Can a patient with depression or anxiety take Lexapro (escitalopram) and Trazodone together?

Can Lexapro and Trazodone Be Taken Together?

Yes, a patient with depression or anxiety can take Lexapro (escitalopram) and trazodone together—this combination is commonly used in clinical practice and is generally considered safe and effective when properly monitored. 1

Rationale for Combination Therapy

The combination of a selective serotonin reuptake inhibitor (SSRI) like escitalopram with low-dose trazodone addresses multiple therapeutic targets:

• Trazodone is frequently added to SSRI therapy to manage insomnia that either accompanies depression/anxiety or emerges as a side effect of SSRI treatment 2, 3
• Clinical experience supports this combination, with guidelines noting that "a wealth of clinical experience with the co-administration of these drugs suggests the general safety and efficacy of this combination" 1
• Trazodone at low doses (25-100 mg at bedtime) functions primarily as a hypnotic through H1 receptor antagonism and 5-HT2A blockade, rather than as a full antidepressant 1, 2
• The combination may improve efficacy by targeting multiple sleep-wake mechanisms while minimizing toxicity from higher doses of a single agent 1

Important Safety Considerations

Serotonin Syndrome Risk

While combining two serotonergic medications theoretically increases risk, serotonin syndrome is rare with this specific combination when used at standard doses 1:

• Monitor for early warning signs: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, hyperreflexia), and autonomic symptoms (tachycardia, diaphoresis) 1
• Symptoms typically appear within 24-48 hours after starting the combination or increasing doses 1
• Start trazodone at low doses (25-50 mg at bedtime) and increase slowly if needed 1

Activation/Jitteriness Syndrome

A small subset of patients may experience activation symptoms when combining these medications 4, 5:

• Watch for: anxiety, agitation, insomnia, irritability, akathisia, or hypomanic symptoms 4, 5
• These symptoms typically occur immediately after adding trazodone or with dose increases 4
• If activation occurs, discontinue trazodone—symptoms usually resolve quickly 4, 5

Monitoring Protocol

Follow patients closely during the initial treatment period 1:

• Assess every few weeks initially to evaluate effectiveness, side effects, and need for ongoing medication 1
• Monitor for daytime sedation, which should be carefully evaluated given the combination of CNS depressants 1
• Avoid combining with alcohol or other CNS depressants, which have additive effects on psychomotor performance 1

Clinical Evidence

The combination has demonstrated benefit in multiple contexts 6, 3:

• Case series data shows that 37.5% of patients had improvements in both sleep and depression when trazodone was added to fluoxetine (another SSRI) 6
• Trazodone is the second most commonly prescribed agent for insomnia in the United States, often used off-label in combination with SSRIs 2, 3
• Low-dose trazodone (25-100 mg) is specifically recommended for insomnia in patients already taking antidepressants 1

Practical Prescribing Approach

When combining these medications 1:

• Continue escitalopram at the established therapeutic dose for depression/anxiety
• Add trazodone 25-50 mg at bedtime for insomnia, increasing to 100 mg if needed and tolerated 1
• Educate patients about: expected benefits, potential side effects (especially daytime sedation), and warning signs of serotonin syndrome 1
• Use the lowest effective maintenance dose of both medications 1
• Reassess need for trazodone periodically, as insomnia may improve as depression/anxiety resolves 1

Common Pitfalls to Avoid

• Do not use trazodone as monotherapy for major depression at these low doses—it requires higher doses (300-400 mg daily) for antidepressant effect 2
• Do not combine with MAOIs, which is absolutely contraindicated due to severe serotonin syndrome risk 1
• Do not ignore persistent activation symptoms—these warrant discontinuation rather than dose adjustment 4
• Do not prescribe without patient education about allowing adequate sleep time and avoiding alcohol 1