Cited by 629Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review

Vaswani, Meera, Linda, Farzana Kadar, Ramesh, Subramanyam·2003·Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI 10.1016/s0278-5846(02)00338-x

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Abstract

The selective serotonin reuptake inhibitors (SSRIs) have emerged as a major therapeutic advance in psychopharmacology. As a result, the discovery of these agents marks a milestone in neuropsychopharmacology and rational drug design, and has launched a new era in psychotropic drug development. Prior to the SSRIs, all psychotropic medications were the result of chance observation. In an attempt to develop a SSRI, researchers discovered a number of nontricyclic agents with amine-uptake inhibitory properties, acting on both noradrenergic and serotonergic neurons with considerable differences in potency. A given drug may affect one or more sites over its clinically relevant dosing range and may produce multiple and different clinical effects. The enhanced safety profile includes a reduced likelihood of pharmacodynamically mediated adverse drug-drug interactions by avoiding affects on sites that are not essential to the intended outcome. SSRIs were developed for inhibition of the neuronal uptake pump for serotonin (5-HT), a property shared with the TCAs, but without affecting the other various neuroreceptors or fast sodium channels. The therapeutic mechanism of action of SSRIs involves alteration in the 5-HT system. The plethora of biological substrates, receptors and pathways for 5-HT are candidates to mediate not only the therapeutic actions of SSRIs, but also their side effects. A hypothesis to explain these immediate side effects is that 5-HT is increased at specific 5-HT receptor subtypes in discrete regions of the body where the relevant physiologic processes are regulated. Marked differences exist between the SSRIs with regard to effects on specific cytochrome P450 (CYP) enzymes, and thus the likelihood of clinically important pharmacokinetic drug-drug interactions. Although no clear relationship exists between the clinical efficacy, plasma concentration of SSRIs, nor any threshold that defines toxic concentrations, but therapeutic drug monitoring (TDM) may be useful in special populations, such as in elderly patients, poor metabolizers (PM) of sparteine (CYP2D6) or mephenytoin (CYP2C19), and patients with liver and kidney impairment. Several meta-analyses have reviewed the comparative efficacy of TCAs and SSRIs, and concluded that both TCAs and SSRIs have similar efficacy in the treatment of depression. SSRIs have demonstrated better efficacy and tolerability in the treatment of obsessive compulsive disorder (OCD). They have also been found to be effective in the treatment for social anxiety disorder both in reducing total levels of social anxiety and in improving overall clinical condition. The benefit of SSRIs in anorexia nervosa (AN) is apparently short-term unless medication is given in the context of nutritional or behavioral therapy. No single antidepressant can ever be recommended for every patient, but in a vast majority of patients, SSRIs should be considered as one of the first-line drugs in the treatment of depression.

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Authors: Vaswani, M., Linda, F. K., & Ramesh, S.
Affiliations: All India Institute of Medical Sciences (IN)
Corresponding author: Vaswani, Meera
Venue: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher: Elsevier BV
Published: 2003-02
Volume: 27
Issue: 1
Pages: 85-102
ISSN: 0278-5846 (ISSN-L)
DOI: 10.1016/s0278-5846(02)00338-x
OpenAlex: W1988612597
Cited by: 612
References: 203
Citations by year: 2026: 16 · 2025: 17 · 2024: 20 · 2023: 30 · 2022: 19 · 2021: 30 · 2020: 10 · 2019: 22 · 2018: 28 · 2017: 27 · 2016: 23 · 2015: 37 · 2014: 24 · 2013: 29 · 2012: 27
FWCI: 3.58
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: selective serotonin reuptake inhibitors, serotonin, serotonin receptors, antidepressant mechanism, adverse drug reactions, drug-drug interactions, cytochrome P450, therapeutic drug monitoring, tricyclic antidepressants, depression, obsessive-compulsive disorder, social anxiety disorder, anorexia nervosa, bulimia nervosa, eating disorders, sleep disorders
MeSH terms: Adolescent, Adult, Age Factors, Aged, Anxiety Disorders, Feeding and Eating Disorders, Child, Depressive Disorder, Female, Humans, Male, Middle Aged, Pregnancy, Pregnancy Complications, Substance Withdrawal Syndrome, Suicide, Attempted, Selective Serotonin Reuptake Inhibitors

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Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review

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