What medications can cause muscle twitches?

Medications That Cause Muscle Twitches

Multiple drug classes can induce muscle twitches through various mechanisms, with stimulants (amphetamines, cocaine, caffeine), selective serotonin reuptake inhibitors (SSRIs), lithium, and neuromuscular blocking agents being the most common offenders. 1, 2

High-Risk Drug Categories

Stimulants and Sympathomimetics

• Amphetamines cause hyperactivity, tremors, and muscle twitching through massive dopamine efflux in the CNS and sympathomimetic effects 1, 3
• Cocaine produces similar neurobehavioral abnormalities including irritability, hyperactivity, tremors, and excessive motor activity 1
• Caffeine induces jitteriness and tremors, particularly in neonates exposed in utero, with symptoms appearing at birth and lasting 1-7 days 1, 4
• Cannabis and "ecstasy" (MDMA) are documented to trigger muscle twitching as part of their stimulant effects 1

Antidepressants

• SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram) commonly cause tremors, jitteriness, and muscle rigidity, especially during initiation or dose escalation 1, 2
• Tricyclic antidepressants (amitriptyline, desipramine) are associated with tremor as a frequent adverse effect 2
• SNRIs (serotonin-norepinephrine reuptake inhibitors) produce similar tremor profiles to SSRIs 2

Mood Stabilizers and Anticonvulsants

• Lithium is one of the most common causes of drug-induced tremor, typically producing a fine postural tremor that can progress to coarse tremor at toxic levels 2
• Valproate frequently causes tremor, particularly at higher doses 2

Cardiovascular Medications

• β-adrenoceptor agonists (salbutamol/albuterol, aminophylline) induce tremor through direct sympathetic stimulation 1, 2
• Amiodarone is associated with tremor and can cause vacuolar myopathy with chronic use 5, 2

Neuromuscular Blocking Agents

• Succinylcholine causes visible fasciculations (muscle twitching) as its initial effect before paralysis, representing depolarization of nicotinic receptors 1
• Reversal of non-depolarizing NMBAs with anticholinesterase agents (neostigmine, pyridostigmine, edrophonium) can produce muscle fasciculations and twitching 1, 6

Dopamine Antagonists and Related Agents

• Dopamine receptor antagonists (antipsychotics, metoclopramide) cause tremor and other movement disorders 2, 7
• VMAT2 inhibitors are documented causes of drug-induced tremor 2

Other Medications

• Barbiturates cause severe tremors, hyperacusis, and increased muscle tone, with onset 1-14 days after exposure and duration up to 4-6 months 1
• Benzodiazepines (chlordiazepoxide, diazepam) produce tremors and hyperreflexia, particularly during withdrawal, lasting days to weeks 1
• Hydroxyzine causes tremors, jitteriness, and myoclonic jerks 1
• Colchicine and chloroquine/hydroxychloroquine cause myopathy with associated muscle symptoms including twitching 5

Clinical Recognition and Risk Factors

Key Risk Factors

• Polypharmacy significantly increases risk of drug-induced tremor 2
• Male gender and older age are associated with higher susceptibility 2
• High doses and immediate-release preparations increase tremor risk 2
• Toxic drug levels (particularly lithium, valproate, digoxin) commonly manifest with tremor 1, 2

Distinguishing Features

• Drug-induced tremor typically resembles essential tremor (postural/action tremor) or parkinsonian tremor (rest tremor) depending on the offending agent 2
• Sudden onset of tremor in a patient on new medication strongly suggests drug etiology 2
• Tremor that is bilateral and symmetric is more typical of drug-induced causes 2

Critical Management Principles

Immediate Actions

• Discontinue the offending medication when drug-induced muscle twitching is suspected—this is the primary intervention 5, 2
• Drug-induced tremor usually resolves after medication discontinuation, though tardive tremor (persistent tremor) may occur in some cases 2
• Monitor for complete or incomplete resolution after drug withdrawal as a diagnostic criterion 5

Important Caveats

• Rechallenge is not advisable due to risk of serious relapse of myotoxicity 5
• Some drug-induced myopathies require vigorous surveillance when high-risk combinations are used (e.g., fibrate plus statin, cyclosporin plus colchicine) 5
• For organophosphate pesticides and nerve agents (sarin), muscle fasciculations and paralysis result from permanent acetylcholinesterase inhibition 1

Drug Interactions That Increase Risk

• CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) increase exposure to amphetamines and risk of neurotoxicity 3
• MAO inhibitors with amphetamines can cause severe neurological toxic effects including malignant hyperpyrexia 3
• Multiple drugs with serotonergic properties used together increase risk of serotonin syndrome with associated muscle rigidity and myoclonus 3

1, 3, 4, 5, 2, 7