Pharmacological Treatment, Hospitalization, Death in Amphetamine Use Disorders

Investigators observed the combined use of lisdexamphetamine, buprenorphine, and 2 or more SUD medications associated with a significantly lower risk for any hospitalization or death compared with the same individual not taking the studied medication.

Improved outcomes among individuals with amphetamine or methamphetamine use disorders were associated with use of lisdexamphetamine. Poor outcomes in this patient population were associated with prescription benzodiazepine use. These are among the study findings published in the Journal of the American Medical Association Psychiatry.

Investigators in Sweden sought to assess the association between pharmacotherapies and hospitalization and death in individuals with amphetamine or methamphetamine use disorder. Primary endpoints were hospitalization due to substance use disorders (SUDs), any hospitalization, and death. The secondary endpoint was all-cause mortality.

The nationwide register-based cohort study included almost 14,000 individuals (mean age 34.4±13.0 years; 30.7% women) aged 16 to 64 years living in Sweden with a first-time diagnosis of amphetamine or methamphetamine use disorder.

This current study, conducted from July 2006 to December 2018, median follow-up time of 3.9 years (IQR 1.0-6.1 years), identified patients from nationwide registries of specialized outpatient care, disability pension, sickness absence, and inpatient care excluding previous diagnoses of bipolar disorder or schizophrenia (National Patient Register, the Causes of Death Register, the Longitudinal Integration Database for Health Insurance and Labor Market Studies register, and the Micro Data for Analyses of Social Insurance register).

Use of antidepressants were associated with an increase in risk for hospitalization due to SUD and any hospitalization or death.

Exposures included medications for SUDs or for attention-deficit/hyperactive disorder (ADHD), antidepressants, mood stabilizers, benzodiazepines and related drugs and antipsychotics.

Investigators found during follow-up, 54% were taking antidepressants, 43.7% benzodiazepines, 36.3% antipsychotics, 28.2% ADHD medications, 10.8% lisdexamphetamine. Additionally, 20.5% were taking SUD medications and 12.2% mood stabilizers.

They noted 74% were hospitalized due to SUDs. They found 82.3% were hospitalized due to any cause or died, and 9.5% died of any cause. They observed only lisdexamphetamine to be significantly associated with a decrease in SUD hospitalization (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.94), any hospitalization or death (aHR, 0.86; 95% CI, 0.78-0.95), and all-cause mortality (aHR, 0.43; 95% CI, 0.24-0.77).

They noted methylphenidate associated with lower all-cause mortality (aHR, 0.56; 95% CI, 0.43-0.74).

They found significantly higher risk for 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) associated with use of benzodiazepines.

Investigators observed the combined use of lisdexamphetamine, buprenorphine, and 2 or more SUD medications associated with a significantly lower risk for any hospitalization or death compared with the same individual not taking the studied medication.

They noted a slight increase with use of antidepressants or antipsychotics associated with a risk for SUD hospitalization, (aHR, 1.07; 95% CI, 1.03-1.11 and aHR, 1.05; 95% CI, 1.01-1.09, respectively), as did hospitalization or death (aHR, 1.10; 95% CI, 1.06-1.14 and aHR, 1.06; 95% CI, 1.03-1.10, respectively). Specifically, mirtazapine (aHR, 1.08; 95% CI, 1.00-1.15), venlafaxine (aHR, 1.13; 95% CI, 1.02-1.25), and citalopram (HR, 1.14; 95% CI, 1.00-1.29) associated with an increased risk for SUD hospitalization. They noted none of the most common antidepressants were associated with a reduced risk.

Study limitations include protopathic bias, data lacking on reduced amphetamine or methamphetamine consumption or abstinence, data lacking on effects of withdrawal symptoms, and data lacking on which medications were indicated for specific comorbidities.

Investigators concluded “Use of lisdexamphetamine was consistently associated with a reduction in risk of death and hospitalization in persons with amphetamine or methamphetamine.” They wrote “Use of antidepressants were associated with an increase in risk of hospitalization due to SUD and any hospitalization or death.” They found poor outcomes were associated with benzodiazepine use.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Heikkinen M, Taipale H, Tanskanen A, Mittendorfer-Rutz E, Lähteenvuo M, Tiihonen J. Association of pharmacological treatments and hospitalization and death in individuals with amphetamine use disorders in a Swedish nationwide cohort of 13 965 patients. JAMA Psychiatry. Published online November 16, 2022. doi:10.1001/jamapsychiatry.2022.3788