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Selective serotonin reuptake inhibitor poisoning

Michael Ganetsky, MD
Section Editors
Stephen J Traub, MD
Michele M Burns, MD, MPH
Deputy Editor
Jonathan Grayzel, MD, FAAEM


The selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s for the treatment of depression. They are generally much safer in overdose than tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Commonly used SSRIs include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram.

In 2015, an SSRI was mentioned in 52,546 ingestions (22,256 single-substance ingestions) reported to US poison centers, 114 major outcomes, and only three fatalities [1]. The incidence of SSRI ingestions has steadily increased and mirrors the increase in SSRI prescriptions [2]. Isolated SSRI ingestions generally produce mild symptoms, although SSRI intoxication can infrequently produce serotonin syndrome, seizures, CNS depression, or various cardiac abnormalities. Citalopram and escitalopram are structurally different from the other SSRIs and potentially more toxic in overdose.

The toxicity and management of acute SSRI overdose will be discussed here. A summary table to facilitate emergency management of SSRI poisoning is provided (table 1). Discussions of the therapeutic use of these medications, and of serotonin syndrome, are found elsewhere. (See "Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects" and "Serotonin syndrome (serotonin toxicity)".)


Serotonin is produced from tryptophan, while norepinephrine and dopamine are produced from tyrosine, through similar chemical pathways in nerve terminals. These neurotransmitters are stored in cytoplasmic vesicles of presynaptic neurons and released into the synapse with nerve depolarization. Transport proteins specific for serotonin, norepinephrine, or dopamine are embedded in the presynaptic terminal cell membrane and are responsible for pumping these neurotransmitters out of the synapse and back into the cytoplasm. Once in the cytoplasm, the neurotransmitters are either repackaged into vesicles for reuse or degraded by monoamine oxidase. (See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Pharmacology'.)

Approximately 98 percent of the body's serotonin is found outside the central nervous system (CNS). Several families of serotonin receptors, with multiple subtypes, have been discovered. In the CNS, serotonergic neurons are found in the brainstem, mostly in the raphe nucleus. They have a role in regulating mood, personality, appetite, wakefulness, emesis, temperature regulation, and sexual behavior [3]. Peripherally, serotonin aids in regulating vascular tone, peristalsis, and platelet activation.

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Literature review current through: Nov 2017. | This topic last updated: Apr 26, 2017.
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