A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome.

BACKGROUND: Previous open-label trials have shown iron to be efficacious in the treatment of restless legs syndrome. We performed a randomized, double-blind, placebo-controlled trial of iron sulfate. METHODS: Twenty-eight patients were randomized to receive either ferrous sulfate 325 mg b.i.d. or placebo for 12 weeks. The primary outcome measure was the dichotomous variable of improvement or no improvement in average quality of sleep as recorded by a visual analog scale nightly over a 2-week period, comparing a pretreatment 2-week baseline to weeks 13-14. Secondary outcome measures included a comparison of the quality of sleep as measured by a visual analog scale, effect of restless legs syndrome on life as a whole as measured by a different visual analog scale, and the percentage of nights patients were symptomatic. RESULTS: No significant differences were noted between iron and placebo groups for both primary and secondary outcome measures. Responders taking iron did have a significant increase in their iron saturation compared to nonresponders taking iron. CONCLUSIONS: Iron sulfate does not appear to be an effective empiric treatment for restless legs syndrome.

Ranitidine-induced cranial dystonia.

We report a case of cranial dystonia related to the administration of ranitidine. The symptoms started shortly after institution of treatment, resolved after discontinuation, and recurred upon repeat administration of the drug. Although there have been a few reports of abnormal involuntary movements related to other histamine2 antagonists, this is only the second reported instance due to ranitidine and the first reported instance of dystonia related to the drug. The pathophysiology of this effect is unclear, but a central cholinergic effect of this agent may be a contributing factor.

Prior stress attenuates the analgesic response but sensitizes the corticosterone and cortical dopamine responses to stress 10 days later.

This study demonstrates that pre-exposure to stress influences subsequent effects of stress on pain sensitivity (stress-induced analgesia) and on plasma corticosterone and brain catecholamine activity. Animals exposed to a 30 min shock session (S1 = 8, 5.0 s shocks) 10 days earlier showed a significant attenuation of shock-induced analgesia, as measured by increased latency of tail withdrawal from a hot water bath immediately after a 40 s, 1.6 mA footshock (S2). Animals exposed to shock 10 days before testing also exhibited a higher plasma corticosterone response to testing than did all other groups. Norepinephrine (NE) levels in the frontal cortex and dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels in the frontal cortex and nucleus accumbens were not altered in any group. However, the DOPAC/DA ratio in the frontal cortex was increased by analgesia testing, and this increase was enhanced only by the combination of shock 10 days before testing and shock immediately before the test (S1 + S2). These results are consistent with previous reports from this laboratory which indicate that an animal's acute response to stress is strongly influenced by its past history of stress.