Pharmacological management

First-Line Antipsychotics - The Psychosis Police

• Second-Generation Antipsychotics (SGAs) are the cornerstone of treatment due to a more favorable side-effect profile, particularly lower risk of extrapyramidal symptoms (EPS) compared to first-generation agents.
• Agents of Choice:
  • Aripiprazole (Abilify)
  • Risperidone (Risperdal)
  • Olanzapine (Zyprexa)
• Dosing Principle: Start low, titrate slow. Aim for the lowest effective dose to minimize side effects.
• Mechanism: Primarily Dopamine ($D_2$) and Serotonin ($5-HT_{2A}$) receptor antagonists.

⭐ High-Yield Fact: Non-adherence is a major cause of relapse. Consider long-acting injectable (LAI) formulations in patients with a history of poor medication adherence.

Second-Line & Adjunctive Tx - Backup Brigade

• Treatment-Resistant Delusional Disorder (TRDD):
  • Switch to another antipsychotic (SGA or FGA) after an adequate trial (~6-8 weeks).
  • Clozapine: Gold standard for refractory psychosis. Requires strict ANC monitoring (risk of agranulocytosis), myocarditis, and metabolic syndrome surveillance.
• Adjunctive Medications: Target comorbid symptoms.
  • SSRIs: For significant depressive, anxious, or obsessive-compulsive features.
  • Benzodiazepines: Short-term use for severe anxiety or agitation.

⭐ In delusional disorder with prominent obsessive features (e.g., delusions of parasitosis), SSRIs can be highly effective, sometimes even as monotherapy.

Dosing, Titration & Duration - The Long Game

• Start Low, Go Slow: Initiate second-generation antipsychotics (SGAs) like aripiprazole or risperidone at low doses, often lower than for schizophrenia.
• Titration: Gradually increase dose over 4-6 weeks, monitoring for efficacy and side effects (e.g., EPS, metabolic changes).
• Maintenance: Continue treatment for at least 1-2 years after full symptom remission to minimize relapse risk. Lifelong therapy may be necessary.

⭐ For patients with poor insight and medication non-adherence, Long-Acting Injectable (LAI) antipsychotics are a crucial tool to ensure treatment continuity and prevent relapse.

Side Effect Management - Damage Control

• General Strategy: Use the lowest effective dose & monitor regularly.
• Tardive Dyskinesia (TD):
  • Stop offending agent.
  • Switch to a low-risk agent (e.g., Clozapine).
  • Administer VMAT2 inhibitors (Valbenazine, Deutetrabenazine).
• Metabolic Syndrome:
  • Regularly monitor weight, BMI, glucose, and lipids.
  • Switch to metabolically neutral agents (Aripiprazole, Ziprasidone).
  • Consider adding Metformin.

⭐ The AIMS (Abnormal Involuntary Movement Scale) is crucial for TD monitoring. Perform at baseline and repeat every 6-12 months for patients on long-term antipsychotic therapy.

High‑Yield Points - ⚡ Biggest Takeaways

• Second-generation antipsychotics (SGAs) like aripiprazole and risperidone are the first-line treatment for delusional disorder.
• They are preferred over first-generation antipsychotics (FGAs) due to a more favorable side-effect profile, particularly lower risk of extrapyramidal symptoms (EPS).
• FGAs such as haloperidol remain an effective alternative.
• Treatment should be initiated at a low dose and titrated gradually.
• Long-term maintenance therapy is often necessary to prevent relapse.
• Consider SSRIs for comorbid depressive symptoms.