The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study

The effects of gamma-hydroxybutyrate (GHB: 25 mg/kg h.s. and 3 h later) vs. placebo on objectively evaluated nighttime sleep and daytime sleepiness in narcolepsy were evaluated in a double-blind, counterbalanced crossover design. Twenty narcolepsy patients were given an overnight polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT) at baseline and on the 1st and 29th days of GHB and placebo treatment. The overnight PSGs indicated that the narcolepsy patients had the following significant results during GHB versus placebo treatment: decreased stage 1 (p = 0.012), increased stage 3 (p = 0.008), increased delta (stage 3 and 4 combined) sleep (p = 0.049), fewer stage shifts (p = 0.002), and fewer awakenings (p = 0.006). Minutes of wakefulness were significantly increased only for the last 2 h of the 8 h sleep period on GHB versus placebo (p = 0.019), which is beyond the time of GHB's direct influence. The MSLTs indicated that the narcolepsy patients had a marginally increased sleep latency mean during GHB versus placebo treatment (p = 0.074) and significantly increased total stage 0 (wakefulness) on day 29 of GHB versus day 29 of placebo treatment (p = 0.038). Female narcolepsy patients had significantly fewer naps with REM sleep (REM naps) on day 29 of GHB vs. day 29 of placebo treatment (p = 0.020). The therapeutic effect of GHB in narcolepsy patients, i.e., decreases cataplexy, appears to be due to its improving nocturnal sleep quality, since its half-life is only 1.5 to 2 h. It is conjectured that GHB, an endogenous neurochemical, may be a sleep neurotransmitter or neuromodulator, since GHB rapidly induces sleep, and increases sleep continuity and delta sleep without suppressing REM sleep in both normals and narcolepsy patients.