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Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 127-128

Fluvoxamine-induced reversible euprolactinemic galactorrhea in a case of obsessive-compulsive disorder

1 Department of Psychiatry, MGM Medical College and Hospital, Mumbai, Maharashtra, India
2 Department of Psychiatry, Bombay Drug Deaddiction Center, Seth GS Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Psychiatry, NKP Salve Institute of Medical Sciences, Nagpur, Maharashtra, India

Date of Web Publication8-Dec-2017

Correspondence Address:
Chetan Dilip Vispute
Department of Psychiatry, MGM Medical College and Hospital, Navi Mumbai - 410 209, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aip.aip_18_17

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Fluvoxamine is one of the commonly used selective serotonin reuptake inhibitors(SSRIs) as a first-line treatment for obsessive-compulsive disorder(OCD). Galactorrhea is a rarely observed adverse effect of SSRIs occurring through complex interactions between serotonergic and dopaminergic systems of brain. We report a case of fluvoxamine-induced reversible euprolactinemic galactorrhea in a 39-year-old woman after initiation of fluvoxamine for OCD. The patient's galactorrhea resolved on discontinuation of fluvoxamine.

Keywords: Fluvoxamine, galactorrhea, serotonin reuptake inhibitor

How to cite this article:
Vispute CD, Parkar SR, Singh DA. Fluvoxamine-induced reversible euprolactinemic galactorrhea in a case of obsessive-compulsive disorder. Ann Indian Psychiatry 2017;1:127-8

How to cite this URL:
Vispute CD, Parkar SR, Singh DA. Fluvoxamine-induced reversible euprolactinemic galactorrhea in a case of obsessive-compulsive disorder. Ann Indian Psychiatry [serial online] 2017 [cited 2023 Jan 31];1:127-8. Available from: https://www.anip.co.in/text.asp?2017/1/2/127/220240

  Introduction Top

Selective serotonin reuptake inhibitors(SSRIs) have been reported to be the most frequent cause of drug-induced hyperprolactinemia among antidepressants. Among those, though sertraline appears to be the most frequent cause of sustained hyperprolactinemia, fluoxetine and paroxetine may also induce pathologic and symptomatic increases in prolactin levels.[1] Literature search on PubMed and Google Scholar reveals that SSRI-induced hyperprolactinemic galactorrhea is associated with escitalopram, citalopram, sertraline, paroxetine, fluoxetine, and more sustained and symptomatic galactorrhea as well with tricyclic antidepressants,[1] which resolves on discontinuation of drug. The authors report a case of euprolactinemic nonpuerperal galactorrhea in a middle-aged woman directly following the administration of fluvoxamine which decreased on gradually tapering and discontinuation of the drug.

  Case Report Top

A 39-year-old female who presented with obsessions of contamination and compulsions of handwashing with secondary depressive features was treated for obsessive-compulsive disorder (OCD) in the outpatient clinic of psychiatry department. She developed the fear that her body and clothes were contaminated with dirt and hence repeatedly washed hands, took bath and washed her clothes multiple times in a day for 5years. The symptoms were time consuming and distressing which resulted in poor care of her children and affected her household commitments. The patient was prescribed the tablet fluvoxamine 50mg along with exposure and response prevention with relaxation techniques, and the dose was gradually escalated to 300mg which she tolerated well. The symptoms of OCD gradually decreased, but she noticed a milky discharge from her nipples bilaterally with pain and tenderness over the breast as the dose of fluvoxamine was increased to 300mg. The patient denied a history of galactorrhea, abnormal breast pathology(like abscess), and menstrual disturbances in the past. No abnormalities were detected on thyroid function tests and other routine blood chemistry tests(complete blood count, renal function test, liver function test, follicle-stimulating hormone, and luteinizing hormone). Her prolactin levels were within normal limits(19.55ng/ml with reference range: 5–25ng/ml).[2] The patient was not on any other medication apart from fluvoxamine, and other organic diseases were ruled out by the endocrinologist. The dose of fluvoxamine was tapered and discontinued over the period of 3weeks. The complaints of galactorrhea with pain and tenderness over the breast decreased and stopped after shifting to clomipramine. The patient was started on tablet clomipramine and the dose was gradually titrated to 150 mg as per response.

  Discussion Top

Antidepressant drugs with serotoninergic activity, such as SSRIs, monoamine oxidase inhibitors(MAOIs), and even tricyclics, can cause hyperprolactinemia.[1],[2],[3] Limited data regarding the effect of antidepressant drugs on prolactin secretion are available at present. Contrasting to neuroleptics, the action of antidepressant drugs on the neuroendocrine system is very variable and not exactly related to their therapeutic effect. Euprolactinemic galactorrhea can be seen and may be related to a neuroendocrine effect of serotonin on prolactin release factors such as vasoactive intestinal peptide(VIP), thyrotropin-releasing hormone(TRH), and other neuropeptides.[4] Although hormone measurements were normal in this case, TRH sensitivity may be another important factor leading to galactorrhea. Furthermore, direct action on the postsynaptic serotonergic receptors in hypothalamus and indirect inhibition of dopamine through the presynaptic serotonergic receptors seem the likely mechanism for galactorrhea.[3],[4] Serotonergic stimulation of GABAergic neurons near the dopamine cells of tuberoinfundibular pathway results in inhibition of tuberoinfundibular dopamine pathway causing galactorrhea by the releasing prolactin.[5] A hypothesis was suggested by aPositron Emission Topographystudy that fluvoxamine has the ability to modify the striatal dopaminergic system by increasing the dopamine D2 receptors and consequently decreasing the dopamine concentration in OCD patients.[6] Fluvoxamine binds strongly to sigma 1 receptors(σ1). The agonist actions of fluvoxamine on σ1 receptors cause the translocation of this receptor from the endoplasmic reticulum to peripheral areas(membranes) of neurons, where σ1 regulates the ion channels and the release of glutamate, dopamine, serotonin, norepinephrine, and acetylcholine among other neurotransmitters.[7] This complex mechanism causing interplay between serotonergic and dopaminergic system in brain probably explains the euprolactinemic galactorrhea symptoms in patients of OCD receiving fluvoxamine. Galactorrhea has been reported with simultaneous use of risperidone and fluvoxamine.[8] To our knowledge, no case report is available regarding euprolactinemic galactorrhea symptoms in patients of OCD receiving fluvoxamine only. In this case, the adverse drug reaction was identified as the “probable” level of causality based on Naranjo Adverse Drug Reaction Probability, with a score of 7.[9]

  Conclusion Top

Antidepressant drugs with serotoninergic activity, such as SSRIs, MAOIs, and some tricyclics, lead to mild and by and large asymptomatic hyperprolactinemia. Hence it is essential for treating psychiatrist and physicians to enquire for signs and symptoms of galactorrhea in patients receiving fluvoxamine and other selective serotonin re-uptake inhibitors (SSRIs). It may or may not be associated with increase in the levels of serum prolactin and related side effects of gynecomastia, sexual dysfunction, menstrual disturbances, infertility and osteoporosis.

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  References Top

NebhinaniN. Sertraline-induced galactorrhea: Case report and review of cases reported with other SSRIs. Gen Hosp Psychiatry 2013;35:576.e3-5.  Back to cited text no. 1
MajumdarA, MangalNS. Hyperprolactinemia. JHum Reprod Sci 2013;6:168-75.  Back to cited text no. 2
[PUBMED]  [Full text]  
ChatterjeeSS, MitraS, MallikN. Emerging hyperprolactinemic galactorrhea in obsessive compulsive disorder with a stable dose of fluoxetine. Clin Psychopharmacol Neurosci 2015;13:316-8.  Back to cited text no. 3
MondalS, SahaI, DasS, GangulyA, DasD, TripathiSK, etal. A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series. Ther Adv Psychopharmacol 2013;3:322-34.  Back to cited text no. 4
MirkesSJ, BetheaCL. Oestrogen, progesterone and serotonin converge on GABAergic neurons in the monkey hypothalamus. JNeuroendocrinol 2001;13:182-92.  Back to cited text no. 5
MorescoRM, PietraL, HeninM, PanzacchiA, LocatelliM, BonaldiL, etal. Fluvoxamine treatment and D2 receptors: Apet study on OCD drug-naïve patients. Neuropsychopharmacology 2007;32:197-205.  Back to cited text no. 6
StahlSM. The sigma enigma: Can sigma receptors provide a novel target for disorders of mood and cognition? J Clin Psychiatry 2008;69:1673-4.  Back to cited text no. 7
PratheeshPJ, PraharajSK, SrivastavaA. Euprolactinemic gynecomastia and galactorrhea with risperidone-fluvoxamine combination. Psychopharmacol Bull 2011;44:70-3.  Back to cited text no. 8
NaranjoCA, BustoU, SellersEM, SandorP, RuizI, RobertsEA, etal. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 9

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