Cough medicine for agitation – Nothing to cough about

To the Editor

There has been some interest in the therapeutic use of dextromethorphan (DXM) in conjunction with quinidine in the treatment of agitation (Chen et al., 2018). DXM is a commonly used antitussive agent and can be purchased without prescription in Australia.

DXM is a centrally acting agent which crosses the blood–brain barrier to act on the cough centre within the brain. DXM itself and its metabolite dextrorphan have both demonstrated NMDA receptor antagonist activity (Logan et al., 2009). DXM also has serotonergic properties as a 5HT₁ inhibitor; the development of serotonin syndrome is a real possibility when DXM is used in conjunction with other serotonergic agents or at toxic doses (Logan et al., 2009).

On literature review, we found one retrospective case series regarding the efficacy of DXM and quinidine for patients with psychosis related agitation (Chen et al., 2018), which indicated that DXM was potentially useful for reducing agitation. One phase II randomised control trial specifies the use of DXM–quinidine in treatment of agitation in the specific patient group of Alzheimer’s Dementia (Cummings et al., 2015), and a clinically significant reduction in agitation (measured by the Neuropsychiatric Inventory Agitation scores) was demonstrated. There are, however, no systemic reviews or meta-analyses on this particular topic. Outside of the Alzheimer’s Dementia population, there is a lack of data regarding the efficacy of DXM in treating agitation, thus limiting external validity. Given this, there is currently insufficient evidence to recommend routine use of DXM to reduce agitation.

Reports exist of DXM being ingested at supratherapeutic doses, leading to its indictment in cases of fatal overdoses (Logan et al., 2009). The recreational use of DXM is likely facilitated by the multiple actions of DXM on chemical receptors in the brain, which can result in perceptual disturbances, hallucinations, delirium and dissociative states (Logan et al., 2009).

Although no current recommendations can be made for DXM in the treatment of agitation, clinicians should be aware of the risks of DXM, and the various mechanisms in which it may exert psychoactive effects at supratherapeutic doses. Specifically, prescribers should be alerted to DXM’s ability to interact with other medications to potentially cause serotonin syndrome, given DXM’s widespread availability and known misuse.