How are prolactin levels impacted by long-acting injectable (LAI) antipsychotic medications?

Hyperprolactinemia is often caused by the use of antipsychotic medications, and this with both oral and LAI formulations, as side effect profiles of LAIs mimic their oral formulation counterparts.

Prolactin can be elevated the most by the following LAI antipsychotics: risperidone (Risperdal Consta, Perseris), paliperidone (Invega Sustenna, Invega Trinza), fluphenazine (Prolixin Decanoate), and relatively less so by haloperidol decanoate (Haldol Decanoate). While other LAIs have demonstrated lower risks of hyperprolactinemia, patients taking any antipsychotic medications may experience elevated prolactin levels.

Among antipsychotics available as long-acting preparations, aripiprazole and olanzapine are considered prolactin-sparing.  Aripiprazole may even lower prolactin levels (a finding of unclear clinical significance).

Available  information on LAI-induced hyperprolactinemia is summarized here:

  • Risperdal Consta FDA label says that this drug increases prolactin levels more than other antipsychotics, at 5-6 times levels (in mice studies).
  • Perseris FDA label notes the prolactin elevation is dose-dependent.
  • Invega Sustenna FDA label notes similar likelihood of prolactin elevation to that of Risperdal, higher levels than with other antipsychotic medications. Elevated prolactin in schizophrenia trial participants 48-52%, higher in females.
  • Invega Trinza FDA label details elevated prolactin in maintenance trial of 27-42%, higher in females.
  • Prolixin Decanoate FDA label notes that neuroleptic drugs elevate prolactin, and no specifics are provided.
  • Haldol Decanoate FDA label reports <1% reports of hyperprolactinemia in clinical trials. In clinical practice, this side effect is seen at higher rates.

What can clinicians do for patients on LAIs with elevated prolactin levels?

  • Assess for undesirable, acute effects, as well as long-term effects
  • Consider switching to one of the aripiprazole LAIs or olanzapine LAI
  • Dose adjustment may resolve for patients on fluphenazine or haloperidol decanoate, but this will rarely have a clinical impact for patients on risperidone or paliperidone LAIs

Read more about the details of antipsychotic-induced elevated prolactin levels, monitoring, and resulting manifestations here.

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