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Other important interactions include phenytoin and carbamazepine (complex bidirectional effects on levels and toxicity), warfarin and other anticoagulants (altered bleeding risk), salicylates such as aspirin (displacement from protein binding and increased free valproate), cimetidine and erythromycin (potentially increased valproate levels), rifampin (reduced levels), and alcohol or sedatives (enhanced CNS depression)

However, toxicity has also been decreased while the circulating plasma half-life has increased, and therefore, higher doses of these agents can be administered

Disruption of spinal glutamate homeostasis impacts WDR neuronal firing in the spinal cord, inducing mechanical hypersensitivity (Robinson et al., 2014a)

Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage