Risk of Substance Use Disorder and Its Associations With Comorbidities and Psychotropic Agents in Patients With Autism.

Importance: The risk of substance use disorder (SUD) in patients with autism spectrum disorder (ASD) remains unclear. Objective: To investigate the risk of SUD in patients with ASD and its associations with comorbidities, psychotropic agents (PAs), and mortality. Design, Setting, and Participants: This retrospective, population-based, cohort study of 1 936 512 participants used data from the Taiwan National Health Insurance Research Database and was conducted from January 1, 2000, to December 31, 2015. Included participants attended at least 3 outpatient visits within the 1-year study period for symptomatic ASD as determined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Individuals diagnosed with ASD before 2000, those diagnosed with SUD before the first visit for ASD, and those with missing data were excluded from the analysis. Patients with ASD and non-ASD controls were matched 1:4 by age, sex, and index date. Exposures: Symptomatic ASD evaluated for at least 3 outpatient visits within the 1-year study period. Main Outcomes and Measures: Adjusted hazard ratios (aHRs) with 95% CIs for SUD, including alcohol use disorder (AUD) and drug use disorder (DUD), and the risk of mortality were calculated. Data were analyzed from March 1 to July 13, 2020. Results: A total of 6599 individuals with ASD (mean [SD] age, 11.9 [5.1] years; 5094 boys [77.2%]; mean [SD] follow-up period, 8.1 [8.3] years; median follow-up period, 4.3 [interquartile range [IQR], 2.3-5.3] years) and 26 396 controls (mean [SD] age, 12.1 [5.8] years; 20 376 boys [77.2%]; mean [SD] follow-up period, 8.6 [8.9] years; median follow-up period, 4.4 [IQR, 2.4-5.4] years) were enrolled in the study. According to multivariable-adjusted analysis, the aHRs for SUD (2.33; 95% CI, 1.89-2.87), AUD (2.07; 95% CI, 1.60-2.63), and DUD (3.00; 95% CI, 2.15-4.58) were significantly higher in the ASD group than in the non-ASD controls. The aHRs for SUD in the ASD subgroups with 1 PA (0.60; 95% CI, 0.43-0.66) and with multiple PAs (0.37; 95% CI, 0.28-0.49) were significantly lower than those in the ASD subgroup with no PAs. Comparisons between patients with ASD and non-ASD controls with the same comorbidities showed higher aHRs for SUD among patients with ASD (range, 1.17-2.55); moreover, the ASD subgroup not receiving any PAs had an aHR of 6.39 (95% CI, 5.11-7.87) for SUD when they had comorbid tic disorder and aHRs of 5.48 (95% CI, 5.12-5.70) for AUD and 5.42 (95% CI, 5.12-5.80) for DUD when they had comorbid impulse control disorder. The mortality risk was significantly higher in patients with ASD and concomitant SUD than in non-ASD controls without SUD (aHR, 3.17; 95% CI, 2.69-3.89). Conclusions and Relevance: These findings suggest that patients with ASD are vulnerable to the development of SUD. Comorbid ASD and SUD were associated with an increase in mortality risk.

Association of Cannabis Use With Self-harm and Mortality Risk Among Youths With Mood Disorders.

Importance: Cannabis use and cannabis use disorder (CUD) are common among youths and young adults with mood disorders, but the association of CUD with self-harm, suicide, and overall mortality risk is poorly understood in this already vulnerable population. Objective: To examine associations of CUD with self-harm, suicide, and overall mortality risk in youths with mood disorders. Design, Setting, and Participants: A population-based retrospective cohort study was performed using Ohio Medicaid claims data linked with death certificate data. The analysis included 204 780 youths (aged 10-24 years) with a diagnosis of mood disorders between July 1, 2010, and December 31, 2017, who were followed up to 365 days from the index diagnostic claim until the end of enrollment, the self-harm event, or death. Statistical analysis was performed from April 4 to July 17, 2020. Exposure: Physician-diagnosed CUD defined using outpatient and inpatient claims from 180 days prior to the index mood disorder diagnostic claim through the 365-day follow-up period. Main Outcomes and Measures: Nonfatal self-harm, all-cause mortality, and deaths by suicide, unintentional overdose, motor vehicle crashes, and homicide. Marginal structural models using inverse probability weights examined associations between CUD and outcomes. Results: This study included 204 780 youths (133 081 female participants [65.0%]; mean [SD] age at the time of mood disorder diagnosis, 17.2 [4.10] years). Cannabis use disorder was documented for 10.3% of youths with mood disorders (n = 21 040) and was significantly associated with older age (14-18 years vs 10-13 years: adjusted risk ratio [ARR], 9.35; 95% CI, 8.57-10.19; and 19-24 years vs 10-13 years: ARR, 11.22; 95% CI, 10.27-12.26), male sex (ARR, 1.79; 95% CI, 1.74-1.84), Black race (ARR, 1.39; 95% CI, 1.35-1.44), bipolar or other mood disorders (bipolar disorders: ARR, 1.24; 95% CI, 1.21-1.29; other mood disorders: ARR, 1.20; 95% CI, 1.15-1.25), prior history of self-harm (ARR, 1.66; 95% CI, 1.52-1.82), previous mental health outpatient visits (ARR, 1.26; 95% CI, 1.22-1.30), psychiatric hospitalizations (ARR, 1.66; 95% CI, 1.57-1.76), and mental health emergency department visits (ARR, 1.54; 95% CI, 1.47-1.61). Cannabis use disorder was significantly associated with nonfatal self-harm (adjusted hazard ratio [AHR], 3.28; 95% CI, 2.55-4.22) and all-cause mortality (AHR, 1.59; 95% CI, 1.13-2.24), including death by unintentional overdose (AHR, 2.40; 95% CI, 1.39-4.16) and homicide (AHR, 3.23; 95% CI, 1.22-8.59). Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models. Conclusions and Relevance: Cannabis use disorder is a common comorbidity and risk marker for self-harm, all-cause mortality, and death by unintentional overdose and homicide among youths with mood disorders. These findings should be considered as states contemplate legalizing medical and recreational marijuana, both of which are associated with increased CUD.

Prediction of psychiatric comorbidity on premature death in a cohort of patients with substance use disorders: a 42-year follow-up.

BACKGROUND: We need to better understand how the use of different substances and psychiatric comorbidity influence premature death generally and cause-specific death by overdose, intoxication and somatic disorders in people with substance use disorders. METHOD: A cohort of 1405 patients consecutively admitted to a Swedish detoxification unit for substance use disorders in 1970-1995 was followed-up for 42 years. Substances were identified by toxicological analyses. Mortality figures were obtained from a national registry. Causes of death were diagnosed by forensic autopsy in 594 patients deceased by 2012. Predictions were calculated by competing risks analysis. RESULTS: Forty-two per cent of the cohort died during follow-up; more men than women (46.3% vs 30.4%). The standardised mortality ratio (SMR) was calculated as the ratio of observed deaths in males and females in specific age groups in the cohort versus expected deaths in corresponding groups in the general population. SMR was 5.68 for men (CI 95%; 5.04-6.11) and 4.98 (CI 95%; 4.08-5.88) for women. The crude mortality rate (number of deaths divided by number of person observation years) was 2.28% for men and 1.87% for women. Opiates predicted increased risk of premature death while amphetamine and cannabis predicted lower risk. Comorbid psychiatric disorders were identified in 378 cases and personality disorders in 763 cases. Primary psychoses or mood/depression and anxiety disorders predicted a higher risk of premature mortality. Death by overdose was predicted by male gender, younger age at admission to substance treatment, opiate use, and comorbid depression and anxiety syndromes. Cannabis and amphetamine use predicted a lower risk of overdose. Death by intoxication was predicted by male gender, use of sedatives/hypnotics or alcohol/mixed substances, primary psychoses and depression/anxiety syndromes. Premature death by somatic disorder was predicted by male gender and alcohol/mixed abuse. CONCLUSION: Psychiatric comorbid disorders were important risk factors for premature drug-related death. Early identification of these factors may be life-saving in the treatment of patients with substance use disorders.

Total population-based study of the impact of substance use disorders on the overall survival of psychiatric inpatients.

BACKGROUND: Patients with severe mental illness have a shortened lifespan, and substance use disorder (SUD) is an especially important diagnosis in this respect. There have been no studies comparing directly SUD to other diagnoses in a nationwide cohort. AIMS: To directly compare differences in mortality rates of psychiatric inpatients with a discharge diagnosis of SUD versus other psychiatric diagnoses. METHODS: A register-based study was made of all patients admitted to psychiatric hospitals in Iceland between 1983 and 2007. Patients were grouped according to discharge diagnoses. Survival with respect to SUD was compared using Cox-proportional hazard ratio, excluding those with an organic mental disorder. Furthermore, the survival of patients with SUD and co-morbid diagnoses was evaluated. RESULTS: A total of 14,281 patients (over the age of 18 years) were admitted to a psychiatric hospital in Iceland during the study period, with a total of 156,356 years of follow-up. For both men and women, a diagnosis of SUD conferred similar mortality as a diagnosis of schizophrenia without SUD, while individuals with a diagnosis of a mood disorder or "other disorders" had significantly lower mortality than SUD. For men with SUD, a co-occurring mental disorder was associated with an increased risk of dying, however, this was not found for women. CONCLUSIONS: SUD was the psychiatric diagnosis that had the highest mortality rate among psychiatric inpatients, in both men and women. An additional psychiatric diagnosis on a pre-existing SUD diagnosis did increase the risk for men but not women.

The hotel study: multimorbidity in a community sample living in marginal housing.

OBJECTIVE: The health of people living in marginal housing is not well characterized, particularly from the perspective of multimorbid illness. The authors investigated this population in a community sample. METHOD: A prospective community sample (N=293) of adults living in single-room occupancy hotels was followed for a median of 23.7 months. Assessment included psychiatric and neurological evaluation, multimodal MRI, and viral testing. RESULTS: Previous homelessness was described in 66.6% of participants. Fifteen deaths occurred during 552 person-years of follow-up. The standardized mortality ratio was 4.83 (95% CI=2.91-8.01). Substance dependence was ubiquitous (95.2%), with 61.7% injection drug use. Psychosis was the most common mental illness (47.4%). A neurological disorder was present in 45.8% of participants, with definite MRI findings in 28.0%. HIV serology was positive in 18.4% of participants, and hepatitis C virus serology in 70.3%. The median number of multimorbid illnesses (from a list of 12) was three. Burden of multimorbidity was significantly correlated with lower role functioning score. Comorbid addiction or physical illness significantly decreased the likelihood of treatment for psychosis but not the likelihood of treatment for opioid dependence or HIV disease. Participants who died during follow-up appeared to have profiles of multimorbidity similar to those of the overall sample. CONCLUSIONS: This marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.

Unintentional prescription opioid-related overdose deaths: description of decedents by next of kin or best contact, Utah, 2008-2009.

BACKGROUND: Little is known about the characteristics that may predispose an individual to being at risk for fatal overdose from prescription opioids. OBJECTIVE: To identify characteristics related to unintentional prescription opioid overdose deaths in Utah. DESIGN: Interviews were conducted (October 2008-October 2009) with a relative or friend most knowledgeable about the decedent's life. SUBJECTS: Analyses involved 254 decedents aged 18 or older, where cause of death included overdose on at least one prescription opioid. KEY RESULTS: Decedents were more likely to be middle-aged, Caucasian, non-Hispanic/Latino, less educated, not married, or reside in rural areas than the general adult population in Utah. In the year prior to death, 87.4 % were prescribed prescription pain medication. Reported potential misuse prescription pain medication in the year prior to their death was high (e.g., taken more often than prescribed [52.9 %], obtained from more than one doctor during the previous year [31.6 %], and used for reasons other than treating pain [29.8 %, almost half of which "to get high"]). Compared with the general population, decedents were more likely to experience financial problems, unemployment, physical disability, mental illness (primarily depression), and to smoke cigarettes, drink alcohol, and use illicit drugs. The primary source of prescription pain medication was from a healthcare provider (91.8 %), but other sources (not mutually exclusive) included: for free from a friend or relative (24 %); from someone without their knowledge (18.2 %); purchase from a friend, relative, or acquaintance (16.4 %); and purchase from a dealer (not a pharmacy) (11.6 %). CONCLUSIONS: The large majority of decedents were prescribed opioids for management of chronic pain and many exhibited behaviors indicative of prescribed medication misuse. Financial problems, unemployment, physical disability, depression, and substance use (including illegal drugs) were also common.

Mortality among substance-using mothers in California: a 10-year prospective study.

AIMS: To examine mortality rates and causes of death among a cohort of substance-using mothers and to identify risk factors that predict mortality. DESIGN, SETTING, PARTICIPANTS: This is a prospective study of a cohort of 4447 substance-using mothers (pregnant or parenting) who were enrolled during 2000-02 in 40 drug abuse treatment programs across California. METHODS: All mothers were assessed at baseline using the Addiction Severity Index. Mortality data were obtained from the National Death Index and causes of death were coded using ICD-10. Standardized mortality ratios (SMR) were calculated relative to women in the general population adjusted for age. Proportional hazard (Cox) regression was used to identify risk factors predicting death. RESULTS: At the end of 2010, 194 deaths were confirmed, corresponding to a crude mortality rate of 4.47 per 1000 person-years and SMR of 8.4 (95% confidence interval: 7.2-9.6). Drug overdose (28.8%), cardiovascular disease (10%), and alcohol or drug disorders (8.9%) were the leading causes of death. Baseline factors associated with higher mortality included older age, being white (relative to African American or Hispanic), heroin, alcohol, cocaine or marijuana (relative to methamphetamine) as the primary drug problem, drug injection and greater severity of employment, medical/health and psychiatric problems. CONCLUSIONS: Substance-using mothers have 8.4 times the mortality than that observed among US women of similar age. Greater severity of employment, medical/health and psychiatric problems contributed to the elevated mortality.

Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers: a prospective longitudinal study 1970-2006.

BACKGROUND: Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades. METHODS: Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis. RESULTS: Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death. CONCLUSIONS: The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.