What is the best approach to manage chronic insomnia in an elderly patient who has been taking Paroxetine and Mirtazapine without relief?

Management of Refractory Chronic Insomnia in an Elderly Patient Currently on Paroxetine and Mirtazapine

This patient requires immediate implementation of Cognitive Behavioral Therapy for Insomnia (CBT-I) as the foundation of treatment, followed by discontinuation of the ineffective paroxetine (which lacks established efficacy for insomnia), optimization of mirtazapine dosing based on recent evidence, and consideration of adding a first-line FDA-approved hypnotic if behavioral interventions prove insufficient. 1, 2, 3

Critical First Step: Implement CBT-I Immediately

CBT-I must be initiated before making any medication changes, as it represents the standard of care with superior long-term efficacy compared to pharmacotherapy alone. 1, 3

• CBT-I produces clinically meaningful improvements sustained for up to 2 years, while pharmacotherapy benefits degrade after discontinuation 3
• The American College of Physicians provides a strong recommendation that all patients with chronic insomnia receive CBT-I as initial treatment 3
• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, or web-based modules—all showing effectiveness 2, 3
• Treatment typically requires 4-8 sessions over 6 weeks and includes stimulus control therapy, sleep restriction therapy, cognitive restructuring, and sleep hygiene education 2, 3

Common pitfall: Do not continue adjusting medications without implementing CBT-I, as this deprives the patient of the most effective and durable therapy 2, 3

Medication Reassessment and Optimization

Discontinue Paroxetine for Insomnia

Paroxetine should be discontinued for insomnia treatment, as it is not FDA-approved for this indication and its efficacy is not well established. 1

• The American Academy of Sleep Medicine explicitly states that antidepressants including paroxetine "are not FDA approved for insomnia and their efficacy for this indication is not well established" 1
• While one small open-label study from 1999 suggested potential benefit, this evidence is insufficient to support continued use after 20 years of treatment failure 4
• If paroxetine is being used for comorbid depression or anxiety, this should be clearly documented; otherwise, taper and discontinue 1

Optimize or Reassess Mirtazapine

Mirtazapine has the strongest recent evidence among sedating antidepressants for treating chronic insomnia in older adults, but requires proper dosing. 5

• A 2025 randomized, double-blind, placebo-controlled trial (the MIRAGE study) demonstrated that mirtazapine 7.5 mg significantly reduced insomnia severity in adults ≥65 years, with mean ISI score improvement of -6.5 points versus -2.9 for placebo (p=0.003) 5
• Mirtazapine improved subjective wake after sleep onset, total sleep time, and sleep efficiency 5
• Critical dosing consideration: The effective dose in older adults is 7.5 mg, not the typical antidepressant doses of 15-30 mg 5
• Six participants discontinued due to adverse events (versus 1 in placebo), indicating tolerability concerns that require monitoring 5

If the patient is already on mirtazapine at higher doses (15-30 mg), consider dose reduction to 7.5 mg specifically for insomnia, as this may improve tolerability while maintaining efficacy. 5

Adding First-Line FDA-Approved Hypnotic Therapy

If CBT-I combined with optimized mirtazapine proves insufficient, add a short-to-intermediate acting benzodiazepine receptor agonist (BzRA) at the lowest effective dose for the shortest duration. 1, 2

Recommended First-Line Options for Elderly Patients:

For combined sleep onset and maintenance insomnia (most common pattern):

• Zolpidem 5 mg (reduced dose mandatory for age ≥65): Effective for both sleep onset and maintenance 2
• Eszopiclone 2 mg (start lower than standard 2-3 mg dose): Addresses both sleep initiation and maintenance 2
• Temazepam 7.5 mg (reduced from standard 15 mg): Short-to-intermediate acting with established efficacy 1, 2

Critical safety considerations in elderly patients:

• The American Geriatrics Society mandates using lowest effective doses due to increased sensitivity, fall risk, and cognitive impairment 2
• All hypnotics carry FDA warnings about daytime impairment, complex sleep behaviors (sleep-driving, sleep-walking), falls, fractures, and potential associations with dementia 1, 2
• Monitor closely for morning sedation, cognitive impairment, and behavioral changes 2

Alternative Second-Line Options:

If BzRAs are contraindicated or ineffective:

• Low-dose doxepin 3-6 mg: Specifically for sleep maintenance insomnia, with strong evidence reducing wake after sleep onset by 22-23 minutes 2
• Ramelteon 8 mg: For sleep-onset insomnia, particularly useful in patients with substance abuse history as it lacks abuse potential 2
• Suvorexant: For sleep maintenance insomnia, works through orexin receptor antagonism (different mechanism than other agents) 2

What NOT to Do

Avoid these common errors that worsen outcomes:

• Do not use trazodone: The American Academy of Sleep Medicine explicitly states trazodone is "not recommended for sleep onset or maintenance insomnia" 2
• Do not use over-the-counter antihistamines (diphenhydramine): Not recommended due to lack of efficacy data, daytime sedation, delirium risk in elderly, and anticholinergic effects including urinary retention 2, 6
• Do not use antipsychotics (quetiapine, olanzapine): Evidence of efficacy is insufficient, with significant risks including weight gain, metabolic dysfunction, and neurological side effects 1
• Do not use long-acting benzodiazepines (flurazepam): Increased risk of residual daytime drowsiness and falls in elderly without clear benefit 1, 2
• Do not combine multiple sedative medications without careful justification, as this significantly increases risks of cognitive impairment, falls, and complex sleep behaviors 2

Treatment Algorithm Summary

Step 1: Initiate CBT-I immediately (4-8 sessions over 6 weeks) 3

Step 2: Discontinue paroxetine if used solely for insomnia (taper appropriately) 1

Step 3: Optimize mirtazapine to 7.5 mg dosing based on 2025 MIRAGE trial evidence 5

Step 4: Reassess after 4-6 weeks of CBT-I + optimized mirtazapine 2

Step 5: If insufficient response, add low-dose BzRA (zolpidem 5 mg, eszopiclone 2 mg, or temazepam 7.5 mg) as supplement to behavioral therapy, not replacement 2

Step 6: Monitor closely for efficacy (sleep latency, maintenance, daytime functioning) and adverse effects (falls, cognitive changes, complex behaviors) after 1-2 weeks 2

Step 7: Reassess need for continued pharmacotherapy periodically, as FDA approves hypnotics for short-term use (4-5 weeks), and taper when conditions allow 1, 2

Essential Monitoring and Follow-Up

Assess for underlying sleep disorders if insomnia persists beyond 7-10 days of treatment: 1, 2

• Screen for obstructive sleep apnea (especially if snoring, witnessed apneas, or daytime sleepiness present)
• Evaluate for restless legs syndrome (uncomfortable sensations in legs with urge to move, worse at rest/evening)
• Consider circadian rhythm disorders (irregular sleep-wake patterns)
• Review all medications for sleep-disrupting effects

Patient education requirements before prescribing any hypnotic: 2

• Explain treatment goals and realistic expectations (gradual improvement with CBT-I)
• Discuss safety concerns (fall risk, driving impairment, complex sleep behaviors)
• Emphasize importance of behavioral treatments as foundation
• Advise taking medication on empty stomach to maximize effectiveness 1
• Warn about avoiding alcohol and other CNS depressants 1
• Ensure adequate sleep opportunity (7-8 hours) when taking medication 1

This algorithmic approach prioritizes evidence-based, guideline-concordant care that addresses both the immediate symptom burden and long-term quality of life in this elderly patient with treatment-refractory insomnia.