Cholinergic Crisis Due to Ingrezza: Critical Clarification
Ingrezza (valbenazine) does not cause cholinergic crisis—it is a vesicular monoamine transporter 2 (VMAT2) inhibitor used to treat tardive dyskinesia and does not have anticholinesterase activity. 1 This question appears to be based on a fundamental misunderstanding of the drug's mechanism of action.
Understanding the Confusion
- Ingrezza's mechanism: Valbenazine reversibly inhibits VMAT2, reducing dopamine release at synapses, which helps control involuntary movements in tardive dyskinesia 1
- Cholinergic crisis causes: True cholinergic crisis results from excessive acetylcholine accumulation due to anticholinesterase agents (organophosphates, nerve agents, or pharmaceutical cholinesterase inhibitors like distigmine or pyridostigmine) 2, 3, 4
- No mechanistic overlap: Ingrezza does not inhibit cholinesterase and therefore cannot cause acetylcholine accumulation or cholinergic crisis 1
If True Cholinergic Crisis Is Present
If a patient on Ingrezza develops symptoms concerning for cholinergic crisis, consider alternative causes:
Actual Cholinergic Crisis Treatment Algorithm
First-line intervention:
- Atropine 2-4 mg IV initially for adults, repeated at 5-10 minute intervals until secretions are controlled and muscarinic symptoms resolve 3
- Pediatric dosing: 0.02-0.05 mg/kg IV, with maximum single dose of 2-3 mg, repeated as needed 3, 5
- Cumulative doses may reach 10-20 mg in first 2-3 hours or up to 50 mg in 24 hours before full muscarinic antagonism appears 2, 3
Second-line intervention:
- Pralidoxime (2-PAM) 1000-2000 mg IV over 15-30 minutes for adults to reactivate cholinesterase at nicotinic receptors and reverse muscle paralysis 3
- Pediatric dosing: 20-50 mg/kg IV 3
- Must be given early before "aging" of the enzyme-inhibitor bond makes reactivation impossible 2
Seizure control:
- Benzodiazepines (diazepam 0.2 mg/kg or midazolam 0.05-0.1 mg/kg IV) for anxiety, agitation, or seizures 2, 3
Supportive care:
- Secure airway and provide mechanical ventilation if respiratory muscle paralysis present 3, 4
- Frequent airway suctioning for excessive secretions 3
- Avoid succinylcholine as it may cause prolonged paralysis 3
- Cardiovascular support with fluids and vasopressors for hypotension 3
- Continuous cardiac monitoring for bradycardia and arrhythmias 3
Common Pitfalls
- Underdosing atropine: Severe cholinergic crisis requires much larger atropine doses than standard cardiac dosing—do not hesitate to give repeated doses until secretions dry 2, 3
- Delayed pralidoxime: Oximes must be given promptly before enzyme aging occurs (within minutes to hours depending on the agent) 2
- Misdiagnosis: In elderly patients, cholinergic crisis is often misdiagnosed as aspiration pneumonia, delaying appropriate treatment 6
Conclusion on Ingrezza
Ingrezza cannot cause cholinergic crisis. If cholinergic symptoms develop in a patient taking Ingrezza, investigate other exposures to anticholinesterase agents (medications like distigmine for neurogenic bladder, organophosphate pesticides, or other environmental exposures) 4, 6. The treatment algorithm above applies only to true cholinergic crisis from anticholinesterase poisoning, not to any adverse effects of valbenazine.