Caring for Hospitalized Adults with Methamphetamine Use Disorder: A Proposed Clinical Roadmap.

Methamphetamine-related overdose is an emergent public health issue.1Hedegaard H Miniño AM Warner M Drug overdose deaths in the United States, 1999-2018.NCHS Data Brief. 2020; 2020: 1-8Google Scholar Trends in hospitalization reflect downstream impacts of this evolving crisis; between 2008 and 2015 amphetamine-related inpatient admissions increased in frequency, had longer lengths of stay, were more frequently associated with in-hospital mortality, and most often paid for by Medicaid.2Winkelman TNA Admon LK Jennings L Shippee ND Richardson CR Bart G Evaluation of amphetamine-related hospitalizations and associated clinical outcomes and costs in the United States.JAMA Network Open. 2018; 1: e183758Crossref PubMed Scopus (88) Google Scholar Of these patients, most were hospitalized primarily for psychiatric disorders (including substance use disorders [SUDs]), infection, congestive heart failure, or diabetes.2Winkelman TNA Admon LK Jennings L Shippee ND Richardson CR Bart G Evaluation of amphetamine-related hospitalizations and associated clinical outcomes and costs in the United States.JAMA Network Open. 2018; 1: e183758Crossref PubMed Scopus (88) Google Scholar These data suggest that this health crisis is directly impacting acute care delivery systems. Unfortunately, health systems, hospitals, and hospitalists have not received guidance on how to best care for inpatients with methamphetamine use disorder (MUD). There is an urgent need to understand how to effectively approach care for this complex hospitalized population. We propose a clinical roadmap (Table) informed by national evidence-based guidelines for ambulatory patients3Substance Abuse and Mental Health Services Administration. Treatment of stimulant use disorders. Available at: https://www.samhsa.gov/resource/ebp/treatment-stimulant-use-disorders. Accessed 11/1/2022.Google Scholar and veterans,4U.S. Department of Health & Human Services. VA/DoD clinical practice guidelines: management of substance use disorders. Available at:https://integrationacademy.ahrq.gov/resources/17256#:∼:text=VA%2FDoD%20Clinical%20Practice%20Guideline%20for%20the%20Management%20of,alcohol%20use%20disorder%2C%20in%20the%20VA%20and%20DoD. Accessed 11/1/2022.Google Scholar peer-reviewed scholarly work, and the expertise of a multi-disciplinary authorship team comprised of peer support specialists and addiction-specialized medicine, psychiatry, and social work.TableSummary of Clinical Domains and RecommendationsDomainRecommendation1. Recognizing Acute Intoxication and WithdrawalIdentify signs and symptoms early in hospitalization to anticipate patient needs.2. Managing Acute and Sub-Acute Methamphetamine-Related SymptomsAddress acute agitation secondary to methamphetamine use with non-pharmacologic and pharmacologic means.3. Assessing and Treating Concurrent Psychiatric DisordersComplete a comprehensive SUD assessment and when applicable a full psychiatric evaluation, with appropriate management.4. Administering Behavioral InterventionsInitiate evidence-based behavioral interventions using the expertise of interprofessional teams.5. Providing Harm Reduction Education and SuppliesOffer harm reduction support to all hospitalized patients with MUD.6. Facilitating Transitions of CareDevelop discharge plans to be patient-centered, focused on recovery goals, and ongoing social needs.SUD = substance use disorder; MUD = methamphetamine use disorder. Open table in a new tab SUD = substance use disorder; MUD = methamphetamine use disorder. Domain 1: Recognizing Acute Intoxication and Withdrawal. Recognizing acute intoxication and withdrawal may be difficult due to symptom heterogeneity,5Schep LJ Slaughter RJ Beasley DMG The clinical toxicology of metamfetamine.Clin Toxicol. 2010; 48: 675-694Crossref PubMed Scopus (117) Google Scholar,6Pennay AE Lee NK Putting the call out for more research: the poor evidence base for treating methamphetamine withdrawal.Drug Alcohol Rev. 2011; 30: 216-222Crossref PubMed Scopus (20) Google Scholar resemblance to psychiatric disorders,7Paulus MP Stewart JL Neurobiology, clinical presentation, and treatment of methamphetamine use disorder: a review.JAMA Psychiatry. 2020; 77: 959-966Crossref PubMed Scopus (107) Google Scholar and medical conditions. Symptoms of acute intoxication may include increased euphoria, hyperexcitability, hypersexuality, locomotor activity, agitation, and psychosis.3Substance Abuse and Mental Health Services Administration. Treatment of stimulant use disorders. Available at: https://www.samhsa.gov/resource/ebp/treatment-stimulant-use-disorders. Accessed 11/1/2022.Google Scholar Objective signs of a methamphetamine-related toxidrome5Schep LJ Slaughter RJ Beasley DMG The clinical toxicology of metamfetamine.Clin Toxicol. 2010; 48: 675-694Crossref PubMed Scopus (117) Google Scholar can include diaphoresis, tachycardia, hyperthermia,8Goldstein S Richards JR Sympathomimetic Toxicity.[Updated 2022 Jul 18]. StatPearls [Internet]. StatPearls Publishing, Treasure Island, FL2022https://www.ncbi.nlm.nih.gov/books/NBK430757/Google Scholar and a positive urine drug test. In contrast, withdrawal is poorly defined due to an insufficient evidence base.6Pennay AE Lee NK Putting the call out for more research: the poor evidence base for treating methamphetamine withdrawal.Drug Alcohol Rev. 2011; 30: 216-222Crossref PubMed Scopus (20) Google Scholar Some researchers propose acute (days 1 to 10 since last use) and sub-acute (2 to 3 weeks since last use) phases.9McGregor C Srisurapanont M Jittiwutikarn J Laobhripatr S Wongtan T White JM The nature, time course and severity of methamphetamine withdrawal.Addiction. 2005; 100: 1320-1329Crossref PubMed Scopus (277) Google Scholar,10Zorick T Nestor L Miotto K et al.Withdrawal symptoms in abstinent methamphetamine-dependent subjects.Addiction. 2010; 105: 1809-1818Crossref PubMed Scopus (144) Google Scholar Others posit a more chronic syndrome lasting for months.6Pennay AE Lee NK Putting the call out for more research: the poor evidence base for treating methamphetamine withdrawal.Drug Alcohol Rev. 2011; 30: 216-222Crossref PubMed Scopus (20) Google Scholar Systematic review suggests that a methamphetamine withdrawal syndrome often includes: 1) depressive symptoms (e.g., dysphoria, anhedonia, anergia), 2) agitation and irritability, 3) fatigue (e.g., increased need for sleep), and 4) cognitive impairment (e.g., poor concentration). Additional symptoms can include red, itchy eyes, mild paranoid ideation, hyperphagia, and cravings.10Zorick T Nestor L Miotto K et al.Withdrawal symptoms in abstinent methamphetamine-dependent subjects.Addiction. 2010; 105: 1809-1818Crossref PubMed Scopus (144) Google Scholar Symptom resolution varies after cessation; within 1 week for depressive symptoms10Zorick T Nestor L Miotto K et al.Withdrawal symptoms in abstinent methamphetamine-dependent subjects.Addiction. 2010; 105: 1809-1818Crossref PubMed Scopus (144) Google Scholar for some patients and a week10Zorick T Nestor L Miotto K et al.Withdrawal symptoms in abstinent methamphetamine-dependent subjects.Addiction. 2010; 105: 1809-1818Crossref PubMed Scopus (144) Google Scholar to a year or more11Glasner-Edwards S Mooney LJ Methamphetamine psychosis: epidemiology and management.CNS Drugs. 2014; 28: 1115-1126Crossref PubMed Scopus (134) Google Scholar for psychotic symptoms. Cravings can continue without significant reduction for up 2 weeks and may continue for up to 5 weeks.10Zorick T Nestor L Miotto K et al.Withdrawal symptoms in abstinent methamphetamine-dependent subjects.Addiction. 2010; 105: 1809-1818Crossref PubMed Scopus (144) Google Scholar Domain 2: Managing Acute and Sub-Acute Methamphetamine-Related Symptoms. The first step in managing acute methamphetamine-related symptoms is to stabilize the patient. If the patient is agitated, the American Association of Emergency Psychiatry recommends: 1) ensuring physical safety for all, 2) managing patient distress, 3) avoiding restraints when possible, and 4) avoiding coercive interventions that escalate agitation.12Richmond JS Berlin JS Fishkind AB et al.Verbal de-escalation of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup.West J Emerg Med. 2012; 13: 17-25Crossref PubMed Scopus (262) Google Scholar Patients may benefit from placement in a quiet non-stimulating environment5Schep LJ Slaughter RJ Beasley DMG The clinical toxicology of metamfetamine.Clin Toxicol. 2010; 48: 675-694Crossref PubMed Scopus (117) Google Scholar and pharmacological interventions (e.g., benzodiazepines, antipsychotics).3Substance Abuse and Mental Health Services Administration. Treatment of stimulant use disorders. Available at: https://www.samhsa.gov/resource/ebp/treatment-stimulant-use-disorders. Accessed 11/1/2022.Google Scholar Sub-acute and chronic withdrawal management pose a challenge because there is no Food and Drug Administration-approved medication for MUD. However, two recent clinical trials may hold promise: a multi-site trial of extended-release intramuscular naltrexone and extended-release oral bupropion13Trivedi MH Walker R Ling W et al.Bupropion and naltrexone in methamphetamine use disorder.N Engl J Med. 2021; 384: 140-153Crossref PubMed Scopus (82) Google Scholar and a single-site study of mirtazapine for cisgender men and transgender women who have sex with men.14Coffin PO Santos GM Hern J et al.Effects of mirtazapine for methamphetamine use disorder among cisgender men and transgender women who have sex with men: A placebo-controlled randomized clinical trial.JAMA Psychiatry. 2020; 77: 246-255Crossref PubMed Scopus (53) Google Scholar Hospital-based practitioners could consider prescribing these medications for concurrent Food and Drug Administration-approved indications (e.g., mirtazapine for depression). Domain 3: Assessing and Treating Concurrent Psychiatric Disorders. Other psychiatric disorders are common for inpatients with MUD2Winkelman TNA Admon LK Jennings L Shippee ND Richardson CR Bart G Evaluation of amphetamine-related hospitalizations and associated clinical outcomes and costs in the United States.JAMA Network Open. 2018; 1: e183758Crossref PubMed Scopus (88) Google Scholar and may complicate acute presentation, hospital management, and post-acute care. Patients may benefit from addiction and psychiatric consultation to help distinguish symptoms and identify concurrent disorders. There is limited evidence to guide the management of concurrent psychiatric diagnoses; however, targeted treatment is recommended (e.g., buprenorphine for opioid use disorder, lithium for bipolar).3Substance Abuse and Mental Health Services Administration. Treatment of stimulant use disorders. Available at: https://www.samhsa.gov/resource/ebp/treatment-stimulant-use-disorders. Accessed 11/1/2022.Google Scholar The literature-base is primarily focused on methamphetamine associated psychosis, which is treated with a second-generation antipsychotic medication.11Glasner-Edwards S Mooney LJ Methamphetamine psychosis: epidemiology and management.CNS Drugs. 2014; 28: 1115-1126Crossref PubMed Scopus (134) Google Scholar Methamphetamine associated psychosis may resolve within 1 week of cessation and longer-term pharmacotherapy may not be necessary.11Glasner-Edwards S Mooney LJ Methamphetamine psychosis: epidemiology and management.CNS Drugs. 2014; 28: 1115-1126Crossref PubMed Scopus (134) Google Scholar For patients with protracted methamphetamine associated psychosis (> 6 months), treatment should focus on cessation11Glasner-Edwards S Mooney LJ Methamphetamine psychosis: epidemiology and management.CNS Drugs. 2014; 28: 1115-1126Crossref PubMed Scopus (134) Google Scholar and an antipsychotic taper. Domain 4: Administering Behavioral Interventions. A systematic review of reviews on stimulant use disorder treatment concluded that contingency management had the strongest evidence for use.15Ronsley C Nolan S Knight R et al.Treatment of stimulant use disorder: a systematic review of reviews.PLoS ONE. 2020; 15e0234809Crossref PubMed Scopus (66) Google Scholar Contingency management uses a reward-based system as positive reinforcement for specific behaviors (e.g., incentivizing negative urine drug screens or attending healthcare visits with small prizes). Contingency management is well-studied in outpatient settings, but little is known about hospital-based implementation. A pilot project in a Canadian hospital suggests that contingency management could be feasible during hospitalization.16Bach P Garrod E Robinson K Fairbairn N An acute care contingency management program for the treatment of stimulant use disorder: a case report.J Addict Med. 2020; 14Crossref PubMed Scopus (2) Google Scholar Future studies could explore adapting contingency management to hospitals. Domain 5: Providing Harm Reduction Education and Supplies. Many hospitalized patients with SUDs desire harm reduction services,17McNeil R Kerr T Pauly B Wood E Small W Advancing patient-centered care for structurally vulnerable drug-using populations: a qualitative study of the perspectives of people who use drugs regarding the potential integration of harm reduction interventions into hospitals.Addiction. 2016; 111: 685-694Crossref PubMed Scopus (67) Google Scholar which should be offered regardless of methamphetamine cessation. Experts suggest asking about route of administration (inhalation vs. rectal vs. injection).18Chan CA Canver B McNeil R Sue KL Harm reduction in health care settings.Medical Clinics. 2022; 106: 201-217Abstract Full Text Full Text PDF Scopus (7) Google Scholar For inhalation, education should discourage pipe sharing to decrease infection risk, encourage the use of mouthpieces to prevent burns to lips and oral mucosa, and to suggest petroleum jelly for skin barrier protection.18Chan CA Canver B McNeil R Sue KL Harm reduction in health care settings.Medical Clinics. 2022; 106: 201-217Abstract Full Text Full Text PDF Scopus (7) Google Scholar Safer use education for rectal administration may include suggestions to mix the substance with sterile water, to use lubrication to protect the skin barrier during administration, and to avoid sharing equipment.18Chan CA Canver B McNeil R Sue KL Harm reduction in health care settings.Medical Clinics. 2022; 106: 201-217Abstract Full Text Full Text PDF Scopus (7) Google Scholar For those who inject, education should promote the use of sterile equipment (e.g., needles) and hygienic administration (e.g., alcohol preps for skin cleaning).18Chan CA Canver B McNeil R Sue KL Harm reduction in health care settings.Medical Clinics. 2022; 106: 201-217Abstract Full Text Full Text PDF Scopus (7) Google Scholar All patients should receive overdose education and take-home naloxone. Domain 6: Facilitating Transitions of Care. Hospitalization is a critical time to engage adults with SUDs with treatment and linkage to care at discharge.19Englander H JA Krawczyk N Patten A Roberts T Korthuis PT McNeely J A taxonomy of hospital-based addiction care models: a scoping review and key informant interviews.J Gen Intern Med. 2022; 37: 2821-2833Crossref PubMed Scopus (12) Google Scholar Health systems can partner with community providers to facilitate referral to the appropriate level of care at discharge3Substance Abuse and Mental Health Services Administration. Treatment of stimulant use disorders. Available at: https://www.samhsa.gov/resource/ebp/treatment-stimulant-use-disorders. Accessed 11/1/2022.Google Scholar and offer referrals to housing supports for those in need. Disposition planning should begin early in hospitalization and focus on individually identified recovery goals. Anticipate challenges to transition for patients with a history of aggression while intoxicated, incarceration, premature patient-initiated discharges, cognitive impairment, and rural residents. In short, hospitalized adults with MUD often have complex needs. To address complexity, we propose an interprofessional and systematic approach to care. A protocolized approach may be effective as demonstrated by a Colorado emergency department pilot project to address methamphetamine associated psychosis.20Simpson SA, Wolf C, Loh RM, Camfield K, Rylander M. Evaluation of the BEAT Meth intervention for emergency department patients with methamphetamine psychosis. J Addict Med. 2023;17(1):67-73Google Scholar There is an urgent need to study, trial, and implement effective treatment approaches for inpatients with methamphetamine use disorder.