Psychosis Precipitated by Mephentermine Use in An Adult Male

Dear Editor,

Mephentermine is an alpha- adrenergic receptor agonist indicated for treating hypotensive states commonly seen in spinal anesthesia, shock, and myocardial infarction. The compound is often misused for its performance-enhancing properties by competitive athletes and bodybuilders. However, data on its dependence potential and propensity to induce psychosis are limited. Greenberg and Lustig ¹ published the first such report of four cases where people developed visual hallucinations following the ingestion of a nasal decongestant preparation of mephentermine. Subsequently, a few other cases of mephentermine-related psychosis have been reported from India.^2–4 We report a case of mephentermine-precipitated psychosis, with a unique time course for appearance and resolution of symptoms, in a young Indian adult bodybuilder.

Case Description

Mr. B was a 32-year-old married physical fitness trainer who presented to the outpatient department with a history of self-administering mephentermine intramuscularly for the past 9 months to improve his tournament performance. Reported symptoms were severe irritability, assaultive tendencies, persecutory and referential delusions, poor sleep, appetite, and personal care for two weeks. On probing, he admitted that he had started with a dose of 30 mg weekly intramuscular injections and gradually increased it to 200 mg/day, in divided doses, over 3 months. The increase in dose was ascribed to tolerance to its effect, withdrawal (fatigue, disturbed appetite, and a sense of dysphoria), and craving. He denied using other psychoactive substances. There was no history of any medical, surgical, or psychiatric illness. His hemogram, metabolic panel, and electrocardiograph (ECG) were unremarkable. The urine screen for other psychoactive substances was negative. There was no contributory past or family history of psychosis. We made a provisional diagnosis of stimulant-induced psychotic disorder.

Since he was unmanageable and reluctant to take oral medicines, we stopped mephentermine, admitted and initiated him on parenteral haloperidol 10 mg and lorazepam 4mg, divided twice daily, given his symptom severity. His aggressive behavior subsided in 3 days, and he agreed to take oral medications. On the fourth day, he was started on Tab. Olanzapine 10mg twice daily in addition to parenteral pro re nata (PRN) haloperidol and lorazepam to control aggression. After 10 days, his aggressive and assaultive tendencies had significantly reduced and his delusions had resolved. On the 11th day, he was discharged and, at follow-up, oral Olanzapine was successfully tapered and stopped over 3 months. Given the severity of his initial presentation, the slow taper-stop was a collaborative decision in consultation with the family. He continued to remain asymptomatic during further follow-up and had not taken mephentermine since then. The Naranjo scale score was 6 (Table 1), indicating a probable association of psychosis with mephentermine use. The patient provided a written consent for publication of this report.

Table 1.

Naranjo Adverse Drug Reaction Probability Scale Score.

Question	Score Obtained
1. Are there previous conclusive reports on this reaction?	1
2. Did the adverse event appear after the suspected drug was administered?	2
3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?	1
4. Did the adverse event reappear when the drug was re-administered?	0
5. Are there alternative causes (other than the drug) that could on their own have caused the reaction?	2
6. Did the reaction reappear when a placebo was given?	0
7. Was the drug detected in blood (or other fluids) in concentrations known to be toxic?	0
8. Was the reaction more severe when the dose was increased or less severe when the dose was decreased?	0
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	0
10. Was the adverse event confirmed by any objective evidence?	0
Total	6

Discussion

Mephentermine-induced psychosis has been described in two young male weightlifters who injected mephentermine to enhance their performance for which they received oral low-dose antipsychotics. Improvement occurred as early as within 2 days of starting antipsychotics.^4,5 In one of these reports, the index patient had a previous history of amphetamine-induced psychosis; ⁵ however, similar reactions have been reported in those with no such risk factors, too. ⁶ In all these cases, psychotic symptoms emerged within days to weeks of initiating the substance or hiking its dose. In the index case, the onset of psychosis occurred after a gap of around ten weeks following a self-determined hike in mephentermine dosing. Stoppage of the offending drug, coupled with antipsychotic treatment, entirely resolved psychotic symptoms in 10 days, supporting the diagnosis of substance-induced psychosis over an independent psychosis. A prior report has described a similar time course for the appearance and attenuation of mephentermine-related psychotic symptoms. ⁷

Our findings add to the body of evidence on mephentermine-related psychosis. Specifically, the relatively delayed onset of psychosis in a patient with no known risk factors following the use of mephentermine is not a typical presentation. More data are needed on the long-term course and outcome of psychosis following mephentermine use. Additionally, there is a need to build awareness among sports professionals regarding the adverse effects of psychostimulants. Enriched surveys of stimulant use among youth and adults visiting gymnasiums or fitness clubs may help gauge the extent of the problem. Specific rules and enforcement by authorities targeting the procurement and use of stimulants may be helpful. We hope this report sensitizes readers to the possibility of delayed onset psychosis among those using not-so-high doses of mephentermine.