Sex-specific Associations of Alcohol Withdrawal in Patients Admitted for the Treatment of Alcohol Use Disorder

Abstract

Objectives: There are sex differences in the pattern of alcohol consumption and in the complications of alcohol use disorder (AUD). We aimed to identify sex-specific differences in the factors associated with alcohol withdrawal syndrome (AWS) among patients that requested a first treatment for AUD. Methods: We enrolled 313 patients (75% men) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis that started treatment between 2014 and 2016. We collected socio-demographics, the type and amount of alcohol and other substances consumed, and clinical and laboratory parameters. According to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD criteria, AWS occurred when patients experienced 2 or more clinical signs/symptoms and/or consumed alcohol to relieve symptoms. Logistic regression models were used to determine factors associated with AWS according to sex. Results: The median age of participants was 50 years (interquartile range [IQR]: 43–54 years). The median age of starting alcohol consumption was 16 years (IQR: 14–18 years). Notably, 69% of participants smoked tobacco, and 61% had a family history of AUD; 18% currently used cannabis, and 7.7% used cocaine. Overall, 73% of patients exhibited AWS criteria, and men (76.5%) were more likely than women (64.6%) to report AWS (P = 0.038). In the adjusted analysis, factors associated with AWS were the age at starting alcohol consumption (odds ratio [OR] for every 5 years = 1.89, 95% confidence interval [CI]: 1.69–2.08), and cannabis use (OR = 2.8, 95% CI: 1.04–7.7) in men, and a family history of AUD in women (OR = 2.85 95% CI: 1.07–7.54). Conclusions: factors associated with AWS differ by sex which may have clinical implications for proactive management of AWS during treatment for AUD.

Alcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey

“…Studies that incorporate item response theory models could shed light on the extent to which each withdrawal symptom contributes to the AWS diagnosis. Our finding of increased odds of AWS among males is consistent with conclusions from prior studies (Desmukh et al, 2003;Martin et al, 2018;Sanvisens et al, 2021;Schuckit et al, 2003). This contrasts with the conclusions of a review that neither age nor gender are significant correlates of alcohol withdrawal (Goodson et al, 2014), though the studies reviewed there focused on specific severe withdrawal symptoms (e.g., delirium tremens), rather than the withdrawal syndrome per se.…”

Behavioral characterization of withdrawal following chronic voluntary ethanol consumption via intermittent two‐bottle choice points to different susceptibility categories

“…Evaluation of the severity in each test revealed that 52% of the EtOH‐exposed mice had a high SS, and only 16% of the mice in the EtOH group had above‐median severity in all behavioral metrics. This is consistent with human population studies that have found that only a subset of individuals with an AUD exhibit AWS, with anxiety being among the most common symptoms of alcohol withdrawal (Caetano et al, 1998; Hall & Zador, 1997; Sanvisens et al, 2021). Therefore, preclinical investigators in the alcohol field are exhorted to take these percentages into consideration when determining sample sizes and designing experiments to examine EtOH withdrawal.…”

Sex difference in alcohol withdrawal syndrome: a scoping review of clinical studies

“…Gómez-Méndez et al ( 67 ) reported that among patients admitted with AWS, whether primary (as reason for admission) or secondary diagnosis of AWS, 88% (49,646/56,393) of them were males. Sanvisens et al ( 8 ) conducted a study with patients who had requested treatment for AUD and found that males [76.5% (179/234)] experience AWS more than females [64.6% (51/79), p = 0.038]. Salottolo et al ( 54 ) reported that among 28,101 patients [57.94% (16,140/28,101) males, 42.06% (11,715/28,101) females] admitted to trauma centers, patients who developed AWS were mostly males [205/246 (83.33%), p < 0.001].…”

“…Schuckit et al ( 39 ) compared 160 men and 51 women with severe AWS, the two groups were not significantly different in the age of onset of alcohol dependence (males vs. females: 24.5 ± 8.9 vs. 23.5 ± 8.8 years), years of heavy drinking (14.2 ± 10.0 vs. 11.0 ± 8.5), frequency of drinking (6.0 ± 1.8 vs. 5.4 ± 2.1 days per week), and total number of alcohol use problems (33.3 ± 6.2 vs. 32.5 ± 6.2). Family history of AUD was found to be a risk factor for AWS in women (OR = 2.85, 95% CI: 1.07–7.54) ( 8 ) while amount of alcohol consumption was a risk factor for AWS in both men and women, although it was more likely in women ( 75 ). Earlier onset of alcohol consumption (OR for every 5 years = 1.89, 95% CI:1.69–2.08) was associated with increased probability of AWS in men ( 8 ).…”

“…Approximately 50% of middle-class, highly functioning individuals with alcohol use disorder (AUD) experience AWS, and more than 80% of hospitalized AUD patients may experience alcohol withdrawal ( 5 ). Even though AWS is highly prevalent and causes significant morbidity and mortality, there is a dearth of information about its prevalence among women or sex-difference in clinical manifestations, treatment response or outcome ( 7 , 8 ).…”