Can I add Lunesta (eszopiclone) to a patient's regimen of Wellbutrin (bupropion) and sertraline who is not responding to Ambien (zolpidem) 7.5mg?

Managing Refractory Insomnia in a Patient on Bupropion and Sertraline

Before adding Lunesta (eszopiclone) to this regimen, first optimize the Ambien dose to 10mg, as 7.5mg is subtherapeutic for most patients, and consider whether the antidepressant combination itself may be contributing to insomnia. 1

Initial Assessment and Optimization

Evaluate Current Medication Contributions to Insomnia

• Bupropion is inherently activating and commonly causes insomnia 1, 2. The second dose should be given before 3 PM to minimize sleep disruption 1. If taken later in the day, this timing should be adjusted first.
• Sertraline can cause sleep disturbances in some patients, though it is generally well-tolerated 3. Consider whether insomnia worsened after starting or increasing either antidepressant.

Optimize Current Hypnotic Before Adding Another Agent

• Ambien 7.5mg is below the standard therapeutic dose of 10mg for most adults 1. The recommended sequence per insomnia guidelines is to try alternate short-intermediate acting benzodiazepine receptor agonists (BzRAs) at appropriate doses before combining hypnotics 1.
• Increase Ambien to 10mg nightly before considering combination therapy, as inadequate dosing is a common pitfall.

If Optimization Fails: Adding Lunesta

Safety Considerations for Combination Therapy

Adding Lunesta to this regimen carries specific risks that must be weighed:

• Serotonin syndrome risk exists when combining bupropion with SSRIs 4. While rare, bupropion inhibits CYP2D6, potentially increasing sertraline levels 4. Adding a third CNS-active medication (eszopiclone) increases complexity and monitoring requirements.
• The combination of two hypnotics (Ambien + Lunesta) is not recommended in standard insomnia guidelines 1. The preferred sequence is to switch to an alternative BzRA (like eszopiclone alone at 2-3mg), not to combine them.

Evidence-Based Alternative Approach

Rather than adding Lunesta to Ambien, the guideline-recommended approach is: 1

1. Switch from Ambien to Lunesta (eszopiclone 2-3mg), as eszopiclone is FDA-approved for long-term use and may be more effective for sleep maintenance 5
2. Add cognitive behavioral therapy for insomnia (CBT-I) as initial behavioral intervention, which should be combined with pharmacotherapy 1
3. Consider a sedating antidepressant adjustment rather than dual hypnotics—options include:
   • Adding low-dose mirtazapine 7.5-15mg at bedtime (promotes sleep and is well-tolerated) 1
   • Adding low-dose trazodone 25-100mg at bedtime 1
   • Switching from sertraline to mirtazapine if depression control allows 1

If Proceeding Despite Guidelines

If you choose to add Lunesta despite guideline recommendations against combining hypnotics: 1

• Start eszopiclone at the lowest dose (1mg) and monitor closely for excessive sedation, cognitive impairment, and complex sleep behaviors
• This represents off-guideline prescribing and requires explicit informed consent discussion with the patient about increased risks
• Schedule close follow-up every 2-4 weeks to reassess necessity and attempt tapering one agent 1
• Document medical decision-making clearly, including why standard approaches were insufficient

Common Pitfalls to Avoid

• Do not combine two hypnotics as first-line therapy—this violates standard insomnia management guidelines 1
• Do not ignore the activating effects of bupropion—timing and dosing adjustments may resolve insomnia without additional medications 1, 2
• Do not prescribe long-term hypnotics without concurrent behavioral therapy—CBT-I should be included when conditions permit 1
• Do not overlook drug-drug interactions—bupropion's CYP2D6 inhibition can increase sertraline levels, and adding a third CNS medication compounds monitoring complexity 4