How do antidepressants affect prolactin levels?

Antidepressants and Prolactin Levels

Antidepressants can cause hyperprolactinemia, though this effect varies significantly by drug class, with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) being most commonly associated with elevated prolactin levels. 1

Mechanism of Action

Antidepressants may elevate prolactin levels through several mechanisms:

1. Serotonergic pathway interference: Antidepressants, particularly SSRIs, increase serotonin levels which can indirectly inhibit dopamine release in the tuberoinfundibular pathway 1

2. Dopamine antagonism: Some antidepressants have mild dopamine receptor blocking properties that can reduce dopamine's inhibitory effect on prolactin secretion 1

3. Indirect modulation: Serotonin can stimulate GABAergic neurons, which in turn may affect prolactin release 1

Incidence and Clinical Significance

• Most antidepressants have been reported to cause hyperprolactinemia, though symptoms are rare 1
• The incidence rates are not clearly established in the literature
• When hyperprolactinemia does occur, it can lead to:
  • Galactorrhea (abnormal milk production)
  • Menstrual disturbances
  • Sexual dysfunction
  • Decreased bone mineral density (with long-term elevation)
  • Potential infertility 2

Antidepressant Classes and Prolactin Effects

SSRIs

• Most commonly associated with hyperprolactinemia among antidepressants
• Cases of galactorrhea have been reported with escitalopram even with normal prolactin levels (euprolactinemic galactorrhea) 3

SNRIs

• Can cause hyperprolactinemia but generally less frequently than SSRIs

Other Antidepressants

• Tricyclic antidepressants and MAOIs have less consistent effects on prolactin

Risk Factors and Potentiating Conditions

• Female gender: Women appear more susceptible to antidepressant-induced hyperprolactinemia 4
• Combination therapy: Co-administration of antidepressants with other medications can increase the risk:
  • Antidepressants + benzodiazepines may potentiate hyperprolactinemia 5, 4
  • Antidepressants + low-dose antipsychotics (e.g., risperidone 0.5-2mg) significantly increase prolactin levels 5

Monitoring and Management

When hyperprolactinemia is suspected in patients taking antidepressants:

1. Measure serum prolactin levels if symptoms such as galactorrhea, menstrual irregularities, or sexual dysfunction occur 1

2. Management options:

   • Change to an antidepressant less likely to affect prolactin levels
   • Consider using the lowest effective dose of the antidepressant
   • In severe cases, dopamine agonists like cabergoline may be considered, though this requires careful monitoring 6, 7

3. Routine monitoring of prolactin levels in asymptomatic patients on antidepressants is not recommended 1

Important Caveats

• Hyperprolactinemia symptoms may be subtle or absent despite elevated levels
• When evaluating elevated prolactin, rule out other causes (pituitary tumors, hypothyroidism, pregnancy)
• Antipsychotics (particularly first-generation and risperidone) cause much more significant hyperprolactinemia than antidepressants 2
• If dopamine agonist therapy (like cabergoline) is needed for persistent symptomatic hyperprolactinemia, start with low doses (0.25mg twice weekly) and monitor closely 7, 8

In conclusion, while antidepressant-induced hyperprolactinemia is possible, it is generally less common and less severe than that caused by antipsychotics. Clinicians should be aware of this potential side effect and evaluate prolactin levels when relevant symptoms occur in patients taking antidepressants.