1032 Reversible central sleep apnea syndrome induced by Valproic acid treatment: a case report

Abstract

Introduction Valproic acid (Depakine) is a commonly used agent in the management of epilepsy and psychiatric disorders. Common side effects include gastrointestinal disturbances, tremor and bodyweight gain, but central sleep apneas have never been observed as side effect. We report here a case of central sleep apnea without Cheyne-stokes breathing, induced by Valproic acid (VPA). Report of case The Patient presented is a 64 years old woman, who complained of snoring, non-restorative sleep and daytime sleepiness. She was treated with VPA for one epileptic seizure from 10 years. A polysomnographic recording showed a central sleep apnea syndrome (CSAS) with an apnea hypopnea index (AHI) of 106,9/h with a central apnea index (CAI) of 61,2/h, without Cheyne-stokes breathing, and associated with obstructive sleep apnea (obstructive apnea/hypopnea index OAHI=43,8/h). Cardiologic examination eliminated heart failure or past stroke. Patient did not suffer from CNS disease and did not receive opioids or codeine which may induce breathing dysregulation and central apnea. CSAS was not due to acute or chronic alcohol intake. On the follow-up polysomnography, 3 months after withdrawal of VPA, with no drug substitution, and without CPAP treatment nor weight loss, the patient presented a decrease of CSAS with a CAI of 12,4/h and a persistent OAHI of 45,7/h. On follow-up 5 months after withdrawal of VPA, polysomnography, performed without CPAP treatment nor weight loss showed resolution of CSAS with a CAI of 1,8/h, and a persistent OAHI of 44/h. Conclusion In our patient, the intrinsic imputability of VPA on occurrence of Central sleep apnea syndrome was considered strong by the drug safety unit because of temporal relationship, exclusion of other possible causes and reversibility when the treatment is withdrawn. A possible depressive role of valproic acid on central control breathing neurons cannot be excluded. Our findings need to be confirmed on a larger sample of patients but already raise attention for clinicians about the adverse effects of valproic acid on nocturnal breathing.