Treatment in the narcoleptic syndrome: self assessment of the action of dexamphetamine and clomipramine

Abstract

Subjective evaluation of the effect of treatment of excessive daytime sleepiness (EDS) with dexamphetamine and of cataplexy with clomipramine was made in 124 subjects with the narcoleptic syndrome. Drug effects were evaluated by self-report of the propensity to EDS and cataplexy as determined by the Epworth Sleepiness Scale and a rating scale of anticipation-associated loss of postural motor tone during long-term therapy. The effects of dexamphetamine alone (60 subjects), clomipramine alone (16 subjects) and combined dexamphetamine-clomipramine treatment (48 subjects) were evaluated. Self-reports indicated that the propensity to EDS was reduced by approximately 20% by dexamphetamine (mean dosage 16 mg/24 h, range 5-60: mean treatment period 21 years, range 2-45). The propensity to cataplexy was reduced by 23% by clomipramine (mean dosage 64 mg/24 h, range 25-125: mean treatment period 14 years, range 1-24). Dexamphetamine alone, in addition to reducing the propensity to EDS also reduced the propensity to cataplexy. Clomipramine alone reduced cataplexy, but not EDS. Combined dexamphetamine-clomipramine treatment caused a reduction in the propensity to EDS and cataplexy of similar magnitude to that caused by dexamphetamine alone. Less than 10% of all subjects with the narcoleptic syndrome reported a daytime sleep propensity in the normal range whilst on dexamphetamine and no subject on clomipramine reported complete control of cataplexy. Long-term treatment with dexamphetamine was associated with weight increase more commonly than weight loss. Weight gain was reported by two-thirds of subjects taking clomipramine alone. Reports of weight loss were as common as reports of weight gain by subjects on combined dexamphetamine-clomipramine treatment. Constipation, dry mouth and impaired sexual function were reported by 25%, 38% and 19% (respectively) of subjects on clomipramine. This retrospective long-term self-report study investigated the propensity to, rather than the frequency of, episodes of EDS and cataplexy in subjects with the narcoleptic syndrome. This study suggests that long-term drug treatment in the narcoleptic syndrome results in only minor reduction in attack propensity, in contrast to the findings of many previous short term objective studies, which suggest 50-80% reduction in attack frequency. Major factors limiting response to dexamphetamine in the narcoleptic syndrome include physician prescription of sub-optimal drug dosages, and a low index between the limited therapeutic efficacy and frequent side-effects of this drug.