

No conflict of interest.

Disclosures and Acknowledgement

The authors have no financial relationships with commercial interests. No grant support was provided for this manuscript.

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Citation: Riaz U, Isidahome E (2025) Current Evidence-Based Treatment for Stimulant Use Disorder. Do we arrive at Definite Conclusion? Case Report- “Methadone Maintained Patient with Attention Deficit Hyperactivity Syndrome, Stimulant Use Disorder (Amphetamine) and Treatment Dilemma”. J Addict Addictv Disord 12: 188.

Copyright: © 2025  Usman Riaz, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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