Minocycline Reduces Poststroke Disability, Even If Used Late

By John Schieszer

Neurology

Minocycline (Dynacin), a semisynthetic second-generation derivative of tetracycline (Sumycin), administered within 6 to 24 hours after suffering an ischemic stroke, significantly reduces poststroke disability, according to a new study published in (2007;69:1404-1410).

Because current treatments only work when given during the first few hours after symptom onset, and because most patients do not reach the hospital within this timeframe, minocycline appears to be a valuable alternative to current therapies.

IMWR

"I hoped to find a positive statistical effect; however, I was very surprised by the significance of these findings," coinvestigator Yair Lampl, MD, of the Sackler School of Medicine, University of Tel-Aviv, Israel, told .

This "may be an effective treatment in stroke even after the first 3 hours. There was no difference of effect between moderate and severe stroke," said Dr Lampl.

This 3-month, open-label, evaluator-blinded study included 152 patients (mean age, 66 years; 35% women) who received either oral minocycline (n = 74) 200 mg/day or placebo (n = 77) for 5 days poststroke. Time to treatment was similar in the 2 groups (13 and 12 hours poststroke, respectively).

After 12 weeks of follow-up, the minocycline group performed 4 times better than the placebo group on the National Institutes of Health Stroke Scale (NIHSS), which measures vision, facial palsy, movement, and speaking ability.

The minocycline group had a NIHSS score of 1.6, which is indicative of little or no disability, compared with a score of 6.5—the high end of mild disability—for the placebo group.

"The improvement was already apparent within a week of the stroke," Dr Lampl said. "This is exciting, because many people who have had a stroke cannot be treated if they don't get to the hospital within 3 hours after symptoms start, which is the timeframe for current available treatments."

Dr Lampl explained that the improvement shown by patients taking minocycline was not from the drug's basic antibiotic effect, but rather from its antiinflammatory properties, and its ability to preserve brain cells.

None of the patients had serious side effects from the drug.

Previous studies have demonstrated that minocycline has neuroprotective effects in animal models of multiple sclerosis, Parkinson's disease, Huntington's disease, and Lou Gehrig's disease. The proposed mechanisms of action for this antibiotic include reductions in microglial activation, matrix metalloproteinase, and nitric oxide production, and inhibition of apoptotic cell death.

Dr Lampl noted that these results must be confirmed by other studies. Further research is also needed to determine whether the dose used in this study is optimal, and whether administering the drug intravenously would be more effective.