Treatment of severe morning sleep inertia with bedtime long-acting bupropion and/or long-acting methylphenidate in a series of 4 patients.

Study Objectives: To assess the benefit of bedtime long-acting bupropion and/or long-acting methylphenidate in the therapy of severe morning sleep inertia (SI), a chronic condition that has major adverse consequences on level of functioning and quality of life, and for which there is no recognized therapy.

Methods: Patients underwent clinical interviews and examinations and completed comprehensive questionnaires. They underwent overnight video-polysomnography and next-day multiple sleep latency testing (apart from 1 case with obstructive sleep apnea). Treatments are described in the case reports.

Results: Case 1, a 16-year-old girl who was very late to school every day from severe morning SI despite obstructive sleep apnea being fully controlled with continuous positive airway pressure therapy, responded to bedtime bupropion-extended release (xl) 150 mg, together with methylphenidate-sr (sustained release), 36 mg (along with 20 mg methylphenidate taken 1 hour before the alarm would go off). She woke up in a timely fashion and has started her classes on time, with benefit maintained at 6-month follow-up. Case 2, a 29-year-old female with idiopathic hypersomnia and major depression and associated severe morning SI while maintained on 20 mg twice-daily generic Adderall, responded immediately (first night) to bedtime bupropion-xl, 150 mg, with benefit maintained at the 4-month follow-up. Case 3, a 74-year-old man with idiopathic hypersomnia and major depression maintained on daily methylphenidate-sr and direct-release methylphenidate, along with 300 mg bupropion-xl, developed progressively severe morning SI that immediately responded to changing his bupropion-xl regimen to 150 mg nightly and 150 mg every morning, with benefit maintained at the 3-year follow-up. Case 4, a 60-year-old female with idiopathic hypersomnia and severe morning SI, was immediately intolerant to bedtime bupropion-xl, which was discontinued.

Conclusions: Bedtime use of long-acting bupropion and/or long-acting methylphenidate can be effective in the therapy for severe morning SI and warrants further clinical use along with systematic research.