Catatonic stupor secondary to gamma-hydroxy-butyric acid (GHB)-dependence and -withdrawal syndrome.

GHB has been formerly used as an anesthetic and developed into a popular psychoactive drug. GBL is primarily used as a solvent in the pharmaceutical industry, is a precursor of and following hepatic hydrolysis by the 1-4 Lactonase converted to GHB. The plasma half-life of GBL is short, can be detected only less than one minute and the main active metabolite is GHB (Schep et al. 2012). The pharmacokinetics of GHB indicate a short action. The time to peak serum levels ranges from 36-57 minutes and the elimination half-life between 30-52 minutes. Addiction occurs when prolonged, repeated GHB use disrupts the balance of brain transmitters and circuits controlling reward, memory and cognition leading to compulsive use. The duration of clinical effects are dose-dependent and range from 2.5-4 hours (Schep et al. 2012). The pharmacodynamics of GHB describes at least two distinct binding sites, the GHBand the GABABreceptor. GHB acts as an agonist at the GHB-receptor, which causes an excitatory effect, and as a weak antagonist at the GABAB-receptor, which causes an inhibitory effect. Activation of both GHBand GABABreceptors is responsible for the addictive properties of GHB. The psychotropic effect involves the release of glutamate, as well as the release and inhibition of release of dopamine. In defined areas of the brain, activation of the GHB-receptor results in the release of glutamate. The dopamine release of GHB is biphasic. Low doses of GHB stimulate dopamine release via the GHB-receptor, higher concentrations then inhibit dopamine release via the GABAB-receptor, and eventually, after an initial phase of inhibition, dopamine release is again increased via the GHB-receptor. More recently, in addition to the action at the low-affinity metabotropic GABAB-receptor, a high affinity binding site at the inotropic -GABAA-receptor site has been identified. However, the precise role of this high-affinity binding site still remains elusive (Bay et al. 2014, Vogensen et al. 2013). The early GHB-withdrawal syndrome resembles the alcohol withdrawal syndrome which is associated with autonomic instability, tremor, anxiety, restlessness, and insomnia. GHB withdrawal usually lasts 3 to 21 days. However, severe withdrawal syndromes can produce acute delirium and psychosis requiring hospitalization, even leading to intensive care management and fatal outcome (Schep et al. 2012). The mainstay of management of the GHB-withdrawal syndrome remains the administration of benzodiazepines which primarily act on the GABAA and high doses are often required (van Noorden et al. 2009). However, more recently, the administration, in particular the titration and tapering of GHB itself has been studied with great success. Only a low level of withdrawal symptoms was experienced, and no patient developed delirium or psychosis (de Jong et al. 2012). Thus, administering GHB could be a superior future approach in the management of GHBwithdrawal. Yet another approach, which at this point has not yet been evaluated, could be the administration of Baclofen, a GABAB-Agonist in conjunction with benzodiazepines. This approach would cover the psychodynamic properties of GHB and could be equally useful than the administration of GHB. However, this approach has not yet been studied to date.