- USES: BusPIRone is used for anxiety disorders. PHARMACOLOGY: BusPIRone is mainly a partial agonist at the serotonin receptor 1A (5-HT1A) and has some antagonist effects on the D2 dopamine receptor. TOXICOLOGY: The toxic effects are an extension of the pharmacology. Serotoninergic effects may be observed when used in combination with other serotoninergic agents. EPIDEMIOLOGY: Poisoning with busPIRone is only rarely reported, probably because it is not widely used. MILD TO MODERATE POISONING: Somnolence, dizziness, irritability, nausea. Worsening anxiety may be observed even with therapeutic doses. SEVERE POISONING: CNS depression, serotoninergic effects (ie, hyperreflexia, clonus, altered mental status, hemodynamic instability) may be observed in combination with other serotoninergic agents. Seizures and delirium have been reported. Akathisia, tremor, and rigidity may be observed with higher doses. Sustained bradycardia was reported after coingestion with fluvoxamine. ADVERSE EFFECTS: Somnolence, dizziness, irritability, blurred vision, headache, nausea, vomiting.
Range of Toxicity:
- TOXICITY: Expect mild toxicity in busPIRone naive patients even at therapeutic dosages. Adding busPIRone to an established therapy with serotoninergic agents may lead to serotonin toxicity. Healthy adults have tolerated 375 mg/day for 30 days with minimal side effects. THERAPEUTIC DOSE: ADULTS: Anxiety: The recommended initial dose is 15 mg daily (7.5 mg twice daily). The dose may be increased by 5 mg/day every 2 to 3 days as needed, to a maximum dose of 60 mg/day. Depression: Doses up to a maximum of 90 mg/day have been used. CHILDREN: Safety and efficacy in children less than 18 years of age have not been established.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Primarily supportive care; activated charcoal may be helpful in patients presenting shortly after ingestion. Give benzodiazepines titrated to effect for anxiety and seizures. MANAGEMENT OF SEVERE TOXICITY: Consider activated charcoal if patients present early after ingestion and are alert or airway is protected. Give benzodiazepines for anxiety, agitation, delirium, and seizures. Treat serotonin toxicity with benzodiazepines, cyproheptadine.
- Decontamination: PREHOSPITAL: Not recommended because of potential for somnolence and seizures. HOSPITAL: Activated charcoal if recent, substantial ingestion, and patient is able to protect airway. Gastric lavage is not generally indicated as life-threatening toxicity is very rare.
- Airway management: Early orotracheal intubation in patients with signs of severe intoxication (ie, CNS depression, seizures, agitation).
- Antidote: None
- Seizure: IV benzodiazepines, barbiturates.
- Serotonin syndrome: Benzodiazepines are the mainstay of therapy. Cyproheptadine, a 5-HT antagonist, is also commonly used. Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with non-depolarizing agents.
- Monitoring of patient: Monitor vitals signs and mental status. BusPIRone plasma levels are not clinically useful or readily available. No specific lab work is needed in most patients. Monitor creatinine phosphokinase and lactate levels in patients with prolonged agitation, seizures, or coma. Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (ie, agitation, seizures, coma, serotonin toxicity).
- Enhanced elimination procedure: There is no role for repeat-dose activated charcoal. Hemodialysis is not useful given the large volume of distribution and high protein binding.
- Patient disposition: HOME CRITERIA: There are no data on pediatric ingestions that can be managed at home; however, given the low toxicity, asymptomatic children with inadvertent overdoses can probably be managed at home. ADMISSION CRITERIA: Admit patients with CNS depression, exacerbated anxiety, agitation, seizure, or suicidal behavior. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, CNS depression, seizures, agitation, serotonin toxicity), or in whom the diagnosis is not clear.