A 16-year-old girl is brought to the emergency department by her parents for evaluation of bizarre behavior. The patient was found in her bedroom surrounded by broken lamps and ripped-up notebooks. Her father says, "She's been a bit irritable for the past few days, probably because she's been studying for final exams nonstop. We heard some noises in the middle of the night and found her wide awake and unable to sit still." The patient has no medical conditions and no psychiatric history; she takes diphenhydramine as needed when she cannot sleep. Family history is significant for bipolar disorder in the patient's older sister. Temperature is 37.6 C (99.7 F), blood pressure is 150/90 mm Hg, pulse is 120/min, and respirations are 18/min. On physical examination, the patient appears diaphoretic and restless. During the cardiovascular examination, the patient removes the physician's stethoscope and says, "I need to get home and finish my paper. It's due in a few hours." Which of the following is the most appropriate pharmacotherapy for this patient?
This patient's agitated and restless behavior, irritability, insomnia, and physical findings of sympathetic hyperactivity in the setting of a protracted period of intense studying are most likely due to stimulant intoxication. Misuse of stimulants, especially prescription stimulants (eg, for attention deficit hyperactivity disorder [ADHD]), is relatively common, with amphetamine-style stimulants representing the second most common illicitly used class of drugs worldwide.
A high-risk group is students, as in this high-school student preparing for final examinations. Misuse is also particularly prevalent on college campuses, where students value being able to remain awake and alert for extended study hours. Manifestations of sympathetic hyperactivity (eg, hypertension, tachycardia, diaphoresis, hyperthermia, mydriasis) are characteristic. Psychiatric symptoms include anxiety, irritability, agitation, and, in severe cases, paranoid psychosis. Cardiac arrhythmias, movement disorders, and seizures can occur in overdose.
In addition to supportive measures, benzodiazepines (eg, lorazepam) are considered first-line therapy to control the psychomotor agitation and sympathetic hyperactivity caused by acute stimulant intoxication. With methamphetamine intoxication, benzodiazepines blunt CNS catecholamine release, with improvements in blood pressure, heart rate, and hyperthermia.
(Choice A) Clonidine is an alpha-adrenergic agonist used in the management of ADHD, opioid withdrawal, and treatment-resistant hypertension. There is no convincing evidence of benefit for the use of clonidine to treat stimulant intoxication.
(Choice B) Although agitation, irritability, and insomnia may be seen in the manic phase of bipolar disorder, this patient's prominent signs of sympathetic hyperactivity in the setting of staying up late to study make stimulant intoxication more likely. In addition, the patient's young age and short duration of symptoms do not support a diagnosis of mania. Lithium is a first-line treatment for bipolar disorder but would not be effective in controlling acute agitation and sympathetic hyperactivity.
(Choice D) Physostigmine is an antidote for anticholinergic poisoning. Although agitation, tachycardia, hypertension, and hyperthermia may be present in both anticholinergic and stimulant toxicity, this patient has diaphoresis (not dry skin and mucous membranes) and lacks other classic anticholinergic signs (eg, urinary retention, decreased bowel sounds).
(Choice E) Beta blockers (eg, propranolol) are not recommended to treat stimulant toxicity because the unopposed alpha-adrenergic vasoconstriction can worsen hypertension. The hypertension associated with stimulant intoxication is generally well controlled with benzodiazepines.
(Choice F) Antipsychotic medications (eg risperidone) are not used as first-line treatment for acute stimulant toxicity due to the risk of lowering the seizure threshold that is already lowered in the setting of stimulant intoxication. Benzodiazepines are superior for treating stimulant intoxication.
Educational objective:
Stimulant misuse should be considered in patients with psychomotor agitation and signs of sympathetic hyperactivity. Benzodiazepines are the treatment of choice.