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CASE REPORT Table of Contents  
Ahead of print publication
Fluvoxamine-induced galactorrhea: A case series


1 Assistant Professor, Department of Psychiatry, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India
2 Junior Resident, Department of Psychiatry, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India
3 Professor, Department of Psychiatry, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India

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Date of Submission31-Oct-2020
Date of Acceptance02-Dec-2021
Date of Web Publication11-Mar-2021
 

  Abstract 


Galactorrhea is a very distressing symptom, especially for unmarried females, and medication-induced galactorrhea is a common etiological factor. Among psychotropics, antipsychotic-induced galactorrhea is commonly reported. However, there is dearth of literature regarding antidepressant-induced galactorrhea. There have been few case reports of galactorrhea induced by the use of selective serotonin reuptake inhibitors such as escitalopram and sertraline. Fluvoxamine is one of the routine first-line medications prescribed for obsessive–compulsive disorder (OCD). However, reports about fluvoxamine-induced galactorrhea have been scant. We report two cases of OCD who developed galactorrhea on treatment with fluvoxamine. One patient had hyperprolactinemia while other had euprolactinemic galactorrhea. In both cases, galactorrhea reversed on stopping of fluvoxamine. The complex interaction of serotonin and dopamine in the pathophysiology of hyperprolactinemia is discussed.

Keywords: Fluvoxamine, galactorrhea, hyperprolactinemia


How to cite this URL:
Kotadia H, Rawat K, Reddy S. Fluvoxamine-induced galactorrhea: A case series. Arch Ment Health [Epub ahead of print] [cited 2021 Nov 29]. Available from: https://www.amhonline.org/preprintarticle.asp?id=311084





  Introduction Top


Antipsychotic medications are known to cause hyperprolactinemia and galactorrhea.[1] This adverse effect is said to be due to the dopamine blockage in the nigrostriatal tract.[1] Although antidepressants mostly lack a significant dopaminergic action, there have been anecdotal reports documenting hyperprolactinemia associated with their use as well.[2],[3],[4] Sertraline, fluoxetine, and escitalopram are the selective serotonin reuptake inhibitors (SSRIs) mostly implicated in hyperprolactinemia and galactorrhea. However, there are only few reports of use of fluvoxamine-causing galactorrhea.[4],[5] We would like to report two cases who developed galactorrhea – one hyperprolactinemic and one euprolactinemic, while undergoing treatment for obsessive–compulsive disorder (OCD) with fluvoxamine. Further, efforts have been made to shed some light on mechanisms of serotonin involvement in the role of hyperprolactinemic and euprolactinemic galactorrhea.


  Case Series Top


Case 1

A 19-year-old unmarried female presented with a gradually progressive 1 year course of illness characterized by complaints of recurrent intrusive thoughts, regarding dirt and contamination. She recognized these thoughts as her own but felt distressing. These thoughts were accompanied with recurrent acts of hand washing and taking bath multiple times a day. There was a significant decline in her academic performance and was unable to fulfill her social responsibilities. She belonged to a middle-class socioeconomic status and had no significant personal or family history, no medical comorbidities, and no history of any previous psychiatric illness. According to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5), she was diagnosed as having OCD with fair insight and her Yale Brown obsessive–compulsive scale (YBOCS) score was 21 (moderate OCD).

She was started on tablet fluvoxamine 50 mg at night which was gradually increased to 100 mg over 15 days. Along with fluvoxamine, exposure and response prevention was also initiated. On the 10th day of taking fluvoxamine 100 mg, the patient reported heaviness in her breasts and noticed a milky white discharge. The same was confirmed on local examination and the discharge was nonhemorrhagic and nonpurulent from bilateral breasts. The patient gave no history of irregular menses, fever, headache, blurring of vision, vesicular skin lesions, or chest trauma. She was not on any other medications, except fluvoxamine. Her serum prolactin level was found raised at 93 ng/ml. Complete blood count (CBC), renal and hepatic parameters, beta human chorionic gonadotropin (beta hCG), thyroid profile, estradiol and follicle-stimulating hormone (FSH) levels, magnetic resonance imaging (MRI) brain, and ultrasonography (USG) whole abdomen were unremarkable.

As no other cause of hyperprolactinemia could be found, it was decided to stop fluvoxamine and switch to clomipramine. She was started on tablet clomipramine 25 mg and was gradually increased to 150 mg over a 4-week period. The patient responded well to the treatment over 8 weeks (YBOCS score of 12) and showed no significant adverse effects this time. Complaints of heaviness of the breast and galactorrhea completely resolved over 5 weeks. Serum prolactin levels were repeated periodically every 4 weeks, and they returned to normal level (<20 ng/ml) after 8 weeks of stopping fluvoxamine.

Case 2

A 22-year-old unmarried female from upper socioeconomic status and working as an interior designer presented with a gradually progressive 9-month course of illness. She complained of recurrent intrusive thoughts, regarding dirt and contamination and recurrent acts of washing her hands around 15–20 times a day. Mother of the patient also reported of repetitive checking of gas stove, switches, and locks by her daughter in the middle of the night. The patient felt that these thoughts were her own and were irrational, but she was not able to reduce her repetitive behavior. These thoughts had started interfering in her work and social relationship. She had no significant personal or family history, no medical comorbidities, and no history of any other psychiatric illness in the past. According to the diagnostic and DSM 5, she was diagnosed as having OCD with fair insight. Her YBOCS score was 19 (moderate OCD).

Tablet fluvoxamine 50 mg at night was initiated. One week later, the patient reported of milky white, nonhemorrhagic, nonpurulent discharge from bilateral breasts. The same was confirmed by a local physical examination. The patient gave no history of irregular menses, fever, headache, blurring of vision, vesicular skin lesions, or chest trauma. She was not on any other medication, except fluvoxamine. Her serum prolactin level was 12.7 ng/ml. CBC, renal and hepatic parameters, beta hCG, thyroid profile, estradiol and FSH levels, MRI brain, and USG abdomen were unremarkable.

It was decided to switch fluvoxamine with escitalopram. She was started on tablet escitalopram 10 mg, which was increased to 20 mg at night after 10 days. Galactorrhea resolved after about 10 days of stopping fluvoxamine. The patient responded well to the treatment with escitalopram with YBOCS score of 10 at the end of 6 weeks and showed no further adverse drug reactions.


  Discussion Top


Our first case developed galactorrhea within 10 days of uptitrating the dose of fluvoxamine to 100 mg and took about 5 weeks to completely resolve after stopping fluvoxamine. The second case developed the same complaint with 50 mg of fluvoxamine within 7 days. The adverse effect stopped after 10 days of stopping medication. In both the cases, the galactorrhea was at “probable” level of causality based on Naranjo adverse drug reaction probability,[6] with a score of 6 each.

Two previous case reports have reported normal[7] as well as elevated[5] prolactin levels in patients receiving fluvoxamine, which reversed on stopping fluvoxamine. Vispute et al. reported[7] a case where the patient complained of euprolactinemic galactorrhea within 2 days of starting of fluvoxamine and took 8 weeks to completely resolve after stopping medication. As in our cases, previous studies reporting galactorrhea with fluvoxamine use have reported self-resolution of the adverse effect after stopping the offending medicine.[5],[7]

Prolactin is a polypeptide hormone secreted by anterior pituitary gland. Hyperprolactinemia is diagnosed by taking fasting levels of prolactin (2 h after waking up) revealing a value >20 ng/ml for men and >25 ng/ml for women.[1] Physiological causes such as pregnancy, breast feeding, breast stimulation, and stress need to be ruled out. A strong suspicion for tumors, liver and renal failure, viral infections, autoimmune diseases, polycystic ovary syndrome, and hypothyroidism must also be kept.[8],[9],[10]

Dopamine is known to modulate the release of prolactin by acting on the tuberoinfundibular pathway. Likewise, even serotonin has been found to be an indirect but potent modulator of prolactin release.[8] The paraventricular nucleus has been recognized as a major regulatory site for serotonin-induced prolactin release via various neurosecretory cells for oxytocin, vasoactive intestinal peptide, and thyrotropin-releasing hormone (TRH).[1] While there is a considerable amount of laboratory-based research available about serotonin and its role in potently modulating prolactin release, clinical literature documenting such hyperprolactinemic galactorrhea with the use of fluvoxamine is scant. Further, not much is known about the mechanism of euprolactinemic galactorrhea that is associated with fluvoxamine usage. Some studies have implicated TRH sensitivity for the same,[8] but still the evidence is inconclusive. Serotonergic SSRIs have been found to have a considerably higher propensity to cause nonpuerperal galactorrhea, with an odds ratio of 12.6:1.7.[11] As opposed to other SSRIs, fluvoxamine has shown to have agonistic effect on sigma 1 receptors as well. These receptors have been linked with modulation of release of neurotransmitters, such as dopamine, norepinephrine, and acetyl choline, which might be another mechanism for causing euprolactinemic galactorrhea.[12]

Symptom of galactorrhea can be very distressing, particularly for a young unmarried woman in a conservative Indian scenario. A psychiatrist should be well aware of the possibility of occurrence of galactorrhea as an adverse event and should enquire about the same while treating patients with fluvoxamine. Further research trying to elucidate prolactin metabolism and possible causes for normoprolactinemic galactorrhea is very much required.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dickson RA, Glazer WM. Neuroleptic-induced hyperprolactinemia. Schizophr Res 1999;35 Supplement-1:S75-86.  Back to cited text no. 1
    
2.
Nebhinani N. Sertraline-induced galactorrhea: Case report and review of cases reported with other SSRIs. Gen Hosp Psychiatry 2013;35:576-e3.  Back to cited text no. 2
    
3.
Kukreti P, Ali W, Jiloha RC. Rising trend of use of antidepressants induced non-puerperal lactation: A case report. J Clin Diagn Res 2016;10:VD01-2.  Back to cited text no. 3
    
4.
Moresco RM, Pietra L, Henin M, Panzacchi A, Locatelli M, Bonaldi L, et al. Fluvoxamine treatment and D2 receptors: A pet study on OCD drug-naïve patients. Neuropsychopharmacology 2007;32:197-205.  Back to cited text no. 4
    
5.
Chakladar A, Singh J, Tak NK, Patra BN, Sagar R. Fluvoxamine-associated galactorrhea: A case report. J Clin Psychopharmacol 2020;40:101-2.  Back to cited text no. 5
    
6.
National Institutes of Health. LiverTox: Clinical and Research Information on Drug-induced Liver Injury. NIH; 2017. Available from: https://livertox. [Last accessed on 2020 Aug 03].  Back to cited text no. 6
    
7.
Vispute CD, Parkar SR, Singh DA. Fluvoxamine-induced reversible euprolactinemic galactorrhea in a case of obsessive-compulsive disorder. Ann Indian Psychiatr 2017;1:127.  Back to cited text no. 7
    
8.
Emiliano AB, Fudge JL. From galactorrhea to osteopenia: Rethinking serotonin-prolactin interactions. Neuropsychopharmacology 2004;29:833-46.  Back to cited text no. 8
    
9.
Nicholas L, Dawkins K, Golden RN. Psychoneuroendocrinology of depression. Prolactin. Psychiatr Clin North Am 1998;21:341-58.  Back to cited text no. 9
    
10.
Majumdar A, Mangal NS. Hyperprolactinemia. In: Ghumman S, editor. Principles and Practice of Controlled Ovarian Stimulation in ART. New Delhi: Springer; 2015. p. 319-28.  Back to cited text no. 10
    
11.
Egberts AC, Meyboom RH, De Koning FH, Bakker A, Leufkens HG. Non-puerperal lactation associated with antidepressant drug use. Br J Clin Pharmacol 1997;44:277-81.  Back to cited text no. 11
    
12.
Stahl SM. 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. 12
    

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Correspondence Address:
Hiral Kotadia,
Department of Psychiatry, Sri Aurobindo Institute of Medical Sciences, Indore - 453 555, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AMH.AMH_54_20





 

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