Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review

Abstract

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study.

Effect of Short Photoperiod on Behavior and Brain Plasticity in Mice Differing in Predisposition to Catalepsy: The Role of BDNF and Serotonin System

“…Many experimental and clinical studies have found a relationship between depressive disorders and serotonin deficiency in the brain [ 10 , 40 ]. Clinically effective antidepressants (for example, SSRI, selective serotonin reuptake inhibitors) increase the amount of serotonin available in the synapses [ 40 , 41 ].…”

“…Many experimental and clinical studies have found a relationship between depressive disorders and serotonin deficiency in the brain [ 10 , 40 ]. Clinically effective antidepressants (for example, SSRI, selective serotonin reuptake inhibitors) increase the amount of serotonin available in the synapses [ 40 , 41 ]. We found that only CBA mice exposed to short-day conditions demonstrated decreased 5-HT and its metabolite 5-HIAA levels in the hypothalamus, a decreased 5-HT level in the hippocampus, and a reduced mRNA level of the Tph2 gene encoding the key enzyme for 5-HT biosynthesis in the midbrain [ 10 ].…”

Pharmacokinetic and pharmacodynamic considerations with psychiatric disorders and migraines

“…Patients should be counseled on these risks. 7 Those prescribed lithium should use NSAIDs with caution due to the risk of developing lithium toxicity, and caffeine-containing products may lower lithium concentrations.…”

Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram

“…Pregabalin's side effects include dizziness and drowsiness [42], and overuse can result in dependence [43]. Paroxetine may cause nausea, a dry mouth, and sexual dysfunction [44], with an increased risk of bleeding associated with overuse [45]. Citalopram can induce nausea and insomnia [46].…”