TREATMENT IN THE NARCOLEPTIC SYNDROME - SELF-ASSESSMENT OF THE ACTIONOF DEXAMPHETAMINE AND CLOMIPRAMINE

Subjective evaluation of the effect of treatment of excessive daytime sleepiness (EDS) with dexamphetamine and of cataplexy with clomipramin e 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 an ticipation-associated loss of postural motor tone during long-term the rapy. 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 propens ity to EDS was reduced by approximately 20% by dexamphetamine (mean do sage 16 mg/24 h, range 5-60: mean treatment period 21 years, range 2-4 5). The propensity to cataplexy was reduced by 23% by clomipramine (me an dosage 64 mg/24 h, range 25-125: mean treatment period 14 years, ra nge 1-24). Dexamphetamine alone, in addition to reducing the propensit y to EDS also reduced the propensity to cataplexy. Clomipramine alone reduced cataplexy, but not EDS. Combined dexamphetamine-clomipramine t reatment 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 sle ep propensity in the normal range whilst on dexamphetamine and no subj ect 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 com mon as reports of weight gain by subjects on combined dexamphetamine-c lomipramine treatment. Constipation, dry mouth and impaired sexual fun ction were reported by 25%, 38% and 19% (respectively) of subjects on clomipramine. This retrospective long-term self-report study investiga ted the propensity to, rather than the frequency of, episodes of EDS a nd cataplexy in subjects with the narcoleptic syndrome. This study sug gests that long-term drug treatment in the narcoleptic syndrome result s in only minor reduction in attack propensity, in contrast to the fin dings 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 prescript ion of sub-optimal drug dosages, and a low index between the limited t herapeutic efficacy and frequent side-effects of this drug.