A review of tolerability and abuse liability of γ-hydroxybutyric acid for insomnia in patients with schizophrenia

Approved therapeutic uses for gamma-hydroxybutyric acid (GHB) (or sodium oxybate), a gamma-aminobutyric acid type B and GHB receptor agonist, include narcolepsy in the United States and Europe and alcohol abuse treatment in Italy. Possible efficacy of GHB in schizophrenia has also been proposed. A tolerability concern regarding use of GHB is its abuse potential. Given the high comorbidity of substance disorders and schizophrenia, a systematic assessment of the published literature is crucial.The aim of this review was to assess the tolerability and abuse liability of GHB in the context of future clinical studies as a potential treatment for insomnia in patients with schizophrenia.A literature search in English (inception through April 2009, inclusive) was conducted of MEDLINE, EMBASE, and PsycINFO using the search term GHB. All articles whose abstracts mentioned human use of GHB were read in their entirety. The reference sections of identified articles were reviewed for publications that might have been missed by the initial search.GHB is abused by a small percentage of people (1%) as a "club drug" and is commonly associated with enhanced sexual experiences (65%), euphoria (41%), somnolence (71%), and confusion (24%), according to a recent study. A review of all available emergency room case series suggests that while GHB can be associated with serious coma necessitating intubation, the number of reported fatal cases associated with GHB appears limited. Clarity on the lethality of GHB is complicated by instability of GHB in postmortem samples and frequent concomitant ingestions. Furthermore, formal abuse liability studies do not support high abuse propensity for GHB, mainly because oversedation and dizziness may lead most individuals to find GHB unpleasant at high doses. As supported by 2 large studies, there is limited evidence to suggest widespread use as an agent in sexual assault. Years of clinical use in narcolepsy do not support the development of tolerance or withdrawal in those subjects without substance dependence.Tolerability and abuse liability issues, while a concern with GHB given its abuse potential, do not preclude further study of the potential use for insomnia in nondually diagnosed schizophrenia. Full cognizance must be taken of risk/benefit tradeoffs, and to the development of improved formulations with decreased abuse liability.