{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:38:39Z","timestamp":1792024719444,"version":"4.4.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"\n Importance<\/jats:title>\n There are no medications approved by authorities for the treatment of amphetamine or methamphetamine dependence, and studies investigating the effectiveness of pharmacological treatments in hard outcomes, such as hospitalization and death, are lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the association between pharmacotherapies and hospitalization and mortality outcomes in persons with amphetamine or methamphetamine use disorder.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This nationwide register-based cohort study was conducted from July 2006 to December 2018 with a median (IQR) follow-up time of 3.9 (1.0-6.1) years. Data were analyzed from December 1, 2021, to May 24, 2022. All residents aged 16 to 64 years living in Sweden with a registered first-time diagnosis of amphetamine or methamphetamine use disorder and without previous diagnoses of schizophrenia or bipolar disorder were identified from nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Medications for substance use disorders (SUDs) or for attention-deficit\/hyperactive disorder, mood stabilizers, antidepressants, benzodiazepines and related drugs, and antipsychotics. Medication use vs nonuse was modeled with the PRE2DUP (from prescription drug purchases to drug use periods) method.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were hospitalization due to SUD and any hospitalization or death, which were analyzed using within-individual models by comparing use and nonuse periods of 17 specific medications or medication classes in the same individual to minimize selection bias. The secondary outcome was all-cause mortality, studied using between-individual analysis as traditional Cox models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n There were 13\u202f965 individuals in the cohort (9671 [69.3%] male; mean [SD] age, 34.4 [13.0] years). During follow-up, 7543 individuals (54.0%) were taking antidepressants, 6101 (43.7%) benzodiazepines, 5067 (36.3%) antipsychotics, 3941 (28.2%) ADHD medications (1511 [10.8%] were taking lisdexamphetamine), 2856 (20.5%) SUD medications, and 1706 (12.2%) mood stabilizers. A total of 10\u202f341 patients (74.0%) were hospitalized due to SUDs, 11\u202f492 patients (82.3%) were hospitalized due to any cause or died, and 1321 patients (9.5%) died of any cause. Lisdexamphetamine was the only medication in this study that was significantly associated with a decrease in risk of 3 outcomes (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.94 for SUD hospitalization; aHR, 0.86; 95% CI, 0.78-0.95 for any hospitalization or death; aHR, 0.43; 95% CI, 0.24-0.77 for all-cause mortality). Methylphenidate use also was associated with lower all-cause mortality (aHR, 0.56; 95% CI, 0.43-0.74). Use of benzodiazepines was associated with a significantly higher risk of SUD hospitalization (aHR, 1.17; 95% CI, 1.12-1.22), any hospitalization or death (aHR, 1.20; 95% CI, 1.17-1.24), and all-cause mortality (aHR, 1.39; 95% CI, 1.20-1.60). Use of antidepressants or antipsychotics was associated with a slight increase in risk of SUD hospitalization (aHR, 1.07; 95% CI, 1.03-1.11 and aHR, 1.05; 95% CI, 1.01-1.09) as well as any hospitalization or death (aHR, 1.10; 95% CI, 1.06-1.14 and aHR, 1.06; 95% CI, 1.03-1.10, respectively).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, use of lisdexamphetamine was associated with improved outcomes in persons with amphetamine or methamphetamine use disorders, encouraging the conduct of randomized clinical trials. Prescription benzodiazepine use was associated with poor outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2022.3788","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T11:00:56Z","timestamp":1668596456000},"page":"31","source":"Crossref","is-referenced-by-count":46,"title":["Association of Pharmacological Treatments and Hospitalization and Death in Individuals With Amphetamine Use Disorders in a Swedish Nationwide Cohort of 13\u202f965 Patients"],"prefix":"10.1001","volume":"80","author":[{"given":"Milja","family":"Hartikainen","sequence":"first","affiliation":[{"name":"Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland"},{"name":"Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Taipale","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland"},{"name":"Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"},{"name":"School of Pharmacy, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Tanskanen","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland"},{"name":"Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellenor","family":"Mittendorfer-Rutz","sequence":"additional","affiliation":[{"name":"Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"L\u00e4hteenvuo","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Tiihonen","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet & Centre for Psychiatry Research, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden"},{"name":"Neuroscience Center, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"yoi220077r2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.3758","article-title":"Evaluation of amphetamine-related hospitalizations and associated clinical outcomes and costs in the United States.","volume":"1","author":"Winkelman","year":"2018","journal-title":"JAMA Netw Open"},{"issue":"4","key":"yoi220077r3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s40263-020-00711-x","article-title":"Pharmacological treatment of methamphetamine\/amphetamine dependence: a systematic review.","volume":"34","author":"Siefried","year":"2020","journal-title":"CNS Drugs"},{"issue":"10","key":"yoi220077r4","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1111\/add.v114.10","article-title":"Mortality among people with regular or problematic use of amphetamines: a systematic review and meta-analysis.","volume":"114","author":"Stockings","year":"2019","journal-title":"Addiction"},{"issue":"March","key":"yoi220077r5","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.drugalcdep.2018.03.053","article-title":"Mortality and causes of death among people who inject amphetamine: a long-term follow-up cohort study from a needle exchange program in Sweden.","volume":"188","author":"\u00c5hman","year":"2018","journal-title":"Drug Alcohol Depend"},{"issue":"12","key":"yoi220077r6","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1111\/add.v114.12","article-title":"Pharmacotherapy for methamphetamine\/amphetamine use disorder\u2014a systematic review and meta-analysis.","volume":"114","author":"Chan","year":"2019","journal-title":"Addiction"},{"issue":"12","key":"yoi220077r7","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1001\/jamapsychiatry.2021.2588","article-title":"Methamphetamine use, methamphetamine use disorder, and associated overdose deaths among US adults.","volume":"78","author":"Han","year":"2021","journal-title":"JAMA Psychiatry"},{"issue":"May","key":"yoi220077r8","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2021.109001","article-title":"Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups\u2014United States, 2004-2019.","volume":"227","author":"Kariisa","year":"2021","journal-title":"Drug Alcohol Depend"},{"issue":"9","key":"yoi220077r9","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1001\/jamapsychiatry.2020.0246","article-title":"Neurobiology, clinical presentation, and treatment of methamphetamine use disorder: a review.","volume":"77","author":"Paulus","year":"2020","journal-title":"JAMA Psychiatry"},{"issue":"10209","key":"yoi220077r11","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1016\/S0140-6736(19)32230-5","article-title":"Responding to global stimulant use: challenges and opportunities.","volume":"394","author":"Farrell","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"yoi220077r12","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1056\/NEJMoa2020214","article-title":"Bupropion and naltrexone in methamphetamine use disorder.","volume":"384","author":"Trivedi","year":"2021","journal-title":"N Engl J Med"},{"issue":"3","key":"yoi220077r13","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1001\/jamapsychiatry.2019.3655","article-title":"Effects of mirtazapine for methamphetamine use disorder among cisgender men and transgender women who have sex with men: a placebo-controlled randomized clinical trial.","volume":"77","author":"Coffin","year":"2020","journal-title":"JAMA Psychiatry"},{"issue":"1","key":"yoi220077r14","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/add.2010.105.issue-1","article-title":"Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence.","volume":"105","author":"Longo","year":"2010","journal-title":"Addiction"},{"issue":"2","key":"yoi220077r15","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/clpt.2010.307","article-title":"A randomized, placebo-controlled trial of sustained-release dextroamphetamine for treatment of methamphetamine addiction.","volume":"89","author":"Galloway","year":"2011","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"yoi220077r16","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1111\/add.2013.108.issue-7","article-title":"Extended-release methylphenidate for treatment of amphetamine\/methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.","volume":"108","author":"Miles","year":"2013","journal-title":"Addiction"},{"issue":"9","key":"yoi220077r17","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1111\/add.2014.109.issue-9","article-title":"Sustained-release methylphenidate in a randomized trial of treatment of methamphetamine use disorder.","volume":"109","author":"Ling","year":"2014","journal-title":"Addiction"},{"issue":"1","key":"yoi220077r18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40199-015-0092-y","article-title":"Sustained-release methylphenidate in methamphetamine dependence treatment: a double-blind and placebo-controlled trial.","volume":"23","author":"Rezaei","year":"2015","journal-title":"Daru"},{"issue":"11","key":"yoi220077r19","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1176\/appi.ajp.2008.08020304","article-title":"Naltrexone for the treatment of amphetamine dependence: a randomized, placebo-controlled trial.","volume":"165","author":"Jayaram-Lindstr\u00f6m","year":"2008","journal-title":"Am J Psychiatry"},{"issue":"5","key":"yoi220077r20","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1176\/appi.ajp.2011.11071121","article-title":"Naltrexone implant for the treatment of polydrug dependence: a randomized controlled trial.","volume":"169","author":"Tiihonen","year":"2012","journal-title":"Am J Psychiatry"},{"issue":"7","key":"yoi220077r21","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1111\/add.2012.107.issue-7","article-title":"Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial.","volume":"107","author":"Elkashef","year":"2012","journal-title":"Addiction"},{"issue":"8","key":"yoi220077r22","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1007\/s00213-020-05563-3","article-title":"Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis.","volume":"237","author":"Tardelli","year":"2020","journal-title":"Psychopharmacology (Berl)"},{"key":"yoi220077r23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/nyas.2010.1187.issue-1","article-title":"Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies.","volume":"1187","author":"Herin","year":"2010","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"yoi220077r24","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-044696","article-title":"Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study.","volume":"11","author":"Ezard","year":"2021","journal-title":"BMJ Open"},{"issue":"1","key":"yoi220077r26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12911-015-0140-z","article-title":"From prescription drug purchases to drug use periods\u2014a second generation method (PRE2DUP).","volume":"15","author":"Tanskanen","year":"2015","journal-title":"BMC Med Inform Decis Mak"},{"key":"yoi220077r28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203241","article-title":"Medication for attention deficit-hyperactivity disorder and criminality.","volume":"367","author":"Lichtenstein","year":"2012","journal-title":"N Engl J Med"},{"issue":"4","key":"yoi220077r29","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S2215-0366(22)00015-3","article-title":"Real-world effectiveness of antipsychotic doses for relapse prevention in patients with first-episode schizophrenia in Finland: a nationwide, register-based cohort study.","volume":"9","author":"Taipale","year":"2022","journal-title":"Lancet Psychiatry"},{"issue":"2","key":"yoi220077r30","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/add.2014.109.issue-2","article-title":"Psychiatric comorbidity in treatment-seeking substance use disorder patients with and without attention deficit hyperactivity disorder: results of the IASP study.","volume":"109","author":"van Emmerik-van Oortmerssen","year":"2014","journal-title":"Addiction"},{"issue":"6","key":"yoi220077r31","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1111\/add.v117.6","article-title":"Real-world effectiveness of pharmacological treatments of opioid use disorder in a national cohort.","volume":"117","author":"Heikkinen","year":"2022","journal-title":"Addiction"},{"issue":"3","key":"yoi220077r32","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1111\/fcp.2016.30.issue-3","article-title":"Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.","volume":"30","author":"Rezaei","year":"2016","journal-title":"Fundam Clin Pharmacol"},{"issue":"8","key":"yoi220077r33","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1111\/add.v116.8","article-title":"Real-world effectiveness of pharmacological treatments of alcohol use disorders in a Swedish nation-wide cohort of 125?556 patients.","volume":"116","author":"Heikkinen","year":"2021","journal-title":"Addiction"},{"issue":"4","key":"yoi220077r34","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/add.2013.108.issue-4","article-title":"Aripiprazole for the treatment of methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.","volume":"108","author":"Coffin","year":"2013","journal-title":"Addiction"},{"issue":"1","key":"yoi220077r35","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1176\/ajp.2007.164.1.160","article-title":"A comparison of aripiprazole, methylphenidate, and placebo for amphetamine dependence.","volume":"164","author":"Tiihonen","year":"2007","journal-title":"Am J Psychiatry"},{"key":"yoi220077r36","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2147\/CLEP","article-title":"Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons.","volume":"8","author":"Taipale","year":"2016","journal-title":"Clin Epidemiol"},{"key":"yoi220077r27","doi-asserted-by":"crossref","DOI":"10.4135\/9781412993869","volume-title":"Fixed Effects Regression Models","author":"Allison","year":"2009"},{"key":"yoi220077r1","unstructured":"United Nations Office on Drugs and Crime. World Drug Report 2021. Publication No. E.21.XI.8. Published 2021. Accessed May 1, 2022. https:\/\/www.unodc.org\/unodc\/en\/data-and-analysis\/wdr2021.html"},{"key":"yoi220077r10","unstructured":"European Monitoring Centre for Drugs and Drug Addiction. Sweden Country Drug Report 2019. Published June 2019. Accessed August 12, 2022. https:\/\/www.emcdda.europa.eu\/publications\/country-drug-reports\/2019\/sweden_en"},{"key":"yoi220077r25","unstructured":"World Health Organization Collaborating Centre for Drug Statistics. The anatomical therapeutic chemical classification system\u2014structure and principles. Published 2011. Accessed May 5, 2022. https:\/\/www.whocc.no\/atc\/structure_and_principles\/"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2798882\/jamapsychiatry_hartikainen_2022_oi_220077_1698956649.2923.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T16:30:28Z","timestamp":1698942628000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2798882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2022.3788","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}