Hyperprolactinaemia and atypical antipsychotic drugs

• aripiprazole, clozapine and quetiapine cause no, or minimal, effects on serum prolactin at therapeutic doses
• olanzapine also seems to cause only mild, usually transient, increases at higher doses
• prolactin-related symptoms can occur with amisulpride, risperidone or zotepine
  • with risperidone, increases in prolactin concentration may be comparable to those with therapeutic doses of haloperidol (1)
• an NHS guideline states (2)
  • risperidone and Amisulpride are main offenders. Clozapine and Quetiapine generally do not raise Prolactin levels. Remaining atypicals such as Olanzapine and Aripiprazole cause small if any elevation

Note that there is no consistent correlation between antipsychotic dose, prolactin concentration and the occurrence of symptoms

• baseline prolactin concentration may be helpful, and if symptoms occur during treatment and hyperprolactinaemia is confirmed, it is reasonable to reduce the dose of antipsychotic provided the patient's condition permits (1) - another option is to switch to a more 'prolactin-sparing' drug
  
  
• How to assess and manage raised prolactin when on an atypical antipsychotic (2)
  • prolactin levels should be routinely checked in patients taking antipsychotic medication for extended periods, (ideally a base line level should be checked prior to commencement of these drugs). If hyperprolactinaemia is confirmed through three separate prolactin levels and pregnancy has been excluded, active management is needed
    
    
  • this guideline states a level of 2000 as a prompt for specialist review
    • if prolactin >2000 or visual/space occupying lesion symptoms or rapidly rising PRL then an MRI and endocrinologist review is indicated
    • however if prolactin < 2000 and distressing symptoms suggestive of hyperprolactinaemia or other abnormal hormone levels then an MRI and endocrinologist review is indicated
      
      
  • practicalities of reviewing of raised PRL if patient on an atypical antipsychotic
    
    
    • consult expert advice
    • confirm raised PRL with three separate blood tests and clinical assessment. Exclude pregnancy. Repeat Prolactin twice in 3 weeks
      • if the first PRL is rasied (<2000) but other two are normal
      • and no symptoms suggestive of hyperprolactinaemia
• then repeat Prolactin in 3 months
  
  
  • if one level above 2,000 then an MRI and endocrinologist review is indicated
    
    
  • if at least two Prolactin levels elevated (<2000)
    • consider whether it is appropriate to reduce/stop/change antipsychotic? Will need psychiatric opinion
      • if appropriate, reduce/stop/change Prolactin inducing medication for 1 month trial and recheck
      • if PRL normal, diagnosis confirmed. Consider different antipsychotic e.g., quetiapine. Recheck 3 months
        
        
  • if PRL < 2000
    • if asymptomatic and other pituitary hormones and cortisol normal, and
      • normal testosterone (males); normal menstruation or > 6 periods a year (females)
        • repeat PRL 6 monthly
    • if asymptomatic and other pituitary hormones and cortisol normal
      • but
        • testosterone reduced (males); amenorrhoea, <6 periods a year or postmenopausal (females)
          • then consider bone scan /endocrine referral
            
            

• medication reduction or withdrawal
  • reducing the dose of the offending medication will generally help, however such reduction or even stopping medication must be done only after careful consideration of the risk/ benefit ratio, preferably discussed with the patient, family/carers multidisciplinary team as appropriate
  • prolactin levels normally fall within days of stopping oral medication, but may take months to return to normal after stopping long acting depot medication. Beware concomitant PRL raising drugs
  • if a patient's condition necessitates recommencement of PRL increasing drugs, continue monitoring PRL six monthly

Notes:

• Clinical Symptoms of Hyperprolactinaemia Prolactin inhibits the sex hormones Oestrogen and Testosterone
  • a) In females symptoms include irregular menstruation or loss of menstruation (amenorrhoea), sub-fertility, loss of libido, genital atrophy and dryness with dyspareunia (painful intercourse), swelling and painful breasts and milk production, (Galactorrhoea)
  • b) In males symptoms include loss of libido, sub-fertility, loss of erectile and ejaculatory function, reduced hair thickness, smooth skin, reduced muscle bulk and reduced testicular size, though less common in males than females galactorrhoea can also occur

Reference:

1. Drug and Therapeutics Bulletin (2004); 42(8):57-60.
2. Tees, Esk and Wear Valleys NHS Trust (May 2011). Guidelines for the Management of Hyperprolactinaemia in Patients Receiving Antipsychotics.