INTRODUCTION

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, and citalopram.

In 2008, single-substance SSRI ingestions accounted for 44,287 reported exposures to US poison centers, 90 major outcomes, and only two 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.

The toxicity and management of acute SSRI overdose will be discussed here. A summary table to facilitate emergent 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) and other antidepressants for treating depressed adults" and "Serotonin syndrome".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY

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.

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.