Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children

ComparativeDrug:Modafinil (Provigil), sodium oxybate (Xyrem), venlafaxine (Effexor), methylphenidate (Concerta), fluoxetine (Prozac), other selective serotonin reuptake inhibitors (citalopram, paroxetine, escitalopram and sertraline), tricyclic antidepressants (protriptyline, amitriptyline, imipramine and clomipramine), atomoxetine (Strattera) and others (lisdexamfetamine, bupropion and duloxetine) were given at an unspecified dose. Duration not stated.DosageDuration:Dosage and duration not stated.Results:The most commonly used and continued medications were modafinil and sodium oxybate, followed by venlafaxine. Continuation of both modafinil and sodium oxybate was remarkably high (71%-100%). Continuation for venlafaxine was moderate (58%-83%) and higher than for fluoxetine (25% overall), tricyclic antidepressants (13%), or other SSRIs (0%). The continuation rates of modafinil, sodium oxybate and venlafaxine were individually higher than those of any other drugs tried. Methylphenidate was also commonly tried, but continuation rates were low (0% for Ritalin, 20% for generic methylphenidate). Atomoxetine also had a moderate continuation rate, having been tried in 6 patients and remaining in use in 2 patients after having been tried (33%). Modafinil and venlafaxine were used sooner than sodium oxybate in prepubertal children but not as much in peripubertal and postpubertal children. Sodium oxybate was self-reported as being effective for all narcolepsy symptoms (including insomnia, hypnagogic hallucinations and sleep paralysis). These effects did not differ across groups except for the effect of sodium oxybate on hypnagogic hallucinations, which was lower in prepubertal children in comparison with others. In contrast, modafinil, Ritalin and methylphenidate were reported to be effective only for sleepiness. Venlafaxine was reported to be primarily effective for cataplexy and had minor effects on sleepiness, sleep paralysis, and hypnagogic hallucinations, all inferior to those reported after the use of sodium oxybate. These compounds had very similar effects in prepubertal vs. peripubertal and postpubertal children. Irritability was the most common side effect of both modafinil and venlafaxine and a common side effect of sodium oxybate. Nausea and weight loss were the most commonly reported side effects for sodium oxybate in all groups. About half of prepubertal cohort was currently treated with sodium oxybate without any other additional treatment or with the addition of only one compound. In older children, however, most patients needed more than 2 drugs, and only 14% to 28% used sodium oxybate alone or with 1 other compound.AdverseEffects:16 (81%) patients had side effects.AuthorsConclusions:This study reports on the clinical features of childhood narcolepsy and documents the safe use of treatments commonly used in adults in young children.FreeText:HLA-DQB1*0602 typing (all tested, and 100% positive), polysomnography or Multiple Sleep Latency Test (76%) and cerebrospinal fluid hypocretin-1 measurements (26%, all with low levels) were conducted. Prospective data on medication response was collected in 78% using a specially designed questionnaire. Clinical features were similar across puberty groups, except for sleep paralysis, which increased in frequency with age. Common features included excessive weight gain (84% ≥4 kg within 6 months of onset of narcolepsy) and earlier puberty (when compared with family members), notably in subjects who gained the most weight. Streptococcus-positive throat infections were reported in 20% of cases within 6 months of onset of narcolepsy. Polysomnographic features were similar across groups, but 3 prepubertal children did not meet Multiple Sleep Latency Test diagnostic criteria. Concomitant drugs: