Cases That Test Your Skills

Psychosis resolves, but menses stop

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References

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.

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