Akathisia Risk: Thorazine vs. Invega Sustenna
Thorazine (chlorpromazine) is more likely to cause akathisia than Invega Sustenna (paliperidone) due to its classification as a low-potency conventional antipsychotic with higher rates of extrapyramidal side effects. 1
Mechanism and Risk Factors for Akathisia
Akathisia is characterized by:
- A sense of severe restlessness
- Physical agitation (often manifesting as pacing)
- Subjective distress
- Difficulty remaining still
Comparison of Medications
Thorazine (Chlorpromazine):
- First-generation/conventional antipsychotic
- Low-potency agent with significant dopamine D2 receptor blockade
- Higher risk of extrapyramidal symptoms including akathisia
- Often misinterpreted as psychotic agitation or anxiety
- Common reason for medication noncompliance 1
Invega Sustenna (Paliperidone):
- Second-generation/atypical antipsychotic (long-acting injectable)
- More balanced receptor profile with less D2 blockade
- Lower incidence of extrapyramidal symptoms
- Better tolerated regarding movement disorders
- Still carries some risk of akathisia, but significantly less than conventional antipsychotics 2
Evidence-Based Comparison
The American Academy of Child and Adolescent Psychiatry guidelines note that conventional antipsychotics like chlorpromazine have a higher incidence of extrapyramidal side effects, including akathisia 1. While second-generation antipsychotics (SGAs) like paliperidone were developed specifically to reduce these side effects.
Research indicates that SGAs produce akathisia at composite rates ranging from 2.9-13.0% across studies, compared to higher rates with conventional agents like chlorpromazine 3. The risk of akathisia with SGAs is approximately half that of conventional antipsychotics, though it still occurs.
Clinical Implications
Management Considerations:
- If akathisia develops:
- Consider dose reduction if clinically feasible
- Antiparkinsonian agents may help but are not consistently effective
- β-blockers (particularly propranolol) and benzodiazepines have shown benefit
- Low-dose mirtazapine may be effective for treatment 4
Monitoring:
- Assess for restlessness, inability to sit still, pacing
- Ask about subjective feelings of inner restlessness or tension
- Monitor particularly after initiation or dose increases
- Be aware that akathisia is often misdiagnosed as anxiety or agitation 1
Important Caveats
- High doses of any antipsychotic increase akathisia risk 3
- Individual patient factors may influence susceptibility
- Akathisia can occur with all antipsychotics, but at different rates
- Young age and male gender are risk factors for extrapyramidal symptoms 1
- Akathisia is a common reason for medication noncompliance and should be addressed promptly
In summary, while both medications can cause akathisia, Thorazine (chlorpromazine) poses a substantially higher risk compared to Invega Sustenna (paliperidone), making the latter a better choice when akathisia is a specific concern.