A young man with psychosis whose heart is racing

Case Agitated and violent
Mr. C, age 19, presents with anxiety, agitation, isolation, social withdrawal, and paranoia. He is admitted to the inpatient unit after attempting to punch his father and place him in a headlock. Mr. C has no history of mental illness, no signifi­cant medical history, and no significant family history of mental illness.

The treatment team determines that this is Mr. C’s first psychotic break. He is given a diag­nosis of psychosis, not otherwise specified and started on risperidone, titrated to 2 mg/d, later discontinued secondary to tachycardia. He is then started on haloperidol, 5 mg/d titrated to 10 mg/d, and psychotic symptoms abate. Mr. C is discharged with a plan to receive follow-up care at an outpatient mental health center.

One year later, Mr. C is readmitted with a similar presentation: paranoia, agitation, anxi­ety, and isolation. After discharge, he starts an intensive outpatient program (IOP) for long-term treatment of adults who have a diagnosis of a schizophrenia spectrum disorder.

Several medication trials ensue, includ­ing risperidone, escitalopram, citalopram, fluphenazine, lorazepam, quetiapine, and haloperidol. Despite these trials over the course of 2 years, Mr. C continues to display paranoia and agitation, and is unable to resume academic and community activities. Within the IOP, Mr. C is placed in a vocational training program and struggles to remain stable enough to continue his job at a small greenhouse.

Concurrently, Mr. C is noted to be abusing alcohol. After the IOP treatment team expresses concern about his abuse, he reduces alcohol intake and he and his parents are educated on the impact of alcohol use on schizophrenia.

Which treatment option would you choose next?
a) initiate a trial of clozapine
b) try a long-acting injectable antipsychotic
c) recommend inpatient treatment

The authors’ observations
Clozapine is an atypical antipsychotic that is FDA-approved for treatment-resistant schizophrenia; it also helps reduce recur­rent suicidal behavior in patients with schizophrenia or schizoaffective disorder.

Clozapine works by blocking D2 recep­tors, thereby reducing positive symptoms. It also blocks serotonin 2A receptors, which enhances dopamine release in certain brain regions, thereby reducing motor side effects. Interactions at 5-HT2C and 5-HT1A recep­tors may address cognitive and affective symptoms. Clozapine can help relieve nega­tive symptoms and can decrease aggression. Because it has a low risk of tardive dyskine­sia, clozapine is useful when treating patients with treatment-resistant schizophrenia.^1-3

Treatment Quick heart rate
Mr. C’s IOP treatment team considers a clo­zapine trial because previous medication tri­als failed. All paperwork for the registry and screening labs are completed and Mr. C is started on clozapine.

Mr. C’s clozapine dosages are:
• Days 1 to 9: 25 mg/d
• Days 10 to 16: 50 mg/d
• Days 17 to 23: 75 mg/d
• Days 24 to 32: 100 mg/d
• Days 33 to 37: 125 mg/d
• Day 38: 150 mg/d.

On Day 45 of the clozapine trial, Mr. C is increasingly paranoid toward his father and thinks that his father is controlling his thoughts. Mr. C tells the attending psychiatrist that he ingested a handful of clonazepam and considered putting a bag over his head with the intent to commit suicide. Mr. C is admitted to the inpatient unit.

Admission vitals recorded a heart rate of 72 beats per minute but, later that day, the rate was recorded in the vital sign book as 137 beats per minute. The treatment team considers dehydration, anxiety, and staff error; Mr. C is observed carefully. Over the next 2 days, heart rate remains between 102 and 119 beats per minute.

Because of persistent tachycardia, the team orders lab studies, a medical consult, and an electrocardiogram (ECG). Thyroid panel, elec­trolytes, and clozapine level are within normal limits; ECG is unremarkable.

Although tachycardia is a known side effect of clozapine,^3,4 we order an echocar­diogram because of Mr. C’s young age and non-diagnostic laboratory workup. The echo study demonstrates reduced left-ventricular ejection fraction (LVEF) of 45%. Tests for HIV infection and Lyme disease are negative. The cardiology team diagnoses cardiomyopathy of unknown origin.

Although Mr. C has a history of alcohol abuse, the cardiology team believes that alco­hol consumption does not adequately explain the cardiomyopathy, given his young age and the limited number of lifetime drinking-years (approximately 4 or 5); the team determines that clozapine is causing secondary cardiomy­opathy and tachycardia, leading to reduced LVEF. Clozapine is stopped because the rec­ommended treatment for toxic secondary cardiomyopathy is to remove the offending agent. At this point, the clozapine dosage is 250 mg/d.

At the medical team’s recommendation, Mr. C is started on metoprolol, a beta blocker, at 25 mg/d.