A young man’s ‘trips’ to heaven and hell
Mr. F hears voices from Jesus and Satan. He has schizophrenia and is addicted to dextromethorphan in cold medications. Which problem is causing his auditory hallucinations?
In the past year, Mr. F was hospitalized 6 times after dextromethorphan-induced psychotic decompensations. He has been unemployed for more than 5 years, has not been in a serious romantic relationship since college, and depends on his father for financial support. He is not abusing other substances.
The authors’ observations
As many as 80% of patients with schizophrenia also have a substance abuse disorder.2 Access to psychoactive substances, kindling associated with schizophrenia, and attempts to stop hallucinations with alcohol or illicit drugs may explain this high prevalence.2 Also, genetic or phenotypic vulnerability in schizophrenia might alter the mesolimbic dopamine system that moderates reward.
Compared with patients with schizophrenia who are substance-free, comorbid substance abuse in schizophrenia increases:
- severity of psychotic symptoms
- likelihood of emergency service use
- risk of suicide, illness, injury, hospitalization, or incarceration.3
How does dextromethorphan cause hallucinations and/or psychosis, and at what doses can these effects occur?
Dextromethorphan, a synthetic dextroisomer of codeine, exerts antitussigenic effects via the sigma opioid receptor but lacks other opioid activity.
In patients age ≥12, dextromethorphan in cold medications is well tolerated at 60 to 120 mg/d in divided doses, with mostly benign adverse reactions such as drowsiness, dizziness, upset stomach, nervousness, and restlessness.7
Hallucinogenic effects surface at 160 to ≥300 mg and psychosis often occurs at >600 mg.8 Nonsuicidal use of 3,600 mg has been described.9
Hallucinogenic effects are caused by dextrorphan, a metabolite of dextromethorphan resulting from degradation by the cytochrome P-450 2D6 isoenzyme. Dextrorphan is serotonergic and blocks N-methyl-D-aspartate glutamate receptors.10
Patients who are extensive metabolizers of CYP-450 2D6 substrates show higher blood dextrorphan and increased potential to abuse dextromethorphan for its dissociative and hallucinogenic effects.10,11
Mr. F responded well to risperidone when he wasn’t abusing cold tablets. After his last hospitalization, we referred him to a comprehensive outpatient program that could have addressed his cold medicine abuse and reintegrated him into the workplace. He avoided seeing the clinic psychiatrist, however, after promising his case manager that he would stop abusing dextromethorphan.
TREATMENT: Back to Betelgeuse
Upon re-admission, we restart risperidone, 6 mg nightly. Mr. F shows extreme somnolence caused by massive cold capsule use and is minimally cooperative with the psychiatrist’s follow-up interview. Over 36 hours, he awakens only for meals and medication and to use the bathroom. Once the somnolence passes, he cannot fall asleep at night.
Six days after admission, Mr. F is organized and hears voices mostly from Jesus with some demonic delusions. Extended urine drug screen taken 3 days after admission shows traces of chlorpheniramine but no dextromethorphan.
By day 7, Mr. F is nearly free of delusions and is discharged the next day. We continue risperidone, 6 mg nightly, to prevent the “voices,” and add diphenhydramine, 50 mg nightly, to regulate his sleep. We arrange follow-up care at an outpatient clinic, but Mr. F again avoids the clinic psychiatrist.
The authors’ observations
Mr. F’s “robo” binge triggered a profound and prolonged psychotic decompensation.
Dextrorphan—a pharmacologically active metabolite of dextromethorphan— might have disrupted cortical and sub-cortical glutamatergic neurotransmission,6 leading to florid psychosis and delayed recovery. Induction of the cytochrome P-450 2D6 isoenzyme, which metabolizes dextromethorphan, also could have prolonged Mr. F’s psychosis (Box 1).7-11
RELAPSE: Return visits
Three weeks after discharge, Mr. F fights with police officers after they find him hallucinating in the streets. Police charge him with disorderly conduct and resisting arrest and bring him back to the psychiatric ER. We again resolve his auditory hallucinations with risperidone, 6 mg nightly. After 8 days we discharge him to police, who then transport him to jail and later release him on bail.
Six months later, Mr. F is hospitalized twice in 2 months after dextromethorphan-induced decompensations. He recovers quickly both times but lacks insight into his mental illness and his “robo” problem.
The authors’ observations
Dextromethorphan, known by many street names (Box 2), is contained in more than 100 OTC preparations, and is sold on the Internet in powder form.
