First-episode psychosis: choosing an antipsychotic
The case
A 23-year-old woman with no psychiatric history is admitted voluntarily after 6 weeks of persistent delusions that government agents are stalking her and sending signals through her phone, with third-person auditory hallucinations criticising her behaviour. Her employer reports 4 months of social withdrawal and declining work performance. CT brain, serum toxicology, full blood count, electrolytes, liver and thyroid function, B12, folate and syphilis serology are normal. Fasting glucose is 6.2 mmol/L (below 5.5), HbA1c 6.1% (4.0–5.5), BMI 31.5 kg/m² and ECG shows sinus rhythm with QTc 420 ms. She is medically stable and denies substance use. What is the most appropriate initial antipsychotic?
Options
- AAripiprazole 10 to 15 mg orally daily
- BHaloperidol 5 mg orally daily
- COlanzapine 10 mg orally daily
- DRisperidone 2 mg orally daily
- EQuetiapine 300 mg orally daily
Think it through before you read on. Which single option is best, and why are the other four wrong?
Show the answer and explanation
Answer
A. Aripiprazole 10 to 15 mg orally daily
Why this is the right answer
This woman has a first episode of psychosis. Persecutory delusions, third-person auditory hallucinations and a 4-month prodrome of withdrawal and functional decline, with an organic screen that is normal, make schizophrenia the likely diagnosis, although a formal diagnosis needs 6 months of symptoms. Treatment starts now regardless of the label.
In first-episode psychosis, the RANZCP schizophrenia guideline (2016) recommends a second-generation antipsychotic at the lowest effective dose, because young people with a first episode respond well to low doses and are very sensitive to side effects. Efficacy among the second-generation drugs is broadly similar (clozapine aside), so the choice is driven by side-effect profile and the individual patient.
Her metabolic profile decides it. She has obesity and prediabetes. Olanzapine and, to a lesser extent, quetiapine and risperidone cause weight gain, insulin resistance and dyslipidaemia, and can push her into diabetes. Aripiprazole has the most favourable metabolic profile of the commonly used agents and does not raise prolactin, which matters in a young woman. Starting at 10 mg and increasing to 15 mg is a standard first-episode approach.
Whichever drug is chosen, metabolic monitoring is mandatory: weight, waist, blood pressure, glucose or HbA1c and lipids at baseline, then at 3 months and yearly. Referral to an early psychosis service and psychosocial support for her and her family are part of treatment from the start.
Haloperidol is effective but its high rate of extrapyramidal effects makes it a poor first choice in a drug-naive young patient.
Why the other options are wrong
- B
A first-generation drug carries a high risk of acute dystonia and parkinsonism in a young drug-naive patient.
- C
Olanzapine has the worst metabolic profile and would worsen her prediabetes and obesity.
- D
Risperidone causes moderate weight gain and marked hyperprolactinaemia, undesirable in a young woman.
- E
Quetiapine is sedating, causes weight gain and is less potent for acute positive symptoms.
High-yield takeaway
First-episode psychosis: a low-dose second-generation antipsychotic chosen by side-effect profile; with obesity or prediabetes, aripiprazole is preferred and metabolic monitoring is compulsory.
Reference: RANZCP Clinical Practice Guidelines for the Management of Schizophrenia and Related Disorders (2016)
Common questions
Which antipsychotics cause the most weight gain?
Olanzapine and clozapine, then quetiapine and risperidone. Aripiprazole has one of the most favourable profiles.
What metabolic monitoring is required on antipsychotics?
Weight, waist circumference, blood pressure, fasting glucose or HbA1c and lipids at baseline, at 3 months, then at least yearly.
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