Can Lunesta (eszopiclone) worsen depression in an adult patient with depression who is currently taking Prestiq (desvenlafaxine)?

Can Lunesta Worsen Depression in Patients Taking Prestiq?

Yes, Lunesta (eszopiclone) carries a specific FDA warning to use with caution in patients with depression, as sedative/hypnotics should be administered cautiously to patients exhibiting signs and symptoms of depression due to increased risk of suicidal tendencies and intentional overdose. 1

Key Safety Considerations

FDA-Mandated Precautions for Eszopiclone in Depression

The FDA drug label explicitly states that sedative/hypnotic drugs should be administered with caution to patients exhibiting signs and symptoms of depression, noting that suicidal tendencies may be present and protective measures may be required. 1 The label further emphasizes that intentional overdose is more common in this group of patients; therefore, the least amount of drug that is feasible should be prescribed at any one time. 1

Risk-Benefit Analysis in Your Patient

While the FDA warning is clear about caution, clinical trial data actually suggests eszopiclone may not worsen—and could potentially improve—depressive symptoms when co-administered with antidepressants:

• In patients with insomnia and comorbid major depressive disorder, eszopiclone 3 mg nightly combined with fluoxetine resulted in significantly greater reductions in Hamilton Depression Rating Scale scores (-14.1 vs -11.2 for placebo; P < .01) and higher response rates (55.6% vs 42.0%; P = .01) at 8 weeks. 2

• A separate economic analysis of the same population showed eszopiclone co-administered with fluoxetine improved both insomnia symptoms and depression outcomes, with an incremental cost-effectiveness ratio of approximately $14,000 per quality-adjusted life year gained. 3

Clinical Decision Algorithm

For your patient on Prestiq (desvenlafaxine) with depression:

1. Assess depression severity and suicide risk first - If active suicidal ideation or severe depression is present, address this before initiating any hypnotic. 1

2. If depression is stable/improving on desvenlafaxine:

   • Eszopiclone can be prescribed cautiously for insomnia
   • Start with the lowest effective dose (1-2 mg in most adults, 1 mg in elderly/debilitated) 4
   • Prescribe only small quantities initially given overdose risk 1
   • Monitor closely for mood destabilization in first 2-4 weeks

3. Key monitoring parameters:

   • Worsening depression symptoms
   • Emergence of suicidal thoughts
   • Complex sleep behaviors (sleep-driving, sleep-eating) which occur more frequently with CNS depressants 1
   • Morning sedation or cognitive impairment

Important Caveats

The eszopiclone studies showing benefit were conducted with SSRIs (fluoxetine, escitalopram), not SNRIs like desvenlafaxine. 2 However, desvenlafaxine has a favorable safety profile with minimal drug-drug interactions due to low impact on cytochrome P450 enzymes, 5, 6 suggesting pharmacokinetic interactions with eszopiclone are unlikely.

Avoid alcohol and other CNS depressants as these substantially increase the risk of complex sleep behaviors and cognitive impairment with eszopiclone. 1

Take eszopiclone immediately before bedtime - taking it while still active increases risk of short-term memory impairment, hallucinations, impaired coordination, and dizziness. 1

Alternative Consideration

If insomnia is a primary symptom of inadequately treated depression rather than a separate disorder, optimizing the desvenlafaxine dose (50-100 mg daily) may be more appropriate than adding a hypnotic, as SNRIs can improve both mood and associated sleep disturbances. 6