# Structural Biochemistry/Selective Serotonin Reuptake Inhibitors
## Overview

Selective Serotonin Reuptake Inhibitors are a class of antidepressants which aim to increase the levels of serotonin available in the synaptic cleft by inhibiting reuptake of serotonin into the pre-synaptic cell. They have varying affinities for other monoamine transporters such are norepinephrine and dopamine, which gives rise to the term “selective” in their name. SSRIs have become the most popular form of antidepressants, replacing monoamine oxidase inhibitors which have more side effects and slightly reduced efficacy. However, debate remains as to the actual benefit of SSRIs, as several meta-studies have indicated that the effect of antidepressants compared to placebos were statistically significant but were not clinically significant. SSRIs are the most common antidepressant medication because it can treat moderate to severe depression with relatively low risk and with fewer side effects. Selective Serotonin Reuptake Inhibitors can be made to be either extended release (XR) or controlled release (CR). The benefit of these types of medication is that it can release the medication over a long period of time slower. Therefore there is less ups and downs associated with the drug and a nice smooth transition onto the drug is made. These drugs can be used for purposes other than as an antidepressant. SSRIs affect every person differently due to how each individual brain reacts to the chemical makeup of the drug. Possible side effects include dry mouth, nausea, nervousness, headache, diarrhea, drowsiness, insomnia etc...

## Pharmacodynamics

SSRIs inhibit the reuptake of serotonin into the presynaptic cell, increasing the available serotonin in the synapse. However, the antidepressant effects require several weeks of administration of SSRIs before the effects are felt. The reason is that the increased levels of serotonin produce two neurological changes: first, it leads to the downregulation of 5-HT2A receptors, which alters the neurotransmitter to receptor ratio. Second, it also triggers autoreceptors on the presynaptic cleft which causes the cell to produce less serotonin as it down regulates in response to the increased levels of serotonin available. Alternatively, SSRIs also influence other pathways such as cyclic AMP (cAMP) on the post synaptic cell, which causes the release of brain derived neurotrophic factor (BDNF). This protein is secreted to regulate neural networks as well as synaptic plasticity.

## Examples of several SSRIs:

* citalopram (Celexa, Cipramil, Cipram, Dalsan, Recital, Emocal, Sepram, Seropram, Citox, Cital)
* dapoxetine (Priligy)
* escitalopram (Lexapro, Cipralex, Seroplex, Esertia)
* fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Ladose, Motivest, Flutop, Fluctin (EUR), Fluox (NZ), Depress (UZB), Lovan (AUS), Prodep (IND))
* fluvoxamine (Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox)
* indalpine (Upstene) (discontinued)
* paroxetine (Paxil, Seroxat, Sereupin, Aropax, Deroxat, Divarius, Rexetin, Xetanor, Paroxat, Loxamine, Deparoc)
* sertraline (Zoloft, Lustral, Serlain, Asentra)
* vilazodone (Viibryd)
* zimelidine (Zelmid, Normud) (discontinued)
* ↑ Severe and anxious depression: Combining definitions of clinical sub-types to identify patients differentially responsive to selective serotonin reuptake inhibitors1
* ↑ SSRI, October 28, 2012
* ↑ Selective serotonin reuptake inhibitors pathway2