Can Compazine (prochlorperazine) cause clonus?

Can Compazine (Prochlorperazine) Cause Clonus?

Yes, prochlorperazine (Compazine) can cause clonus as part of its extrapyramidal side effect profile, particularly in the context of serotonin syndrome where it may exacerbate existing neuromuscular abnormalities.

Mechanism and Risk Factors

Prochlorperazine is a phenothiazine antipsychotic medication commonly used as an antiemetic. It works primarily as a dopamine receptor antagonist, which explains its potential to cause various extrapyramidal symptoms (EPS):

• Prochlorperazine blocks dopamine receptors in the central nervous system, disrupting the balance between dopaminergic and cholinergic neurotransmission
• This imbalance can manifest as various movement disorders, including clonus
• Clonus specifically involves involuntary and rhythmic muscle contractions at a frequency of 5-8 Hz 1

Clinical Presentation of Prochlorperazine-Induced Movement Disorders

Prochlorperazine can cause several types of movement disorders that may include clonus:

1. Acute dystonic reactions - may include:

   • Facial grimacing
   • Muscle spasms in oral musculature
   • Reduced range of motion
   • Difficulty speaking due to spasms 2

2. Akathisia - most common early extrapyramidal symptom:

   • Occurs within a week of starting treatment
   • Reported in up to 14% of patients taking prochlorperazine 3

3. Tardive dyskinesia - with long-term use:

   • Involuntary movements that can persist even after medication discontinuation 4

4. Clonus and hyperreflexia - particularly concerning when:

   • Patient is taking other serotonergic medications
   • There are signs of serotonin syndrome 5

Serotonin Syndrome Connection

Prochlorperazine is particularly concerning in the context of serotonin syndrome:

• According to the modified Dunkley criteria, clonus (spontaneous, ocular, or inducible) is a key diagnostic feature of serotonin syndrome 5
• Prochlorperazine is listed among antiemetics that can contribute to serotonergic effects 5
• The combination of prochlorperazine with other serotonergic medications increases the risk of developing clonus as part of serotonin syndrome

Management of Prochlorperazine-Induced Movement Disorders

If clonus or other extrapyramidal symptoms develop:

1. Immediate interventions:

   • Discontinue prochlorperazine
   • Administer diphenhydramine 50 mg intramuscularly for acute symptoms 2
   • Consider benzodiazepines for agitation and muscle spasms 5

2. Alternative antiemetics to consider:

   • Ondansetron or granisetron (5-HT3 antagonists) which have lower risk of movement disorders 4
   • Metoclopramide (though it also carries EPS risk, albeit different)
   • Atypical antipsychotics like perospirone have shown significantly lower rates of extrapyramidal symptoms (0% vs 14% with prochlorperazine) 3

Prevention and Risk Mitigation

To reduce the risk of prochlorperazine-induced clonus:

• Use the lowest effective dose
• Limit duration of treatment
• Avoid combining with other medications that can cause serotonin syndrome
• Be particularly cautious in patients with:
  • History of movement disorders
  • Concurrent use of serotonergic medications
  • Advanced age
  • Dehydration

Conclusion

Clinicians should maintain vigilance for clonus and other extrapyramidal symptoms when prescribing prochlorperazine, particularly in patients taking other serotonergic medications. Early recognition and prompt management are essential to prevent progression to more severe manifestations.