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Adult Attention-Deficit/Hyperactivity Disorder and Quality of Life in High-Dose Benzodiazepine and Related Z-Drug Users

Authors:
Fabio Lugoboni at Azienda Ospedaliera Universitaria Integrata Verona
Fabio Lugoboni
Anna Bertoldi at Azienda Ospedaliera Universitaria Integrata Verona
Anna Bertoldi
Rebecca Casari at Azienda Ospedaliera Universitaria Integrata Verona
Rebecca Casari
Elisa Mantovani at University of Verona
Elisa Mantovani
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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 Department of Medicine, Addiction Medicine Unit, Verona University Hospital, Italy, from July 2016 to July 2019 for detoxification from high-dose BZD or Z-drug dependence. Demographic and clinical variables and QoL measures were recorded. The World Health Organization ADHD Self-Report Scale version 1.1 Symptom Checklist Part A was used to detect adult ADHD. Results: In our sample, 39.4% of patients were positive to adult ADHD testing (ADHD+), with some clinical features differing in comparison to patients negative to ADHD testing (ADHD-). QoL was worse in high-dose BZD/Z-drug users than the general population. The ADHD+ group showed significantly worse QoL measures than the ADHD- group. Multivariate analysis, including potential covariates showed adult ADHD and age to have the most robust and consistent positive effect for age (i.e., higher QoL) and negative effect for ADHD (i.e., lower QoL) on QoL measures. Conclusions: Adult ADHD is associated with worse QoL measures in high-dose BZD/Z-drug users. Future studies should explore whether appropriate BZD/Z-drug detoxification might improve QoL measures and whether the most appropriate detoxification protocol differs in ADHD+ versus ADHD- populations.
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Research Article
Eur Addict Res 2020;26:274–282
Adult Attention-Deficit/Hyperactivity Disorder
and Quality of Life in High-Dose Benzodiazepine
and Related Z-Drug Users
Fabio Lugoboni
a Anna Bertoldi
a Rebecca Casari
a Elisa Mantovani
b
Laura Morbioli
a, b Stefano Tamburin
b
aDepartment of Medicine, Addiction Medicine Unit, Verona University Hospital, Verona, Italy; bDepartment of
Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Received: January 27, 2020
Accepted: April 10, 2020
Published online: June 22, 2020
Dr. Stefano Tamburin
Department of Neurosciences, Biomedicine and Movement Sciences
University of Verona
Piazzale Scuro 10, IT–37134 Verona (Italy)
stefano.tamburin @ univr.it
© 2020 S. Karger AG, Basel
karger@karger.com
www.karger.com/ear
DOI: 10.1159/000507852
Keywords
Addiction · Attention-deficit/hyperactivity disorder ·
Benzodiazepine · Patient-centered outcomes · Quality of
life · Substance use disorder
Abstract
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 atten-
tion-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 re-
cruited 393 patients (205 men and 188 women) consecutive-
ly admitted to the Department of Medicine, Addiction Med-
icine Unit, Verona University Hospital, Italy, from July 2016 to
July 2019 for detoxification from high-dose BZD or Z-drug
dependence. Demographic and clinical variables and QoL
measures were recorded. The World Health Organization
ADHD Self-Report Scale version 1.1 Symptom Checklist Part
A was used to detect adult ADHD. Results: In our sample,
39.4% of patients were positive to adult ADHD testing
(ADHD+), with some clinical features differing in comparison
to patients negative to ADHD testing (ADHD−). QoL was
worse in high-dose BZD/Z-drug users than the general pop-
ulation. The ADHD+ group showed significantly worse QoL
measures than the ADHD− group. Multivariate analysis, in-
cluding potential covariates showed adult ADHD and age to
have the most robust and consistent positive effect for age
(i.e., higher QoL) and negative effect for ADHD (i.e., lower
QoL) on QoL measures. Conclusions: Adult ADHD is associ-
ated with worse QoL measures in high-dose BZD/Z-drug us-
ers. Future studies should explore whether appropriate BZD/
Z-drug detoxification might improve QoL measures and
whether the most appropriate detoxification protocol dif-
fers in ADHD+ versus ADHD− populations.
© 2020 S. Karger AG, Basel
Introduction
Benzodiazepines (BZDs) and BZD-related Z-drugs are
gamma-amino-butyric acid type A-positive allosteric
modulators that are widely prescribed worldwide for anx-
iety and insomnia [1, 2]. Long-term use of BZDs and re-
lated Z-drugs is reported in 6–76% of patients [3], with
moderate-to-severe symptoms of withdrawal in 15–44%
[4] and misuse or dependence in 3–4% [1].
The problematic use of BZDs and Z-drugs at high dos-
es and for a long period of time is a substance use disorder
... Country of the study Asia and Australia (n = 7) Harnod et al., 2015;Hata et al., 2018;Kim et al., 2017;Rintoul et al., 2013;Takeshima et al., 2016;Tien et al., 2020;Wen et al., 2014 Canada (n = 3) Egan et al., 2001;Sketris et al., 1985;Sullivan & Sellers, 1992 France (n = 2) Etchepare et al., 2016;Imbert et al., 2016 Germany (n = 4) Brinkers et al., 2016;Holzbach et al., 2010;Janhsen et al., 2015;Kaendler et al., 1996 BeNeLux (n = 2) Cloos et al., 2015;Voshaar et al., 2003 Mediterranean Europe (n = 12) Faccini et al., 2016Faccini et al., , 2019Federico et al., 2020Federico et al., , 2017Lekka et al., 1997Lekka et al., , 2002Lugoboni et al., 2020Lugoboni et al., , 2014Lugoboni et al., , 2018Martinez-Cano et al., 1996;Quaglio et al., 2012;Tamburin et al., 2017 Scandinavia (n = 12) Andenaes et al., 2016;Bajwah et al., 2018;Bjerrum et al., 1994;Fredheim et al., 2019Fredheim et al., , 2020Fride Tvete et al., 2015;Johansson et al., 2003;Neutel et al., 2012;Nordfjaern et al., 2014Nordfjaern et al., , 2013Sidorchuk et al., 2018;Vorma et al., 2003 South America (n = 1) Moreno-Gutíerrez et al., 2020 ...
... Switzerland (n = 4) Liebrenz, Schneider et al., 2015;Liebrenz et al., 2016aLiebrenz et al., , 2016b UK (n = 2) Perera & Jenner, 1987;Seivewright & Dougal, 1993 USA (n = 7) Conry et al., 2009;Ellinwood et al., 1990;Hanlon et al., 2009;Hermos et al., 2007Hermos et al., , 2005Kroll et al., 2016;Soumerai et al., 2003 Not applicable (n = 2) Alexander & Perry, 1991;Teboul & Chouinard, 1991 Type of study Systematic review (n = 5) Alexander & Perry, 1991;Brinkers et al., 2016;Janhsen et al., 2015;Kim et al., 2017;Teboul & Chouinard, 1991 Randomized controlled trial (n = 2) Conry et al., 2009;Ellinwood et al., 1990 Epidemiological study (n = 13) Andenaes et al., 2016;Bajwah et al., 2018;Egan et al., 2001;Etchepare et al., 2016;Federico et al., 2017;Hanlon et al., 2009;Harnod et al., 2015;Holzbach et al., 2010;Johansson et al., 2003;Nordfjaern et al., 2014Nordfjaern et al., , 2013Rintoul et al., 2013;Soumerai et al., 2003 National or large registry (n = 9) Cloos et al., 2015;Fredheim et al., 2019Fredheim et al., , 2020Fride Tvete et al., 2015;Moreno-Gutíerrez et al., 2020;Neutel et al., 2012;Sidorchuk et al., 2018;Takeshima et al., 2016;Wen et al., 2014 Local register (n = 8) Bjerrum et al., 1994;Faccini et al., 2016;Federico et al., 2020;Hata et al., 2018;Hermos et al., 2007;Lugoboni et al., 2020Lugoboni et al., , 2014Tamburin et al., 2017; Selected patients (n = 20) Faccini et al., 2019;Hermos et al., 2005;Imbert et al., 2016;Kaendler et al., 1996;Kroll et al., 2016;Lekka et al., 1997Lekka et al., , 2002Liebrenz, Schneider et al., 2015;Liebrenz et al., 2016aLiebrenz et al., , 2016bLugoboni et al., 2018;Martinez-Cano et al., 1996;Perera & Jenner, 1987;Quaglio et al., 2012;Seivewright & Dougal, 1993;Sullivan & Sellers, 1992;Tien et al., 2020;Vorma et al., 2003;Voshaar et al., 2003 Selected physicians (n = 1) Sketris et al., 1985 Length of follow-up Less than 3 months (n = 4) Andenaes et al., 2016;Bjerrum et al., 1994;Ellinwood et al., 1990;Etchepare et al., 2016 3 months to 1 year (n = 16) Conry et al., 2009;Egan et al., 2001;Faccini et al., 2016;Federico et al., 2017;Holzbach et al., 2010;Johansson et al., 2003;Quaglio et al., 2012;Seivewright & Dougal, 1993;Lekka et al., 1997;Lugoboni et al., 2014, Neutel et al., 2012Perera & Jenner, 1987;Sketris et al., 1985;Tamburin et al., 2017;Vorma et al., 2003;Wen et al., 2014 (Continues) CLOOS ET AL. ...
... More than 1 year (n = 30) Bajwah et al., 2018;Cloos et al., 2015;Faccini et al., 2019;Fredheim et al., 2019Fredheim et al., , 2020Fride Tvete et al., 2015;Hanlon et al., 2009;Harnod et al., 2015;Hata et al., 2018;Hermos et al., 2007Hermos et al., , 2005Imbert et al., 2016;Janhsen et al., 2015;Kaendler et al., 1996;Kroll et al., 2016;Lekka et al., 2002;Liebrenz, Schneider et al., 2015;Liebrenz et al., 2016aLiebrenz et al., , 2016bMoreno-Gutíerrez et al., 2020;Nordfjaern et al., 2014Nordfjaern et al., , 2013Rintoul et al., 2013;Sidorchuk et al., 2018;Soumerai et al., 2003;Sullivan & Sellers, 1992;Takeshima et al., 2016;Tien et al., 2020;Voshaar et al., 2003 Not applicable (n = 8) Alexander & Perry, 1991;Brinkers et al., 2016;Federico et al., 2020;Kim et al., 2017;Lugoboni et al., 2020Lugoboni et al., , 2018Martinez-Cano et al., 1996;Teboul & Chouinard, 1991 Characteristics of study population References ...
Benzodiazepine high‐doses: The need for an accurate definition
Article
Full-text available
  • Jul 2021
Objectives A clear definition of what we understand of high‐dose misuse or of a ‘markedly increased dose’ (as stated by the DSM‐5) is important and past definitions may be inadequate. The aim of this review is to describe the different definitions used and to test these definitions for their accuracy. Methods A narrative PubMed literature review was conducted based on articles published between 1 January 1990 and 31 December 2020 describing benzodiazepines (in MeSH Terms or MeSH Major Topic) and high‐dose (or high‐dosage). Specific definitions were applied to a population sample to show how definitions affect high‐dose benzodiazepine prevalence. Results Multiples of an equivalent‐diazepam dose or of the World Health Organization ‘defined daily dosage’ were used more frequently than the overstep of the recommended maximum therapeutic dosage as a cut‐off point. Conclusion High‐dose use is rare but the prevalence in the general population varies among studies, mainly due to different definitions, making both clinical and epidemiological comparisons between studies difficult. Defining a high‐dose user as a person who takes at least a higher dose than the maximum usual therapeutic dose over a defined period of time therefore appears to be clinically more consistent.
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... 4 In Italy, lormetazepam has also shown to be the most abused intravenous drug for heroin addicts. 5 Istvan and colleagues also highlight the fact that addiction and abuse are prevalent in populations suffering from mental illnesses. In our experience, this has not been confirmed: about half of our patients had no history of psychiatric illnesses, nor a history of addiction to illicit substances or alcohol. ...
... 2,6 Lastly, regarding zolpidem's hazardousness, we would like to report the fact that zolpidem was significantly preferred by addicts with a positive ADHD test result. 5 These data should be kept in mind by institutions and services that study and handle neurodevelopmental issues. ...
Zolpidem: A masked hero. A reply to ZORRO study
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We have read the article by Istvan and colleagues, which recently appeared on your Journal, 1 with great interest. Among doctors, the use of zolpidem has been driven by the still-widespread false belief that, since zolpidem is not chemically a benzodiazepine, it cannot lead to addiction and tolerance. Indeed, it took almost 30 years from when the drug was introduced on the market for pharmacovigilance authorities of various countries to start taking action in regulating its use, as described by Istvan and colleagues. However, due to the fact that our operating unit, which is entirely dedicated to the abuse of medications, has treated an extremely high number of cases of addiction to high doses of benzodiazepines and related hypnotics, we would like to contribute to better highlighting certain characteristics of zolpidem and its potential as a substance of abuse. In their paper, Istvan and colleagues hint at the similarities between the regulation policies of flunitrazepam and zolpidem to draw conclusions about zolpidem's use. Italy has enacted the most restrictive regulations in the world on flunitrazepam, although this did not avoid that its use and abuse would overflow towards other molecules, starting from lormetazepam. Indeed, of the about 1400 cases of hospitalization for addiction to high doses of benzodiazepines and the like in our institution, none were due to flunitrazepam, while more than half of them were due to lormetazepam. Zolpidem was in fourth place among the 29 molecules present on the Italian market. 2 Furthermore, we believe the term "Z-drugs" to be inappropriate: zolpidem, zopiclone, and zaneplon all have different chemical structures, they bind to different receptors, and they have completely different abuse potentials. 3 Indeed, both zopiclon and zaneplon were virtually absent from the cases that were brought to the attention of our institution, albeit both molecules being commonly used in Italy. Lormetazepam, which is vastly prescribed by French doctors, deserves a separate discussion. Reports about its peculiar addictiveness are quite scarce in literature and virtually only come from Italy and Spain, which to our knowledge are the only countries in which the drug is sold in the form of drops. Of the cases we treated, 99% of the abusers that were hospitalized for addiction to lormetazepam were addicted to its soluble formula, unlike all other molecules for which tablets were found to be the most addictive. 3 This phenomenon is still unclear, but it is so evident in Italy that other countries should beware of introducing such a formula. 4 In Italy, lormetazepam has also shown to be the most abused intravenous drug for heroin addicts. 5 Istvan and colleagues also highlight the fact that addiction and abuse are prevalent in populations suffering from mental illnesses. In our experience, this has not been confirmed: about half of our patients had no history of psychiatric illnesses, nor a history of addiction to illicit substances or alcohol. 2,6 Lastly, regarding zolpidem's hazardousness, we would like to report the fact that zolpidem was significantly preferred by addicts with a positive ADHD test result. 5 These data should be kept in mind by institutions and services that study and handle neu-rodevelopmental issues. We would like to conclude with an appeal regarding drug regulation policies.
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... Failure to adhere to recommendations and contraindications in the product label can occur in patients at risk of drug-drug interactions, patients with certain pre-existing medical conditions, or patients who are at a high risk for treatment-related adverse events (74,75). For instance, high-dose use of BZDs and ZDs were found to be associated with attention deficit hyperactivity disorder (ADHD) (103), and use of high dose levels of long-acting BZDs, short-acting BZDs and Z-drugs were all found to significantly increase the risk of fall-related injuries requiring hospitalization in people aged 65 years and older (104). Due to the increased risk of falls, care is recommended when using BZDs in elderly subjects (27). ...
Long-term use of benzodiazepines in chronic insomnia: a European perspective
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Chronic insomnia occurs in ~10% of the general population and has numerous negative health effects. The recommended first line treatment of cognitive behavior therapy for insomnia is not widely available for patients in Europe, so pharmacotherapies such as benzodiazepine receptor agonist agents (benzodiazepines and Z-drugs) are commonly used. However, their use is only recommended for ≤4 weeks due to unproven long-term efficacy in treatment of chronic insomnia, and the risk of tolerance, and the potential for dependence and misuse. In Europe, recommendations limiting the use of benzodiazepines (lowest dose and shortest duration) in chronic insomnia are not always followed, likely due to the lack of approved effective alternative therapies. Here we present a recent pilot survey of the pharmacological treatment landscape in chronic insomnia in five European countries (France, Germany, Italy, Spain, and the United Kingdom) and physicians’ attitude toward treatment. The results suggest that benzodiazepines and Z-drugs are the most widely used treatments in chronic insomnia and are being used for longer than their recommended duration. Country variations in prescription rates were observed. Due to the known association between long-term benzodiazepine use and potential for developing dependence, further analysis of the literature was performed on the use and misuse of benzodiazepines. The results show that long-term use of benzodiazepines is associated with multiple consequences of treatment, including dependence, but also that previous use of benzodiazepines may increase the risk of opioid use disorder.
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... There were many studies among patients with alcohol use disorder over the years, showing similar results with a high ADHD prevalence (about 20%) [25,[29][30][31][32][33]. Recent studies in patients with benzodiazepine use disorder show even higher ADHD prevalence rates, which lie between 31% [34] and 39% [35,36], but there are also studies in populations of patients with cocaine use disorder showing high ADHD prevalence between 14% [37] and 20% [38]. Thus, people with adult ADHD might adjust their substance abuse to their most disruptive ADHD symptoms. ...
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(1) Background: Attention deficit hyperactivity disorder (ADHD) is a common comorbid condition in opioid use disorder (OUD) and is associated with a more severe course of substance use. Patients with severe OUD who have not responded to oral opioid maintenance treatment can be treated with intravenous diamorphine up to three times per day. Here, we investigated the prevalence of ADHD among patients undergoing either daily diamorphine maintenance treatment or daily oral opioid maintenance treatment. (2) Methods: We assessed all participants with the WURS-k and the ADHD-SR. The Diagnostic Interview for ADHD in Adults (DIVA) was performed with all participants who met the cut-off in the WURS-k and/or ADHD-SR. (3) Results: The overall prevalence of ADHD was 17.9%. Prevalence of ADHD among patients undergoing daily diamorphine maintenance treatment was 14.3%. Prevalence of ADHD among patients undergoing daily oral opioid maintenance treatment was 20.3%. The combined presentation of ADHD was the most prevalent condition. In urine samples of participants with comorbid ADHD, heroin was detected the most and cocaine the least frequently. (4) Conclusions: Almost one out of five patients with OUD suffered from comorbid ADHD. In 83.3%, ADHD had not been diagnosed prior to participation in this study. Thus, patients with SUD could benefit from being routinely screened for ADHD.
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... Our vision, as a natural consequence of several decades of experience in the study and treatment of smoking and SUDs, which in recent years has increasingly involved the evaluation of the impact of adult ADHD on all behaviors of abuse [28,46,47], leads us to summarize the problem of the relationship between ADHD, smoking, and SUDs, in the following key points: ...
Combined Prevention for Substance Use and Mental Health Problems in Youth: A Glance at Two Conditions at High Risk for Addiction
Chapter
  • May 2022
Attention-deficit hyperactivity disorder (ADHD) is a widespread neurodevelopmental disorder in children and adolescents, persisting into adulthood in a majority of them. The discovery of the persistence of ADHD into adolescence and adulthood has progressively oriented the interest of researchers towards the study of its implications for the development of different forms of psychological distress. Comorbidity between ADHD and other disorders is particularly frequent, especially for internalizing and externalizing disorders. Also, ADHD and substance use disorders (SUDs) commonly co-occur in adult population. It has not yet been clarified to what extent ADHD pharmacological treatment contributes to the development of SUDs. On the contrary, treating ADHD patients with methylphenidate may reduce their risk for SUD. Adolescents exhibit greater sensitivity than adults to nicotine reinforcement, and ADHD increases the risk for early-onset smoking. ADHD, especially when comorbid with tobacco abuse, is an important condition to monitor, because an early nicotine exposure could be the gateway to other addictive behaviors. Early-onset SUD is associated with elevated rates of risk behaviors and poor outcomes, including, but not limited to, suicidal behavior, academic failure, and job failure. Neuropsychiatrists dealing with ADHD should carefully monitor the possible copresence of ADHD and nicotine, in an attempt to prevent the development of SUD and other behavioral problems in these high-risk young patients.
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... Then, among all patients prescribed any benzodiazepines, the aim was to report the dose, the percentage of patients prescribed long-term benzodiazepines, the percentage with a benzodiazepine dose reduction, and the percentage switched to longacting benzodiazepines. Although patients taking higher dosages of benzodiazepines may tolerate larger reductions better than patients taking lower dosages (15), definitions of high dose range from .10 mg to .50 mg diazepam-equivalent daily dose (EDD) (16)(17)(18)(19). Dose reduction and switch to long-acting benzodiazepines are important because clinical guidelines recommend that patients discontinue long-term benzodiazepine use by gradual tapering combined with this switch (20). ...
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Objective: Although long-term benzodiazepine use is not recommended, patients are often prescribed benzodiazepines for >30 days (long-term use). Data from the Veterans Health Administration (VHA) may inform efforts to discontinue such use. This study sought to describe benzodiazepine use and discontinuation among VHA patients and compared patients who continued and discontinued use. Methods: The study used nationwide electronic health record data for all VHA-enrolled patients (age ≥18) from fiscal year (FY) 2019 (N=6,032,613). The primary outcome, benzodiazepine discontinuation, was defined as no prescription refill for 120 days. Results: In FY2019, 3.5% of VHA enrollees were prescribed benzodiazepines for >30 days, which was 72.0% of those prescribed benzodiazepines. One-third of veterans prescribed long-term benzodiazepines discontinued use. Continuation was more likely among patients who were older, not Black, taking benzodiazepines longer, and taking higher doses. When demographic factors were controlled, patients who continued long-term use were more likely to have a diagnosis of anxiety, posttraumatic stress disorder (PTSD), bipolar disorder, or psychosis and less likely to have depression or an alcohol or drug use disorder. Continuation was associated with a lower likelihood of sleep and cardiopulmonary disorders and of dementia. Conclusions: Higher discontinuation prevalence among patients with substance use disorders, dementia, or cardiopulmonary disorders is encouraging. However, the challenge remains of discontinuing long-term use among patients who are White, older, or diagnosed as having anxiety, PTSD, bipolar disorder, or psychosis. There is a need to identify provider, patient, and contextual factors driving long-term benzodiazepine use in these patient groups to effectively apply evidence-based discontinuation strategies.
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... The association was especially notable for major depression and anxiety disorders in a recent systematic review and metaanalysis. 7 The preference for zolpidem in patients who screened positive for adult attention-deficit/hyperactivity disorder (ADHD) in the study of Lugoboni et al. 8 could be explained, at least in part, by its paradoxical effects (stimulants) in the context of self-medication, as ADHD is treated by amphetaminic drugs and cocaine is known to relieve ADHD symptoms. 9 Even if benzodiazepines and related benzodiazepines include different medications, we can assume that the abuse and dependence of these substances are similar to "communicating vessels." ...
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Zolpidem is indicated in cases of severe insomnia in adults and, as for BDZs, its assumption should be limited to short periods under close medical supervision. Since several drugs cause corrected QT interval (QTc) elongation, the authors investigated whether high daily doses of Zolpidem could cause QTc elongation. The study was conducted in the Addiction Medicine Unit of the G.B. Rossi University Hospital in Verona. The data were collected from hospitalizations carried out between January 2015 and February 2020 and refer to a total of 74 patients, 38 males and 36 females, who were treated for detoxification from high doses of Zolpidem with the “Verona Detox Approach With Flumazenil.” One patient out of 74 had QTc elongation (479 ms). The patient was male and took a daily dose of 50 mg of Zolpidem; he did not take concomitant therapies that could cause QTc lengthening. He had no electrolyte alterations, no contemporary or previous intake of barbiturates, heroin, cocaine, THC, alcohol, NMDA or nicotine which could cause an elongation of the QTc interval. The present study highlights the low risk of QTc elongation due to high dosages of Zolpidem; however, if, on one hand, we can affirm that Zolpidem is a safe drug, on the other, the widespread use of high dosages of this drug for prolonged periods of time is problematic and worrying.
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Tackling Urbanicity and Pollution in Mental Health Prevention Strategies
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Globalization in the last decades has led to an increase of exchanges through the globe and an expansion of global markets as well as an increase of levels of urbanization through the continents. In particular, urbanization includes environmental, social, and economic changes and factors that may affect the mental health of the general population. In fact, emerging evidence reports higher rates of mental disorders in the urban settings than in rural areas, and social disparities and insecurity may impact on the mental health of the weaker groups of society. Also, the lack of contact with nature in the city and higher levels of pollution are associated with a remarkable rate of psychological distress. Pollution, in particular, is tightly related to the level of industrialization and employment of technology. It has been demonstrated that environmental pollutants (e.g., air pollutants, noise, ionizing radiations, etc.) may impact directly or indirectly on mental health: there may be a direct biological consequence of pollution on the human central nervous system as well as a range of psychological stress generated by the lasting exposure to pollutant agents. This chapter reports emerging evidence regarding the impact of urbanicity and pollution on public mental health and suggests further research and action in order to develop strategies of prevention of mental illness due to the burden of global urbanization.
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Association between Adult Attention Deficit/Hyperactivity Disorder and Intravenous Misuse of Opioid and Benzodiazepine in Patients under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study
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  • Aug 2020
  • EUR ADDICT RES
Background: Intravenous misuse and attention-deficit/hyperactivity disorder (ADHD) are common in patients under opioid maintenance treatment (OMT), who often misuse benzodiazepine (BZD). Objectives: To explore the rate of adult ADHD among patients under OMT in Italy and whether screening positive for adult ADHD is associated with OMT and BZD misuse and emergency room (ER) admission because of misuse. Methods: We recruited 1,649 patients from 27 addiction units (AUs) in Italy and collected data on the self-reported rate of OMT intravenous misuse (prevalence, repeated misuse, main reason, temporal pattern in relation to AU access, experience), concurrent intravenous and intranasal BZD misuse (prevalence, type of misused BZD), ADHD and ER admissions because of misuse complications. Results: Screening positive for adult ADHD was found in 11.2% patients (ADHD+), with a significant gender difference (women: 15.3%, men: 10.3%). OMT misuse was reported by 24.4 and 18.5% patients during lifetime and in the previous 6 months respectively. BZD misuse was reported by 20.0 and 8.6% patients for intravenous and intranasal route respectively. Misuse was significantly more common in ADHD+ (OMT 27.4-33.1%, BZD 14.5-31.5%) than ADHD- group (OMT 17.4-23.3%, BZD 7.9-18.3%). The multivariate logistic regression model showed positive screening for ADHD to be significantly associated with intravenous OMT misuse in the previous 6 months, and intravenous/intranasal BZD misuse, independently of age, gender and route of previous heroin administration. Conclusions: Screening positive for adult ADHD was associated with OMT and BZD misuse. AU physicians and medical personnel should focus on OMT patient's features that are associated with a higher likelihood of misuse, in particular ADHD.
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Attention-deficit/hyperactivity disorder (ADHD) is related to multiple neuropsychological deficits. However, most previous studies, especially studies of adult samples, have not taken the overlap between different neuropsychological deficits into account. In addition, the link between neuropsychological deficits and daily life functioning and quality of life needs to be further investigated. The aim was therefore to investigate the independent effects of executive deficits, delay-related behaviors and emotion dysregulation on ADHD symptom levels, daily life functioning, and quality of life in a non-clinical sample of younger adults. Results showed independent effects of all three neuropsychological deficits on the two ADHD symptom domains. With regard to daily life functioning and quality of life, bivariate relations were found to all three neuropsychological deficits. However, it was primarily the associations to executive deficits that remained significant when studying independent effects. Executive deficits were related to daily life functioning and quality of life also when controlling for ADHD symptom levels. Conclusively, this study shows that ADHD is related to multiple neuropsychological deficits, even in adulthood. Previous studies may have overestimated the importance of delay-related behaviors and emotion dysregulation for daily life functioning, as they have failed to control for the effects of executive deficits.
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Full-text available
  • Nov 2019
Importance An increasing prevalence of adult attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment has been reported in clinical settings and administrative data in the United States. However, there are limited data on recent trends of adult ADHD diagnosis among racial/ethnic subgroups. Objective To examine trends, including associated demographic characteristics, psychiatric diagnoses, and negative outcomes, in the prevalence and incidence of adult ADHD diagnosis among 7 racial/ethnic groups during a 10-year period. Design, Setting, and Participants This cohort study investigated trends in the diagnosis of ADHD in adults who identified as African American or black, Native American, Pacific Islander, Latino or Hispanic, non-Hispanic white, Asian American, or other using the Kaiser Permanente Northern California health plan medical records. A total of 5 282 877 adult patients and 867 453 children aged 5 to 11 years who received care at Kaiser Permanente Northern California from January 1, 2007, to December 31, 2016, were included. Data analysis was performed from January 2017 through September 2019. Exposures Period of ADHD diagnosis. Main Outcomes and Measures Prevalence and incidence of licensed mental health clinician–diagnosed ADHD in adults and prevalence of licensed mental health clinician–diagnosed ADHD in children aged 5 to 11 years. Results Of 5 282 877 adult patients (1 155 790 [21.9%] aged 25-34 years; 2 667 562 [50.5%] women; 2 204 493 [41.7%] white individuals), 59 371 (1.12%) received diagnoses of ADHD. Prevalence increased from 0.43% in 2007 to 0.96% in 2016. Among 867 453 children aged 5 to 11 years (424 449 [48.9%] girls; 260 236 [30.0%] white individuals), prevalence increased from 2.96% in 2007 to 3.74% in 2016. During the study period, annual adult ADHD prevalence increased for every race/ethnicity, but white individuals consistently had the highest prevalence rates (white individuals: 0.67%-1.42%; black individuals: 0.22%-0.69%; Native American individuals: 0.56%-1.14%; Pacific Islander individuals: 0.11%-0.39%; Hispanic or Latino individuals: 0.25%-0.65%; Asian American individuals: 0.11%-0.35%; individuals from other races/ethnicities: 0.29%-0.71%). Incidence of ADHD diagnosis per 10 000 person-years increased from 9.43 in 2007 to 13.49 in 2016. Younger age (eg, >65 years vs 18-24 years: odds ratio [OR], 0.094; 95% CI, 0.088-0.101; P < .001), male sex (women: OR, 0.943; 95% CI, 0.928-0.959; P < .001), white race (eg, Asian patients vs white patients: OR, 0.248; 95% CI, 0.240-0.257; P < .001), being divorced (OR, 1.131; 95% CI, 1.093-1.171; P < .001), being employed (eg, retired vs employed persons: OR, 0.278; 95% CI, 0.267-0.290; P < .001), and having a higher median education level (OR, 2.156; 95% CI, 2.062-2.256; P < .001) were positively associated with odds of ADHD diagnosis. Having an eating disorder (OR, 5.192; 95% CI, 4.926-5.473; P < .001), depressive disorder (OR, 4.118; 95% CI, 4.030-4.207; P < .001), bipolar disorder (OR, 4.722; 95% CI, 4.556-4.894; P < .001), or anxiety disorder (OR, 2.438; 95% CI, 2.385-2.491; P < .001) was associated with higher odds of receiving an ADHD diagnosis. Adults with ADHD had significantly higher odds of frequent health care utilization (OR, 1.303; 95% CI, 1.272-1.334; P < .001) and sexually transmitted infections (OR, 1.289; 95% CI 1.251-1.329; P < .001) compared with adults with no ADHD diagnosis. Conclusions and Relevance This study confirmed the reported increases in rates of ADHD diagnosis among adults, showing substantially lower rates of detection among minority racial/ethnic subgroups in the United States. Higher odds of negative outcomes reflect the economic and personal consequences that substantiate the need to improve assessment and treatment of ADHD in adults.
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Psychiatric Comorbidity and Addiction Severity Differences in Patients With ADHD Seeking Treatment for Cannabis or Cocaine Use Disorders
Article
Full-text available
Objective: The objective of this study was to compare psychiatric comorbidity and consumption-related variables in ADHD patients seeking treatment for cocaine, cannabis, or both. Method: Assessment was conducted using European Addiction Severity Index (EuropASI), Conners’ Adult ADHD Diagnostic Interview (CAADID), Structured Clinical Interview for DSM Disorders (SCID), Adult Self-Report Scale (ASRS), Wender Utah Rating Scale (WURS), Barratt Impulsiveness Scale-11 (BIS-11), and FIDI, with statistical analyses of analysis of variance (ANOVA), Student’s t test, chi-square test, and multinomial regression model. Results: In total, 1,538 patients with substance use disorder (SUD) were evaluated for ADHD; 239 (15.5%) had ADHD, with cannabis 41, cannabis/cocaine 36, and cocaine 74. Men represented 80%, with mean age of 32.9 ± 10 years. Significant variables were—in bivariate analysis—more years of cannabis use in cannabis group and younger age for cocaine use disorder in cannabis/cocaine group, and—in multivariate analysis—lifetime anxiety disorder and younger age at onset of any SUD in cannabis group and working affected scale in cannabis and polysubstance use in cannabis/cocaine group. Conclusion: Groups with cannabis use had higher severity. ADHD features were similar in all groups. The assessment of ADHD and comorbid disorders is important.
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Sleep disorders in patients with ADHD: impact and management challenges
Article
Full-text available
  • Dec 2018
Attention deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed disorders in childhood, enduring through adolescence and adulthood and presenting with symptoms of inattention, hyperactivity, and/or impulsivity and significantly impairing functioning. Primary sleep disorders such as sleep-disordered breathing, restless leg syndrome, circadian rhythm sleep disorder, insomnia, and narcolepsy are commonly comorbid in these individuals but not often assessed and are therefore often left untreated. Sleep disturbances in individuals with ADHD can result in significant functional impairments that affect mood, attention, behavior, and ultimately school/work performance and quality of life. Previous reviews have described findings related to sleep but have neglected to examine potential impacts of these sleep disorders and ADHD on daytime functioning. This review investigates empirical findings pertaining to sleep abnormalities and related cognitive, behavioral, emotional, and physical impairments in individuals with ADHD and comorbid primary sleep disorders across the life span. It discusses implications to management and highlights existing limitations and recommended future directions.
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Health-related quality of life and burden of illness in adults with newly diagnosed attention-deficit/hyperactivity disorder in Sweden
Article
Full-text available
  • Jul 2018
  • BMC PSYCHIATRY
Background This observational, cross-sectional, retrospective chart review aimed to identify factors determining health-related quality of life (HRQoL) in adults with newly diagnosed attention-deficit/hyperactivity disorder (ADHD) in Sweden. Methods Adult participants with a new clinical diagnosis of ADHD were enrolled from two specialist outpatient clinics in Stockholm, Sweden, from 2013 to 2015. Data extracted from patient records included demographics, clinical characteristics and comorbid psychiatric diagnoses identified using the Mini International Neuropsychiatric Interview (MINI). Depression severity was assessed using the Montgomery–Åsberg Depression Rating Scale – Self-reported (MADRS-S). The self-rated five-dimension EuroQol questionnaire (EQ-5D) was used to measure HRQoL. Predictors of EQ-5D index score were identified using multivariate linear regression adjusting for age, sex, education level, and main income source. ResultsThe mean age of the 189 enrolled patients was 35.2 years (standard deviation [SD], 12.3), and 107 (57%) were female. Psychiatric comorbidities were present in 92 patients (49%), with anxiety and depression being the most common diagnoses. The mean EQ-5D index score was 0.63 (SD, 0.28). Low EQ-5D index scores were significantly associated with high MADRS-S scores, multiple comorbid psychiatric disorders, low educational achievement, female sex, and not having a main income derived from employment or self-employment. Conclusions These findings suggest that adults with newly diagnosed ADHD experience low HRQoL, which may often be exacerbated by psychiatric comorbidities such as anxiety and depression. Patients presenting with ADHD and psychiatric comorbidities in adulthood may require particular care and resources in the management of their ADHD.
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Adult ADHD and comorbid disorders: Clinical implications of a dimensional approach
Article
Full-text available
  • Aug 2017
  • BMC PSYCHIATRY
Attention-deficit/hyperactivity disorder (ADHD) in the adult population is frequently associated with comorbid psychiatric diseases that complicate its recognition, diagnosis and management. The prevalence of ADHD in the general adult population is 2.5% and it is associated with substantial personal and individual burden. The most frequent comorbid psychopathologies include mood and anxiety disorders, substance use disorders, and personality disorders. There are strong familial links and neurobiological similarities between ADHD and the various associated psychiatric comorbidities. The overlapping symptoms between ADHD and comorbid psychopathologies represent challenges for diagnosis and treatment. Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first. Early recognition and treatment of ADHD and its comorbidities has the potential to change the trajectory of psychiatric morbidity later in life. The use of validated assessment scales and high-yield clinical questions can help identify adults with ADHD who could potentially benefit from evidence-based management strategies.
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High-dose lormetazepam dependence: strange case of Dr. Jekyll and Mr. Hyde
Article
  • May 2019
High-dose benzodiazepine (BZD) abuse is emerging as a substance use disorder (SUD). The aim of the study is to explore the impact of high-dose lormetazepam (LMZ) abuse and the characteristics of patients affected by this SUD in a tertiary referral addiction unit. We have retrospectively evaluated 1112 patients admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. LMZ was the most common BZD, with an increasing prevalence from January 2003 to June 2018. Socio-demographic (more women; higher age and education) and clinical features (higher daily diazepam dosage equivalent, BZD abuse duration, age of first BZD intake; BZD prescribed more frequently for sleep disorders; less frequent history of other SUDs, previous/active alcohol, previous opioids abuse; more frequent overall major psychiatric diseases and major depression; less-frequent bipolar disorders and other psychoses, personality disorders, and more than one psychiatric disease) of LMZ vs. other BZD abusers significantly differed. 96.7% LMZ abusers took oral solution, while two-thirds of other BZD abusers took tablets. Oral solution, BZD abuse duration and prescription of BZD for sleep disorders increased, while history of other SUDs, previous/active alcohol and active cannabinoids SUD reduced the risk of high-dose LMZ vs. other BZDs abuse. The large prevalence of high-dose LMZ abusers in Italy may be strongly related to the availability and characteristics of oral formulation that may transform the innocuous Dr. Jekyll tablets into an evil Mr. Hyde. Restriction to the market of LMZ oral formulation might reduce the risk of high-dose abuse.
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Factors associated with lifetime suicidal ideation and suicide attempts in outpatients with substance use disorders
Article
  • Sep 2017
  • PSYCHIAT RES
Risks factors for suicide are multiple and highly prevalent in addicted patients (previous suicide attempts, substance abuse, impulsivity, history of sexual abuse and other factors). The aim of this study is to identify and to compare the clinical and socio-demographic profile of SUD outpatients with lifetime suicidal behavior (previous suicidal ideation and/or suicide attempts) and to analyze the factors related to it. A retrospective cohort study of 696 addicted patients, according to DSM-IV-TR criteria (APA, 2000) were collected from the Addiction Unit of Vall d'Hebron University Hospital. Lifetime suicidal ideation in addicted patients is associated with presence of: borderline personality disorder (BPD), depressive disorders, sexual abuse, polydrug abuse, attention-deficit hyperactivity disorder, and motor impulsivity. The factors associated with suicide attempts were: borderline personality disorder, lifetime abuse (whether emotional, physical or sexual), co-occurrent psychotic disorders, polydrug abuse, anxiety disorders and depressive symptoms. We conclude that previous suicidal ideation and lifetime suicide attempts should be considered in the clinical care of addicted patients. Factors related to both suicidal behaviors share similarities and differences according to our findings and need to be deeply explored in the future.
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