Clinical progress note: Management of the hospitalized patient who uses methamphetamine

Abstract

Methamphetamine is a potent amphetamine-type stimulant (ATS) that increases dopaminergic, noradrenergic, and serotonergic activity within the brain resulting in euphoria, arousal, and disinhibition, among other effects. During World War II, ATS were used by soldiers to increase wakefulness and suppress appetite. Over the following decades, ATS were widely prescribed for fatigue, emotional distress, and obesity. In 1970, the Controlled Substances Act, which laid the initial framework for the categorization and regulation of controlled substances, began curtailing medical prescribing of ATS, opening a market for illicitly manufactured methamphetamine. For the remainder of the twentieth century, the production and distribution of illicit methamphetamine (also known as “meth,” “crank,” “speed,” “crystal,” or “ice”) centered on the Western United States. In the twenty-first century, methamphetamine use has increased dramatically and spread throughout North America.¹ Methamphetamine-related overdose deaths have risen sharply during this time, disproportionately affecting American Indian and Alaska Native populations and Black men.²

The most common route of methamphetamine use is smoking, followed by injection and snorting. However, methamphetamine use via injection is increasing and is associated with higher rates of overdose and infectious complications.² Individuals with co-use of methamphetamine and opioids face increased acute care utilization, infectious complications, and risk of overdose, with lower engagement in treatment compared to those who only use opioids.³

Methamphetamine use and methamphetamine use disorder (MaUD) may lead to acute and chronic neuropsychiatric, cardiovascular, infectious, and traumatic complications.³ Acute care utilization related to methamphetamine increased four- to sixfold during the past decade, resulting in at least $2 billion in costs.⁴ Among hospitalized patients, methamphetamine use is associated with longer lengths of stay, increased in-hospital mortality, and decreased linkage to postdischarge care.⁵ Hospitalists will increasingly need to diagnose and manage sequelae of methamphetamine use.

We obtained relevant society guidelines and searched the PubMed database using three Medical Subject Heading (MeSH) term queries: “methamphetamine/toxicity,” “methamphetamine AND hospitalization,” and “methamphetamine AND substance withdrawal syndrome,” which yielded a total of 299 English language articles published between 2019 and 2024. We reviewed the search results and guidelines for applicable recommendations on managing sequelae of methamphetamine use in hospitalized patients including acute intoxication, withdrawal, MaUD, and chronic complications (Table 1).

Methamphetamine causes an acute sympathomimetic toxidrome that can lead to several life-threatening complications (Table 2).⁶ The half-life of methamphetamine is 90 min but its principal metabolite, d-amphetamine, has a half-life of 9–12 h.⁷ When evaluating a patient with suspected methamphetamine intoxication, hospitalists should consider a differential diagnosis that includes other sympathomimetic toxidromes (e.g., cocaine, phencyclidine), primary psychotic disorders, endocrinopathies (e.g., hyperthyroidism), and sepsis. The latter can be challenging to diagnose in the context of acute methamphetamine intoxication since methamphetamine use can both mimic sepsis and predispose patients to infection.

Hospitalists should be aware that urine immunoassays for amphetamines are particularly prone to false positive results (up to 10%) and may be insensitive for novel psychostimulants.⁸ Many common medications cross-react with screening assays, including bupropion, sildenafil, atenolol, tramadol, duloxetine, aripiprazole, venlafaxine, atomoxetine, and prescribed stimulants (e.g., lisdexamfetamine, dextroamphetamine). Positive results in a patient not reporting methamphetamine use should be sent for confirmatory mass spectrometry.

Management of acute methamphetamine intoxication is primarily supportive and involves providing a low-stimulus environment, identifying and correcting volume depletion and metabolic derangements, and providing reorientation and reassurance.⁸ For acute agitation unresponsive to nonpharmacologic measures, benzodiazepines are considered first-line therapy. If benzodiazepines are ineffective or contraindicated, or when psychosis symptoms predominate, antipsychotics may be used with caution to avoid over-sedation if coadministered with benzodiazepines. For refractory agitation, intravenous or intramuscular ketamine may be administered by an experienced clinician.⁸

If significant hypertension and tachycardia persist despite treatment of agitation and hyperactivity with benzodiazepines, it is reasonable to add an alpha-agonist such as clonidine or a beta-blocker such as labetalol to reduce the risk of cardiovascular complications.⁸ If there is a concern for a true hypertensive emergency with end-organ damage, short-acting antihypertensives should be used in accordance with standard practice.

Acute methamphetamine withdrawal (sometimes referred to as “washout”) is characterized by increased sleepiness and appetite along with dysphoria, inactivity, irritability, and vivid dreams. Hypersomnia in particular can be significant and persistent, peaking at 72 h after abstinence and lasting for up to 1 week.⁷ Treatment is largely supportive by allowing patients to rest, managing acute medical issues, and providing symptom-based treatment.⁷ Following the acute withdrawal period, many patients experience a protracted postacute withdrawal syndrome lasting up to 6 months. This period is characterized by cognitive dysfunction, dysphoria, anxiety, and cravings.⁷ Medical management of methamphetamine withdrawal has been attempted with agents such as modafinil, methylphenidate, and mirtazapine, but there is insufficient evidence to recommend the use of these medications.⁸

The hypersomnia associated with methamphetamine withdrawal can complicate the assessment of patients who are experiencing concurrent opioid toxicity or withdrawal. In contrast to opioid toxicity, somnolence related to methamphetamine withdrawal should not cause hypoventilation and hypercarbia. When caring for patients who use both methamphetamine and opioids, hospitalists should remain vigilant for opioid withdrawal symptoms and treat them with guideline-recommended medications including methadone, buprenorphine, and nonopioid adjuncts.⁹

MaUD is a clinical syndrome marked by an inability to control methamphetamine use despite harmful consequences arising from that use; methamphetamine use alone does not establish a MaUD diagnosis. Hospitalists can diagnose MaUD by ascertaining that a patient meets two or more of the diagnostic criteria for stimulant use disorder listed in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5).³

Patients engage best when substance use is addressed in an open-ended and judgment-free manner by a clinician who seeks to understand the patient's reason for use, motivation for change, and individual goals.³ Clinicians should avoid language such as “addict” or “drug abuse” in favor of nonstigmatizing, person-first terminology such as “person who uses methamphetamine” and “drug use.” A patient's goals may include cessation, reduction in use, mitigation of harms, or completing treatment for their acute medical concerns and returning to use. Hospitalists should support the patient's autonomy and help them achieve the best health outcomes possible under the circumstances.

Chronic methamphetamine use results in sympathetic toxicity and direct toxic effects on cardiac and vascular tissue, increasing the risk for cardiomyopathy, atherosclerotic cardiovascular disease, and pulmonary hypertension.³ Relative to patients with other cardiomyopathies, patients with methamphetamine-associated cardiomyopathy are generally younger, with higher acute care utilization and mortality.¹⁵ There is no specific recommendation for enhanced cardiovascular screening in patients who use methamphetamine.⁸ Patients with methamphetamine-associated cardiomyopathy should be initiated on guideline-directed medical therapy for heart failure, referred for cardiology care, and offered aggressive management for any underlying substance use disorders, as methamphetamine cessation is associated with improved outcomes including ejection fraction recovery.¹⁵ Multidisciplinary addiction medicine and cardiology clinics offering contingency management to patients with methamphetamine-associated cardiomyopathy have demonstrated feasibility and promise.¹⁵

Chronic methamphetamine use is associated with neuropsychiatric morbidity including persistent psychosis, stroke, cognitive impairment, and Parkinson's disease.³ The neuropsychiatric disinhibition related to methamphetamine use has been linked to an increased risk of traumatic death, suicide, and acquisition of HIV and other sexually transmitted infections.³ At least annually, patients who use methamphetamine should be offered testing for HIV, hepatitis C, and sexually transmitted infections. Hospitalization may be a time when patients who use methamphetamine can be provided immunization against hepatitis A, hepatitis B, HPV, tetanus, diphtheria, pertussis, pneumococcus, meningococcus, influenza, and coronavirus disease 2019 (COVID-19) to reduce their risk of future acquisition of acute and chronic infections.³

Methamphetamine use is increasingly common in the community and among hospitalized patients, leading to acute and chronic complications. Hospitalists should be familiar with the initial evaluation and management of methamphetamine intoxication and withdrawal, identification and treatment of chronic conditions that arise from methamphetamine use, and current approaches to addressing methamphetamine use and MaUD in hospitalized patients (Table 1). Further research is needed on the effective management of acute methamphetamine withdrawal, behavioral and pharmacologic treatments for MaUD, and strategies for preventing complications of chronic use, including cardiomyopathy.

The authors declare no conflict of interest.