Why is the patient unable to sleep with their current medications, such as suvorexant (Belsomra) or doxepin (Sinequan)?

Why Current Medications May Not Be Working for Sleep

The patient's current medications (suvorexant and doxepin) may be failing due to subtherapeutic dosing, drug interactions with concurrent CNS depressants, inadequate time for therapeutic effect, or the presence of an underlying undiagnosed condition that requires re-evaluation.

Subtherapeutic Dosing as Primary Cause

• Suvorexant's efficacy is highly dose-dependent, and doses below 10 mg show minimal clinical benefit 1, 2
• The recommended starting dose is 10 mg, with increases up to 20 mg if the 10 mg dose is well-tolerated but ineffective 3
• At 10 mg, suvorexant increases total sleep time by only 22 minutes compared to placebo, whereas at 20 mg it increases by approximately 50 minutes 2
• If the patient is on a dose lower than 10 mg (such as 3-5 mg), this would explain treatment failure as these doses fall below the therapeutic threshold 1

Doxepin Dosing Considerations

• Doxepin demonstrates efficacy for sleep maintenance at doses of 3-6 mg in adults 4
• Low-to-moderate quality evidence shows doxepin improves total sleep time and wake after sleep onset in both general and older populations 4
• If the patient is on a higher dose intended for depression (>6 mg), this may paradoxically worsen sleep architecture or cause excessive daytime sedation 1

Drug Interaction and Timing Issues

• Concurrent use of multiple CNS depressants significantly reduces the efficacy of individual agents and increases adverse effects 3
• The FDA explicitly states that "the use of BELSOMRA with other drugs to treat insomnia is not recommended" 3
• Taking suvorexant with or soon after meals delays time to effect and reduces absorption 3
• If the patient is consuming alcohol or taking other sedatives (benzodiazepines, opioids), this creates additive CNS depression that impairs natural sleep architecture 3

Inadequate Treatment Duration

• Insomnia medications require 7-10 days of consistent use before failure can be declared 3
• If treatment has been less than one week, the patient may not have reached steady-state therapeutic levels
• The FDA warns that "failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated" 3

Undiagnosed Comorbid Conditions

Common pitfalls include failing to identify underlying causes:

• Sleep apnea or chronic respiratory disease - Suvorexant has not been studied in severe OSA or COPD and may worsen respiratory function 3
• Primary psychiatric disorders - Depression, anxiety, or other psychiatric conditions may present as insomnia and require specific treatment 3
• Medication-induced insomnia - Stimulants, corticosteroids, beta-blockers, or SSRIs taken by the patient may counteract hypnotic effects
• Circadian rhythm disorders - These require chronotherapy rather than hypnotics

Adverse Effects Causing Treatment Discontinuation

• Somnolence occurs in approximately 7% of suvorexant patients (vs 3% placebo), which may lead to patient non-adherence 4, 2
• Complex sleep behaviors (sleep-walking, sleep-driving) occur with suvorexant and require immediate discontinuation if present 3
• Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms increase with dose and may frighten patients into stopping medication 3
• Dose-dependent increases in suicidal ideation have been observed with suvorexant, particularly in depressed patients 3

Algorithmic Approach to Treatment Failure

Step 1: Verify adequate dosing

• Confirm suvorexant dose is at least 10 mg; increase to 20 mg if 10 mg ineffective 3
• Confirm doxepin dose is 3-6 mg for insomnia (not higher antidepressant doses) 1

Step 2: Eliminate drug interactions

• Discontinue alcohol and other CNS depressants 3
• Ensure suvorexant is taken on empty stomach, 30 minutes before bed, with at least 7 hours remaining for sleep 3
• Verify no concurrent use of strong CYP3A inhibitors (which require dose reduction to 5 mg) or inducers (which reduce efficacy) 3

Step 3: Assess treatment duration

• If less than 7-10 days, continue current regimen and reassess 3

Step 4: Screen for comorbidities

• Evaluate for sleep apnea, particularly if patient has obesity, snoring, or daytime fatigue 3
• Screen for depression, anxiety, and suicidal ideation 3
• Review all medications for sleep-disrupting agents

Step 5: Consider alternative therapy

• Cognitive behavioral therapy for insomnia (CBT-I) should always be first-line treatment 4
• If pharmacotherapy continues to fail, consider switching to a different class (e.g., ramelteon for sleep onset, low-dose doxepin for sleep maintenance) 4
• The American College of Physicians recommends CBT-I as initial treatment, with pharmacotherapy only when CBT-I is unsuccessful 4

Critical Safety Monitoring

• Immediately evaluate any new behavioral changes, worsening depression, or suicidal ideation 3
• Monitor for next-day impairment and caution against driving, especially with 20 mg dose 3
• Elderly patients face higher fall risk due to drowsiness 3
• Prescribe the lowest feasible number of tablets in patients with depression due to overdose risk 3