The pharmacogenomics of selective serotonin reuptake inhibitors.
The introduction of selective serotonin (5-HT) reuptake inhibitors (SSRIs) has significantly improved the pharmacological treatment of a range of psychiatric disorders. Nevertheless, despite the undoubted advantages of antidepressant treatment in terms of improved tolerability to therapy while maintaining a high level of efficacy, not all patients benefit from it; an appreciable proportion do not respond adequately, while others may show adverse reactions. The necessary change of the initial treatment choice often requires extended periods for the remission of symptomatology. Such difficulties could be avoided if it should be possible to determine more quickly the most suitable drug. Several factors have been thought to influence the outcome of antidepressant therapy. Among the factors influencing the interindividual variability in response to treatment with SSRI, differences in genetic features may play a significant role. Several genetic polymorphisms have been associated with therapeutic SSRI response, including genetic variants of the 5-HT transporter, 5-HT-2A-receptor, tryptophan hydroxylase, brain-derived neurotrophic factor, G-protein beta3 subunit, interleukin-1beta and angiotensin-converting enzyme, although with conflicting results; also cytochrome P450 drug-metabolising enzymes may bear a particular importance, although further corroboration of the findings is necessary, and further key participating genes remain to be identified. The hope is that the identification of these genetic components will eventually facilitate the development of a customised SSRI treatment.
Serretti
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Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan Italy. serretti@alessandro@hsr.it
Artioli
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D000928:Antidepressive Agents / Q000627:therapeutic use; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D008995:Monoamine Oxidase / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods*; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D014365:Tryptophan Hydroxylase / Q000235:genetics
D000928:Antidepressive Agents; D008995:Monoamine Oxidase; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase