Dextromethorphan is a dextroisomer of codeine with a chemical structure similar to opioids with the potential for abuse at high doses. We describe a patient presenting with dextromethorphan intoxication whose psychosis did not resolve after several days of inpatient treatment, prompting further investigation that revealed covert neurosyphilis.
A 24-year-old man with a reported history of “schizophrenia from cough and cold pills,” a diagnosis he reported he had received from employees at a dollar store, presented to the emergency department (ED) stating that he had been travelling between cities but could not find a bus. He was thus trying to walk to the next city, until he was forced to seek treatment for severe scrotal pain in the context of a history of scrotal warts. Per ED notes, he originally presented for abscesses of the scrotum, but he appeared confused and psychotic. He denied prior psychiatric treatment or hospitalization. Initially, he was disoriented to date but relatively oriented to self, city, and hospital (although not to hospital name). He was disheveled, malodorous, and unkempt. A physical examination indicated the presence of multiple irritated condylomas. Laboratory tests indicated elevated creatinine (1.61 md/dL), elevated aspartate aminotransferase (52 unit/L), and low glomerular filtration rate (53 mL/min). Urinary toxicology was negative. Due to thought disorganization and internal stimulation, he was admitted to an inpatient psychiatric unit.
The patient believed the admission was to address his drug problem, so he described a history of heavy dextromethorphan misuse beginning at age 18 years. It was unclear from his history if he had ever been prescribed dextromethorphan, and he was currently abusing over-the-counter (OTC) cold and cough tablets that contain dextromethrophan. During his initial psychiatric interview, he revealed sometimes using an entire box of OTC cold and cough tablets that contain dextromethorphan, “to feel like something special.” He could not estimate the frequency of his dextromethorphan abuse, nor could he describe how he paid for it. He reported a history of multiple overdoses on dextromethorphan from OTC cold medication and alcohol in the previous year, but later denied significant alcohol use. He endorsed cannabis use 1 to 3 times a month, adding that marijuana made him paranoid. He endorsed auditory and visual hallucinations. On admission, he was homeless and unemployed but said he received money from people “who do favors” for him. He identified as homosexual and had been sexually active since age 18 years. He denied prostitution but endorsed having sex “to make friends.” He denied any association between sexual relations and dextromethorphan use because it inhibited his sexual performance.
Collateral information obtained from his mother indicated good premorbid functioning. He was accepted at a local college but struggled with performance and attendance. After age 18 years, his mother said he began “acting out,” abusing dextromethorphan (from cough syrup), and was often aggressive upon withdrawal. He became increasingly disheveled, stopped showering, and was “living like a bum.” At the time of admission, his parents had not communicated with him in more than 1 month.
Risperidone at a dose of 0.5 mg twice daily was started on admission and titrated to 1 mg twice daily to target his psychotic symptoms. The risperidone was used to help control symptomatology with the initial hope that he would recover as the dextromethorphan was metabolized. It was our belief that the patient was struggling with substance-induced psychosis; however, his symptoms did not improve during hospitalization despite the structured setting and compliance with risperidone. He remained pleasantly disorganized and reported persistent disturbing auditory and visual hallucinations. These resistant symptoms, despite escalating doses of antipsychotics and time for dextromethorphan withdrawal, indicated other causes for psychosis and prompted further investigation.
Medical examination of scrotal and anal lesions while in the ED revealed that he was suffering from herpes virus, prompting initiation of a course of acyclovir and more aggressive evaluation for potential infectious or sexually transmitted diseases. HIV testing was negative, but rapid plasma reagin (RPR) testing was reactive, with a titer of 1:256. A test for syphilis IgG was conducted and showed an antibody index value greater than 8. The infectious disease department was consulted. Due to the elevation in syphilis antibodies, inefficacy of medications, and dextromethorphan detoxification, he underwent a lumbar puncture. CSF examination revealed a reactive VDRL (1:8) and lymphocytes (56 nucleated cells). Brain magnetic resonance imaging did not demonstrate any significant atrophy, mass effect, or changes in vasculature. There was no evidence of syphilitic gummas on brain imaging. These laboratory results indicated the presence of neurosyphilis, which was believed to be the cause of his psychotic symptoms.
This diagnosis prompted initiation of intravenous penicillin G at a dose of 4 million units every 4 hours for 2 weeks while hospitalized.1 The patient was discharged to a nursing facility for continued treatment. He stayed for the initial 2 weeks of treatment, and after 2 weeks laboratory tests revealed a persistently positive RPR indicating a need for continued penicillin G. However, before he could receive an additional 2 weeks of penicillin G, he had secretly left the nursing facility so recommendations could not be communicated. We received a report that he was seen 1 month later in an ED in a neighboring city for alcohol intoxication and altered mental status; he was discharged after receiving intravenous fluids.
Dextromethorphan is found in many readily available cough and cold medications. Approximately 5% of people age 12 to 35 years misuse these medications, which among other ingredients contain dextromethorphan, and misuse/abuse/overdose accounts for 8 of every 100,000 ED visits per year.2 Slang names for dextromethorphan include “purple drank,” “poor man's PCP,” “DXM,” “skittles,” “triple C,” “candy DEX”, “Drex,” “red devil,” “rojo,” “Tussin,” “velvet,” and “vitamin D.”2
Ingesting more than 600 mg of dextromethorphan from OTC cough syrup typically causes symptoms of dissociation, disinhibition, a sense of well-being, bizarre auditory and visual (and more rarely tactile) hallucinations, thought blocking, and thought disorganization.3 At extremely high doses, dextromethorphan can result in coma.4 The psychogenic properties are due to the active metabolite of dextromethorphan, dextrophan, which is an NMDA receptor antagonist.5 In high doses, this may create an effect similar to phencyclidine,6 and urine toxicology may reveal a false positive for phencyclidine.2 Additionally, dextromethorphan may also create a hyperserotonergic state via presynaptic reuptake inhibition.2 In the peripheral nervous system, it may cause hypertension, tachycardia, and diaphoresis,2 and at high doses may be cardiotoxic.5 Importantly, in reference to our case, the literature suggests that resolution of intoxication symptoms typically occurs within 3 to 4 days of discontinuation, and psychotic symptoms often remit without the use of antipsychotics.6
Syphilis is a multisystem disease caused by T. pallidum and has been described as the “great masquerader,” as it may present with a wide array of clinical symptoms and mimic a variety of other diseases. Neurosyphilis can occur during any stage of syphilis7 and presenting at any time from within a few months to years after the initial infection. However, much of the literature describes a 10- to 25-year period before symptoms present,8 with up to 30% of untreated syphilis cases resulting in central nervous system invasion.9 Syphilis often targets the meninges and vasculature, and invasion of the meninges may frequently result in gummas that can be mistaken for tumors.10 In the past 15 years, there has been a 10-fold increase in the rate of syphilis,7 with homosexual men most likely to contract it. Additionally, HIV has been associated with this recent rise in neurosyphilis.10 As a result of this increase, in 2004, the US Preventive Services Task Force recommended routine screening for syphilis in patients with risk factors.9 The World Health Organization reports that 60% of syphilis cases in 2008 were in Africa or Southeast Asia.10
The disease often presents initially with worsening cognition and memory deficits,8 and as it progresses it can present as mania, depression, or psychosis.5 Literature review reveals several case reports of neurosyphilis, typically presenting in middle-age or older adult patients. One report described a middle-aged man presenting with 1 year of personality changes, aggression, and hallucinations secondary to neurosyphilis, progressing eventually to dysarthria and incontinence.8 Another case described a 53-year-old man with new onset persecutory and religious delusions progressing to combativeness and incarceration, and while jailed he was diagnosed with and treated for neurosyphilis.9 Although most cases occur in middle age or later, one case described a 15-year-old girl presenting with visual hallucinations, persecutory delusions, and parkinsonian symptoms 2 years after being exposed to syphilis,11 reminding us that it is possible for this disease to quickly spread to the central nervous system.
This patient's presentation is notable for several confounders, including his younger age (24 years), psychogenic substance use, bizarre delusions and hallucinations, and an apocryphal history of schizophrenia diagnosis. Initially, his symptoms were thought to be due to significant abuse of OTC cough medications with dextromethorphan, but they did not remit in the absence of the substance. A trial of risperidone did not ameliorate his symptoms. His history of possible prostitution and the presence of genital herpes, as well as his atypical lack of response to interventions, prompted a more aggressive evaluation. This revealed his underlying neurosyphilis.
Neurosyphilis may present as changes in mentation, disorganization, or psychosis, but is difficult to treat due to difficulties of medicines penetrating the blood-brain barrier. This case is a reminder to test for syphilis (especially in the homosexual male population), and the use of OTC cough medications with dextromethorphan as a drug of abuse among youth. This case raises awareness of a systemic disease that can cause psychosis, as well as the confounding factors that may muddle this picture. We attempted to highlight the complexity inherent in differentiating between the myriad potential etiologies for psychosis while underscoring the importance of a thorough history, laboratory testing, and collateral information when assessing patients with psychotic behaviors.
- US Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines: syphilis. Accessed October 28, 2020. https://www.cdc.gov/std/tg2015/syphilis.htm
- Modi D, Bhalavat R, Patterson JC II, . Suicidal and homicidal behaviors related to dextromethorphan abuse in a middle-aged woman. J Addict Med. 2013;7(2):143–144. doi:10.1097/ADM.0b013e318281a547 [CrossRef] PMID:23388679
- Dickerson DL, Schaepper MA, Peterson MD, Ashworth MD. Coricidin HBP abuse: patient characteristics and psychiatric manifestations as recorded in an inpatient psychiatric unit. J Addict Dis. 2008;27(1):25–32. doi:10.1300/J069v27n01_03 [CrossRef] PMID:18551885
- Finkelstein Y, Goel G, Hutson JR, et al. Toxicology Investigators Consortium (ToxIC). Drug misuse in adolescents presenting to the emergency department. Pediatr Emerg Care.2017;33(7):451–456. doi:10.1097/PEC.0000000000000571 [CrossRef] PMID:26466148
- Miller SC. Dextromethorphan psychosis, dependence and physical withdrawal. Addict Biol.2005;10(4):325–327. doi:10.1080/13556210500352410 [CrossRef] PMID:16318953
- Price LH, Lebel J. Dextromethorphan-induced psychosis. Am J Psychiatry. 2000;157(2):304–304. doi:10.1176/appi.ajp.157.2.304 [CrossRef] PMID:10671422
- Nyatsanza F, Tipple C. Syphilis: presentations in general medicine. Clin Med (Lond). 2016;16(2):184–188. doi:10.7861/clinmedicine.16-2-184 [CrossRef] PMID:27037391
- Toptan T, Ozdilek B, Kenangil G, Ulker M, Domac FM. Neurosyphilis: a case report. North Clin Istanb. 2015;2(1):66–68. doi:10.14744/nci.2015.96268 [CrossRef] PMID:28058343
- Faden J, O'Reardon J. Misdiagnosed neurosyphilis associated with prolonged psychosis. Acta Neuropsychiatr.2016;28(6):362–364. doi:10.1017/neu.2016.23 [CrossRef] PMID:27264158
- Marra CM. Neurosyphilis. Continuum (Minneap Minn). 2015;21(6):1714–1728. doi:10.1212/CON.0000000000000250 [CrossRef] PMID:26633785
- Yin L, Zou S, Huang Y. Neurosyphilis with psychotic symptoms and Parkinsonism in a young girl. Neuropsychiatr Dis Treat. 2015;11:375–377. doi:10.2147/NDT.S76897 [CrossRef] PMID:25733837