Is it safe to use Cymbalta (duloxetine) and trazodone together?

Combining Cymbalta (Duloxetine) and Trazodone

Yes, duloxetine and trazodone can be used together safely, as clinical experience supports the general safety and efficacy of combining antidepressants from different classes, though careful monitoring for additive CNS effects and daytime sedation is essential. 1

Safety Profile of the Combination

The combination of duloxetine (an SNRI) and trazodone (a serotonin antagonist and reuptake inhibitor) is commonly used in clinical practice, particularly when treating depression with comorbid insomnia or when augmenting antidepressant therapy. 1

Key safety considerations:

• No specific contraindication exists for combining these medications, and a wealth of clinical experience suggests general safety when co-administering antidepressants from different classes 1

• The combination may improve efficacy by targeting multiple sleep-wake mechanisms while minimizing toxicity that could occur with higher doses of a single agent 1

• Trazodone shows moderate efficacy for improving sleep quality and duration when used at lower-than-antidepressant doses for insomnia 1

Monitoring Requirements

Monitor carefully for these potential adverse effects:

• Daytime sedation is the primary concern and should be carefully monitored, as both medications have CNS depressant properties 1

• Additive CNS effects can occur with concomitant use of centrally acting drugs 2

• Serotonin syndrome risk exists theoretically when combining serotonergic agents, though this is rare with this specific combination 2

• Blood pressure changes should be monitored, as duloxetine can cause increases in blood pressure (mean increases of 0.5 mm Hg systolic and 0.8 mm Hg diastolic) 2

Practical Prescribing Approach

Start with low doses and titrate cautiously:

• Begin trazodone at 25-50 mg at bedtime for insomnia when combined with duloxetine 1

• Use the lowest effective doses of each medication to minimize side effects 1

• Allow appropriate sleep time and avoid combining with alcohol or other sedatives 1

• In elderly patients, use extra caution and downward dosage adjustment due to increased sensitivity to CNS effects and risk of falls 1

Clinical Context

This combination is particularly useful when:

• Depression with insomnia is present, as duloxetine addresses depression and pain while trazodone improves sleep 1

• Chronic pain conditions exist, since duloxetine is effective for neuropathic pain, fibromyalgia, and musculoskeletal pain 1

• Single-agent therapy has failed, as combination therapy from different classes may provide better outcomes 1

Important Caveats

Avoid this combination in patients with:

• Substantial alcohol use, as duloxetine should not be prescribed to patients with heavy alcohol intake due to severe liver injury risk 2

• Compromised respiratory function (asthma, COPD, sleep apnea), where additive CNS depression poses greater risk 1

• Hepatic impairment, as duloxetine is extensively metabolized by the liver 2

Drug interaction considerations:

• Duloxetine is a moderate CYP2D6 inhibitor and could theoretically increase trazodone levels, though this is rarely clinically significant 2

• Both medications should be tapered when discontinuing to reduce risk of withdrawal or discontinuation syndrome 1, 2