Idiopathic Hypersomnia: Clinical Features and Response to Treatment

Idiopathic hypersomnia (IH) is a primary disorder of hypersomnolence that is distinguished from narcolepsy by virtue of the absence of electrophysiologic and other features of rapid-eye-movement (REM) sleep disturbance. Further subcategorization of IH is described within the International Classification of Sleep Disorders Second Edition (ICSD-II), which separates the condition into 2 forms based on whether or not “long sleep time” is described. Afflicted individuals with this descriptor classically exhibit prolonged unrefreshing sleep bouts and may also describe profound sleep inertia, often referred to as “sleep drunkenness” (see Table 1).1 Table 1 International Classification of Sleep Disorders-2 Criteria for the Diagnosis of Idiopathic Hypersomnia Due in part to the recent publication of the second edition of this manual (2005), the existing IH knowledge base employs discrepant diagnostic criteria.2–8 Of the 7 reports in the literature to date, none utilizes a diagnostic schema that is entirely consistent with that listed in the ICSD-II, although only 1 study3 was published subsequent to its inception.2–8 Inclusion criteria for the majority of these studies (with the exception of that authored by Bassetti and colleagues5) either do not mandate threshold Multiple Sleep Latency Test (MSLT) values2–4,6,8 (consistent with the first edition ICSD description)9 or require MSLT thresholds that are either inconsistent with current requirements5 or indeterminate in nature.7 As can be seen in Table 1, under the current criteria, such data are compulsory to assign a diagnosis of IH without long sleep. Since prolonged nocturnal polysomnography is typically not performed in clinical practice, such values are also arguably requisite to ascribe a diagnosis of IH with long sleep. Although the debate regarding the requirement of this criterion is meritorious,3 the variations and/or lack of diagnostic criteria in the accumulated literature raise the possibility that studies included heterogenous patient populations, a prospect deemed further probable by virtue of the fact that IH lacks the hallmark features seen in other primary hypersomnias, such as narcolepsy with cataplexy or Kleine-Levin syndrome. In the largest series to date, Anderson and colleagues recently reported on the clinical and polysomnographic characteristics of 77 patients with IH compared to patients with narcolepsy.3 Inclusion criteria were described as consistent with those listed in the ICSD-II, but MSLT and nocturnal polysomnography requirements were omitted. Notwithstanding these limitations, significant contributions to the sparse IH treatment literature were provided. The study reported responses to pharmacotherapy in 61 patients over a mean follow-up of 3.8 years. Eighty-nine percent of participants (54/61) commenced treatment with modafinil. Thirty-nine remained on monotherapy (72%, 39/54), and approximately 60% (24/39) demonstrated a sustained improvement in daytime sleepiness (assessed with Epworth Sleepiness Scale [ESS] scores), although 75% (18/24) required higher than recommended doses (i.e., > 400 mg). The remaining patients switched to dexamphetamine because of modafinil side effects (15%, 8/54) or added either caffeine or dexamphetamine due to lack of efficacy with modafinil alone (11%, 6/54). One patient remained on modafinil despite lack of efficacy. Among those who commenced treatment with a medication other than modafinil, 3% (2/61) received dexamphetamine, and 3% (2/61) used either pemoline or methylphenidate. Although their smaller numbers limit comparative analyses, the response rate for those using drugs other than modafinil and/or combinations of drugs was similar to those using modafinil alone, at 57%. Three patients (5%, 3/61) from this study abstained from pharmacotherapy entirely. In an effort to further expand the literature regarding IH, we studied the clinical and polysomnographic characteristics of a larger number of patients, adhering more stringently to ICSD-II and other criteria. Because the paucity of treatment studies in particular has recently been highlighted,10,11 subjective response to pharmacotherapy was examined in detail. Our higher number of IH patients treated with agents other than modafinil (specifically methylphenidate) afforded an opportunity for comparison that has not been previously realized.