Would you still offer antipsychotics, such as risperidone (atypical antipsychotic), to a patient clearing from substance-induced psychosis?

Antipsychotics in Substance-Induced Psychosis: When to Treat

In patients clearing from substance-induced psychosis, delay antipsychotic treatment unless symptoms persist beyond one week with significant distress/functional impairment, or if there are immediate safety concerns to self or others. 1

Key Decision Point: Timing and Symptom Assessment

The most recent international schizophrenia guidelines (2025) provide explicit direction: a delay in antipsychotic initiation should be considered where symptoms are clearly related to substance use and do not pose safety concerns. 1 This represents the highest-quality guidance available and should frame your approach.

When to Withhold Antipsychotics

• If psychotic symptoms are clearly substance-related and the patient is actively clearing (improving mental status, decreasing hallucinations/delusions), observe without antipsychotics 1
• If there are no safety concerns (no suicidal ideation, homicidal ideation, severe agitation, or inability to care for self), watchful waiting is appropriate 1
• Most substance-induced psychoses resolve within days to weeks after cessation of the substance, making antipsychotic exposure potentially unnecessary 1

When to Initiate Antipsychotics

Start antipsychotics if:

• Psychotic symptoms persist for one week or more with associated distress or functional impairment 1
• Earlier initiation is appropriate if symptoms cause severe distress or safety concerns exist 1
• The patient remains severely agitated, dangerous, or in significant distress despite the substance clearing 1

Practical Algorithm for Substance-Induced Psychosis

Step 1: Immediate Safety Assessment (First 24-48 Hours)

• If severe agitation with safety risk: Use benzodiazepines (lorazepam or midazolam) as first-line monotherapy rather than antipsychotics 1
• If cooperative but agitated: Consider oral lorazepam alone initially 1
• Reassess diagnosis and contributing factors (other medical conditions, ongoing substance use) 1

Step 2: Days 3-7 Observation Period

• Monitor for symptom trajectory: Are psychotic symptoms improving, stable, or worsening? 1
• Reassess substance use status: Confirm abstinence and rule out continued use 1
• If symptoms are clearly improving: Continue observation without antipsychotics 1
• If symptoms persist at one week with distress/impairment: Initiate antipsychotic treatment 1

Step 3: Antipsychotic Selection (If Indicated)

If treatment becomes necessary after the observation period:

• Use shared decision-making based on side-effect profiles 1
• Consider risperidone, paliperidone, amisulpride, or olanzapine (with metformin) as reasonable first-line options 1
• Start at therapeutic doses and assess response at 4 weeks 1

Evidence for Risperidone in Substance-Induced Psychosis

Research specifically supports risperidone's efficacy in substance-induced psychosis:

• Methamphetamine-associated psychosis: Risperidone (2-8 mg) effectively treats positive psychotic symptoms, with effects stabilizing within 2 weeks 2
• Amphetamine-induced psychosis: Risperidone 4 mg daily significantly reduces positive symptoms (mean SAPS reduction of 16.20 points over 6 weeks) 3
• Rapid onset: Fast-dissolving risperidone tablets achieve calmness in median 70 minutes in acute psychosis 4

Critical Pitfalls to Avoid

Do not reflexively start antipsychotics in all substance-induced psychosis cases. The 2025 guidelines explicitly recommend delay when symptoms are substance-related without safety concerns 1. This represents a shift toward more conservative prescribing.

Distinguish between acute agitation management and psychosis treatment:

• For acute agitation alone, benzodiazepines are equally or more effective than antipsychotics 1
• Antipsychotics are specifically indicated for persistent psychotic symptoms, not just behavioral control 1

Avoid unnecessary long-term exposure: If antipsychotics are started and symptoms resolve quickly, reassess the need for continuation rather than defaulting to extended treatment 1

Monitoring If Treatment Is Initiated

• Assess response at 4 weeks with therapeutic dosing 1
• If no significant improvement at 4 weeks: Reassess diagnosis, consider that this may represent primary psychosis rather than substance-induced, and adjust treatment accordingly 1
• Consider clozapine only if diagnosis evolves to treatment-resistant schizophrenia after failed trials of two antipsychotics 1