How to treat antipsychotic-induced hyperprolactinemia?

Treatment of Antipsychotic-Induced Hyperprolactinemia

For symptomatic hyperprolactinemia or when action is warranted, switch to a D2 partial agonist (aripiprazole) or add adjunctive low-dose aripiprazole to the current regimen. 1

Initial Assessment and Counseling

Before initiating treatment, counsel patients on the risks of untreated asymptomatic hyperprolactinemia, which include:

• Reduced bone mineral density in both men and women 1
• Clinically significant increased risk of breast cancer in women 1
• Sexual dysfunction, infertility, amenorrhea, and galactorrhea 2

Confirm hyperprolactinemia with repeat measurement and exclude other causes including pregnancy, primary hypothyroidism, renal insufficiency, and other medications before attributing it to antipsychotics 3, 4, 5

Treatment Algorithm

First-Line: Switch to Prolactin-Sparing Antipsychotic

When psychiatric stability allows, switch from prolactin-raising antipsychotics (typical antipsychotics, risperidone, paliperidone, amisulpride) to prolactin-sparing agents (aripiprazole, clozapine, olanzapine, quetiapine). 1, 2

• Aripiprazole possesses the strongest evidence as a switching option due to its D2 partial agonist activity 6
• This approach addresses the root cause while maintaining antipsychotic efficacy 7, 6
• Common pitfall: Switching carries risk of psychiatric decompensation, so this must be weighed against severity of hyperprolactinemia symptoms 6, 5

Second-Line: Adjunctive Aripiprazole

If switching is not feasible due to psychiatric stability concerns, add low-dose aripiprazole (5-15 mg/day) to the current antipsychotic regimen. 1, 4

• Aripiprazole augmentation is safe and effective in lowering prolactin levels within normal limits 7
• This strategy also improves negative symptoms and reduces weight gain 1, 4
• Monitor for increased extrapyramidal symptoms every 3-6 months using standardized scales, as polypharmacy increases this risk 4
• Be aware that polypharmacy increases global side-effect burden including sedation and cognitive impairment 1, 4

Third-Line: Dopamine Agonists (Use with Extreme Caution)

Reserve dopamine agonists for exceptional circumstances only, as they can worsen psychiatric illness. 5

If dopamine agonists must be used:

Cabergoline (Preferred Dopamine Agonist)

• Start at 0.25-0.5 mg once or twice weekly, titrating up to maximum 2 mg/week 3, 8
• Superior efficacy compared to bromocriptine (83% vs 59% prolactin normalization) 3
• Critical monitoring requirement: Baseline echocardiogram before initiation 3, 8
• For doses ≤2 mg/week: Echocardiographic surveillance every 5 years 3, 9, 8
• For doses >2 mg/week: Annual echocardiography mandatory due to cardiac valvulopathy risk 3, 8
• Absolute contraindication: History of cardiac or extracardiac fibrotic disorders 8
• Monitor for pleural/pericardial/retroperitoneal fibrosis with chest x-ray and clinical assessment 8

Bromocriptine (Alternative)

• Less effective than cabergoline but lower risk of cardiac complications 7
• Start at 1.25 mg daily, increase gradually to 2.5-7.5 mg daily in divided doses 7

Major caveat: Dopamine agonists can exacerbate psychosis and should only be used when benefits clearly outweigh risks 5, 2

Fourth-Line: Dose Reduction

Reduce the dose of the offending antipsychotic while remaining within the therapeutic range, if positive symptoms are well controlled 1, 6

• This approach has limited evidence but may be effective in some patients 6, 2
• Risk of psychiatric relapse must be carefully monitored 7

Monitoring During Treatment

Establish baseline measurements before starting antipsychotics: 1

• Prolactin level (fasting, morning sample preferred) 9
• BMI, waist circumference, blood pressure
• HbA1c, glucose, lipids
• Liver function, renal function, full blood count

Recheck prolactin after 3 months of stable-dose treatment or if symptoms of hyperprolactinemia appear 5

For patients on aripiprazole augmentation, assess for: 4

• Extrapyramidal symptoms every 3-6 months
• Sedation and cognitive effects
• Overall medication burden

Special Considerations for Asymptomatic Hyperprolactinemia

For asymptomatic hyperprolactinemia, intervention may not be immediately necessary, but patients must be counseled on long-term risks (bone loss, potential breast cancer risk in women) 1

Consider bone mineral density screening if: 2

• Female patient with amenorrhea for ≥1 year
• Prolonged hyperprolactinemia with hypogonadism

Adjunctive Hormonal Management

For hypoestrogenic women with amenorrhea, consider oral contraceptives to prevent bone loss and osteoporosis, though this does not address the underlying hyperprolactinemia 5, 2

What NOT to Do

• Do not use metformin as primary treatment for hyperprolactinemia (causes only mild prolactin reduction) 7
• Do not rely on herbal supplements (chamomile, Peony-Glycyrrhiza decoction) due to insufficient evidence 7
• Do not ignore patient-reported sexual dysfunction - clinicians consistently underestimate prevalence of these symptoms 5, 2
• Do not prescribe dopamine agonists without cardiac screening and ongoing monitoring 8