In a 71‑year‑old man with obstructive sleep apnea treated with continuous positive airway pressure (CPAP), depression managed with venlafaxine (Effexor) and buspirone (Buspar), and hypothyroidism controlled with levothyroxine (Synthroid), who has an Epworth Sleepiness Scale (ESS) score of 17, what is the next step in managing his excessive daytime sleepiness?

Management of Persistent Excessive Daytime Sleepiness in OSA Despite CPAP

The first step is to verify CPAP adherence and efficacy through objective tracking data, assess for non-OSA causes of sleepiness (particularly medication effects from venlafaxine and buspirone), and optimize thyroid management before considering wake-promoting agents like modafinil.

Immediate Assessment Priorities

Verify CPAP Adherence and Efficacy

• Download and review CPAP tracking data to confirm adequate usage (target >4 hours/night minimum), assess residual apnea-hypopnea events, and evaluate mask leak. 1
• The American Thoracic Society recommends patients use CPAP whenever asleep, and adherence is defined as >4 hours/night with progress toward improved daytime sleepiness or >2 hours/night if making measurable progress. 2
• Even one night off CPAP can cause return of sleepiness, so verify consistent nightly use. 1
• Check for suboptimal pressure settings or significant mask leak, both of which contribute to residual sleepiness despite apparent CPAP use. 1

Evaluate Medication-Induced Sleepiness

• Both venlafaxine and buspirone can contribute to sedation and excessive daytime sleepiness, particularly in elderly patients. 2
• The American Geriatrics Society emphasizes that careful withdrawal of sedating medications is prudent when managing excessive sleepiness, preferably under guidance of both a sleep specialist and primary care physician. 2
• Venlafaxine specifically is noted as a medication that can affect sleepiness, though it's also used to treat REM-related symptoms in some sleep disorders. 2

Optimize Thyroid Management

• Verify thyroid function is truly optimized with recent TSH level, as hypothyroidism is a common medical cause of excessive sleepiness that must be controlled. 2, 3
• Even patients on levothyroxine may have suboptimal dosing contributing to persistent fatigue and sleepiness. 3

Address Non-OSA Causes of Sleepiness

Screen for Sleep Deprivation and Behavioral Factors

• Clinicians should routinely inquire about non-OSA causes including sleep restriction, alcohol use, and sedating medications. 2
• Ensure adequate opportunity for nighttime sleep (typically 7-8 hours) to exclude insufficient sleep syndrome as the cause. 2
• The American Geriatrics Society recommends adopting good sleep hygiene techniques and maintaining a regular sleep-wake schedule. 2

Evaluate Depression Severity

• Depression itself significantly contributes to excessive sleepiness and may not fully resolve with CPAP alone, even when OSA is well-controlled. 4, 5
• A multicenter study found that 41.7% of OSA patients with depressive symptoms at diagnosis had persistent depressive symptoms after an average of 529 days of CPAP therapy. 4
• Persistent depressive symptoms were independently associated with persistent excessive daytime sleepiness (OR 2.72), suggesting bidirectional relationship. 4

Pharmacological Management if Residual Sleepiness Persists

Modafinil as First-Line Wake-Promoting Agent

• Modafinil 200 mg once daily in the morning is FDA-approved specifically for excessive sleepiness in OSA patients on CPAP and is the recommended first-line pharmacological intervention. 6
• The FDA label explicitly states modafinil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with OSA, but emphasizes it treats excessive sleepiness and not the underlying obstruction. 6
• For elderly patients (age 71), the American Geriatrics Society recommends starting at 100 mg once upon awakening, with weekly increases as necessary to typical doses of 200-400 mg/day. 2
• Consideration should be given to lower doses and close monitoring in geriatric patients. 6
• Common adverse reactions include nausea, headaches, and nervousness; monitor for hypertension, palpitations, or arrhythmias. 2, 3

Important Contraindications and Monitoring

• The American Thoracic Society suggests NOT using stimulant medications for the sole purpose of reducing driving risk in suspected OSA, but modafinil is appropriate once OSA is confirmed and CPAP optimized. 2
• Modafinil significantly improved self-reported sleepiness by 5.08 points on ESS compared to placebo with high-certainty evidence. 7
• Frequent reassessment is necessary when starting or adjusting stimulant doses, monitoring for adverse effects and nocturnal sleep disturbances. 2

Clinical Pitfalls to Avoid

Don't Prescribe Stimulants Without CPAP Optimization

• A maximal effort to treat with CPAP for an adequate period should be made prior to initiating modafinil for excessive sleepiness. 6
• Stimulants mask the underlying problem if CPAP adherence or efficacy issues remain unaddressed. 1

Recognize Driving Safety Implications

• An ESS of 17 indicates severe excessive daytime sleepiness with significantly increased motor vehicle crash risk. 2
• Sleepiness accounts for 15-20% of crashes on monotonous roads, typically involving running off the road or rear-end collisions. 2
• Clinicians should develop a practice-based plan to inform patients about drowsy driving risks and behavioral methods to reduce those risks. 2
• The drowsy driving risk should be reassessed at subsequent visits. 2

Monitor for Persistent Depression

• Active monitoring of depressive symptoms is needed in OSA patients treated with CPAP, as CPAP alone may not resolve depression. 4
• Interventional trials suggest antidepressants, cognitive behavioral therapy, or both may be needed for comorbid depression in OSAHS patients. 4
• Studies show significant reduction in depressive symptoms after CPAP treatment, but this is not universal. 8, 5

Follow-Up Strategy

Reassess Outcomes After Interventions

• Measure subjective daytime sleepiness with ESS, assess self-reported improvement in presenting symptoms, and evaluate quality of life measures. 2
• The American Thoracic Society considers patients adherent if using CPAP >4 hours/night OR >2 hours/night with measurable progress toward improved daytime sleepiness as measured by ESS or subjective quality of life improvement. 2
• Early intervention for non-adherence improves long-term treatment success. 1

Consider Objective Testing if Symptoms Persist

• If excessive sleepiness persists despite optimized CPAP and medication adjustments, objective measures like Psychomotor Vigilance Test or Maintenance of Wakefulness Test may be warranted. 2
• The ESS is highly variable when administered sequentially to clinical OSA populations, so objective testing provides additional data. 2