SNRIs

SNRIs, or serotonin-norepinephrine reuptake inhibitors, are a class of medications that increase synaptic levels of the neurotransmitters serotonin and norepinephrine by blocking their reuptake into presynaptic neurons. Most SNRIs have balanced effects on both transmitters, but norepinephrine reuptake inhibition often rises with higher doses; some agents may also affect dopamine at high concentrations.

They are approved for major depressive disorder and various anxiety disorders, and are used for certain chronic pain conditions. Venlafaxine and duloxetine are among the most prescribed SNRIs, with desvenlafaxine as an active metabolite of venlafaxine. Duloxetine is approved for fibromyalgia and diabetic neuropathy, among other indications; venlafaxine is used for generalized anxiety disorder, social anxiety disorder, and panic disorder, in addition to depression.

Common adverse effects include nausea, dry mouth, insomnia or sleepiness, dizziness, and sweating. Because of norepinephrine activity, some patients experience increased blood pressure or heart rate, especially at higher doses. Sexual dysfunction, weight changes, and sleep disturbances are possible. There is a risk of serotonin syndrome when combined with other serotonergic drugs. Withdrawal symptoms may occur on abrupt discontinuation. Caution is advised in bipolar disorder and in people with cardiovascular disease; interactions with monoamine oxidase inhibitors and other serotonergic or hypertensive agents are important.

Onset typically requires several weeks, with dose titration to balance efficacy and tolerability. Compared with SSRIs, SNRIs may offer additional benefit for patients with pain symptoms due to noradrenergic pathways. They are chosen when depressive symptoms are accompanied by chronic pain or when responses to SSRIs are insufficient.