Section 06 · Monograph

Duloxetine

Reviewed Nov 2026FDA label

CymbaltaSNRI

Black Box Warning

Antidepressants increased the risk of suicidal thinking and behavior compared to placebo in short-term studies in children, adolescents, and young adults (ages 18-24) with MDD and other psychiatric disorders
This risk must be balanced against clinical need; depression itself is associated with increased risk of suicide
Not approved for use in pediatric patients for depression
Patients of all ages started on therapy should be monitored closely for clinical worsening, suicidality, and unusual changes in behavior, especially during initial months of therapy and at times of dose changes

Major depressive disorder (MDD) in adultsFDA-labeled
Generalized anxiety disorder (GAD) in adults and pediatric patients ≥7 yearsFDA-labeled
Diabetic peripheral neuropathic pain (DPNP)FDA-labeled
Fibromyalgia in adults and pediatric patients ≥13 yearsFDA-labeled
Chronic musculoskeletal pain, including chronic low back pain and osteoarthritis painFDA-labeled

Serotonin-norepinephrine reuptake inhibitor (SNRI): potent inhibitor of neuronal serotonin and norepinephrine reuptake, with weak dopamine reuptake inhibition
Increased synaptic serotonin/norepinephrine availability is believed to underlie both antidepressant/anxiolytic effects and analgesic effect on neuropathic/musculoskeletal pain via descending inhibitory pain pathways
Precise mechanism of analgesic effect independent of mood improvement is not fully established

DPNP: 60 mg once daily; some patients may benefit from starting at 30 mg once daily for 1 week before increasing to 60 mg
MDD: initial 40-60 mg/day; may titrate up to a maximum of 120 mg/day, though no added benefit generally seen above 60 mg
GAD: initial 60 mg once daily; max 120 mg/day
Fibromyalgia: 30 mg once daily for 1 week, then increase to 60 mg once daily
Capsules must be swallowed whole; do not chew, crush, or open and sprinkle on food
Taper gradually rather than abrupt cessation to minimize discontinuation symptoms

Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease: not recommended

Not recommended in any degree of hepatic insufficiency or in patients with substantial alcohol use

Concomitant use with MAOIs or use of an MAOI within 14 days of stopping duloxetine (risk of serotonin syndrome)
Initiation in a patient being treated with linezolid or intravenous methylene blue
Uncontrolled narrow-angle glaucoma
Known hypersensitivity to duloxetine

MAOIs: contraindicated — risk of serotonin syndrome and hypertensive crisis
Potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin): markedly increase duloxetine exposure — avoid concomitant use
CYP2D6 inhibitors: increase duloxetine concentrations; duloxetine itself is a moderate CYP2D6 inhibitor and can raise levels of TCAs and Type 1C antiarrhythmics
Thioridazine: contraindicated due to QT prolongation risk
Serotonergic drugs: increased risk of serotonin syndrome
Anticoagulants/antiplatelets: increased risk of abnormal bleeding
Alcohol: increased risk of hepatic injury

Monitor for suicidal ideation/behavior and clinical worsening
Blood pressure at baseline and periodically
Liver function tests if signs of hepatic injury develop
Serum sodium, especially in elderly or volume-depleted patients
Signs/symptoms of serotonin syndrome when combined with other serotonergic agents
Glycemic control in diabetic patients
Signs of abnormal bleeding

No adequate, well-controlled human studies; use only if potential benefit justifies potential fetal risk
Neonates exposed late in third trimester may develop poor neonatal adaptation syndrome
Duloxetine Pregnancy Registry maintained to collect outcome data
Present in human milk; breastfeeding generally not recommended during treatment given limited infant safety data