A 28-year-old man with first-episode psychosis presents with prominent auditory hallucinations, disorganized speech, and social withdrawal for 3 weeks. He has no prior psychiatric history and normal renal and hepatic function. What is the drug of choice for initiating antipsychotic therapy?

Explanation

## First-Episode Psychosis: Antipsychotic Selection **Key Point:** Second-generation antipsychotics (SGAs) are preferred first-line agents in first-episode psychosis due to superior efficacy-to-side-effect ratio compared to first-generation antipsychotics (FGAs). ### Why Risperidone? **High-Yield:** Risperidone is the most commonly recommended first-line SGA for first-episode psychosis because it offers: - Rapid onset of action (efficacy seen within 2–4 weeks) - Moderate potency with balanced D~2~ and 5-HT~2A~ antagonism - Favorable side-effect profile at low doses (5–6 mg/day) - Good oral bioavailability and predictable pharmacokinetics - Lower risk of metabolic complications compared to olanzapine or clozapine at equivalent doses ### Comparative Antipsychotic Profiles | Agent | Generation | First-Line Status | Key Limitation | |-------|-----------|-------------------|----------------| | **Risperidone** | 2nd | **Yes** | Dose-dependent hyperprolactinemia; orthostatic hypotension at higher doses | | Haloperidol | 1st | No | High extrapyramidal side effects (EPS), tardive dyskinesia risk, neuroleptic malignant syndrome | | Olanzapine | 2nd | Yes (alternative) | Greater metabolic burden (weight gain, hyperglycemia, dyslipidemia) | | Clozapine | 2nd | No (reserved) | Requires regular blood monitoring; agranulocytosis risk; used only for treatment-resistant psychosis | | Paliperidone palmitate | 2nd (long-acting) | No (not for first-episode) | Indicated for maintenance after stabilization, not initiation | **Clinical Pearl:** In first-episode psychosis, oral antipsychotics are preferred over long-acting injectables; long-acting formulations are reserved for maintenance therapy after stabilization and confirmed tolerability. ### Treatment Algorithm for First-Episode Psychosis ```mermaid flowchart TD A[First-Episode Psychosis]:::outcome --> B[Assess baseline: prolactin, glucose, lipids, weight, EPS risk]:::action B --> C{SGA vs FGA?}:::decision C -->|SGA preferred| D[Risperidone, Olanzapine, or Quetiapine]:::action C -->|FGA only if SGA contraindicated| E[Haloperidol or Chlorpromazine]:::action D --> F[Start low dose, titrate gradually over 2-4 weeks]:::action F --> G{Response at 4-6 weeks?}:::decision G -->|Yes| H[Continue; monitor for metabolic, EPS, prolactin effects]:::outcome G -->|No| I[Optimize dose or switch SGA]:::action I --> J{Persistent non-response after 2 SGAs?}:::decision J -->|Yes| K[Consider Clozapine]:::action ``` **Mnemonic:** **RISE** (Risperidone, Iloperidone, Sertraline-adjunct, Efficacy) — though the last two are less standard, this helps recall that risperidone is the **R**ecommended first-line. **Warning:** Do not use haloperidol as first-line in first-episode psychosis; the risk of acute dystonia, akathisia, and tardive dyskinesia is unacceptably high compared to SGAs.