What is most true about conventional antipsychotics, such as haloperidol (Haloperidol) and chlorpromazine (Chlorpromazine), in terms of their therapeutic and side effect profiles?

Conventional Antipsychotics: Therapeutic and Side Effect Profiles

Conventional antipsychotics are very similar in therapeutic profile but differ significantly in side effect profiles (option C).

Therapeutic Profile Similarities

Conventional antipsychotics (also called typical or first-generation antipsychotics) share a common therapeutic mechanism of action and similar clinical efficacy:

• All conventional antipsychotics work primarily through dopamine D2 receptor blockade in the brain 1, 2
• They have comparable efficacy for treating positive symptoms of psychosis 3
• Haloperidol has the best evidence base among conventional antipsychotics for treating agitation, but studies show similar therapeutic efficacy among different agents 3
• The antipsychotic threshold occupancy of D2 receptors for therapeutic effect remains at about 65% for all conventional antipsychotics 1

Side Effect Profile Differences

Despite similar therapeutic effects, conventional antipsychotics differ substantially in their side effect profiles:

Potency-Based Differences

• High-potency agents (e.g., haloperidol):

  • Higher risk of extrapyramidal symptoms (EPS)
  • Lower sedation
  • Fewer anticholinergic effects 3, 4

• Low-potency agents (e.g., chlorpromazine, thioridazine):

  • More sedating
  • More anticholinergic side effects
  • Greater risk of orthostatic hypotension
  • Lower risk of EPS 3, 4

Specific Side Effect Comparisons

• Movement disorders: Haloperidol causes significantly more movement disorders than chlorpromazine (RR 2.2, NNH 5) 5
• Cardiovascular effects: Chlorpromazine is significantly more likely to cause hypotension than haloperidol (NNH 7) 5
• QTc prolongation: Different conventional antipsychotics have varying effects on QTc interval, with thioridazine having the greatest QTc change 3

Clinical Implications

When selecting a conventional antipsychotic, consider:

1. Patient-specific factors:

   • Elderly patients may be more sensitive to sedation and anticholinergic effects of low-potency agents
   • Patients with cardiovascular issues may be poor candidates for agents with greater hypotensive effects
   • Patients at risk for EPS should avoid high-potency agents

2. Monitoring requirements:

   • All patients require monitoring for EPS, particularly with high-potency agents
   • Monitor blood pressure with low-potency agents
   • Consider ECG monitoring with agents known to prolong QTc interval

Common Pitfalls

• Failing to recognize that while therapeutic efficacy is similar, side effect profiles differ substantially
• Overlooking the importance of matching the side effect profile to patient characteristics
• Misinterpreting akathisia (restlessness) as worsening psychosis rather than a medication side effect
• Using excessive doses that increase side effects without improving efficacy

Conclusion

The evidence clearly demonstrates that conventional antipsychotics share a similar therapeutic profile through their common mechanism of D2 receptor blockade, but they differ significantly in their side effect profiles based on their potency and receptor binding characteristics 4, 1. This understanding is crucial for appropriate medication selection to maximize therapeutic benefit while minimizing adverse effects.