What is Drug-Induced Myoclonus?
Myoclonus is an involuntary movement disorder characterized by sudden, brief, shock-like jerking or twitching of a muscle or group of muscles [1.2.5]. When this condition is triggered as a side effect of a medication, it is known as drug-induced myoclonus [1.3.8]. These movements can range from minor, localized twitches to generalized jerks that affect the entire body. The presentation can be focal, multifocal, or generalized, and can occur at both therapeutic and toxic doses of a drug [1.4.1, 1.4.4]. Risk factors that can increase susceptibility include renal or hepatic dysfunction, polypharmacy (using multiple medications), advanced age, and pre-existing neurological conditions [1.3.1, 1.4.1].
Common Drug Classes That Cause Myoclonus
A vast array of medications across several pharmacological classes has been associated with myoclonus. It's a recognized adverse effect, though its exact frequency can be hard to determine as it often relies on case reports [1.6.1].
Opioids
Opioids, frequently used for pain management, are a well-documented cause of myoclonus. This side effect can occur with oral, intravenous, or intrathecal administration and is often associated with high doses, although it can be unpredictable [1.5.1, 1.5.5]. The accumulation of neuroexcitatory metabolites, especially in patients with renal impairment, is thought to play a significant role [1.5.2, 1.5.5].
- Common Examples: Morphine, Fentanyl, Hydromorphone, Tramadol, Methadone, Meperidine [1.2.1, 1.5.2, 1.5.6].
Antidepressants
All classes of antidepressants have been reported to cause myoclonus [1.4.1]. Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs) are commonly implicated [1.4.2]. The risk increases significantly when these are combined with other serotonergic drugs, potentially leading to serotonin syndrome, a serious condition where myoclonus is a key feature [1.4.1].
- SSRI Examples: Fluoxetine, Sertraline, Citalopram, Escitalopram [1.2.2, 1.4.1].
- TCA Examples: Amitriptyline, Clomipramine, Imipramine [1.4.1].
- Other Antidepressants: Venlafaxine (SNRI), Bupropion, Mirtazapine [1.2.9, 1.4.1].
Antipsychotics
Both typical and atypical antipsychotics can induce myoclonus, often as part of a spectrum of extrapyramidal side effects [1.2.2]. Clozapine, in particular, has a notable association with myoclonus, with incidence rates varying widely in reports [1.6.3]. The risk can be dose-dependent and may be higher during the initial titration phase [1.6.3].
- Common Examples: Clozapine, Olanzapine, Risperidone, Quetiapine, Haloperidol [1.2.2, 1.4.3].
Anticonvulsants
Ironically, some drugs used to treat seizures (epilepsy) can also cause or worsen myoclonus, particularly in patients with pre-existing myoclonic epilepsy syndromes [1.2.7]. Medications like gabapentin and pregabalin are known to induce myoclonus, especially in patients with impaired renal function, which can lead to toxic accumulation [1.2.4].
- Common Examples: Gabapentin, Pregabalin, Lamotrigine, Phenytoin, Carbamazepine, Valproic Acid, Vigabatrin [1.2.1, 1.2.4].
Antibiotics
Certain classes of antibiotics are known to have neurotoxic potential, leading to myoclonus. This is particularly prevalent in patients with renal failure, where drug clearance is reduced [1.2.4]. Penicillins, cephalosporins, and quinolones are among the most frequently cited [1.2.1, 1.6.2].
- Common Examples: Penicillins, Cephalosporins (e.g., Cefepime), Fluoroquinolones (e.g., Ciprofloxacin), Carbapenems [1.2.1, 1.6.1].
Other Notable Medications
- Anesthetics: Propofol, Etomidate, and Lidocaine can cause myoclonus during induction or administration [1.2.1].
- Cardiac Medications: Certain drugs used for heart conditions, such as amiodarone and some calcium channel blockers, have been linked to myoclonus [1.2.1, 1.4.1].
- Chemotherapeutic Agents: Several agents used in cancer treatment, including ifosfamide and chlorambucil, can cause myoclonus [1.2.1, 1.6.2].
- Lithium: Used as a mood stabilizer, lithium can cause myoclonus, especially at toxic levels or in combination with other neuroleptic drugs [1.3.1, 1.4.1].
Pathophysiology and Mechanisms
The exact mechanisms behind drug-induced myoclonus are complex and vary depending on the drug class. Several neurotransmitter systems are often involved [1.4.4].
- Serotonergic System: Many implicated drugs, particularly antidepressants (SSRIs, TCAs), opioids, and lithium, enhance serotonergic transmission. Excessive serotonin activity is a key factor in the development of myoclonus and serotonin syndrome [1.3.5, 1.4.1].
- GABAergic System: Some drugs, like penicillin, may cause myoclonus by inhibiting the neurotransmitter GABA (gamma-aminobutyric acid), which is the brain's primary inhibitory signal. Reduced GABAergic inhibition can lead to neuronal hyperexcitability and spontaneous muscle discharges [1.2.4].
- Dopaminergic System: Alterations in dopamine pathways by antipsychotics and anti-Parkinsonian drugs can also lead to movement disorders, including myoclonus [1.2.2, 1.4.3].
Comparison of Common Myoclonus-Inducing Drug Classes
| Drug Class | Common Examples | Typical Onset/Presentation | Key Mechanism |
|---|---|---|---|
| Opioids | Morphine, Fentanyl, Hydromorphone | Often with high doses or in renal failure; can be multifocal or generalized [1.5.1, 1.5.5]. | Accumulation of neuroexcitatory metabolites [1.5.2]. |
| Antidepressants | SSRIs (Sertraline), TCAs (Amitriptyline) | Can occur at therapeutic doses; risk increases with polypharmacy; often part of serotonin syndrome [1.4.1]. | Increased serotonergic transmission [1.3.5]. |
| Antipsychotics | Clozapine, Olanzapine | Can be dose-dependent, especially during titration; may be focal or generalized [1.6.3]. | Complex, involving dopamine, serotonin, and GABA systems [1.4.4]. |
| Anticonvulsants | Gabapentin, Pregabalin | Can exacerbate pre-existing myoclonus; risk increases with renal impairment [1.2.4, 1.6.6]. | Varies; some block neuronal excitation in a way that paradoxically causes myoclonus [1.2.4]. |
| Antibiotics | Penicillins, Ciprofloxacin | Higher risk in patients with renal dysfunction; often presents with encephalopathy [1.6.2]. | GABA antagonism or other neurotoxic effects [1.2.4]. |
Diagnosis and Management
The primary step in diagnosing drug-induced myoclonus is taking a comprehensive medication history to establish a temporal link between starting a drug and the onset of symptoms [1.5.4]. The cornerstone of management is to identify and, if possible, withdraw the offending agent, which typically leads to the resolution of the myoclonus [1.3.5, 1.3.8].
If the medication is essential, other strategies include:
- Dose Reduction: Lowering the dose may alleviate the myoclonic jerks [1.4.1].
- Switching Medications: Changing to a different drug within the same class or a different class altogether can be effective. For example, 'opioid rotation' is a common strategy [1.5.3].
- Symptomatic Treatment: In cases where the offending drug cannot be stopped, medications like benzodiazepines (e.g., clonazepam) may be used to manage the myoclonic symptoms [1.3.2, 1.3.4].
It is crucial for patients experiencing myoclonic jerks not to stop any medication abruptly without consulting their healthcare provider [1.2.2].
Conclusion
Drug-induced myoclonus is a significant adverse effect linked to a wide variety of common medications, including opioids, antidepressants, antipsychotics, and antibiotics. The mechanisms often involve disruption of key neurotransmitter systems like serotonin, GABA, and dopamine. While often reversible, it requires careful diagnosis, primarily through a thorough review of a patient's medications. Management revolves around discontinuing or adjusting the causative drug, highlighting the importance of physician oversight in safely handling this neurological side effect.
For more information, consider visiting the National Institute of Neurological Disorders and Stroke (NINDS). [1.3.3]
