Benzodiazepines like diazepam (Valium) act by coupling to the benzodiazepine–GABA(A) receptor–chloride ionophore complex.31 Binding of benzodiazepine to the GABA(A) receptor increases chloride conductance, resulting in presynaptic inhibition in the spinal cord.32,33
Diazepam is the most commonly used benzodiazepine in the treatment of spasticity, having efficacy in patients with spinal cord injury, hemiplegia, and multiple sclerosis (MS).34–37 It frequently is used as an adjunct to baclofen in treating spasticity.41 Diazepam is less commonly used as a single agent.
From and Heltberg38 studied 17 patients with MS in a double-blind crossover trial with baclofen and diazepam. Each patient received 4 weeks of therapy with each drug. No differences were seen in efficacy of reducing spasticity, clonus, and flexor spasms or improving gait or bladder function. Side effect profiles differed slightly, with more patients reporting sedation while on diazepam, but the severity of side effects was similar in both groups. When patients still masked to treatment assignment were asked which agent they preferred, baclofen was significantly favored.38
Other studies confirmed comparable antispasticity effects of baclofen and diazepam in reducing muscle tone and frequency of spasms, but baclofen was not necessarily favored over diazepam by these patients.39,40
Diazepam is well absorbed orally and reaches a peak level in approximately 1 hour. It is 98% protein-bound and is metabolized by the liver to active compounds nordiazepam and oxazepam. Total half-life can range between 20 and 80 hours.
Doses may be initiated at 2 mg twice daily and may be increased as needed to a desired effect. Alternatively, single 5-mg doses at night may be effective for nocturnal symptoms. In patients with hepatic dysfunction, doses should be titrated carefully.
Side effects include sedation and cognitive impairment, and there is a potential for dependence. The benzodiazepine withdrawal syndrome is characterized by anxiety, dysphoria, tremor, and sympathetic activation.
Seizures can occur in susceptible patients (i.e., those with a low seizure threshold) or in those who undergo rapid withdrawal after chronic use.23
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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