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Int J Psychiatry Clin Pract. 2004;8 Suppl 1:3-10. doi: 10.1080/13651500410005487.

Selectivity of SSRIs: individualising patient care through rational treatment choices.

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Chairman, Neuroscience Education Institute, Adjunct Professor, University of California, CA, San Diego.


Despite a common mode of action [inhibition of the 5-hydroxytryptamine (5-HT) neuronal reuptake transporter], proven antidepressant efficacy and a similar range of indications (depression and a variety of anxiety disorders), the unique secondary binding properties of each selective serotonin reuptake inhibitor (SSRI) account for clinically significant differences in tolerability and side-effect profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combination of actions at noradrenergic, dopaminergic, muscarinic cholinergic, histaminergic and sigma receptors. In addition, most SSRIs inhibit at least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetic interactions with co-prescribed drugs. Although secondary properties of SSRIs can be associated with side effects, sometimes these same actions can be harnessed to good therapeutic effect through rational, informed treatment choices. In this way, agents that more consistently cause central nervous system activation (such as fluoxetine and sertraline) can be used to boost energy in patients whose depression is accompanied by fatigue and apathy, while the anxiolytic, sedative properties of others (particularly paroxetine and fluvoxamine) can be beneficial in patients with insomnia and agitation. When secondary properties are experienced as undesirable side effects, agents with greater selectivity for the serotonin transporter and without significant secondary binding properties, such as citalopram and escitalopram, may be desirable. This article explains how an understanding of the secondary binding properties of the SSRIs can guide individualised treatment across the spectrum of depressive and anxious states.


5-HT receptor; anxiety disorders; binding sites; cytochrome P450; depression; selective serotonin reuptake inhibitor

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