What are the FDA-approved treatments for psychosis in adolescents?

FDA-Approved Psychosis Treatments for Adolescents

For adolescent psychosis, risperidone, quetiapine, and aripiprazole are FDA-approved first-line options, with risperidone and quetiapine specifically approved for schizophrenia in adolescents aged 13-17 years. 1, 2

FDA-Approved Medications by Indication

Schizophrenia (Ages 13-17)

• Risperidone is FDA-approved for adolescents aged 13-17 years with schizophrenia, demonstrated effective in two short-term controlled trials (6 and 8 weeks) involving 417 adolescents 1
• Quetiapine is FDA-approved for adolescents aged 13-17 years with schizophrenia, proven effective in one 6-week double-blind, placebo-controlled trial 2
• Aripiprazole is FDA-approved for adolescents with schizophrenia, though specific age range starts at 13 years 3

Bipolar I Disorder - Acute Mania (Ages 10-17)

• Risperidone is FDA-approved for children and adolescents aged 10-17 years for acute manic or mixed episodes, demonstrated in one 3-week controlled trial with 169 patients 1
• Quetiapine is FDA-approved for children and adolescents aged 10-17 years for bipolar mania, proven effective in one 3-week trial 2
• Aripiprazole is FDA-approved for bipolar mania in this age group 3

Autistic Disorder - Irritability (Ages 5-16)

• Risperidone is FDA-approved for irritability associated with autistic disorder in children aged 5-16 years, established in two 8-week trials with 156 patients 1

Treatment Selection Algorithm

First-Line Treatment Approach

• Start with risperidone, olanzapine, or aripiprazole as first-line atypical antipsychotics, each requiring at least 4-6 weeks at therapeutic dose before determining efficacy 4, 3
• Atypical antipsychotics are preferred over typical antipsychotics due to lower risk of extrapyramidal symptoms and better tolerability, though efficacy for positive symptoms is comparable 4, 5
• Individual medication choice should be based on side effect profile rather than efficacy differences, as no atypical antipsychotic (except clozapine for treatment resistance) shows clear superiority over others 4, 6

Dosing Considerations

• Adolescents may require standard doses rather than lower doses for optimal response, particularly with risperidone where standard dosing showed superior symptom reduction compared to low doses 6
• For aripiprazole and ziprasidone, lower doses may be equally effective as higher doses 6
• Adequate therapeutic trials require sufficient dosages over 4-6 weeks before switching medications 4

Treatment-Resistant Cases

When to Consider Clozapine

• Clozapine should be initiated after failure of at least two adequate trials with different antipsychotic medications (at least one should be an atypical agent) 4, 3
• Clozapine has documented superior efficacy for treatment-resistant schizophrenia in both adults and youth with childhood-onset schizophrenia 4, 3
• Target dose is 300-450 mg/day by end of 2 weeks, with maximum dose of 900 mg/day 3
• Titrate to achieve plasma level ≥350 ng/mL, with target range of 350-550 ng/mL for optimal efficacy 3

Clozapine Monitoring Requirements

• Weekly white blood cell counts are mandatory for the first 6 months, then every 2 weeks thereafter due to agranulocytosis risk 3
• Initiate at 12.5 mg once or twice daily with slow titration to minimize orthostatic hypotension, bradycardia, and syncope 3
• Always co-prescribe metformin with clozapine to attenuate weight gain 3, 7
• Monitor for seizures, sedation, hypersalivation, orthostatic hypotension, tachycardia, and metabolic changes 3

Critical Monitoring and Side Effects

Pre-Treatment Assessment

• Obtain BMI, waist circumference, blood pressure, blood glucose, lipids, prolactin, liver function tests, electrolytes, complete blood count, and electrocardiogram before starting treatment 7
• Document baseline abnormal movements to avoid later mislabeling as medication side effects 4
• Document target symptoms for tracking treatment response 4

Ongoing Monitoring

• Check fasting glucose 4 weeks after initiation 7
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks 7
• For quetiapine specifically, FDA recommends baseline and 6-month follow-up eye examinations due to cataract risk in animal studies 4

Medication-Specific Side Effect Profiles

Weight Gain and Metabolic Effects:

• Olanzapine, risperidone, and clozapine are commonly associated with significant weight gain 5, 6
• Quetiapine causes significant weight gain as the most common problem 8
• Aripiprazole is not associated with dyslipidemia 5, 6

Prolactin Effects:

• Risperidone causes the highest prolactin elevation among atypical antipsychotics 4
• Aripiprazole is not associated with increased prolactin 5, 6

Extrapyramidal Symptoms:

• Risperidone has the highest risk of extrapyramidal symptoms among atypical antipsychotics, though still lower than typical antipsychotics 4, 8
• Quetiapine has lower risk of extrapyramidal symptoms 8

Cardiovascular Effects:

• Quetiapine may cause QT prolongation on electrocardiogram 4, 8
• Orthostatic hypotension occurs more frequently in adults (4-7%) compared to adolescents (<1%) 2
• Blood pressure increases (both systolic and diastolic) occurred in children and adolescents but not in adults 2

Maintenance Treatment

Duration of Treatment

• First-episode patients should receive maintenance psychopharmacological treatment for 1-2 years after the initial episode given the risk for relapse 4
• Continue baseline antipsychotic for at least 12 months after achieving remission 7
• Most patients (70%) require long-term, often lifetime medication to control symptoms 7
• Approximately 65% of patients receiving placebo will relapse within 1 year compared to 30% receiving antipsychotics 4

Dose Adjustments

• Higher dosages may be required during acute phases, with smaller dosages during residual phases 4
• Attempts to gradually lower dosage may be indicated to decrease side effects, but must be carefully monitored to avoid relapse 4

Common Pitfalls to Avoid

• Do not use antipsychotic polypharmacy until after failed trials of adequate dose and duration of monotherapy, including clozapine 7
• Avoid typical antipsychotics as first-line treatment due to high extrapyramidal symptom risk and association with tardive dyskinesia 7
• Do not institute large dosages during early treatment as this does not hasten recovery and more often results in excessive doses and side effects 4
• Do not discontinue treatment prematurely—adequate therapeutic trials require 4-6 weeks at sufficient dosages 4

Required Documentation and Consent

• Obtain adequate informed consent from parent/youth depending on legal age requirements 4
• Document target symptoms, baseline and follow-up laboratory monitoring, treatment response, and suspected side effects 4
• Monitor for known side effects including extrapyramidal symptoms, weight gain, agranulocytosis (with clozapine), and seizures 4