Management of Stimulant Use Disorder

Publication Date: November 8, 2023
Last Updated: April 23, 2024

Key Points

Key Points

Background

  • Rates of stimulant use disorders (StUD) are rising, as are stimulant potency and rates of stimulant use in combination with opioids. These factors have contributed to overdose death rates increasing three-fold for cocaine and twelve-fold for other stimulants—including methamphetamine, amphetamine, and prescription stimulants—in the past ten years.
  • Drug overdose deaths involving stimulants (cocaine and psychostimulants) rose from 12,122 in 2015 to 53,495 in 2021*.
  • Beyond overdose deaths, StUD can cause a range of serious and long-term health problems, including cardiac, psychiatric, dental, and nutritional complications. Injection stimulant use increases the risk of acquiring human immunodeficiency virus (HIV), viral hepatitis, and other infectious diseases. The stable or rising availability of stimulants, low prices, and potential contamination of stimulants with fentanyl are expected to exacerbate risks.
  • Taken together, these factors have propelled StUD and stimulant use to an urgent health crisis. This guideline aims to assist clinicians with the prevention and treatment of StUD.
  • This guideline focuses on the identification, diagnosis, treatment, and promotion of recovery for patients with StUD, stimulant intoxication, and stimulant withdrawal.
  • It also includes recommendations related to screening for risky stimulant use and secondary and tertiary prevention of StUD.
* https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates

Key Takeaways

1. Contingency management (CM) has demonstrated the best effectiveness in the treatment of StUDs compared to any other intervention studied and represents the current standard of care. CM can be combined with other psychosocial interventions and behavioral therapies, such as community reinforcement approach (CRA) and cognitive behavioral therapy (CBT) (See Recommendations 5-6).

2. Pharmacotherapies, including psychostimulant medications, may be utilized off-label to treat StUD (See Recommendations 9-20).
  • When prescribing controlled medications, clinicians should closely monitor patients and perform regular ongoing assessment of risks and benefits for each patient.
  • Psychostimulant medications should only be prescribed to treat StUD by:
    • physician specialists who are board certified in addiction medicine or addiction psychiatry; and
    • physicians with commensurate training, competencies, and capacity for close patient monitoring.
  • Non-psychostimulants such as bupropion, mirtazapine, topiramate and naltrexone can also be used to treat StUD.
3. Co-occurring conditions—including but not limited to attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, eating disorders, and other substance use disorders (SUDs)—are common in patients with StUD. Any co-occurring psychiatric disorders or SUDs should be treated concurrently alongside StUD with care coordination (See Recommendations 21-25).
  • Evidence supports the use of pharmacotherapy, including psychostimulant medication, to treat ADHD in individuals with co-occurring StUD.
  • Some pharmacotherapies that can be considered to treat StUD off-label have demonstrated efficacy in treating common co-occurring psychiatric disorders and SUDs and can be given additional consideration.
4. Clinicians should provide adolescents and young adults who use stimulants with the same treatment, harm reduction, and recovery support services (RSS) as adults in a developmentally responsive manner (See the Adolescent and Young Adult Section).

5. Acute stimulant intoxication can result in several life-threatening complications that include but are not limited to cardiovascular complications (eg, acute coronary syndrome [ACS], hypertensive emergency, myocardial infarction), hyperthermia, and acidosis, among others. These acute issues should be addressed immediately in an appropriate level of care (See Recommendations 55-72).

6. Treating symptoms of stimulant withdrawal may help support ongoing treatment engagement (See the Stimulant Withdrawal section).
  • Post-acute symptoms of stimulant withdrawal—which include depression, anxiety, insomnia, and paranoia—can last for weeks to months. It is important to assess for and treat these symptoms to reduce the risk for decompensation and return to stimulant use.
7. Secondary and tertiary prevention strategies should be used to reduce harms related to overdose risk, risky sexual practices, injection drug use, tooth decay, and nutritional deficiencies (See Recommendations 79-92).

Diagnosis

Diagnosis

Assessment of Stimulant Use Disorder

Note: Amphetamine-type stimulant (ATS) Use Disorder and Cocaine Use Disorder are discussed separately because of the different pharmacological mechanisms of action, which may impact the effectiveness of pharmacotherapies. ATS include amphetamine and its derivatives, including methamphetamine.

Initial Assessment

1. When assessing patients for StUD, the first clinical priority should be to identify any urgent or emergent biomedical or psychiatric signs or symptoms, including acute intoxication or overdose, and provide appropriate treatment or referrals. (S, CC)
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Non-acute issues and complications of stimulant use include but are not limited to:    
  • General complications, including weight change (eg, body mass index [BMI]) and deficits in hygiene
  • Cardiovascular complications, such as hypertension, arrhythmia, ischemia, pulmonary hypertension, and heart failure
  • Dental complications, such as poor dentition, dental caries, and abscesses
  • Dermatologic complications, such as picking, neurodermatitis, cellulitis, abscesses, and other skin or soft tissue infections
  • Hepatic complications, such as drug-induced hepatitis
  • Infectious complications, including sexually transmitted infections (STIs) (eg, HIV, hepatitis C virus [HCV])
  • Neurologic complications, such as involuntary movement disorders, rigidity, tremor, seizures, stroke, and cognitive impairment (eg, deficits in memory and/or attention)
  • Nutritional deficits, such as malnutrition, cachexia, and sequalae involving specific vitamin deficiencies
  • Oropharyngeal complications, such as teeth grinding and jaw clenching, earache, headache, and facial pain
  • Renal complications, such as acute kidney injury and chronic kidney disease
  • Rhinologic complications such as rhinitis, mucosal atrophy, rhinorrhea, anosmia, oronasal fistula, and septum perforation
  • Sexual dysfunction (use trauma-sensitive screening practices)

Comprehensive Assessment

2. After first addressing any urgent biomedical or psychiatric signs or symptoms, patients should undergo a comprehensive assessment that includes:
2a. assessment for StUD based on diagnostic criteria (eg, current DSM) (S, CC)
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2b. a StUD-focused history and physical examination (S, CC)
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2c. a mental status exam to identify co-occurring psychiatric conditions, such as signs and symptoms of psychoses, ADHD, mood disorders, cognitive impairment, and risk of harm to self or others (S, CC)
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2d. a full biopsychosocial assessment (S, CC)
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3. Clinicians treating StUD should conduct routine baseline laboratory testing. (S, CC)
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3a. Clinicians should conduct other clinical tests as necessary based on each patient’s clinical assessment findings. (C, CC)
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In non-acute care settings, clinicians should order the following clinical tests for most patients:
  • Complete blood count (CBC)
  • Comprehensive metabolic panel (CMP) (eg, renal panel, liver function test [LFTs])
  • Screening for infectious diseases in accordance with current guidance
  • HIV and HCV for all patients
  • Hepatitis B virus (HBV) for patients at increased risk for infection
  • Screening for STIs (eg, gonorrhea, chlamydia, syphilis)
  • Pregnancy testing for all patients with childbearing potential
Clinicians can also consider ordering the following clinical tests:
  • Tuberculosis (TB) for patients at increased risk for infection
  • HAV for patients at increased risk for infection
  • Other clinical tests as necessary based on clinical assessment, such as creatine kinase (CK) if signs of rhabdomyolysis are present (eg, increased muscle tone/rigidity, elevated temperature)
4. When evaluating patients with long-term or heavy stimulant use, clinicians should exercise:
4a. an elevated degree of suspicion for cardiac disorders (C, CC)
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4b. a lower threshold for considering ECG testing based on findings of the history and physical exam (C, CC)
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4c. a lower threshold for considering creatine kinase (CK) testing for rhabdomyolysis based on findings of the history and physical exam (S, CC)
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4d. an elevated degree of suspicion for renal disorders (C, CC)
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Treatment

Treatment

Behavioral Treatment

5. Contingency Management (CM) should be a primary component of the treatment plan in conjunction with other psychosocial treatments for StUD. (S, H )
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6. The following three interventions have the most supportive evidence and are preferred alongside CM:
6a. Community Reinforcement Approach (CRA) (C, L )
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6b. Cognitive Behavioral Therapy (CBT) (S, M )
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6c. the Matrix Model (C, M )
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Technology-Based Interventions

7. Clinicians can consider offering evidence-based behavioral interventions delivered via digital therapeutics or web-based platforms as add-on components to treatment for StUD, but they should not be used as standalone treatment. (S, L )
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8. Clinicians should consider using telemedicine to deliver behavioral treatment for StUD to patients who may face challenges accessing in-person care. (S, M )
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Pharmacotherapy

Non-Psychostimulant Medication

Cocaine Use Disorder: Bupropion
9. For patients with cocaine use disorder, clinicians can consider prescribing bupropion to promote cocaine abstinence. (C, L )
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9a. Clinicians can give bupropion additional consideration for patients with co-occurring tobacco use disorder (TUD), as this medication can also reduce nicotine/tobacco use. (C, L )
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9b. Clinicians can give bupropion additional consideration for patients with co-occurring depressive disorders, as this medication can also treat depression. (C, L )
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Cocaine Use Disorder: Topiramate
10. For patients with cocaine use disorder, clinicians can consider prescribing topiramate to reduce cocaine use. (C, L )
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10a. Clinicians can give topiramate additional consideration for patients with co-occurring alcohol use disorder (AUD), as this medication can also reduce alcohol consumption. (C, L )
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Amphetamine-Type Stimulant Use Disorder: Bupropion
11. For patients with amphetamine-type stimulant (ATS) use disorder with low- to moderate-frequency (ie, less than 18 days per month) stimulant use, clinicians can consider prescribing bupropion to promote reduced use of ATS. (C, L )
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11a. Clinicians can give bupropion additional consideration for patients with co-occurring TUD, as this medication can also reduce nicotine/tobacco use. (C, L )
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11b. Clinicians can give bupropion additional consideration for patients with co-occurring depressive disorders, as this medication can also treat depression. (C, L )
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Amphetamine-Type Stimulant Use Disorder: Bupropion and Naltrexone
12. For patients with ATS use disorder, clinicians can consider prescribing bupropion in combination with naltrexone to promote reduced use of ATS. (C, M )
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12a. Clinicians can give bupropion in combination with naltrexone additional consideration for patients with co-occurring AUD, as naltrexone can also reduce alcohol consumption. (C, M )
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12b. Clinicians can give bupropion in combination with naltrexone additional consideration for patients with co-occurring TUD, as bupropion can also reduce nicotine/tobacco use. (C, M )
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12c. Clinicians can give bupropion in combination with naltrexone additional consideration for patients with co-occurring depressive disorders, as bupropion can also treat depression. (C, M )
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Amphetamine-Type Stimulant Use Disorder: Topiramate
13. For patients with ATS use disorder, clinicians can consider prescribing topiramate to reduce use of ATS. (C, L )
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13a. Clinicians can give topiramate additional consideration for patients with co-occurring AUD, as this medication can also reduce alcohol consumption. (C, L )
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Amphetamine-Type Stimulant Use Disorder: Mirtazapine
14. For patients with ATS use disorder, clinicians can consider prescribing mirtazapine to promote reduced use of ATS. (C, L )
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14a. Clinicians can give mirtazapine additional consideration for patients with co-occurring depressive disorders, as this medication can also treat depression. (C, L )
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Psychostimulant Medication

General Psychostimulant Medication
15. Recommendations related to the prescription of psychostimulant medications to treat StUD are only applicable to:
  • physician specialists who are board certified in addiction medicine or addiction psychiatry
  • physicians with commensurate training, competencies, and capacity for close patient monitoring
(S, CC)
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16. When prescribing psychostimulant medications for StUD, clinicians should maintain a level of monitoring commensurate with the risk profile for the given medication and patient. Monitoring may include pill counts, drug testing, more frequent clinical contact, and more frequent prescription drug monitoring program (PDMP) checks. (S, CC)
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Cocaine Use Disorder: Modafinil
17. For patients with cocaine use disorder and without co-occurring AUD, clinicians can consider prescribing modafinil to reduce cocaine use and improve treatment retention. (C, L )
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Cocaine Use Disorder: Topiramate and Extended-Release Mixed Amphetamine Salts
18. For patients with cocaine use disorder, clinicians can consider prescribing a combination of topiramate and MAS-ER to reduce cocaine use and cocaine craving. (C, M )
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18a. Clinicians can give a combination of topiramate and MAS-ER additional consideration for patients with co-occurring AUD, as topiramate can also reduce alcohol consumption. (C, M )
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18b. Clinicians can give a combination of topiramate and MAS-ER additional consideration for patients with co-occurring ADHD, as MAS-ER can also reduce ADHD symptoms. (C, M )
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Cocaine Use Disorder: Amphetamine Formulation
19. For patients with cocaine use disorder, clinicians can consider prescribing a long-acting amphetamine formulation psychostimulant to promote cocaine abstinence. (C, L )
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19a. Clinicians can give long-acting amphetamine formulation psychostimulants additional consideration for patients with co-occurring ADHD, as these medications can also reduce ADHD symptoms. (C, L )
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19b. When prescribing a long-acting amphetamine formulation psychostimulant, clinicians can consider dosing at or above the maximum dose approved by the FDA for the treatment of ADHD to effectively reduce cocaine use. (C, L )
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Amphetamine-Type Stimulant Use Disorder: Methylphenidate Formulations
20. For patients with ATS use disorder, clinicians can consider prescribing a long-acting MPH formulation to promote reduced use of ATS. (C, L )
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20a. Clinicians can give long-acting MPH formulations additional consideration for patients with moderate or higher frequency of ATS use at treatment start (ie, 10 or more days per month). (C, L )
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20b. Clinicians can give long-acting MPH formulations additional consideration for patients with co-occurring ADHD, as these medications can also reduce ADHD symptoms. (C, L )
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20c. When prescribing a long-acting MPH formulation, clinicians can consider dosing at or above the maximum dose approved by the FDA for the treatment of ADHD to effectively reduce ATS use. (C, L )
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Table 1. Medication Dosing in Clinical Trialsa

Having trouble viewing table?
Drug Dose SUD
Modafinil 100–400 mg/day (or 200 mg BID) Cocaine
Modafinil 400 mg/day Cocaine, ATS
Topiramate + MAS-ER Topiramate max 100–150 mg BID + MAS-ER max 60 mg/day Cocaine
MAS-ER 60–80 mg/day Cocaine
Dextroamphetamine
(d-AMP-SR)		 20–60 mg/day Cocaine
Methylphenidate ER 54–72 mg/day ATS
Methylphenidate SR 20–40 mg BID Cocaine
Methylphenidate SR 54 mg/day ATS
Methylphenidate short acting 20–60 mg/day
(Mean 37.6 mg/dayb)		 ATS
Methylphenidate 5–10 mg/day ATS
a This appendix presents a summary of dosing strategies used in the clinical trials reviewed, but is not intended as a dosing guide.
See full text guideline appendices for references. Available at: https://www.asam.org/quality-care/clinical-guidelines/stimulant-use-disorders.
b Patients self-titrated within this dose range.

ATS, amphetamine-type stimulant; BID, two times per day; d-AMP, dextroamphetamine; d-AMP-SR, sustained-release dextroamphetamine; ER, extended release; LDX, lisdexamfetamine; MAS-ER, extended-release mixed amphetamine salts; SR, sustained release

Co-occurring Disorders: General Guidance

21. Clinicians should treat both StUD and co-occurring disorder(s) concurrently. (S, VL )
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22. Clinicians should use an integrated behavioral treatment approach that addresses both conditions when available. Otherwise, clinicians should tailor recommended behavioral therapy for StUD (eg, CM, CBT, CRA) to address possible interactions between a patient’s StUD and co-occurring disorder(s). (S, VL )
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23. Symptoms of psychosis or mania should be treated with indicated pharmacotherapy. (S, M )
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23a. If stimulant-induced psychosis or mania is suspected, clinicians should consider a gradual taper off antipsychotic medication after a period of remission of psychotic symptoms. (S, M )
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24. When developing a treatment plan for symptoms of depression, anxiety, insomnia, and/or attentional problems observed during periods of stimulant use or withdrawal, clinicians should:
24a. consider pharmacotherapy based on symptom severity and duration, even if symptoms are stimulant induced. (S, VL )
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24b. consider whether the patient’s clinical presentation follows the expected time course of stimulant-induced symptoms given the phase of use (ie, active use, waning intoxication, acute withdrawal, post-acute withdrawal, post-withdrawal abstinence) or are present at other times. (S, VL )
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25. Clinicians initiating treatment for StUD in a patient with a preexisting co-occurring diagnosis should:
25a. review the patient’s existing treatment plan, ideally in coordination with the patient’s existing treatment provider(s). (S, CC)
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25b. continue current medications as appropriate (Clinical consensus, Strong Recommendation), with consideration for safety in the context of the patient’s potential continued use of stimulants and other substances. (S, CC)
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Concurrent Management of StUD and ADHD

26. For patients with co-occurring StUD and ADHD, clinicians should:
26. address ADHD symptoms as part of the treatment of StUD. (S, L )
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26a. consider prescribing psychostimulant medications to manage ADHD when the benefits of the medication outweigh the risks. (S, L )
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26b. consider prescribing non-stimulant medications to manage ADHD when the benefits of psychostimulant medications do not outweigh the risks. (S, L )
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26c. consider behavioral approaches. (S, L )
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27. When prescribing psychostimulant medications to a patient with co-occurring StUD and ADHD, clinicians should consider:
27a. using extended-release formulations. (S, CC)
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27b. maintaining a level of monitoring commensurate with the risk profile for the given medication and patient—monitoring may include pill counts, drug testing, more frequent clinical contact, and more frequent PDMP checks. (C, CC)
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28. For adolescent and young adult patients with co-occurring StUD and ADHD, clinicians should additionally consider:
28a. arranging for a parent, health professional (eg, trained school nurse), or other trusted adult to directly observe administration of the medication, especially if using a short-acting formulation. (S, CC)
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28b. counseling families on the importance of safely storing and restricting access to controlled medications. (C, CC)
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Figure 1. Management of Stimulant Use Disorder

Parentheses contain co-occurring disorders for which the medication has demonstrated efficacy. Clinicians can give additional consideration to these medications patients presenting with these comorbidities

ADHD, attention-deficit/hyperactivity disorder; ATS, amphetamine-type stimulant; AUD, alcohol use disorder; CBT, cognitive behavioral therapy; CRA, community reinforcement approach; MAS-ER, extended-release mixed amphetamine salts; TUD, tobacco use disorder

Population-Specific Considerations

Adolescents and Young Adults

Adolescent and Young Adult Assessment and Treatment Planning
29. Clinicians should avoid routine drug testing to screen adolescents and young adults for StUD. (S, CC)
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29a. When considering drug testing in patients under the age of 18, clinicians should ask patients for permission to test, even if parental/guardian consent was given, unless obtaining assent is not possible (eg, loss of consciousness). (S, CC)
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30. Clinicians should pay particular attention to signs or symptoms of ADHD and eating disorders in adolescent and young adult patients. (S, CC)
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31. If available, clinicians should refer adolescent and young adult patients to age-specific treatment and support programs to address identified biopsychosocial needs. (S, CC)
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Adolescent and Young Adult Treatment
32. When treating adolescents and young adults for StUD, clinicians should:
32a. consider delivering behavioral interventions that have been demonstrated to be effective in the treatment of other SUDs in adolescents and young adults (eg, CM, CBT, CRA, family therapy) and in the treatment of StUDs in adults (eg, CM, CBT, CRA). (S, L )
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32b. use an adolescent- and young adult-specific treatment model (eg, adolescent CRA [A-CRA]) or tailor existing treatments to be developmentally responsive. (S, M )
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32c. use peer-age groups for behavioral treatment in group formats when possible and avoid incorporating adolescents and young adults into group behavioral treatment with older adults. (S, VL )
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32d. consider treating adolescents and young adults with StUD with the off-label pharmacotherapies detailed in the Pharmacotherapy section when the developmentally contextualized benefits outweigh the harms. (C, VL )
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32e. counsel parents/guardians to not conduct home drug tests to assess stimulant use in adolescents and young adults without the oversight of a trained clinician. (S, CC)
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32f. recognize that involvement of family members is often beneficial in the treatment of adolescents and young adults with SUDs and involve family members and/or trusted adults when appropriate. (S, CC)
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32g. be familiar with state laws on adolescents’ ability to consent to treatment when treating minors under age 18; in some states, minors can proceed with treatment without involvement of a parent or legal guardian in their care, whereas in other states, parental/guardian consent may be required before proceeding with some or all aspects of treatment. (S, CC)
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32h. understand that while parental/guardian consent is not required for treatment of young adults, clinicians should initiate a conversation with the young adult patient about whether their treatment plan might be enhanced by involving a trusted adult. (S, CC)
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Pregnant and Postpartum Patients

Pregnant and Postpartum Patients Assessment
33. Clinicians should incorporate additional elements into the comprehensive assessment of StUD for patients who are pregnant, including:
33a. providing referrals to prenatal care providers if not already established. (S, L )
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33b. reviewing eligibility criteria for locally available programs that specifically address biopsychosocial needs related to pregnancy and parenting (eg, childcare, WIC programs). (S, L )
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34. Coordination of prenatal care and treatment of StUD is encouraged. (S, L )
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35. When screening for acute issues, complications, and sequalae associated with stimulant use in patients who are pregnant, clinicians should pay particular attention to factors that impact pregnancy and fetal development. (S, L )
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36. Since the ramifications of a positive drug test result for patients who are pregnant may be more severe than the general populations, before conducting drug testing in patients who are pregnant, clinicians should:
36a. know their state’s requirements on mandatory reporting and ramifications of reporting. (S, CC)
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36b. weigh the potential benefits with the risks of utilizing drug testing in this population. (S, CC)
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36c. obtain informed consent, unless there is immediate clinical need and obtaining consent is not possible (eg, loss of consciousness). (S, CC)
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Pregnant and Postpartum Patients Treatment
37. Risk versus benefit to the fetus or infant should be considered when medications are used to manage StUD, stimulant intoxication, or stimulant withdrawal. (S, VL )
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38. Wherever possible, clinicians should incorporate psychosocial treatments targeted toward meeting the additional needs of patients who are pregnant, including:
38a. Parent-focused treatment modalities (eg, parenting skills training). (S, CC)
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38b. family-based treatment modalities. (S, CC)
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39. Clinicians should consider CM to incentivize attendance at prenatal appointments, if feasible, in addition to usual targets (eg, stimulant abstinence). (S, L )
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40. Clinicians should consider providing additional treatment support around the time of birth, as the postpartum period may be a time of increased stress and risk of return to stimulant use. (C, VL )
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Breastfeeding
41. Clinicians should educate patients who use stimulants on the risks of use while breastfeeding and counsel patients not to breastfeed if they are actively using stimulants (except as prescribed). (S, VL )
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Additional Population-Specific Considerations

Sexual Orientation and Gender Identity
42. Clinicians should consider referring sexual and gender minoritized (SGM) patients with StUD to SGM-affirming programs when their history and/or behavior suggest they may not be comfortable fully participating in a general population setting (eg, distress related to their identities, difficulties discussing drug-related sexual activities, inner conflicts, trauma histories). (S, L )
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Patients Involved in the Criminal and/or Legal Systems
43. Initiation of treatment for StUD is recommended for individuals in the criminal and/or legal systems, including within jails and prisons. (S, CC)
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Patients Experiencing Homelessness or Unstable Housing
44. For patients experiencing homelessness, housing insecurity, food insecurity, and/or poverty, clinicians might consider:
44a. providing case management services or a referral to a case manager or other appropriate service provider(s) who can help the patient navigate health and social safety net resources. (S, CC)
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44b. providing a referral to a recovery residence based on the patient’s needs. (S, CC)
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Stimulant Intoxication and Withdrawal

Assessment and Diagnosis

Initial Assessment
45. The clinical examination should first identify any acute concerns and complications of stimulant intoxication or withdrawal that would indicate the patient requires a higher level of care. This includes an assessment of hyperadrenergic symptoms, including tachycardia, hypertension, hyperthermia, and agitation. (S, CC)
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46. The initial clinical examination when evaluating for suspected stimulant intoxication or withdrawal should include:
  • a clinical interview (as feasible)
  • physical examination
  • observation of signs and patient-reported symptoms
  • review of any available collateral information
  • a safety assessment of the patient’s risk of harm to self and others
(S, CC)
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Acute issues and complications of stimulant intoxication and withdrawal include but are not limited to:
  • Electrolyte and fluid imbalances (eg, dehydration, acidosis, hyperkalemia, hyponatremia)
  • Hyperthermia
  • Agitation
  • Psychosis
  • Cardiovascular dysfunction such as cardiac arrhythmias, hypertensive emergency, acute decompensated heart failure, and takotsubo cardiomyopathy
  • Acute neurologic complications such as seizures and cerebrovascular accidents
  • Serious infections such as infective endocarditis, osteomyelitis, epidural abscesses, septic arthritis, serious skin infections, bacteremia, and sepsis
  • Rhabdomyolysis
  • Movement disorders
  • Gastrointestinal perforation
  • Trauma and trauma-related complications
  • Risk for harm to self or others
Comprehensive Assessment
47. Stimulant intoxication and withdrawal are primarily diagnosed based on the patient history and physical examination, as well as findings from any clinical, diagnostic, and/or toxicology testing. (S, CC)
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48. If some elements of the medical workup are not available in given a setting, the results from a basic assessment of vital signs and focused mental status evaluation should be used to determine the urgency of further medical evaluation or referral for more comprehensive medical evaluation. (S, CC)
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49. Clinical testing should be based on presenting signs and symptoms and should include a complete blood count (CBC), a comprehensive metabolic panel (CMP), LFTs, markers for muscle breakdown (eg, CK, lactate [in cases of muscle breakdown and acidosis]) or cardiac injury (eg, CK, troponin). (S, CC)
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50. When analyzing CBC results for patients with cocaine intoxication or withdrawal, clinicians should be alert to neutrophil levels, as levamisole is a common adulterant in the cocaine supply and can cause immunosuppression—in particular, neutropenia—and small vessel vasculitis. (C, CC)
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Toxicology Testing
51. In patients presenting with stimulant intoxication or withdrawal, clinicians can use toxicology testing to:
51a. inform clinical thinking regarding the differential diagnosis, along with other clinical information. (S, CC)
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51b. identify substance use that could produce drug–drug interactions when considering pharmacotherapy to manage signs and symptoms of stimulant intoxication or withdrawal. (C, CC)
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52.s if stimulant intoxication is suspected but presumptive testing is negative. (C, CC)
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Setting Determination

53. Patients with severe clinical concerns or complications related to stimulant intoxication should be managed in acute care settings. (C, CC)
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54. Some patients with acute stimulant intoxication can be safely managed in lower acuity clinical settings if:
  • the patient is cooperative with care
  • the patient is responsive to interventions (eg, verbal and nonverbal de-escalation strategies, medications) that can be managed in the clinical setting
  • the patient is not experiencing more than mild hyperadrenergic symptoms or is responsive to medications that can be managed in the clinical setting
  • clinicians are able to:
    • assess for acute issues and complications of stimulant intoxication
    • monitor vital signs
    • assess and monitor suicidality
    • monitor for worsening signs and symptoms of intoxication and emergent complications related to stimulant intoxication
    • provide adequate hydration
    • provide a low-stimulation environment
    • manage the risk of return to stimulant use
    • coordinate clinical testing as indicated
(C, CC)
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Managing Stimulant Intoxication and Withdrawal

Behavioral and Psychiatric Symptoms of Stimulant Intoxication
55. Clinicians should evaluate the patient to identify causal factors for agitation and/or psychosis other than stimulant intoxication; treatment should address all underlying causes. (S, CC)
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56. Clinicians should use verbal and nonverbal de-escalation strategies to calm patients who are agitated, delirious, and/or psychotic to support their cooperation with care. (S, CC)
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57. Clinicians can consider treating stimulant-induced agitation or confusion with medication. (C, H )
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57a. Benzodiazepines can be considered a first-line treatment for managing stimulant-induced agitation and/or confusion. (C, H )
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58. De-escalation strategies should not delay the use of medication to manage patients who are agitated, delirious, and/or psychotic and at imminent risk for severe complications. (S, H )
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59. Clinicians should treat stimulant-induced psychotic symptoms with an antipsychotic medication. (S, H )
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59a. The urgency, formulation, and duration of antipsychotic pharmacotherapy should be based on etiology and symptomatology. (S, H )
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59b. Clinicians should avoid the use of chlorpromazine and clozapine for stimulant-induced psychosis as these medications may place patients at increased risk for seizures. (S, H )
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60. For agitation and/or psychosis that is moderate to severe or escalating, clinicians should:
60a. conduct a medical evaluation focused on identifying life-threatening medical signs and symptoms that require referral for emergent hospital workup and management. (S, CC)
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60b. conduct a mental status evaluation focused on evaluating the patient’s danger to self and others that would require immediate referral for full psychiatric assessment and/or involuntary containment and evaluation. (S, CC)
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61. If agitation and/or psychosis does not respond to the setting’s available de-escalation and/or medication management interventions, clinicians should coordinate transition to a more intensive level of care. (S, CC)
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61a. When possible, interventions that address agitation, confusion, delirium and/or psychosis should be initiated while arranging for transport. (S, CC)
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62. Clinicians should monitor for progression of psychiatric symptoms, breakthrough psychosis, suicidality, and emergence of trauma-related symptoms; in particular, suicidality may increase during waning intoxication and acute withdrawal. (C, CC)
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Hyperadrenergic Symptoms of Stimulant Intoxication
63. When patients present with hyperadrenergic symptoms, clinicians should provide ongoing monitoring and management of vital signs—especially heart rate and blood pressure—to prevent complications that may result from untreated sympathomimetic toxicity. (S, CC)
620
64. Clinicians should treat patients in a stimulant-induced hyperadrenergic state with GABAergic agents (eg, benzodiazepines, phenobarbital, propofol); benzodiazepines can be considered first-line treatment for this purpose. (S, L )
620
65. If the hyperadrenergic state persists despite appropriate improvement in agitation and neuromuscular hyperactivity following treatment with benzodiazepines or other GABAergic agent, clinicians can consider adjunctive treatment with the following medications:
65a. A beta blocker with concomitant alpha-1 antagonism (eg, carvedilol, labetalol). (C, M )
620
65b. An alpha-2 adrenergic agonist (eg, dexmedetomidine for severe symptoms, clonidine for mild to moderate symptoms). (C, M )
620
65c. Where beta blockers are contraindicated, clinicians can consider other pharmacological options such as calcium channel blockers, alpha-1 adrenergic antagonists, alpha-2 adrenergic agonists, and nitric oxide-mediated vasodilators, with consideration of other clinically relevant signs and symptoms. (C, M )
620
65d. While calcium channel blockers, alpha-1 adrenergic antagonists, alpha-2 adrenergic agonists, and nitric oxide-mediated vasodilators may be most beneficial in treating hypertension and vasospasm, clinicians should be alert to potential side effects, including poor control over tachycardia or reflex tachycardia. (S, M )
620
66. If a patient with stimulant intoxication is experiencing a hypertensive emergency, clinicians should:
66a. use short-acting agents such as sodium nitroprusside, phentolamine, or dihydropyridine calcium channel blockers. (S, VL )
620
66b. avoid long-acting antihypertensives to avoid abrupt hemodynamic collapse. (S, VL )
620
66c. use nitroglycerin if the patient exhibits signs or symptoms of cardiac ischemia. (S, VL )
620
Acute Issues and Complications
Chest Pain
67. For patients experiencing chest pain during stimulant intoxication, clinicians should initiate treatment for the underlying intoxication with GABAergic agents (eg, benzodiazepines, phenobarbital, propofol) as long as there are no clinical contraindications. (C, M )
620
68. Alternative agents (eg, calcium channel blockers, vasodilators) are generally preferred for management of cardiac ischemia in patients experiencing stimulant intoxication. However, if beta blockers are used in patients with stimulant intoxication, clinicians should consider using a medication with concomitant alpha-1 antagonism (eg, carvedilol, labetalol). If an unopposed beta blocker was used in a patient who is or was recently stimulant intoxicated, clinicians should also consider providing a coronary vasodilator (eg, nitroglycerin, calcium channel blocker). For complex cases, consult with cardiology and/or medical toxicology. (C, L )
620
69. While treating underlying stimulant intoxication in patients experiencing chest pain, clinicians should concomitantly evaluate for ACS and other causes of acute chest pain in stimulant intoxication (eg, pulmonary, musculoskeletal [MSK]). Chest pain that does not fully resolve as signs and symptoms of stimulant intoxication improve should be evaluated and treated following current standards of care. (S, M )
620
QRS Widening
70. Cocaine has local anesthetic-like effects at sodium channels and can cause QRS widening with impairment in cardiac contractility during severe cocaine intoxication. If these issues are identified, in addition to treating intoxication, clinicians should administer sodium bicarbonate to improve the conduction block and contractility; this will also improve metabolic acidosis if present. (S, H )
620
Seizure
71. When a patient presents to the emergency department (ED) with seizures following stimulant use, full neurological workup is not necessary if the seizures are well explained by substance use or withdrawal. (C, CC)
620
71a. When the etiology of the seizures is not well explained by stimulant use, the workup and management of seizures should proceed according to usual best practices. (S, CC)
620
72. For stimulant intoxication-related seizures or concomitant alcohol- or sedative-related seizures, clinicians should treat with benzodiazepines. (S, H )
620
72a. If seizures are refractory to benzodiazepines, clinicians can consider treating with either phenobarbital or propofol. (S, H )
620
Follow Up
73. Clinicians should screen patients for StUD and engage them in brief interventions using motivational interviewing (MI) or motivational enhancement therapy (MET) to facilitate referral for assessment for StUD, if indicated. (C, VL )
620
Table 2. Medications for Managing Intoxicationa
Having trouble viewing table?
Agent/Class Mechanism Example dosing Indications Other considerations
Sedatives Benzodiazepines (BZDs) (first line) GABAergic Initial dosing:

Lorazepam 1–2 mg intravenous (IV) based on clinical signs and symptoms and duration of effects

Diazepam 5–10 mg per os (by mouth/oral) (PO) for less severe symptoms based on patient parameters

Midazolam 5 mg intramuscular (IM) or 0.01–0.05 mg/kg IV for acute agitation in adult patients

Redosing frequency and dose should be guided by the degree and duration of the clinical effects of the initial dose		 Excitatory symptoms
Anxiety/ Agitation
Neuromuscular excitation
Seizures		 Parenteral vs. PO administration based on signs and symptom severity and drug availability (eg, parenteral BZD shortages). IM administration allows for administration in agitated patients without IV access.

Lorazepam has very slow IM onset (15–30 min)

Midazolam has very rapid IV onset, allowing for easy titration, and a relatively fast IM onset

If psychosis is primary symptom, antipsychotics should be considered primarily or adjunctively
Sedatives Phenobarbital (PBO) GABAergic Incremental 130–260 mg IM/IV/PO based on symptoms and patient parametersLoading strategy (eg, 5–10 mg/kg)Titrate based on clinical effects BZD shortages or contraindications

Patient not responding to escalating doses of BZDs

Severe sympathomimetic intoxication		 High oral bioavailability; PO dosing can be similar to parenteral dosing

Onset of effects, while slower than IV, is still fairly quick compared to other PO medications
Sedatives Propofol GABAergic + N-methyl-D-aspartate (NMDA) receptor antagonism 10–50 μg/kg/min based on symptoms and patient parameters For critically ill patients in the intensive care unit (ICU)

Severe sympathomimetic intoxication not responding to other agents		 Patients can be administered BZDs, PBO, and/or propofol concomitantly

Intubation is almost always required for propofol administration
Sympatholytics Clonidine Alpha-2 agonism +/– other 0.1–0.2 mg PO every 4 hours as needed Anxiety Useful medication adjunct to BZDs

Maintain hydration to avoid orthostatic symptoms
Sympatholytics Dexmedetomidine Alpha-2 agonism Start at 0.2–0.4 μg/kg/hr and titrate every 30 min up to maximum of 1.5 μg/kg/hr For critically ill patients in the ED or ICU as primary or secondary medication for sedation Useful medication adjunct to BZDs or other sedation agents

Onset of effects generally 30–60 min
Sedation without impairments in ventilation
Antipsychotics Butyrophenones (2nd gen) Dopamine antagonism Haloperidol or droperidol 5 mg IM Acute agitation with psychosis

Agitation not responding to BZDs

Toxic psychosis		 Consider atypical or newer generation antipsychotics as alternatives

Consider risk of QT prolongation
Antipsychotics Atypical Dopamine antagonism +/– other Olanzapine 5 mg PO
Quetiapine 50–100 mg PO at night		 Anxiety or agitation with psychotic features
Stimulant-induced psychosis

Stimulant-induced sleep derangements		 Consider risk of QT prolongation

For olanzapine, degree of symptoms to balance need for PO vs. IM
Other Ketamine NMDA receptor antagonism 1–5 mg/kg IM depending on degree of agitation For severe agitation as primary or secondary agent Rapid IM onset of action compared to other agents
a The information in this table is intended to guide management of stimulant intoxication in a variety of settings. The choice of medication, medication dosing (including initial and redosing), and route of administration should be guided by the patient’s signs and symptoms, degree of intoxication, the level of care, and the resources of the setting. This does not represent a comprehensive list but rather provides illustrative examples of medications discussed in the narrative.

Secondary and Tertiary Prevention

Screening

74. When general healthcare providers screen adolescents or adults for risky substance use per USPSTF guidelines, they should include screening for stimulant misuse (ie, nonmedical or nonprescribed use). (S, VL )
620
75. Clinicians should consider more frequent screening for stimulant medications. (S, VL )
620
76. Clinicians should check their state’s PDMP prior to prescribing psychostimulant medications. (S, M )
620

Assessment

77. For patients who screen positive for stimulant misuse, clinicians should:
77a. conduct a focused history and clinical exam to evaluate complications of use related to route of administration and type of preparation used and provide treatment or referrals as appropriate. (S, VL )
620
77b. assess risky patterns of stimulant use to determine harm reduction service and counseling needs, including:
  • frequency and amount of use, including binge use
  • use of stimulants with no one else present
  • concurrent use of prescribed and nonprescribed medications and other substances, particularly opioids, alcohol, and other central nervous system depressants
  • history of overdose
  • history of stimulant-related ED visits and hospitalizations
(S, H )
620
77bii. assess routes of administration, particularly injection drug use, to determine harm reduction service and counseling needs. (S, VL )
620
77biii. assess risky sexual behaviors, to determine harm reduction service and counseling needs. (S, H )
620
77c. consider asking patients about:
  • the context of their stimulant use (eg, chemsex, weight loss, academic or work performance, staying awake
  • trauma
  • intimate partner violence (IPV)
(S, CC)
620
77d. conduct baseline laboratory testing based on clinical assessment of risk factors (see Assessment). (S, CC)
620
78. Patients who engage in nonmedical use of prescription stimulants should be evaluated for ADHD, which may also require treatment. (S, CC)
620

Early Intervention for Risky Stimulant Use

Interventions to Reduce Risky Stimulant Use
79. Clinicians should consider providing brief interventions to patients with any risky stimulant use using MI techniques to encourage patients to reduce or stop their use. (S, VL )
620
80. Clinicians should be aware of some of the unique motivators of stimulant use and be prepared to discuss and suggest safer alternatives as part of brief interventions for stimulant use (eg, chemsex, weight loss, academic or work performance, staying awake). (S, CC)
620
Referral to Treatment for Stimulant Use Disorder
81. For patients who screen positive for risky stimulant use, clinicians should conduct or offer referrals for comprehensive assessment and treatment for potential StUD with linkage support, including warm handoffs. (S, VL )
620
82. For patients who are ambivalent about referrals for StUD assessment or treatment, clinicians should consider using interventions to enhance motivation for treatment (eg, MI, MET). (S, VL )
620
83. Clinicians should consider the use of peer navigators to link patients to StUD assessment and treatment. (C, VL )
620

Harm Reduction

Harm Reduction Education
84. For patients who engage in risky stimulant use, clinicians should:
84a. offer basic harm reduction education about safer stimulant use. (S, L )
620
84b. tailor harm reduction education to the patient’s patterns of substance use (eg, context of use, route of administration, type of preparation). (S, L )
620
84c. refer to relevant local harm reduction services as indicated based on the patient’s clinical assessment. (S, L )
620
84d. offer harm reduction education on overdose prevention and reversal. (S, H )
620
84e. offer harm reduction education regarding safer sexual practices. (S, H )
620
Overdose Prevention and Reversal
85. For patients who use stimulants from nonmedical sources or are socially engaged with others who do, clinicians should prescribe or distribute overdose reversal medications (eg, naloxone) or refer patients to locations where they can obtain these medications in the community. (S, H )
620
86. Clinicians should recommend that patients perform comprehensive drug checking, including using fentanyl test strips, every time they obtain a new batch of stimulants from nonmedical sources and review the technique for using fentanyl test strips when permitted by state law. (C, M )
620
87. Clinicians should consider referring individuals to local supervised consumption sites (SCS) when available. (S, M )
620
Safer Sexual Practices and Contraception
88. For patients who engage in risky sexual behaviors, clinicians should:
88a. offer or refer for sexually transmitted infection (STI) testing at least every 3 to 6 months or more frequently depending on the individual patient’s risk. (S, M )
620
88ai. consider providing information about local STI testing services where patients can obtain free or low-cost testing. (S, M )
620
88b. consider offering a referral to a local psychosocial sex education program or harm reduction program that addresses risky sexual behavior for additional or continuing harm reduction intervention. (S, L )
620
88c. offer condoms and lubrication or advice about where to obtain them. (S, CC)
620
Injection Drug Use
89. For patients who inject stimulants, clinicians should:
89a. provide or refer for harm reduction education on safer injection practices and include information specific to the patient’s stimulant(s) and preparation(s) of choice (eg, safer acid pairings for crack cocaine injection). (S, L )
620
89b. provide or refer for safe injection supplies and harm reduction services. (S, M )
620
HIV Preexposure Prophylaxis
90. Clinicians should offer HIV preexposure prophylaxis (PrEP) to patients who use stimulants and are at increased risk for HIV, including those who:
  • engage in risky sexual behaviors
  • access postexposure prophylaxis (PEP) regularly
  • inject drugs
(S, H )
620
Oral Health
91. People who use stimulants are at high risk of dental complications, such as poor dentition, dental carries, abscesses, and subsequent malnutrition. Clinicians should:
  • encourage patients who use stimulants to maintain good oral hygiene and receive regular dental care
  • offer referrals to dental care providers if needed
(S, H )
620
Nutrition
92. People who use stimulants may experience appetite suppression and go for long periods without appropriate nutrition, placing them at high risk for nutritional deficits such as malnutrition, cachexia, and sequalae involving specific vitamin deficiencies. Clinicians should:
92a. inquire about diet, nutrition, and food security. (S, CC)
620
92b. encourage patients who use stimulants to eat nutritious food. (C, CC)
620

Recommendation Grading

Abbreviations

  • A-CRA: Adolescent Community Reinforcement Approach
  • ACS: Acute Coronary Syndrome
  • ADHD: Attention-deficit/hyperactivity Disorder
  • ATS: Amphetamine-type Stimulant
  • AUD: Alcohol Use Disorder
  • BID: Two Times Per Day
  • BZD: Benzodiazepines
  • CBC: Complete Blood Count
  • CBT: Cognitive Behavioral Therapy
  • CK: Creatine Kinase
  • CM: Contingency Management
  • CMP: Comprehensive Metabolic Panel
  • CRA: Community Reinforcement Approach
  • DSM: Diagnostic And Statistical Manual Of Mental Disorders
  • ECG: Electrocardiogram
  • ED: Emergency Department
  • ER: Extended Release
  • FDA: United States Food And Drug Administration
  • GABA: Gamma-aminobutyric Acid
  • HBV: Hepatitis B Virus
  • HCV: Hepatitis C Virus
  • HIV: Human Immunodeficiency Virus
  • ICU: Intensive Care Unit
  • IM: Intramuscular
  • IPV: Intimate partner Violence
  • IV: Intravenous
  • LDX: Lisdexamfetamine
  • LFT: Liver Function Test
  • MAS-ER: Extended-release Mixed Amphetamine Salts
  • MET: Motivational Enhancement therapy
  • MI: Motivational Interviewing
  • MPH: Methylphenidate
  • MSK: Musculoskeletal
  • NMDA: N-methyl-D-aspartate
  • PBO: Phenobarbital
  • PDMP: Prescription Drug monitoring Program
  • PEP: Postexposure Prophylaxis
  • PO: Per Os (by Mouth/oral)
  • PrEP: Preexposure Prophylaxis
  • RSS: Recovery Support Services
  • SCS: Supervised Consumption Sites
  • SGM: Sexual And Gender Minoritized
  • STI: Sexually Transmitted Infection
  • SUDs: Substance Use Disorders
  • StUD: Stimulant Use Disorder
  • TID: Three Times Per Day
  • TUD: Tobacco Use Disorder
  • USPSTF: United States Preventive Services Task Force
  • WIC: Special Supplemental Nutrition Program For Women, Infants, And Children
  • d-AMP: Dextroamphetamine
  • d-AMP-SR: Sustained-release Dextroamphetamine

Expert Authors/Reviewers

Guideline Committee Members
Steven Batki, MD; Daniel Ciccarone, MD, MPH; Scott E. Hadland, MD, MPH; Brian Hurley, MD (Co-Chair); Kimberly Kabernagel, DO; Frances Levin, MD; James McKay, PhD; Larissa Mooney, MD (Co-Chair); Siddarth Puri, MD; Richard Rawson, PhD; Andrew Saxon, MD; Kevin Sevarino, MD, PhD; Kevin Simon, MD; Timothy Wiegand, MD

Disclaimer

This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.