Antipsychotics Overview

Antipsychotic Drug Overview

• Antipsychotics reduce hallucinations, delusions, agitation, and psychomotor excitement in conditions like schizophrenia and mania.
• Effective treatment occurs when D2-receptor occupancy is between 60-70%.

Types of Antipsychotics

• Conventional Antipsychotics (First Generation)

  • Examples: chlorpromazine, haloperidol.
  • Function primarily as dopamine-receptor antagonists.

• Atypical Antipsychotics (Second Generation)

  • Produce effects with fewer extrapyramidal side effects.
  • Higher risk of tardive dyskinesia is not common except with risperidone.

Common Antipsychotic Agents

• Phenothiazines:
  • Chlorpromazine, Trifluoperazine.
• Thioxanthenes:
  • Flupenthixol, Clopenthixol.
• Butyrophenones:
  • Haloperidol.
• Dibenzodiazepines:
  • Clozapine, Olanzapine.
• Dibenzothiazepine:
  • Quetiapine.
• Substituted Benzamides:
  • Sulpiride, Amisulpride.
• Benzisoxazole:
  • Risperidone.
• Quinolinone:
  • Aripiprazole.

Side Effects of Atypical Antipsychotics

• Amisulpride: EPS, prolactin elevation, weight gain. Side effects include insomnia and QT prolongation.
• Sulpiride: Similar profile to amisulpride.
• Clozapine: Zero EPS or prolactin elevation, significant weight gain potential, and associated with agranulocytosis.
• Olanzapine: Variable EPS, high weight gain. Side effects include somnolence and diabetes.
• Quetiapine: No EPS or prolactin elevation. Monitor for somnolence and metabolic effects.
• Risperidone: Higher risk of EPS and prolactin elevation. Side effects include insomnia and anxiety.

Pharmacology Highlights

• Atypical antipsychotics act as 5-HT2-D2-receptor antagonists.
• Most are metabolized by the liver; exceptions include sulpiride and amisulpride excreted unchanged by the kidneys.
• Typical half-life of antipsychotics is around 20 hours; quetiapine requires twice-daily dosing.
• Steady-state drug levels achieved after several weeks.

Common Side Effects

• Antidopaminergic Effects: Acute dystonia, akathisia, parkinsonism, tardive dyskinesia.
• Other Effects: Weight gain, sedation, cardiac arrhythmias, metabolic syndrome, endocrine changes (e.g., galactorrhea).
• Serious Risks: Neuroleptic malignant syndrome (NMS), especially with high-potency compounds.

Tardive Dyskinesia

• Characterized by involuntary movements primarily of the face, increased susceptibility in women and elderly.
• Lower occurrence in atypical agents like clozapine and olanzapine compared to haloperidol.
• Possible treatment includes clozapine or clonazepam.

Depot Antipsychotic Administration

• Infrequently used antipsychotics available in depot forms for long-term treatment.
• Includes agents like flupenthixol decanoate, haloperidol decanoate, and risperidone microspheres.
• Various dosing intervals and clinical dosages, emphasizing monitoring.

Clinical Monitoring and Intervention

• Regular monitoring of body mass index, blood glucose, lipid profile, and blood pressure.
• Recommend lifestyle interventions and potential switching to drugs with a better side effect profile.
• Metformin may assist with weight management.

Clozapine Monitoring

• Requires weekly blood counts at initiation due to risk of leukopenia, transitioning to bi-weekly then monthly.
• Potential side effects include drowsiness, weight gain, and seizures at higher doses.

Contraindications

• Avoid in conditions like myasthenia gravis, Addison’s disease, and glaucoma.
• Increased risk of severe movement disorders in dementia patients.
• Caution with liver diseases and potential cardiac risks associated with certain medications.

Treatment of Acute Behavioral Disturbances

• Medications like lorazepam, olanzapine, or haloperidol are commonly used for rapid tranquillization.
• ECG monitoring is advised prior to administration of parenteral antipsychotics.