Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels.Neuropathic pain, stress incontinence, fibromyalgia ( SNRIs).Major depressive disorder (first-line: SSRIs).Selective serotonin reuptake inhibitors ( SSRIs e.g., fluoxetine, sertraline, citalopram) St John's Wort: induces cytochrome P450.Other serotonergic drugs: ↑ risk of serotonin syndrome.Use with caution in bipolar disorder ( ↑ risk of provoking mania).Downregulation of β-adrenergic receptors and inhibition of glutamate release.Serotonin syndrome may occur as a complication of serotonergic antidepressant use TCA toxicity is also possible, as is antidepressant discontinuation syndrome, which is caused by abrupt withdrawal or dose reduction of an antidepressant taken for ≥ 4 weeks. While MAOIs and TCAs also have a high degree of efficacy, they are no longer widely used because of their undesirable side-effect profiles. SSRIs are the first-line treatment for the vast majority of patients with depression because of their efficacy and favorable side-effect profile. Most of these drugs work by increasing levels of serotonin, norepinephrine, or dopamine within the synaptic cleft. The most widely used classes of antidepressants are selective serotonin reuptake inhibitors ( SSRIs), serotonin-norepinephrine reuptake inhibitors ( SNRIs), monoamine oxidase inhibitors ( MAOIs), and tricyclic antidepressants ( TCAs). Antidepressants are used primarily to treat major depressive disorder ( MDD), although they are also indicated for the treatment of many other neuropsychiatric conditions.
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