A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series

Abstract

Clinical casesCase one A 35-year-old married woman consulted the psychiatry department in February 2010 for depression for the past 1.5 years which had become aggravated during the past 3 months. Using the Montgomery-Åsberg Depression Rate Scale (MADRS) [Montgomery and Åsberg, 1979] the patient scored 25 points and was diagnosed having depression and was prescribed fluoxetine 20 mg/day. After 21 days, the dose was increased to 40 mg/day along with alprazolam 0.5 mg/day for poor treatment response and persistent insomnia. After 2 weeks, she showed significant improvement although she experienced slight nausea and headache. During her subsequent follow up, the dose of alprazolam was reduced to 0.25 mg/day and tapered to complete cessation over the next week, and fluoxetine was continued with excellent therapeutic response.However, in July 2011, she complained of amenorrhea for five consecutive cycles and her serum prolactin level was found to be 25 ng/ml (normal 0-20 ng/ml). The dose of fluoxetine was reduced A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series Somnath Mondal, Indranil Saha, Saibal Das, Abhrajit Ganguly, Debasis Das and Santanu Kumar Tripathi Abstract: With the exception of fluoxetine, all selective serotonin reuptake inhibitors (SSRIs) commonly cause hyperprolactinemia through presynaptic mechanisms indirectly via 5-hydroxytryptamine (5-HT)-mediated inhibition of tuberoinfundibular dopaminergic neurons. However, there is little insight regarding the mechanisms by which fluoxetine causes hyperprolactinemia via the postsynaptic pathway. In this text, analysis of five spontaneously reported clinical cases of hyperprolactinemia resulting in overt symptoms of amenorrhea with or without galactorrhea, were scrupulously analyzed after meticulously correlating relevant literature and an attempt was made to explore the putative postsynaptic pathway of fluoxetine inducing hyperprolactinemia. Hypothetically, serotonin regulates prolactin release either by increasing oxytocin (OT) level via direct stimulation of vasoactitive intestinal protein (VIP) or indirectly through stimulation of GABAergic neurons. The pharmacodynamic exception and pharmacokinetic aspect of fluoxetine are highlighted to address the regulation of prolactin release via serotonergic pathway, either directly through stimulation of prolactin releasing factors (PRFs) VIP and OT via 5-HT 2A receptors predominantly on PVN (neurosecretory magnocellular cell) or through induction of 5-HT 1A -mediated direct and indirect GABAergic actions. Prospective molecular and pharmacogenetic studies are warranted to visualize how fluoxetine regulate neuroendocrine system and cause adverse consequences, which in turn may explore new ways of approach of drug development by targeting the respective metabolic pathways to mitigate these adverse impacts.

Late-Onset Normoprolactinemic Galactorrhea Associated with Fluoxetine Use: a Case Report

“…Although all of the SSRIs share the same mechanism of actions, therapeutic and side effect profiles, each patient reacts differently to a particular SSRI. No two SSRIs have identical secondary pharmacological characteristics 10 . Although there are several case reports about the endocrinological side effects of sertraline such as galactorrhea 2,5,8 , we observed no significant adverse effects in our case during a one-year follow-up.…”

“…Although there are several case reports about the endocrinological side effects of sertraline such as galactorrhea 2,5,8 , we observed no significant adverse effects in our case during a one-year follow-up. With the exception of fluoxetine, all SSRIs commonly cause hyperprolactinaemia through presynaptic mechanisms indirectly via 5-hydroxytryptamine-mediated inhibition of tuberoinfundibular dopaminergic neurons 10 . Hypothetically serotonin regulates prolactin release either by increasing the oxytocin level via direct stimulation of vasoactive intestinal protein or indirectly through stimulation of GABAergic neurons 10,13 .…”

“…There are a significant number of studies reporting that all selective serotonin reuptake inhibitors (SSRI) are associated with galactorrhea and/or prolactin abnormalities (hyperprolactinaemia), but the number of reported cases is limited [2][3][4][5][6]8,9 . Endocrine side effects of fluoxetine are uncommon and galactorrhea is rarely mentioned 10 . A detailed search of medical literature in English and Turkish revealed just eight cases of fluoxetine-induced galactorrhea 4,7,9,10,11 .…”

“…Endocrine side effects of fluoxetine are uncommon and galactorrhea is rarely mentioned 10 . A detailed search of medical literature in English and Turkish revealed just eight cases of fluoxetine-induced galactorrhea 4,7,9,10,11 . We present a case, which developed galactorrhea following treatment with fluoxetine.…”

Ovulation, A Sign of Health

“…Stress (Johansson, Karonen, and Laakso 1983) and/or the use of antidepressant drugs (Mondal et al 2013) may also cause an increase in prolactin production. High prolactin levels inhibit GnRH by negative modulation of kisspeptinergic neurons (Araujo-Lopes et al 2014) and by activation of dopaminergic neurons in the hypothalamus (Koike et al 1991).…”