Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level. 1. Introduction Benzodiazepines (BZDs) are prescribed in the medical management of anxiety, insomnia, seizures, and muscle spasms, but, in some patients, it can lead to significant complications, including misuse, abuse, tolerance, dependence, and addiction [1–4]. Because of these dangers, prescribing BZDs is debatable, especially in patients with severe mental illness, particularly those affected by mood, anxiety disorder [3–6], and substance use disorder, such as heroin addicts and/or alcoholics [7–9]. Indeed, the misuse of BZDs is widespread among multidrug users in the club scene; these are subjects who also exhibit high levels of other health and social problems [10]. Data from animal models which focus on the cellular and molecular basis that might underlie the addictive properties of BZDs reveal how benzodiazepines, by acting through specific receptor subtypes, activate midbrain dopamine neurons, and how this could hijack the mesolimbic reward system [11]. Due to the possibility of abuse [12], many physicians are reluctant to prescribe BZDs [13]. Most guidance recommends that BZDs should be prescribed only for short periods and only in a minority of patients. Even so, evidence from pharmacoepidemiological studies and prescribing practice surveys show that some doctors still prescribe for longer periods and to a large number of patients [6]. Long-term benzodiazepine intoxication produces a variety of side effects, including sedation, anterograde amnesia, impaired visuospatial and visuomotor abilities, difficulties in motor coordination, psychomotor speed, and cognitive
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