Letters to the Editor
Galactorrhea With Aripiprazole
Dear Editor:
Aripiprazole is a new-generation atypical antipsychotic agent. It is a partial agonist at the dopamine D2 and serotonin1A (5-HT1A) receptor sites; it is an antagonist at the 5-HT2 receptor site (1). Data from the aripiprazole clinical trials suggest that the drug may reduce serum prolactin levels (2). However, we have observed a case of raised serum prolactin and galactorrhea in association with aripiprazole. To the best of our knowledge, this is the first case of aripiprazole-induced galactorrhea in world literature.
Case Report
Mrs S, aged 36 years, presented with a 2-month history of suspiciousness, withdrawal, and neglect of personal care. She fulfilled DSM-IV criteria for schizophreniform disorder. She was drug-naive for the episode, and was prescribed aripiprazole in a dosage that was titrated from 10 mg daily to 15 mg daily over a period of 2 weeks. At week 3 of aripriprazole therapy, she developed tremor, rigidity, salivation, and bradykinesia, along with simultaneous breast tenderness and a milky discharge from the nipples. Her serum prolactin was found to be elevated to 27 ng/mL (normal range, 1.5 to 19.0 ng/mL). All other investigations, including thyroid profile and brain CT scan, were normal.
The extrapyramidal symptoms resolved with the addition of trihexyphenidyl (4 mg daily). At week 5 of aripripazole therapy the hyperprolactinemia (23.5 ng/mL) and galactorrhea persisted despite a lowered dosage of aripiprazole to 5 mg daily. Aripiprazole was subsequently replaced with quetiapine in a dosage that was raised from 100 mg daily to 300 mg daily over a period of 5 weeks. By week 6 of quetiapine therapy, the patient’s serum prolactin had dropped to 6.0 ng/mL, and the breast tenderness and galactorrhea had resolved completely.
Three years previously, Mrs S had a similar episode of psychosis. For 6 months, she received trifluoperazine (15 mg daily) and trihexyphenidyl (2 mg daily) without developing endocrine problems.
The association between aripiprazole and breast tenderness and galactorrhea is irrefutable in our patient; the complaints developed shortly after the introduction of aripiprazole monotherapy, were associated with hyper-prolactinemia, and resolved after the replacement of aripiprazole with quetiapine. The patient had received no other medication that might have explained the adverse effects.
How and why did these adverse effects arise? The partial D2 agonistic action of aripiprazole implies that the drug will augment dopamine hypoactivity, as is likely in the prefrontal areas, and block dopamine hyperactivity, as is likely in the mesolimbic areas. In patients with schizophrenia, dopamine neurotransmission is probably normal in the nigrostriatal and tuberoinfundibular systems. One might therefore expect aripiprazole to interfere with normal functioning in these pathways, resulting in extrapyramidal symptoms and the consequences of raised serum prolactin. Aripiprazole does indeed cause extrapyramidal symptoms, possibly to the same extent as the typical antipsychotics (2). Hyperprolactinemia, however, may be either an idiosyncratic response or a dosage-dependent adverse effect in sensitive individuals. Future studies should address the epidemiology of endocrinal disturbances with aripiprazole.
References
1. Lieberman JA. Dopamine partial agonists: a new class of antipsychotic. CNS Drugs 2004;18:251–67.
2. El-Sayeh H, Morganti C. Aripiprazole for schizophrenia. Cochrane Database Syst Rev 2004;2:CD004578.
DN Mendhekar, DPM, MD
New Delhi, India
Chittaranjan Andrade, MD
Bangalore, India
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