SNRI

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, are a class of antidepressants that increase brain levels of the neurotransmitters serotonin and norepinephrine by inhibiting their reuptake into neurons. By affecting both pathways, SNRIs aim to improve mood and affective symptoms while generally lacking the strong anticholinergic effects associated with older tricyclic antidepressants.

Compared with selective serotonin reuptake inhibitors (SSRIs), SNRIs have a broader pharmacologic effect, which can be beneficial in some patients but may also produce more dose-dependent adverse effects. They are approved for major depressive disorder and several anxiety disorders, and they are used in some chronic pain conditions such as fibromyalgia and neuropathic pain.

Common SNRIs include duloxetine, venlafaxine, desvenlafaxine, and milnacipran. Duloxetine is effective for mood disorders and pain; venlafaxine is dose-dependent in norepinephrine reuptake inhibition; milnacipran provides balanced serotonin and norepinephrine activity; desvenlafaxine is the active venlafaxine metabolite with similar uses.

Safety and tolerability: common adverse effects include nausea, dry mouth, sweating, dizziness, constipation, and sexual dysfunction. Venlafaxine and milnacipran can raise blood pressure, particularly at higher doses. Abrupt discontinuation may cause withdrawal symptoms. Serious interactions include serotonin syndrome when combined with other serotonergic drugs or MAO inhibitors; caution is advised in bipolar disorder and during pregnancy.

Pharmacokinetics: SNRIs are usually taken orally with varying half-lives and are primarily metabolized in the liver, with drug interactions involving cytochrome P450 enzymes (for example, duloxetine by CYP1A2/CYP2D6 and venlafaxine by CYP2D6). Dose titration and monitoring are recommended to minimize adverse effects and withdrawal risk.