How to best manage insomnia and anxiety in a 54-year-old patient with a history of long-standing sleep issues, currently taking citalopram (Selective Serotonin Reuptake Inhibitor) and Vyvanse (Lisdexamfetamine), with previous ineffective treatments including quetiapine, Dayvigo (Lemborexant), Doxepin, Trazodone, Amitriptyline, and Hormone Replacement Therapy (HRT)?

Management of Refractory Insomnia in a 54-Year-Old Woman

Immediate Medication Recommendations

Discontinue quetiapine immediately and initiate low-dose doxepin 3-6mg at bedtime as your primary pharmacologic intervention. 1 This patient has failed multiple treatments and requires a medication with proven efficacy for sleep maintenance insomnia in her age group, combined with aggressive pursuit of cognitive behavioral therapy for insomnia (CBT-I).

Why Low-Dose Doxepin is the Optimal Choice

• Low-dose doxepin (3-6mg) is the most appropriate medication for sleep maintenance insomnia in adults, with demonstrated improvement in Insomnia Severity Index scores, sleep latency, total sleep time, and sleep quality. 1, 2
• Unlike quetiapine, doxepin does not carry black box warnings and has a favorable safety profile at low doses. 1
• The patient's primary complaint is middle-of-the-night awakening (waking at 2 AM or 4 AM), which is classic sleep maintenance insomnia—doxepin's specific indication. 2
• Quetiapine is listed as a last-line agent only suitable for patients with comorbid conditions who may benefit from its primary antipsychotic action, which does not apply here. 2

Quetiapine Discontinuation

• Yes, she can discontinue quetiapine after one week of tapering, as it is no longer effective and may be contributing to weight gain. 2
• Quetiapine falls into the category of "other sedating agents" that should only be used when standard treatments have failed and when the patient has comorbid psychiatric conditions requiring antipsychotic treatment. 2
• The patient correctly identifies quetiapine as potentially contributing to weight gain, which is a known adverse effect. 2

Critical Issue: Vyvanse Timing and Insomnia

The patient's Vyvanse 30mg daily is likely a significant contributor to her insomnia and must be addressed immediately. 2

• Stimulant medications like lisdexamfetamine (Vyvanse) are well-documented causes of sleep disturbance and can impair both sleep onset and maintenance. 2
• Evaluate whether Vyvanse is being taken early enough in the day (ideally upon awakening) and consider dose reduction or discontinuation if insomnia persists despite other interventions. 2
• The combination of a stimulant with chronic insomnia creates a vicious cycle that no hypnotic can adequately overcome. 2

Optimize Current Antidepressant Therapy

Consider increasing citalopram back to 40mg from the current 20mg dose to better address the underlying anxiety that is driving her "racing mind." 2, 3

• The patient has a history of tolerating citalopram 40mg well, and she was reduced to 20mg at some point. 3
• Her primary sleep complaint is a "racing mind," which indicates inadequately treated anxiety. 2
• When insomnia is comorbid with anxiety, optimizing the antidepressant is a critical first step before adding hypnotics. 3
• SSRIs at therapeutic doses can reduce the anxiety that perpetuates insomnia, though they may initially worsen sleep in some patients. 3

Non-Negotiable: Cognitive Behavioral Therapy for Insomnia (CBT-I)

CBT-I must be pursued aggressively as it is the only treatment with sustained long-term efficacy for chronic insomnia. 2, 4

Why CBT-I is Essential for This Patient

• The American College of Physicians provides a strong recommendation that all patients with chronic insomnia receive CBT-I as the initial treatment intervention. 4, 2
• CBT-I produces clinically meaningful improvements sustained for up to 2 years, unlike pharmacotherapy which shows degradation of benefit after discontinuation. 4, 2
• This patient has tried multiple medications without sustained benefit—she needs the durable solution that only CBT-I provides. 4

Addressing the Cost Barrier

• Digital CBT-I is an effective and scalable alternative when in-person therapy is cost-prohibitive. 4
• Multiple evidence-based digital CBT-I programs exist (e.g., Sleepio, CBT-I Coach app) that cost significantly less than traditional therapy. 4
• Treatment typically requires 4-8 sessions over 6 weeks, making even paid programs more cost-effective than ongoing medication trials. 4
• The patient's concern about "starting over with another counselor" can be addressed by explaining that CBT-I is highly structured, protocol-driven therapy focused specifically on sleep—not open-ended psychotherapy. 4

Core CBT-I Components to Implement

• Sleep restriction therapy: Limit time in bed to match actual sleep time (currently 4-5 hours), then gradually increase as sleep efficiency improves. 2
• Stimulus control: Use bed only for sleep and sex; leave bedroom if unable to sleep within 20 minutes. 2
• Cognitive restructuring: Address catastrophic thinking about sleep consequences and the anxiety of anticipating poor sleep. 2, 4
• Sleep hygiene optimization: The patient has already implemented some measures (avoiding electronics, trying melatonin/magnesium), but these alone are insufficient without the other CBT-I components. 2

Addressing Comorbid Factors

Life Stress and Psychosocial Support

• The patient's insomnia coincides with significant life stressors (divorce after 35 years, daughter living with ex-partner, isolation). 2
• While cost is a barrier, reconnecting with mental health support is critical—consider community mental health centers, sliding-scale therapists, or support groups for divorced individuals. 2
• The racing mind and chest tightness suggest inadequately treated anxiety that requires both pharmacologic optimization and psychotherapy. 3

Hormone Replacement Therapy Considerations

• The patient stopped HRT believing it caused weight gain and made her feel worse. 5
• Her recent migraines may indeed be related to HRT discontinuation, as estrogen withdrawal is a known migraine trigger in perimenopausal/menopausal women. 5
• However, HRT alone has not been shown to be an effective treatment for chronic insomnia and should not be restarted solely for sleep. 5
• If vasomotor symptoms (hot flashes) are disrupting sleep, this would be a separate indication to reconsider HRT. 5

Rule Out Sleep Apnea

• Although the patient denies symptoms of obstructive sleep apnea (OSA), her age, weight concerns, and sleep maintenance insomnia warrant screening. 5
• Use the STOP-BANG questionnaire or similar tool; if score is elevated, pursue home sleep apnea testing or polysomnography. 5
• Undiagnosed OSA would render hypnotic medications less effective and potentially dangerous. 5

Medications to Avoid

Do not trial the following medications, as they have insufficient evidence or unfavorable risk profiles: 2, 1

• Benzodiazepines: Risk of dependency, falls, cognitive impairment, and respiratory depression. 1
• Trazodone: Limited efficacy evidence despite widespread use; the patient has already failed this. 1, 2
• Antihistamines (OTC sleep aids): Antimuscarinic effects, tolerance development, and lack of efficacy data. 1, 2
• Melatonin: Insufficient evidence for chronic insomnia in adults; patient has already tried without benefit. 2
• Ramelteon or Dayvigo: Patient has already failed Dayvigo (lemborexant); ramelteon has limited evidence for sleep maintenance insomnia. 2

Alternative Pharmacologic Options if Doxepin Fails

If low-dose doxepin is ineffective after 2-4 weeks, consider suvorexant (orexin antagonist) as a second-line agent. 1, 2

• Suvorexant has moderate-quality evidence for improving treatment response and sleep outcomes in mixed adult populations. 2
• It has a different mechanism of action than the medications she has already tried. 2
• Start at the lowest dose (5mg for women) and titrate as needed. 2

Monitoring and Follow-Up Plan

Schedule follow-up in 2 weeks to assess response to doxepin and citalopram optimization, then monthly thereafter. 2

• Use sleep logs to track sleep onset latency, wake after sleep onset, total sleep time, and sleep efficiency. 5
• Monitor for adverse effects including morning grogginess, dry mouth, and any worsening of mood symptoms. 2
• Reassess the need for ongoing pharmacotherapy at 4-6 weeks; medications should be used short-term while CBT-I provides long-term benefit. 2
• If insomnia persists despite these interventions, refer to a sleep medicine specialist for comprehensive evaluation. 5

Common Pitfalls to Avoid

• Do not continue ineffective medications out of inertia—this patient has already wasted 1.5 years on quetiapine that stopped working. 2
• Do not prescribe hypnotics without simultaneously pursuing CBT-I—pharmacotherapy alone will not provide durable improvement. 2, 4
• Do not ignore the contribution of Vyvanse to her insomnia—stimulants are a well-known cause of sleep disturbance. 2
• Do not dismiss the psychosocial stressors—her "nervous system feels on fire" indicates severe anxiety requiring comprehensive treatment. 3
• Do not expect immediate results—counsel the patient that CBT-I improvements are gradual but sustained, unlike the immediate but temporary effects of medications. 4