Psychosis resolves, but menses stop

CASE Paranoid and hallucinating
Ms. S, age 30, is an unmarried graduate stu­dent who has been given a diagnosis of schizophrenia, paranoid type, during inpatient hospitalization that was prompted by impair­ment in school functioning (difficulty turning in assignments, poor concentration, making careless mistakes on tests), paranoid delu­sions, and multisensory hallucinations. She says that her roommate and classmates are working together to make her leave school, and recalls seeing them “snare and smirk” as she passes by. Ms. S says that she feels her classmates are calling her names and talking badly about her as soon as she is out of sight.

Ms. S is antipsychotic-naïve and has a base­line body mass index of 17.8 kg/m², indicat­ing that she is underweight. We believe that olanzapine, 20 mg/d, is a good initial treat­ment because of its propensity for weight gain; however, she experiences only marginal improvement. Ms. S does not have health insurance, and cannot afford a brand name medication; therefore, she is cross-tapered to perphenazine, 8 mg, and benzatropine, 0.5 mg, both taken twice daily (olanzapine was not available as a generic at the time).

At discharge, Ms. S does not report any hallucinatory experiences, but is guarded, voices suspicions about the treatment team, and asks “What are they doing with all my blood?”—referring to blood draws for labora­tory testing during hospitalization.

As an outpatient, Ms. S is continued on the same medications until she has to be switched because she cannot afford the out-of-pocket cost of the antipsychotic, perphenazine ($80 a month). Clozapine is recommended, but Ms. S refuses because of the mandatory weekly blood monitoring. She briefly tries fluphen­azine, 2.5 mg/d, but it is discontinued because of malaise and lightheadedness without extrapyramidal symptoms.

Clozapine is again recommended, but Ms. S remains suspicious of the necessary blood draws and refuses. After several trials of antipsychotics, Ms. S starts paliperidone using samples from the clinic, titrated to 6 mg at bedtime. Once tolerance and therapeutic improvement are observed, she is continued on this medication through the manufactur­er’s patient assistance program.

Within 3 months, Ms. S and her fam­ily find that she has improved signifi­cantly. She no longer reports hallucinatory experiences, is less guarded during ses­sions, and has followed through with paid and volunteer job applications and inter­views. She soon finds a job teaching entry-level classes at a community college and is looking forward to a summer trip abroad.

During a follow-up appointment, Ms. S reports that she had missed 2 consecutive menstrual cycles without galactorrhea or fractures. A urine pregnancy test is negative; the prolactin level is 72 μg/L.

Hyperprolactinemia in women is defined as a plasma prolactin level of 

a)>2.5 µg/L
b) >5 µg/L
c) >10 µg/L
d) >20 µg/L
e) >25 µg/L


The authors’ observations
A prolactin level >25 μg/L is considered abnormal.¹ A level of >250 μg/L may identify a prolactinoma; however, levels >200 μg/L have been observed in patients taking an antipsychotic.¹ Given Ms. S’s clinically significant elevation of prolactin, she is referred to her primary care physi­cian. We decide to augment her regimen with aripiprazole, 10 mg/d, because this drug has been noted to help in cases of hyperprolactinemia associated with other antipsychotics.^2,3

Prolactin serves several roles in the body, including but not limited to lacta­tion, sexual gratification, proliferation of oligodendrocyte precursor cells, surfac­tant synthesis of fetal lungs at the end of pregnancy, and neurogenesis in maternal and fetal brains (Figure 1 and Figure 2). A 2004 review reported secondary amenor­rhea, galactorrhea, and osteopenia as com­mon symptoms of hyperprolactinemia.⁵ Hyperprolactinemia has been seen with most antipsychotics, both typical and atypical. Although several studies docu­ment prolactin elevation with risperidone, fewer have examined the active metabolite (9-hydroxyrisperidone) paliperidone.^5-7

a) menstrual disturbance
b) galactorrhea
c) breast engorgement
d) sexual dysfunction
e) all of the above


The authors’ observations
Acutely, hyperprolactinemia can cause menstrual abnormalities, decreased libido, breast engorgement, galactorrhea, and sexual dysfunction in women.⁸ In men, the most common symptoms of hyperprolac­tinemia are loss of interest in sex, erectile dysfunction, infertility, and gynecomas­tia. Osteoporosis has been associated with chronic elevation of the prolactin level⁸ (Table).

TREATMENT Adjunctive aripiprazole
After 8 weeks of adjunctive aripiprazole, Ms. S’s prolactin level decreases to 42 μg/L, but menses do not return. Because her family and primary care providers are eager to have the prolactin level return to nor­mal, reducing her risk of complications, we decide to decrease paliperidone to 3 mg at bedtime.
Eight weeks later, Ms. S shows functional improvement. A repeat test of prolactin is 24 μg/L; she reports a 4-day period of spotting 1 week ago. One month later, the prolactin level is 21 μg/L, and she reports having a normal menstrual period. She continues treatment with paliperidone, 3 mg/d, and aripiprazole, 10 mg/d, experiences regular menses, and continues teaching.


Pharmacotherapy of hyperprolactinemia includes

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.

CASE Paranoid and hallucinating
Ms. S, age 30, is an unmarried graduate stu­dent who has been given a diagnosis of schizophrenia, paranoid type, during inpatient hospitalization that was prompted by impair­ment in school functioning (difficulty turning in assignments, poor concentration, making careless mistakes on tests), paranoid delu­sions, and multisensory hallucinations. She says that her roommate and classmates are working together to make her leave school, and recalls seeing them “snare and smirk” as she passes by. Ms. S says that she feels her classmates are calling her names and talking badly about her as soon as she is out of sight.

Ms. S is antipsychotic-naïve and has a base­line body mass index of 17.8 kg/m², indicat­ing that she is underweight. We believe that olanzapine, 20 mg/d, is a good initial treat­ment because of its propensity for weight gain; however, she experiences only marginal improvement. Ms. S does not have health insurance, and cannot afford a brand name medication; therefore, she is cross-tapered to perphenazine, 8 mg, and benzatropine, 0.5 mg, both taken twice daily (olanzapine was not available as a generic at the time).

At discharge, Ms. S does not report any hallucinatory experiences, but is guarded, voices suspicions about the treatment team, and asks “What are they doing with all my blood?”—referring to blood draws for labora­tory testing during hospitalization.

As an outpatient, Ms. S is continued on the same medications until she has to be switched because she cannot afford the out-of-pocket cost of the antipsychotic, perphenazine ($80 a month). Clozapine is recommended, but Ms. S refuses because of the mandatory weekly blood monitoring. She briefly tries fluphen­azine, 2.5 mg/d, but it is discontinued because of malaise and lightheadedness without extrapyramidal symptoms.

Clozapine is again recommended, but Ms. S remains suspicious of the necessary blood draws and refuses. After several trials of antipsychotics, Ms. S starts paliperidone using samples from the clinic, titrated to 6 mg at bedtime. Once tolerance and therapeutic improvement are observed, she is continued on this medication through the manufactur­er’s patient assistance program.

Within 3 months, Ms. S and her fam­ily find that she has improved signifi­cantly. She no longer reports hallucinatory experiences, is less guarded during ses­sions, and has followed through with paid and volunteer job applications and inter­views. She soon finds a job teaching entry-level classes at a community college and is looking forward to a summer trip abroad.

During a follow-up appointment, Ms. S reports that she had missed 2 consecutive menstrual cycles without galactorrhea or fractures. A urine pregnancy test is negative; the prolactin level is 72 μg/L.

Hyperprolactinemia in women is defined as a plasma prolactin level of 

a)>2.5 µg/L
b) >5 µg/L
c) >10 µg/L
d) >20 µg/L
e) >25 µg/L


The authors’ observations
A prolactin level >25 μg/L is considered abnormal.¹ A level of >250 μg/L may identify a prolactinoma; however, levels >200 μg/L have been observed in patients taking an antipsychotic.¹ Given Ms. S’s clinically significant elevation of prolactin, she is referred to her primary care physi­cian. We decide to augment her regimen with aripiprazole, 10 mg/d, because this drug has been noted to help in cases of hyperprolactinemia associated with other antipsychotics.^2,3

Prolactin serves several roles in the body, including but not limited to lacta­tion, sexual gratification, proliferation of oligodendrocyte precursor cells, surfac­tant synthesis of fetal lungs at the end of pregnancy, and neurogenesis in maternal and fetal brains (Figure 1 and Figure 2). A 2004 review reported secondary amenor­rhea, galactorrhea, and osteopenia as com­mon symptoms of hyperprolactinemia.⁵ Hyperprolactinemia has been seen with most antipsychotics, both typical and atypical. Although several studies docu­ment prolactin elevation with risperidone, fewer have examined the active metabolite (9-hydroxyrisperidone) paliperidone.^5-7

a) menstrual disturbance
b) galactorrhea
c) breast engorgement
d) sexual dysfunction
e) all of the above


The authors’ observations
Acutely, hyperprolactinemia can cause menstrual abnormalities, decreased libido, breast engorgement, galactorrhea, and sexual dysfunction in women.⁸ In men, the most common symptoms of hyperprolac­tinemia are loss of interest in sex, erectile dysfunction, infertility, and gynecomas­tia. Osteoporosis has been associated with chronic elevation of the prolactin level⁸ (Table).

TREATMENT Adjunctive aripiprazole
After 8 weeks of adjunctive aripiprazole, Ms. S’s prolactin level decreases to 42 μg/L, but menses do not return. Because her family and primary care providers are eager to have the prolactin level return to nor­mal, reducing her risk of complications, we decide to decrease paliperidone to 3 mg at bedtime.
Eight weeks later, Ms. S shows functional improvement. A repeat test of prolactin is 24 μg/L; she reports a 4-day period of spotting 1 week ago. One month later, the prolactin level is 21 μg/L, and she reports having a normal menstrual period. She continues treatment with paliperidone, 3 mg/d, and aripiprazole, 10 mg/d, experiences regular menses, and continues teaching.


Pharmacotherapy of hyperprolactinemia includes

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.

CASE Paranoid and hallucinating
Ms. S, age 30, is an unmarried graduate stu­dent who has been given a diagnosis of schizophrenia, paranoid type, during inpatient hospitalization that was prompted by impair­ment in school functioning (difficulty turning in assignments, poor concentration, making careless mistakes on tests), paranoid delu­sions, and multisensory hallucinations. She says that her roommate and classmates are working together to make her leave school, and recalls seeing them “snare and smirk” as she passes by. Ms. S says that she feels her classmates are calling her names and talking badly about her as soon as she is out of sight.

Ms. S is antipsychotic-naïve and has a base­line body mass index of 17.8 kg/m², indicat­ing that she is underweight. We believe that olanzapine, 20 mg/d, is a good initial treat­ment because of its propensity for weight gain; however, she experiences only marginal improvement. Ms. S does not have health insurance, and cannot afford a brand name medication; therefore, she is cross-tapered to perphenazine, 8 mg, and benzatropine, 0.5 mg, both taken twice daily (olanzapine was not available as a generic at the time).

At discharge, Ms. S does not report any hallucinatory experiences, but is guarded, voices suspicions about the treatment team, and asks “What are they doing with all my blood?”—referring to blood draws for labora­tory testing during hospitalization.

As an outpatient, Ms. S is continued on the same medications until she has to be switched because she cannot afford the out-of-pocket cost of the antipsychotic, perphenazine ($80 a month). Clozapine is recommended, but Ms. S refuses because of the mandatory weekly blood monitoring. She briefly tries fluphen­azine, 2.5 mg/d, but it is discontinued because of malaise and lightheadedness without extrapyramidal symptoms.

Clozapine is again recommended, but Ms. S remains suspicious of the necessary blood draws and refuses. After several trials of antipsychotics, Ms. S starts paliperidone using samples from the clinic, titrated to 6 mg at bedtime. Once tolerance and therapeutic improvement are observed, she is continued on this medication through the manufactur­er’s patient assistance program.

Within 3 months, Ms. S and her fam­ily find that she has improved signifi­cantly. She no longer reports hallucinatory experiences, is less guarded during ses­sions, and has followed through with paid and volunteer job applications and inter­views. She soon finds a job teaching entry-level classes at a community college and is looking forward to a summer trip abroad.

During a follow-up appointment, Ms. S reports that she had missed 2 consecutive menstrual cycles without galactorrhea or fractures. A urine pregnancy test is negative; the prolactin level is 72 μg/L.

Hyperprolactinemia in women is defined as a plasma prolactin level of 

a)>2.5 µg/L
b) >5 µg/L
c) >10 µg/L
d) >20 µg/L
e) >25 µg/L


The authors’ observations
A prolactin level >25 μg/L is considered abnormal.¹ A level of >250 μg/L may identify a prolactinoma; however, levels >200 μg/L have been observed in patients taking an antipsychotic.¹ Given Ms. S’s clinically significant elevation of prolactin, she is referred to her primary care physi­cian. We decide to augment her regimen with aripiprazole, 10 mg/d, because this drug has been noted to help in cases of hyperprolactinemia associated with other antipsychotics.^2,3

Prolactin serves several roles in the body, including but not limited to lacta­tion, sexual gratification, proliferation of oligodendrocyte precursor cells, surfac­tant synthesis of fetal lungs at the end of pregnancy, and neurogenesis in maternal and fetal brains (Figure 1 and Figure 2). A 2004 review reported secondary amenor­rhea, galactorrhea, and osteopenia as com­mon symptoms of hyperprolactinemia.⁵ Hyperprolactinemia has been seen with most antipsychotics, both typical and atypical. Although several studies docu­ment prolactin elevation with risperidone, fewer have examined the active metabolite (9-hydroxyrisperidone) paliperidone.^5-7

a) menstrual disturbance
b) galactorrhea
c) breast engorgement
d) sexual dysfunction
e) all of the above


The authors’ observations
Acutely, hyperprolactinemia can cause menstrual abnormalities, decreased libido, breast engorgement, galactorrhea, and sexual dysfunction in women.⁸ In men, the most common symptoms of hyperprolac­tinemia are loss of interest in sex, erectile dysfunction, infertility, and gynecomas­tia. Osteoporosis has been associated with chronic elevation of the prolactin level⁸ (Table).

TREATMENT Adjunctive aripiprazole
After 8 weeks of adjunctive aripiprazole, Ms. S’s prolactin level decreases to 42 μg/L, but menses do not return. Because her family and primary care providers are eager to have the prolactin level return to nor­mal, reducing her risk of complications, we decide to decrease paliperidone to 3 mg at bedtime.
Eight weeks later, Ms. S shows functional improvement. A repeat test of prolactin is 24 μg/L; she reports a 4-day period of spotting 1 week ago. One month later, the prolactin level is 21 μg/L, and she reports having a normal menstrual period. She continues treatment with paliperidone, 3 mg/d, and aripiprazole, 10 mg/d, experiences regular menses, and continues teaching.


Pharmacotherapy of hyperprolactinemia includes

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.