Dextromethorphan–quinidine promising for agitation in Alzheimer’s patients

By Eleanor McDermid, Senior medwireNews Reporter

The combination of dextromethorphan hydrobromide and quinidine sulphate shows promising efficacy against agitation in a phase 2 trial in patients with Alzheimer’s disease (AD).

During the first stage of the trial, 93 patients received 5 weeks of treatment with dextromethorphan–quinidine, starting at 20/10 mg once daily for the first week, increasing to the same dose twice daily for weeks 2 and 3 and to 30/10 mg twice daily for the final 2 weeks.

Over this time, the patients’ average score on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain fell from 7.1 to 3.8, which was a significantly greater difference than the reduction from 7.0 to 5.3 achieved by the 127 patients who were given placebo.

In the second phase of the trial, Jeffrey Cummings (Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, USA) and co-researchers accounted for the effect of the placebo response by taking the 119 patients who did not have at least a 25% reduction in their NPI Agitation/Aggression domain score in response to placebo and randomly assigning them to switch to active treatment or continue on placebo.

In this group, active treatment resulted in a reduction in the average score from 5.8 to 3.8, which was significantly greater than the 6.7 to 5.8 change associated with continued placebo, the team reports in JAMA.

The 93 patients who received active treatment for the whole 10 weeks of the trial achieved an average 3.6-point reduction in NPI Agitation/Aggression domain score, compared with a 1.9-point reduction among the 66 patients who received placebo for the whole study duration, which was again a significant difference.

In a linked editorial, Anne Corbett and colleagues, from King’s College London in the UK, say that the NPI Agitation/Aggression domain does not have an established minimum clinically important difference, making the primary outcome result “difficult to interpret” and the overall findings “important, but not overwhelming”.

However, they note that almost all current treatment for agitation in AD patients involves off-label use of atypical antipsychotics.

“Within this clinical treatment environment, pending further evidence, there is a reasonably strong case to prioritize dextromethorphan-quinidine as an off-label treatment for agitation, possibly as a safer alternative to atypical antipsychotics”, they say.

But they call for a “robust international expert consensus” on the prioritisation of these off-label treatments, “to improve the consistency of clinical practice.”

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