a) haloperidol
b) perphenazine
c) bromocriptine
d) olanzapine
e) risperidone
The authors' observations
Our goal in treating Ms. S was to address her schizophrenia symptoms and improve her overall functioning. Often, finding an effective treatment can be challenging, and there is little evidence to support the efficacy of one antipsychotic over another.4 In Ms. S’s case, our care was stymied by the cost of medication, challenges related to delusions intrinsic to the illness (she refused clozapine because of required blood draws), and adverse effects. When Ms. S developed amenorrhea while taking paliperidone— the only medication that showed significant improvement in her psychotic symptoms—our goal was to maintain her functional level without significant long-term adverse effects.
Managing hyperprolactinemia
Management of iatrogenic hyperprolactinemia includes decreasing the dosage of the offending agent, using a prolactin-sparing antipsychotic, or initiating a dopamine agonist, such as bromocriptine or cabergoline, in addition to an antipsychotic.1,4 Aripiprazole is considered to be a prolactin-sparing agent because of its propensity to increase the prolactin level to less of a degree than what is seen with other antipsychotics; in fact, it has been shown to reduce an elevated prolactin level.9-11
Most typical and atypical antipsychotics are dopamine—specifically D2—receptor antagonists. These antipsychotics prevent dopamine from binding to the D2 receptor and from inhibiting prolactin release, therefore causing hyperprolactinemia. Aripiprazole differs from other antipsychotics: It is a partial D2 receptor agonist with high affinity, and therefore suppresses prolactin release.8 In a randomized controlled trial, aripiprazole had a lower rate of prolactin elevation compared with placebo.12
Aripiprazole’s ability to reduce an elevated prolactin level caused by other antipsychotics has been demonstrated in several studies with haloperidol,13 olanzapine,14,15 and risperidone.15-17 There has been 1 case report,18 but no controlled studies, of aripiprazole being used to decrease the prolactin level in patients treated with paliperidone.
In Ms. S’s case, adding aripiprazole, 10 mg/d, reduced her prolactin level by approximately 50%. Because several studies have shown that adjunctive aripiprazole with a D2 antagonist normalizes the prolactin level,19 it is reasonable to conclude that adding aripiprazole facilitated reduction of her prolactin level and might have continued to do so if given more time. Regrettably, because of patient and family concerns, paliperidone was reduced before this could be determined. It is unclear whether normalization of Ms. S’s prolactin level and return of her menstrual cycle was caused by adding aripiprazole or by reducing the dosage of paliperidone.
Although additional randomized controlled trials should be conducted on the utility of this approach, it is reasonable to consider augmentation with aripiprazole when treating a patient who is stable on an antipsychotic, including paliperidone, but has developed hyperprolactinemia secondary to treatment.
BOTTOM LINE
Hyperprolactinemia is a relatively common, underreported side effect of both typical and atypical antipsychotics. Paliperidone and risperidone have been shown to have the highest risk among the atypical antipsychotics; aripiprazole has the lowest risk. Treatment of an elevated prolactin level should include reduction or discontinuation of the offending agent and augmentation with aripiprazole.
Related Resources
• Peuskens J, Pani L, Detraux J, et al. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review [published online March 28, 2014]. CNS Drugs. doi: 10.1007/s40263-014-0157-3.
• Li X, Tang Y, Wang C. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials. PLoS One. 2013;8(8):e70179. doi: 10.1371/journal.pone.0070179.
Drug Brand Names
Aripiprazole • Abilify Haloperidol • Haldol
Benzatropine • Cogentin Olanzapine • Zyprexa
Bromocriptine • Parlodel Paliperidone • Invega
Cabergoline • Dostinex Perphenazine • Trilafon
Clozapine • Clozaril Risperidone • Risperdal
Fluphenazine • Prolixin
DisclosureThe authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.