What can be prescribed for an elderly female patient with insomnia, taking mirtazapine 15 mg at bedtime, Seroquel (Quetiapine) 100 mg at bedtime, buspirone (Buspirone) 10 mg twice daily, and sertraline (Sertraline) 50 mg daily, with no insurance coverage for doxepin?

Optimizing Sleep in an Elderly Female with Refractory Insomnia

Given this patient's already substantial sedating medication regimen (mirtazapine 15 mg, quetiapine 100 mg, buspirone, and sertraline), the most appropriate next step is to optimize her existing medications before adding another agent—specifically, increase mirtazapine to 30 mg at bedtime, as this dose is more effective for sleep and is already guideline-recommended for insomnia. 1, 2

Critical Assessment of Current Regimen

This patient is already on two potent sedating agents (mirtazapine and quetiapine) yet remains unable to sleep, which suggests:

• Suboptimal dosing of existing medications rather than need for additional agents 2
• Potential paradoxical effects from polypharmacy 1
• Underlying sleep disorder (e.g., sleep apnea, restless legs) that medications cannot address 1

Primary Recommendation: Optimize Before Adding

Increase mirtazapine from 15 mg to 30 mg at bedtime, as the current 15 mg dose is at the lower end of the therapeutic range for insomnia (7.5-30 mg), and higher doses provide more robust sleep promotion while also addressing her anxiety through sertraline augmentation. 1, 2

Rationale for Mirtazapine Optimization

• Mirtazapine is already guideline-recommended for insomnia at doses up to 30 mg 1
• It promotes appetite, does not suppress REM sleep, and addresses anxiety—all beneficial in elderly patients 2
• Increasing an existing medication avoids polypharmacy risks inherent in adding yet another sedating agent 1

If Optimization Fails: Evidence-Based Additions

First-Line FDA-Approved Options

Zolpidem 5 mg at bedtime (starting with 5 mg in elderly, not 10 mg) is the strongest guideline-recommended option for both sleep onset and maintenance insomnia. 1, 2, 3

• The American Academy of Sleep Medicine provides a WEAK recommendation for zolpidem based on moderate-quality evidence 1
• Lower 5 mg dose is critical in elderly to minimize fall risk, cognitive impairment, and next-day sedation 2, 3
• Alternative: Eszopiclone 1-2 mg has longer half-life for sleep maintenance throughout the night 1, 2

Ramelteon 8 mg at bedtime is particularly appropriate if the primary complaint is sleep onset difficulty, with no dependence risk and no DEA scheduling—ideal for elderly patients. 1, 2, 3

• Recommended specifically for sleep onset insomnia by AASM guidelines 1
• Very short half-life reduces sleep latency without affecting maintenance 2
• No risk of falls, cognitive impairment, or dependence 2, 3

Second-Line Options (If Standard Agents Fail)

Temazepam 7.5-15 mg (starting at 7.5 mg in elderly) is effective for both sleep initiation and maintenance, though carries higher risk of residual morning sedation. 1, 2

Zaleplon 5 mg (reduced from standard 10 mg in elderly) is specifically for sleep onset difficulty with minimal next-day effects due to ultra-short half-life. 1, 2

Critical Safety Concerns in This Elderly Patient

Quetiapine Risks at Current Dose

The patient's current quetiapine 100 mg dose is concerning, as recent 2025 evidence demonstrates that even low-dose quetiapine for insomnia in older adults is associated with:

• 3.1-fold increased mortality risk compared to trazodone (HR 3.1,95% CI 1.2-8.1) 4
• 8.1-fold increased dementia risk compared to trazodone (HR 8.1,95% CI 4.1-15.8) 4
• 2.8-fold increased fall risk compared to trazodone (HR 2.8,95% CI 1.4-5.3) 4
• 7.1-fold increased dementia risk compared to mirtazapine (HR 7.1,95% CI 3.5-14.4) 4

Consider tapering quetiapine while optimizing mirtazapine, as the risks of quetiapine in elderly patients for insomnia now outweigh benefits based on this high-quality 2025 comparative safety study. 4

Polypharmacy and CNS Depression

This patient is already on multiple CNS depressants, which increases risk of:

• Respiratory depression, especially if undiagnosed sleep apnea exists 5
• Falls and fractures 3, 4
• Cognitive impairment and delirium 3
• Drug-drug interactions 1

What NOT to Prescribe

Trazodone is specifically NOT recommended by the American Academy of Sleep Medicine for insomnia treatment (WEAK recommendation against), as it reduces sleep latency by only 10 minutes compared to placebo at 50 mg doses. 1, 2, 3

Avoid benzodiazepines (lorazepam, clonazepam, diazepam) in this elderly patient due to:

• High risk of dependence, tolerance, and withdrawal 1, 2
• 58% rate of moderate-to-severe side effects 5
• Accumulation with long half-lives leading to falls 5, 3
• Worsening of potential sleep apnea 5

Do not use antihistamines (diphenhydramine) as AASM specifically recommends against them, with serious anticholinergic side effects in elderly patients. 1

Avoid melatonin, valerian, and L-tryptophan as AASM recommends against these due to insufficient efficacy data. 1

Non-Pharmacologic Imperative

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be strongly pursued as adjunct to any medication adjustment, particularly given her anxiety component and medication-refractory insomnia. 1, 2

• CBT-I includes stimulus control, sleep restriction, and progressive muscle relaxation 1
• Facilitates eventual medication tapering 1
• Addresses underlying anxiety-related sleep dysfunction 2

Screen for primary sleep disorders (sleep apnea, restless legs syndrome, periodic limb movements) that would explain medication failure, as these require specific treatment beyond hypnotics. 1

Clinical Algorithm

1. Optimize existing regimen: Increase mirtazapine to 30 mg at bedtime 1, 2
2. Consider quetiapine taper given 2025 safety data in elderly 4
3. If still inadequate after 1-2 weeks: Add zolpidem 5 mg OR ramelteon 8 mg at bedtime 1, 2, 3
4. If BzRAs fail or contraindicated: Trial ramelteon (if not already tried) 1, 2
5. Integrate CBT-I throughout to address underlying sleep dysfunction 1, 2
6. Screen for primary sleep disorders if no response to optimized pharmacotherapy 1

Key Pitfalls to Avoid

• Do not reflexively add another medication without first optimizing existing agents 1
• Do not continue quetiapine long-term in elderly for insomnia given 2025 mortality/dementia data 4
• Do not use standard adult doses of hypnotics in elderly—always start at half-dose 2, 3
• Do not prescribe trazodone despite its popularity, as guidelines recommend against it 1, 2
• Do not ignore potential sleep apnea, which would explain medication failure and be worsened by sedatives 1, 5