Valproic acid for treating cyanotic breath holding spells

Hamed SA, Elhadad AF, Farghaly HS. Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study. Expert Rev Clin Pharmacol. 2020 Nov;13(11):1263-1270. doi: 10.1080/17512433.2020.1828059. Epub 2020 Nov 1. PMID: 32969724.

Abstract

Background: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. 

Methods: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. 

Results: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. 

Conclusion: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism.