Harmen Beurmanjer

13 General Introduction 1 Treatment for GHB use disorder The risks associated with GHB withdrawal pose a challenge from a clinical point of view. In clinical practice two pharmacological treatment regimens are commonly used to counteract withdrawal symptoms during GHB detoxification: tapering with benzodiazepines (BZD) (McDonough, Kennedy, Glasper, & Bearn, 2004) and tapering with pharmaceutical GHB (Dijkstra et al., 2017). While both detoxification methods are currently in use, studies comparing both methods had not been conducted at the start of this thesis. During BZD tapering diazepam or lorazepam are usually administered to supress withdrawal symptoms. BZD have an allosteric effect on GABA-A-receptors, resulting in increased sensitivity for GABA (Lorenz-Guertin, Bambino, Das, Weintraub, & Jacob, 2019). Benefits of BZD’s are the wide availability, low costs and patients can directly quit their GHB use. However, a large number of (case-)studies have been published suggesting BZD resistance in patients with GUD(M. S. van Noorden, Kamal, Dijkstra, Mauritz, & de Jong, 2015), resulting in having to use extremely high doses of BZD’s in order to treat withdrawal (Craig, Gomez, McManus, & Bania, 2000; Neu, 2018). In spite of these high doses, delirium was common (Delic, 2019; Harris, Harburg, & Isoardi, 2020; Neu, 2018) and often additional medication such as phenobarbital (Sivilotti, Burns, Aaron, & Greenberg, 2001) and propofol (Dyer, Roth, & Hyma, 2001) was needed to treat the fulminant course of GHB withdrawal. Pharmaceutical GHB is the preferred detoxification method in the Netherlands. This is prescribed off-label to patients during GHB detoxification (Kamal et al., 2014). The inpatient detoxification starts with a titration phase where the right dose of pharmaceutical GHB is found on which patients are stable and experience neither withdrawal nor sedation. After one or two days the detoxification phase starts, where patients receive GHB every two to three hours. During this phase the dose of pharmaceutical GHB is tapered off gradually each day. GHB tapering has shown to be associated with a high success rate and limited adverse events in several large non-randomized trials (Beurmanjer H, Verbrugge CAG, Schrijen S & DeJong CAJ, 2016; Dijkstra et al., 2017). After detoxification patients with GUD either continue with inpatient treatment or receive outpatient care. The treatment of GUD relies mostly on generic substance use disorder treatments, based on the principles of cognitive behavioural therapy. It is also common that patients receive help with debts, daytime activities and (finding new) housing or are placed in an assisted living facility (Beurmanjer H, Verbrugge CAG, Schrijen S & DeJong CAJ, 2016; Joosten, Van Wamel, Beurmanjer, & Dijkstra, 2020). One of the main problems in the treatment of patients with GUD is the fast relapse and high drop-out rates in patients with GUD (M. S. van Noorden et al., 2017). This results in many patients leaving care before treatment has properly started. Subsequently, it may add to demoralisation of both patients and treatment staff, when patients frequently relapse into GHB use. It is important to get more insight in treatment needs and factors contributing to these high relapse rates.