(50) Reduced Robo-Readmissions: Buprenorphine For Dextromethorphan Use Disorder

Background & Introduction: Dextromethorphan (DXM) is an antitussive available without a prescription. It is a centrally active N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 receptor agonist, and the d-isomer of the codeine analog, levorphanol. Researchers have indicated that DXM and its metabolite, dextrorphan, have specific serotonergic and sigma-1 opioidergic properties; others have indicated that DXM has little to no analgesic or addictive properties and may even antagonize opioid receptors. There is growing literature indicating DXM misuse (defined as ingesting quantities greater than recommended) and dependence among adolescents and adults, and it is thought that exceedingly high doses of DXM are misused because its activity on the NMDA-receptor can lead to psychotropic effects such as hallucinations, euphoria, and dissociation. There is no FDA-approved medication for DXM-use disorder. Case reports of DXM-dependence have been documented, and a recent article describes the successful treatment of DXM-use disorder with naltrexone and gabapentin. Additional pharmacotherapy options are needed. This case describes the successful treatment of DXM-use disorder with buprenorphine, a partial mu-opioid receptor agonist.

Case Description: A 44-year old male with DXM-use disorder, chronic post-traumatic lower back pain with L3-L5 spinal fusion, unspecified anxiety and depression, and experiencing unsheltered homelessness reported taking 80-200 generic DXM/guaifenesin 20/600 mg tablets daily. The max daily DXM recommended dose is 120 mg. In the year prior to the current treatment episode, he was treated at least 15 times for DXM intoxication, including intensive care unit (ICU) admission, supportive care for serotonin syndrome, and brief intubation for obtundation. During the ICU admission, he underwent psychiatric evaluation. He reported symptoms consistent with anxiety, post-traumatic stress disorder (PTSD), and depression, confounded by severe DXM-use disorder. There was a longstanding history of psychiatric medication polypharmacy with low patient adherence. There was no previous opioid misuse or opioid use disorder. In a shared decision making model with the patient, his outpatient medication regimen was simplified and buprenorphine was commenced for DXM-use disorder and severe, chronic musculoskeletal pain.

Buprenorphine-naloxone sublingual films were started at 6 mg total daily dose prior to ICU discharge. The patient was connected to a federally qualified healthcare center addiction medicine clinic. Counseling, linkage to higher levels of addiction treatment, and co-located psychiatric treatment were offered and declined. Case management was engaged in transportation assistance, as the patient remained unsheltered homeless throughout the duration of this treatment episode.

During his treatment in-clinic, the patient described the efficacy of buprenorphine as “the change was almost immediate.” At his first appointment, he was up-titrated to 12 mg daily dose. At follow up one week later, he reported that cravings had abated. Confusion, memory loss, and stutter-present since the ICU–resolved. With increase to 16 mg daily dose, he no longer experienced cravings, and at 20 mg daily he described feeling like he had a “safety net.” Urine toxicology studies, both point of care immunoassays and send-out buprenorphine metabolites, are consistent with reports of taking medication as prescribed.

Although abstinence from DXM was successfully achieved with buprenorphine 20 mg daily, issues with insomnia and anxiety persisted. On reflection, he reports prior use was driven by anxiety, PTSD related to prior incarceration, and chronic pain. The patient continued to have improved functional outcomes, including engagement with specialists in application for disability, housing, and enrollment in community college. 13 months after stabilizing on buprenorphine he continues to follow in an outpatient clinic and has not required emergency or inpatient care.

Conclusion & Discussion: There are limited reports of DXM-use disorder pharmacotherapy. One previous report discussed efficacy with naltrexone, a mu-opioid receptor antagonist, and gabapentin, a GABA-release modulator. Multiple case reports discuss reversal of DXM-overdose with naloxone, also a mu-opioid receptor antagonist. Interestingly, studies have explored the use of NMDA-receptor antagonists, like DXM, for opioid withdrawal symptom alleviation and opioid use disorder. These suggest a link between DXM and mu-opioid receptors, though an exact mechanism is unknown. Buprenorphine may influence NMDA receptor signaling at therapeutic doses; through this mechanism and partial mu-opioid receptor agonism, it is possible that activity at these receptors attenuate cravings and DXM withdrawal symptoms.

Due to worsening dysfunction, including frequent hospitalizations, the patient was willing to try pharmacotherapy to help reduce DXM use. Due to its mechanism, buprenorphine was considered an appropriate alternative that the patient was amenable to. This is a single case report of successful DXM-use disorder treatment with buprenorphine with limitations including lack of generalizability and no urine toxicology to corroborate DXM-abstinence. Further research is warranted to evaluate the efficacy of buprenorphine in DXM-use disorder.

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