Serotonin reuptake inhibitor

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

SRIs are not synonymous with selective serotonin reuptake inhibitors (SSRIs), as the latter term is usually used to describe the class of antidepressants of the same name, and because SRIs, unlike SSRIs, can either be selective or non-selective in their action. For example, cocaine, which non-selectively inhibits the reuptake of serotonin, norepinephrine, and dopamine, is an SRI but not an SSRI.

SRIs are used predominantly as antidepressants (e.g., SSRIs, SNRIs, and TCAs), though they are also commonly used in the treatment of other psychological conditions such as anxiety disorders and eating disorders. Less often, SRIs are also used to treat a variety of other medical conditions including neuropathic pain and fibromyalgia (e.g., duloxetine, milnacipran), and premature ejaculation (e.g., dapoxetine) as well as for dieting (e.g., sibutramine). Additionally, some clinically used drugs such as chlorpheniramine, dextromethorphan, and methadone possess SRI properties secondarily to their primary mechanism of action(s) and this contributes to their side effect and drug interaction profiles.

A closely related type of drug is a serotonin releasing agent (SRA), an example of which is fenfluramine.

Medication	SERTTooltip Serotonin transporter	NETTooltip Norepinephrine transporter	DATTooltip Dopamine transporter
Citalopram	1.16	4070	28100
Desmethylcitalopram	3.6	1820	18300
Escitalopram	1.1	7841	27410
Femoxetine	11.0	760	2050
Fluoxetine	0.81	240	3600
Fluvoxamine	2.2	1300	9200
Norfluoxetine	1.47	1426	420
Paroxetine	0.13	40	490
Sertraline	0.29	420	25
Desmethylsertraline	3.0	390	129
Zimelidine	152	9400	11700
Levomilnacipran^[3]	19.0	10.5	ND
Venlafaxine	8.9	1060	9300
Vilazodone^[3]	1.6	ND	ND
Vortioxetine^[3]	5.4	ND	ND
Amitriptyline	4.30	35	3250
Clomipramine	0.28	38	2190
Imipramine	1.40	37	8500

Medication	Dosage range (mg/day)^[4]	~80% SERT occupancy (mg/day)^[5]^[6]	Ratio (dosage / 80% occupancy)
Citalopram	20–40	40	0.5–1
Escitalopram	10–20	10	1–2
Fluoxetine	20–80	20	1–4
Fluvoxamine	50–350	70	0.71–5
Paroxetine	10–60	20	0.5–3
Sertraline	25–200	50	0.5–4
Duloxetine	20–120	30	0.67–2
Venlafaxine	75–375	75	1–5
Clomipramine	50–250	10	5–25

Comparison of SRIs