About this term
- Quick definition
- Serotonin-norepinephrine reuptake inhibitor. A class of antidepressants that increases both serotonin and norepinephrine signaling.
- Full clinical definition
- SNRIs block both the serotonin transporter and the norepinephrine transporter. Examples include venlafaxine, duloxetine, desvenlafaxine, and levomilnacipran. The norepinephrine effect grows as the dose rises for some SNRIs (notably venlafaxine), which is one reason dose changes are paced over weeks.
- Epidemiology
- SNRIs are the second most prescribed class of antidepressants in the United States after SSRIs. Duloxetine and venlafaxine are the most common. Antidepressant use among U.S. adults reached 13.2 percent by 2018 (NCHS Data Brief, 2020), with SNRIs accounting for a meaningful share.
- Common uses
- Major depressive disorder, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, neuropathic pain (duloxetine has FDA indications for diabetic peripheral neuropathy and fibromyalgia), and chronic musculoskeletal pain.
- What it can feel like
- Similar trajectory to SSRIs. Sleep, appetite, and energy often shift in the first two to four weeks. Mood lifts later. People treated for both depression and a chronic pain condition sometimes notice the pain effect within the first two to four weeks, which can come before mood improvement.
- How clinicians assess response
- PHQ-9 is the standard tracking tool for depression. For pain conditions, a clinician usually tracks pain ratings and function in parallel. A full trial is six to eight weeks at a therapeutic dose.
- Common side effects
- Similar to SSRIs (nausea, headache, sleep changes, sexual side effects), with the addition of dose-dependent increases in blood pressure for some drugs in the class. Sweating and dry mouth are more common than with SSRIs for some patients. Venlafaxine in particular has a short half-life and a higher rate of discontinuation symptoms if stopped abruptly. A taper over weeks is preferred.
- SNRIs at a glance
Drug Typical adult range Half-life Notable for Venlafaxine XR (Effexor XR) 75 to 225 mg/day 5 hours (parent), 11 hours (active metabolite) Norepinephrine effect grows with dose; dose-dependent blood pressure rise; pronounced discontinuation symptoms. Duloxetine (Cymbalta) 30 to 120 mg/day About 12 hours FDA indications for depression, GAD, diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain. Desvenlafaxine (Pristiq) 50 to 100 mg/day About 11 hours Active metabolite of venlafaxine; simpler dosing; fewer CYP2D6 interactions. Levomilnacipran (Fetzima) 40 to 120 mg/day About 12 hours Stronger norepinephrine effect than other SNRIs; FDA approved for major depressive disorder only. Information only, not a prescription. Dosing decisions belong with a prescriber.
- Treatment implications
- SNRIs are reasonable first-line options or second-line after an SSRI trial. Duloxetine is sometimes chosen when depression and a chronic pain condition coexist. Blood pressure should be monitored, especially with venlafaxine at higher doses.
- Related terms
- Antidepressant. SSRI. Bupropion. Medication management.
- Related articles
- Treatment. Antidepressant comparison. Stopping antidepressants. Major depressive disorder.
Sources
- Cipriani A, et al. Lancet. 2018.
- American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder.
- NICE Guideline NG222.
- Brody DJ, Gu Q. Antidepressant Use Among Adults: United States, 2015 to 2018. NCHS Data Brief No. 377. CDC, 2020.