Can Thorazine (chlorpromazine) cause extrapyramidal symptoms (EPS)?

Thorazine (Chlorpromazine) and Extrapyramidal Symptoms

Yes, Thorazine (chlorpromazine) does cause extrapyramidal symptoms (EPS) as a common and serious side effect. 1 The FDA drug label explicitly lists various extrapyramidal symptoms among the adverse reactions to chlorpromazine.

Types of Extrapyramidal Symptoms Caused by Thorazine

Chlorpromazine can cause several types of EPS:

1. Acute Dystonia:

   • Characterized by prolonged abnormal muscle contractions
   • Often affects neck muscles, potentially progressing to throat tightness
   • Can cause swallowing difficulty, breathing problems, and tongue protrusion
   • More common in males and younger patients 1

2. Pseudo-parkinsonism:

   • Symptoms include mask-like facial expression, drooling, tremors
   • Pill-rolling motion, cogwheel rigidity, and shuffling gait 1

3. Motor Restlessness/Akathisia:

   • Presents as agitation, jitteriness, and sometimes insomnia 1

4. Tardive Dyskinesia:

   • Characterized by rhythmical involuntary movements of tongue, face, mouth or jaw
   • Can include protrusion of tongue, puffing of cheeks, puckering of mouth
   • May be irreversible even after discontinuation 1
   • More common in elderly patients, especially elderly women 1

Risk Factors for Developing EPS with Thorazine

Several factors increase the risk of developing EPS when taking chlorpromazine:

• Age: Older adults (65+) have increased risk 2
• Genetic factors: Presence of the A1 allele of the D2 dopamine receptor gene increases risk 2
• Higher doses: Risk increases with higher doses of the medication 1, 3
• Duration of treatment: Longer treatment periods increase risk, especially for tardive dyskinesia 1
• Previous history of EPS, CNS damage, or Parkinson's disease 2
• Concomitant medications that affect dopamine or serotonin systems 2

Mechanism of Action

EPS occurs due to dopamine blockade or depletion in the basal ganglia. This lack of dopamine mimics idiopathic pathologies of the extrapyramidal system 4. Chlorpromazine, as a conventional antipsychotic, acts primarily as a dopamine antagonist, which is the mechanism responsible for both its therapeutic effects and its EPS side effect profile 5.

Comparison with Other Antipsychotics

Conventional antipsychotics like chlorpromazine have a higher risk of causing EPS compared to atypical antipsychotics:

• A study found that the prevalence of EPS was highest with conventional antipsychotics (like chlorpromazine), intermediate with risperidone, and lowest with clozapine 6
• The point-prevalence of akathisia was 23.8% in patients treated with conventional antipsychotics, compared to 13% with risperidone and 7.3% with clozapine 6
• Similarly, rigidity was observed in 35.7% of patients on conventional antipsychotics, compared to 17.4% with risperidone and only 4.9% with clozapine 6

Management of EPS from Thorazine

When EPS occurs with chlorpromazine, several approaches can be taken:

1. Dose reduction: Often the first step when symptoms appear 1
2. Anti-parkinsonian agents: Commonly used to control pseudo-parkinsonism symptoms 1
3. Benzodiazepines: May help control certain EPS symptoms 1
4. Propranolol: Can be used specifically for akathisia 7
5. Medication switch: Consider switching to an atypical antipsychotic with lower EPS risk 5, 6

Important Considerations and Cautions

• Regular monitoring: Patients on chlorpromazine should be regularly assessed for abnormal movements using standardized scales like the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months 7
• Tardive dyskinesia risk: This condition may be irreversible and has no known effective treatment 1
• Neuroleptic Malignant Syndrome: A potentially fatal complication characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability 1
• Special populations: Elderly patients and those with pre-existing movement disorders require extra caution 7, 1

Thorazine's propensity to cause EPS is one of the main reasons why newer atypical antipsychotics are often preferred as first-line agents in many clinical scenarios, despite chlorpromazine's established efficacy for psychotic symptoms.