Current Pharmacological and Behavioral Treatments for Stimulant Use Disorder
No FDA-Approved Medications Exist
There are currently no FDA-approved pharmacological treatments for stimulant use disorder (cocaine or methamphetamine), making behavioral interventions the cornerstone of evidence-based care. 1
First-Line Treatment: Contingency Management Plus Community Reinforcement Approach
Contingency Management (CM) combined with Community Reinforcement Approach (CRA) is the most effective treatment for stimulant use disorder, with a number needed to treat of only 4 patients to achieve one additional abstinent patient compared to usual care. 2, 3 This represents the strongest evidence for improving morbidity, mortality, and quality of life outcomes in this population.
Evidence Hierarchy for Behavioral Interventions
CM alone or combined with CBT demonstrates superior efficacy compared to treatment as usual, with high-certainty evidence showing reduced dropout rates (RR 0.82,95% CI 0.74-0.91) and increased continuous abstinence at end of treatment (RR 1.89,95% CI 1.20-2.97). 4
CM produces better retention and lower stimulant use rates during active treatment compared to cognitive-behavioral therapy alone, though CBT produces comparable longer-term outcomes at follow-up. 5
CBT should be used as an alternative when CM+CRA is unavailable, though it shows less efficacy than contingency management approaches. 2, 3 The evidence for CBT specifically for amphetamine-type stimulants remains insufficient, with only low-quality evidence from small trials. 6
Off-Label Pharmacological Options: Insufficient Evidence
Medications Lacking Adequate Evidence
Despite extensive investigation, no pharmacological agent has demonstrated consistent efficacy for stimulant use disorder treatment:
Psychostimulants (e.g., methylphenidate, amphetamines): Insufficient evidence to support or discount use, though they show potential for future research. 7
N-Acetylcysteine: Insufficient evidence despite some promising preliminary data. 7
Opioid agonist therapy: Insufficient evidence for stimulant use disorder specifically. 7
Disulfiram: Insufficient evidence to support routine use. 7
Antidepressants, dopamine agonists, antipsychotics, and anticonvulsants: Results do not support their use for stimulant use disorder. 7
Critical Exception: Co-occurring Opioid Use Disorder
For patients with both opioid and stimulant use disorders, medications for opioid use disorder (methadone, buprenorphine, naltrexone) should be initiated without delay, as treating the opioid use disorder takes priority and does not require waiting for stimulant abstinence. 2, 3
Special Population: ADHD with Active Stimulant Use Disorder
Atomoxetine (60-100 mg daily) is the first-line pharmacotherapy for patients with ADHD and active stimulant use disorder, as it is an uncontrolled substance with no abuse potential. 8 This recommendation prioritizes patient safety over the superior efficacy of stimulants (70-80% response rate), which carry high risk for diversion and worsening substance use patterns. 1, 8
Alternative Non-Stimulant Options for ADHD
Clonidine or guanfacine may be considered as first-line options when ADHD co-occurs with substance use disorders, though they have smaller effect sizes than stimulants. 1
Bupropion can serve as an alternative or adjunct if atomoxetine fails or additional ADHD symptom control is needed. 8
Never combine MAO inhibitors with stimulants or bupropion due to severe hypertension risk and potential cerebrovascular accidents. 8
Comprehensive Treatment Algorithm
Step 1: Screening and Assessment
Integrate substance use screening into routine care for high-risk populations rather than relying on drug testing alone, which has low sensitivity as a general screening tool. 2, 3
Evaluate cardiovascular complications including coronary artery spasm, tachycardia, and hypertension, as these are common medical sequelae of stimulant use. 2
Screen for co-occurring mental health conditions including depression, anxiety, and psychosis, as these frequently complicate stimulant use disorder. 2, 3
Step 2: Initiate Behavioral Treatment
Implement CM+CRA as first-line treatment when available, using vouchers or other reinforcers contingent on stimulant-free urine samples. 2, 3, 5
Use CBT as an alternative when CM is not feasible, focusing on cognitive restructuring, relapse prevention, and coping skills. 2, 3
Ensure treatment retention through innovative service delivery including extended hours, mobile clinics, telehealth, and peer support, as dropout rates are high in this population. 2
Step 3: Harm Reduction Services
Offer comprehensive harm reduction regardless of abstinence status, including:
- Naloxone dispensation and overdose prevention education 2, 3
- Fentanyl test strips to detect contaminated stimulants 2
- Safe use education to reduce injection-related complications 2
- Referral to syringe services programs 2, 3
Step 4: Manage Co-occurring Disorders
For co-occurring opioid use disorder: Initiate buprenorphine, methadone, or naltrexone immediately. 2, 3
For co-occurring ADHD: Start atomoxetine rather than stimulants. 8
For co-occurring depression: Add SSRI if depressive symptoms are severe or persist after ADHD treatment, as no single agent treats both conditions effectively. 8
Critical Pitfalls to Avoid
Do not rely solely on drug testing without clinical context, as standard laboratory tests detect substance presence but not causation of observed symptoms. 2, 3
Do not use selective β1-blockers in patients with ongoing cocaine use, as this causes unopposed α-adrenergic stimulation and worsens coronary vasoconstriction. 2, 3
Do not prescribe stimulants for ADHD in patients with active stimulant use disorder, despite their superior efficacy, as this prioritizes symptom control over patient safety and long-term outcomes. 8
Do not focus solely on abstinence rather than harm reduction, as many patients require substantial time and therapeutic effort to achieve complete abstinence, and retention in treatment reduces risks even without immediate abstinence. 4
Do not assume treating ADHD alone will resolve co-occurring depression, as these require separate, targeted interventions even though ADHD-related impairment can contribute to secondary depressive symptoms. 8
Monitoring Requirements
Assess for suicidality and clinical worsening regularly, particularly when initiating atomoxetine, which carries a black box warning for increased suicidal ideation. 8
Monitor cardiovascular parameters including blood pressure and pulse at baseline and regularly during treatment. 2, 8
Implement regular urine drug screening to ensure compliance and detect return to substance use, though not as a standalone screening tool. 2, 8