Hyperprolactinemia is a side effect most commonly associated with antipsychotic use. Hyperprolactinemia can be completely asymptomatic or be very distressing to patients when they experience associated symptoms such as amenorrhea, galactorrhea, infertility, or sexual dysfunction. The most significant consequence of hyperprolactinemia is hypogonadism that results in estrogen or testosterone deficiency. Elevation of prolactin levels can occur as soon as 6 days after initiation of treatment.[1]

The mechanism of action is thought to be at the anterior pituitary gland, which resides outside the blood brain barrier. Consistent D2 antagonism contributes to elevated prolactin levels.

All typical antipsychotics are associated with hyperprolactinaemia to varying degrees.

Initially, it was thought that because of the 5-HT2A receptor affinity of atypical antipsychotics this would prevent them increasing prolactin levels. However, risperidone and paliperidone both increase prolactin levels much like typical antipsychotics. Prolactin levels have been found to correlate with blood levels of paliperidone rather than risperidone.[2]

Signs and Symptoms of Hyperprolactinemia

Females Males
Breast Tissue Changes • Galactorrhea • Galactorrhea
• Gynecomastia
Menstrual Changes • Amenorrhea
• Irregular menstrual cycle
• Premature menopause
Sexual Changes • Sexual dysfunction
• Loss of libido
• Infertility
• Sexual dysfunction
• Loss of libido
• Infertility
• Erectile dysfunction
  • In patients on long-term antipsychotics, prolactin levels can be elevated 40% of the time
  • Prolactin levels above 10000 are concerning for prolactinomas
  • Prolactin levels are usually elevated in the 100s from antipsychotic use

Switching to an antipsychotic with less D2 antagonism (and as a result less hyperprolactinemia) such as aripiprazole, quetiapine, olanzapine, or clozapine.[3]

Hormonal deficiencies can be supplemented, adding dopamine agonist, or adjunctive aripiprazole.[4]