Background: Problematic high-dose benzodiazepine (BZD) and related Z-drug use for a long period is a substance use disorder previously found to be associated with adult attention-deficit/hyperactivity disorder (ADHD) and worse quality of life (QoL). Whether adult ADHD impacts QoL in high-dose BZD/Z-drug users has not been explored. Aim: The aim of the study was to explore the impact of adult ADHD on QoL in high-dose BZD and related Z-drug users. Methods: We recruited 393 patients (205 men and 188 women) consecutively admitted to the

Benzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1.The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales.

An effective approach in the treatment of benzodiazepine (BZD) overdosing and detoxification is flumazenil (FLU). Studies in chronic users who discontinued BZD in a clinical setting suggested that multiple slow bolus infusions of FLU reduce BZD withdrawal symptoms. The aim of this study was to confirm FLU efficacy for reducing BZD withdrawal syndrome by means of continuous elastomeric infusion, correlated to drugs plasma level and patients' compliance.Methods: Seven-day FLU 1 mg/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, and lorazepam were assessed by HPLC-MS/MS in serum of patients before and after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS).Results: Fourteen patients (mean age ± SD 42.5 ± 8.0 years, 5 male and 9 female), admitted to the hospital for high-dose BZD detoxification, were enrolled in the study. Serum FLU concentrations significantly decreased from 0.54 ± 0.33 ng/ml (mean ± SD) after 4 days of treatment to 0.1 ± 0.2 ng/ml at the end of infusion. Lormetazepam concentrations were 502.5 ± 610.0 ng/ml at hospital admission, 26.2 ± 26.8 ng/ml after 4 days, and 0 at the end of treatment. BWS values decreased during FLU treatment temporal period. FLU was well-tolerated by patients.Conclusions: Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms.

High-dose use of benzodiazepines (BZDs) and Z-drugs was found to be associated with adult attention deficit/hyperactivity disorder (ADHD) and multidomain cognitive deficits, but the interplay between these factors and its effect on quality of life (QoL) is unclear. We explored (a) whether cognitive dysfunction differs in high-dose BZD/Z-drug users with and without adult ADHD and (b) the impact of cognitive deficits and adult ADHD on QoL in this substance-use disorder (SUD). From January 2015 to December 2019, we recruited 207 high-dose BZD/Z-drug users seeking treatment. We assessed the presence of adult ADHD with a screening tool, which was validated in SUD patients, and collected demographic, clinical and QoL data from the 76 included patients. A neuropsychological battery explored five cognitive domains. We found that: (a) screening for adult ADHD was frequently positive; (b) Short Form-36 (SF-36), a self-administered QoL questionnaire, was worse than the general population and worse in patients positive (ADHD+) vs. those negative (ADHD−) to ADHD screening tool; (c) executive function was significantly worse in ADHD+ than ADHD− patients; (d) some SF-36 dimensions were negatively influenced by executive dysfunction; (e) multivariate analysis showed an interplay between adult ADHD and cognitive dysfunction in worsening QoL. We documented a complex interplay between adult ADHD, cognitive dysfunction and QoL in high-dose BZD/Z-drug users. Assessing adult ADHD, neuropsychological measures and QoL may offer a full scenario of these patients, who are frequently impaired in everyday activities. Future research should explore whether pharmacological treatment might improve cognitive dysfunction and QoL in this SUD.

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