Withdrawal from GABAergic agents can be lifethreatening. The withdrawal from benzodiazepines, barbiturates, GHB, GBL, and baclofen, as in ethanol, is mediated primarily through GABAergic signaling. During drug cessation from GABAergic agents, there is a state of decreased GABA-mediated inhibitory tone and increased NMDA-mediated excitatory tone, resulting in the predominantly excitatory picture of withdrawal. The primary goal of therapy for withdrawal includes restoration of the inhibitory tone with medications that demonstrate cross-tolerance with that agent.
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