Can Neostigmine Overdose Cause Muscle Twitches?
Yes, neostigmine overdose can cause muscle twitches (fasciculations) as part of excessive nicotinic receptor stimulation, which is a hallmark feature of cholinergic crisis. 1, 2
Mechanism of Muscle Twitches in Overdose
Neostigmine inhibits acetylcholinesterase, causing acetylcholine to accumulate in the synaptic cleft, which leads to excessive stimulation of nicotinic receptors at the neuromuscular junction—this directly produces fasciculations (muscle twitches). 1, 2
Clinical Presentation of Neostigmine Overdose
The FDA label explicitly describes that overdosage can be monitored by "carefully monitoring the muscle twitch response to peripheral nerve stimulation," acknowledging that muscle twitching is an expected finding. 3
Overdose manifests as cholinergic crisis with two distinct symptom categories:
Muscarinic Symptoms
Nicotinic Symptoms (Including Muscle Twitches)
- Fasciculations (muscle twitches) as part of excessive nicotinic receptor stimulation 1
- Progressive muscle weakness that can advance through respiratory muscles 1, 3
- This weakness paradoxically occurs despite the twitching, as the sustained depolarization eventually leads to depolarizing neuromuscular blockade 4, 5
Critical Distinction: Cholinergic Crisis vs. Myasthenic Crisis
The FDA emphasizes that cholinergic crisis from neostigmine overdose is "characterized by increasing muscle weakness, and through involvement of the muscles of respiration, may result in death." 3
This is critically different from myasthenic crisis (worsening of underlying myasthenia gravis), and the distinction is "extremely important because increases in the dose of neostigmine...in the presence of cholinergic crisis...could have grave consequences." 3
Evidence of Dose-Dependent Neuromuscular Effects
Research in healthy volunteers demonstrates that even therapeutic doses (35 μg/kg) can cause depolarizing neuromuscular blockade with decreased single twitch height by 14%, and a second dose further decreased it by 25%. 4 This confirms that excessive acetylcholine from neostigmine overdose produces measurable neuromuscular dysfunction that would manifest as both twitching and weakness.
Management of Overdose with Muscle Twitches
The FDA recommends immediate withdrawal of neostigmine and prompt administration of atropine for cholinergic crisis. 3
- Atropine addresses muscarinic symptoms but does not reverse nicotinic effects (fasciculations and muscle weakness) 3
- Ventilation should be supported artificially until spontaneous respiration adequacy is assured 3
- Cardiac function must be monitored 3
Common Pitfall
Atropine can mask gastrointestinal and other muscarinic signs of overdosage, potentially leading to "inadvertent induction of cholinergic crisis" if dosing continues. 3 Therefore, the presence of muscle twitches and progressive weakness should prompt immediate cessation of neostigmine, regardless of whether muscarinic symptoms are controlled.