Acting strange after trying to ‘get numb’

CASE Numb and confused
Mr. L, age 17, is admitted to the hospital after ingesting 24 diphenhydramine 25-mg tablets in 3 hours as a possible suicide attempt. His parents witnessed him behaving strangely and brought him to the hospital. They state that their son was visibly agitated and acting inap­propriately. He was seen talking to birds, trees, and the walls of the house.

Mr. L says he is upset because he broke up with his girlfriend a week earlier after she asked if they could “take a break.” He says that he took the diphenhydramine because he wanted to “get numb” to deal with the emotional stress caused by the break-up.

After the break-up, Mr. L experienced middle-to-late insomnia and was unable to get more than 3 or 4 hours of sleep a night. He reports significant fatigue, depressed mood, anhedonia, impaired concentration, and psy­chomotor retardation. He denies homicidal ide­ation or auditory and visual hallucinations.

As an aside, Mr. L reports that, for the past year, he had difficulties with gender identity, sometimes thinking that he might be better off if he had been born a girl and that he felt uncomfortable in a male body.

Which treatment option would you choose for Mr. L’s substance abuse?
a) refer him to a 12-step program
b) begin supportive measures
c) administer activated charcoal
d) prescribe a benzodiazepine to control agitation

The authors’ observations
As youths gain increasing access to medical and pharmaceutical knowledge through the Internet and other sources, it appears that adolescent drug abuse has, in part, shifted toward more easily attain­able over-the-counter (OTC) medications. Diphenhydramine, a first-generation anti­histamine, can be abused for its effects on the CNS, such as disturbed coordination, irritability, paresthesia, blurred vision, and depression. Effects of diphenhydramine are increased by the presence of alcohol, monoamine oxidase inhibitors, diazepam, hypnotics, sedatives, tranquilizers, and other CNS depressants. In 2011, diphen­hydramine abuse was involved in 19,012 emergency room visits, of which 9,301 were for drug-related suicide attempts.¹

Diphenhydramine is an inverse agonist of the histamine H1 receptor.² It is a mem­ber of the ethanolamine subclass of antihis­taminergic agents.³ By reversing the effects of histamine on capillaries, diphenhydramine can reduce the intensity of allergic symptoms. Diphenhydramine also crosses the blood–brain barrier and antagonizes H1 receptors centrally.

Used as a common sleep aid and allergy medication, the drug works primarily as an H1 receptor partial agonist, but also is a strong competitive antagonist at musca­rinic acetylcholine receptors.4 It is abused for its sedative effects and its capacity to cause delirium and hallucinations.5 Diphenhydramine can have a stimula­tory effect in children and young adults, instead of the sedating properties seen in adults.6 Such misuse is concerning because diphenhydramine overdose can lead to delirium, confusion, and halluci­nations, tachycardia, seizures, mydria­sis, xerostomia, urinary retention, ileus, anhidrosis, and hyperthermia. In severe cases it has been associated with cardiac arrhythmias, rhabdomyolysis, status epi­lepticus, and death.4,6 Neurologic symp­toms of diphenhydramine overdose are listed in Table 1.

HISTORY Polysubstance abuse
Mr. L has a 2-year history of major depressive disorder and a history of Cannabis abuse with physiological dependence; Robitussin (base active ingredient, guaifenesin) and hydroco­done abuse with physiological dependence; 3,4-methylenedioxymethamphetamine (MDMA) abuse; and diphenhydramine abuse. He also has a history of gender dysphoria, although he reports that these feelings have become less severe over the past year.

Mr. L attends bi-weekly appointments with an outpatient psychiatrist and report­edly adheres to his medication regimen: fluoxetine, 40 mg/d, and risperidone, 1 mg at bedtime. He denies previous suicidal ide­ation, suicide attempts, homicidal ideation, or homicidal attempts. He reports no history of physical, sexual, or emotional abuse. He gets good grades in school and has no outstanding academic problems.

Mr. L began using Cannabis at age 14; his last use was 3 weeks before admission. He is guarded about his use of Robitussin, hydroco­done, and MDMA. However, Mr. L reports that he has researched diphenhydramine on the internet and believes that he can safely take up to 1,200 mg without overdosing. He reports normally taking 450 mg of diphenhydramine daily. Mr. L reports difficulty urinating after using diphenhydramine but no other physical complaints.

Mr. L lives with his father and stepmother and has a history of one psychiatric hospital­ization at a different facility 2 months ago, fol­lowed by outpatient therapy. He obtained his Graduate Equivalency Diploma (GED) and plans to attend college.

At age 5, Mr. L emigrated from Turkey to the United States with his parents. His mother returned to Turkey when he was age 6 and has had no contact with her son since. Whenever Mr. L visits Turkey with his father, the patient refuses to see her, as per collaterals. He gets along well with his stepmother, who is his maternal aunt. Mr. L has been bullied at school and reportedly has few friends.