The effect of drug therapy on the perceived symptom and ADL experiences of narcoleptics.
Narcolepsy is a disabling neurological disorder primarily characterized by excessive daytime sleepiness. This sleep disorder has no known cure and is estimated to be more prevalent than multiple sclerosis in the United States. Besides excessive daytime sleepiness (EDS) and uncontrollable sleep attacks, the classic symptoms of narcolepsy include: cataplexy (short episodes of muscle weakness and/or paralysis without change in consciousness that are precipitated by strong emotion); sleep paralysis (the inability to move muscles while falling asleep or on awakening); and hypnagogic or hypnopompic hallucinations (dreamlike images occurring at sleep onset or on awakening, respectively).[2,5,22] Mitler et al suggested that nocturnal sleep disruption also be added to this symptom cluster. The pathophysiological cause of narcolepsy is unknown; a biochemical abnormality associated with neurotransmitter dysfunction is suspected of disrupting the sleep-wake cycle. Medication remains the primary treatment for narcoleptics. Central nervous system (CNS) stimulants are used to control EDS and sleep attacks and tricyclic antidepressants help control the rapid eye movement (REM)-sleep related symptoms of cataplexy, sleep paralysis and hypnagogic/ hypnopompic hallucinations.[14,21,22] Despite taking medication, many narcoleptics perceive their symptoms, particularly their sleepiness, to be poorly controlled.[19,21] Several studies have documented how narcolepsy adversely affects a person's life, establishing this chronic disorder as a debilitating condition.[6-8,12,16,23]
The purpose of this secondary analysis was to ascertain if pharmacological therapy subjectively improves the quality of life for people with narcolepsy. This paper describes the symptom experience and performance of daily living activities as perceived by a sample of people with narcolepsy. These perception levels were then compared between medicated and non-medicated narcoleptics.
In its 1993 report to the United States Congress, The National Commission on Sleep Disorders Research (Sleep Commission) defined healthy sleep as the quantity and quality of sleep required to maintain optimal alertness during desired waking hours. Normal adult human sleep consists of two distinct states which alternate cyclically approximately every 90-100 minutes during the night: non-rapid eye movement (NREM) sleep and REM sleep.[17,22] NREM sleep occurs first and is divided into four stages which reflect the depth of sleep. Up to 80% of nocturnal sleep is spent in NREM. REM sleep correlates highly with dreaming and is characterized by bursts of rapid eye movements, an increase in both respiration and heart rates along with atonia of many limb, trunk and neck muscles.[15-22] REM sleep does not normally appear until after a person has first experienced all four NREM stages. The first REM episode is usually short (about 5-10 minutes) with each successive REM episode lasting longer. Hence as the night progresses, REM sleep occupies a greater percentage of the sleep cycle.
Narcolepsy may result from an inappropriate expression of REM sleep and its components during wakefulness.[2,15] This abnormal exhibition of REM sleep may be due to a defect in the monoaminergic regulation of cholinergic REM sleep mechanisms. A decrease in production or utilization of norepinephrine, dopamine and serotonin and/or hypersensitive cholinergic receptors in the brain are the suspected underlying biochemical pathologies.
Sleep attacks are caused by the abnormal tendency of REM sleep to disrupt the normal diurnal sleep-wake cycle, such that sleep occurs in short, irrepressible bouts. The electrographic hallmark of narcolepsy is the tendency to go from wakefulness to REM sleep with little, if any, NREM sleep in between.[2,21] Narcoleptics achieve the same amount of sleep over a 24-hour period as do non-narcoleptics; the excessive sleepiness and frequent nocturnal awakenings exhibited in narcolepsy result in a pattern of unconsolidated sleep. Since untreated narcoleptics lack the well-defined boundaries between REM sleep, NREM sleep and wakefulness, no amount of nocturnal or daytime sleep can alleviate EDS and produce alertness.[1,2] Sleep attacks occur when daytime drowsiness increases to the point at which the narcoleptic simply falls asleep. Narcoleptics become habituated to their chronic state of sleepiness and may not be aware of their worsening drowsiness until it overwhelms them.
Cataplexy is almost uniquely associated with narcolepsy. Although it does not always occur, cataplexy may develop within a few months to ten years after the onset of inappropriate sleepiness.[2,21,22] Sixty-five to eighty percent of the narcoleptic population eventually develop cataplexy. This singular association of cataplexy in the presence of EDS lends itself to the clinical diagnosis of narcolepsy; objective testing in a sleep laboratory is nevertheless recommended for a definitive diagnosis.[2,14,21]
Cataplexy, sleep paralysis and hypnagogic/ hypnopompic hallucinations are all abnormal manifestations of REM sleep.[1,2,22] The muscle atonia in cataplexy and sleep paralysis is physiologically similar to the atonia occurring normally during REM sleep. The visual, auditory or tactile hallucinations are physiologically similar to those sensations experienced during normal dreaming.
Only about 10% of the narcoleptic population exhibit all of the classic symptoms of narcolepsy. While all people with narcolepsy have some degree of EDS and most have cataplexy, 50-60% also have sleep paralysis and 25-50% have hallucinations.[5,9] Other symptoms occasionally associated with narcolepsy, besides disturbed nocturnal sleep, include automatic behavior, visual or ocular difficulties, memory or concentration problems and depression.[2,5,23] Narcolepsy usually develops in the period between adolescence and the early twenties; the associated sleepiness evolves over several months and then remains stable throughout the affected person's life. The cataplexy, sleep paralysis and hallucination symptoms may improve with age. Nocturnal sleep disturbances tend to worsen faster with advancing age in narcoleptics compared to unaffected individuals, but daytime sleepiness does not increase unless other sleep disorders are present.
The treatment goal for people with narcolepsy is to achieve adequate control of EDS and any auxiliary symptoms, thereby allowing them to function effectively during daily living activities. Due to the different pathological mechanisms that produce the various symptoms of narcolepsy, pharmacological therapy usually consists of a combination of drugs. CNS stimulants are prescribed to control the somnolent symptoms while tricyclic antidepressants are prescribed to control the REM-sleep symptoms.[21,22] However, the available stimulant medications currently provide narcoleptics with only 70% of the alertness level of non-narcoleptics.[20,22] Thus, these drugs only reduce the severity of EDS and sleep attacks; they do not alleviate them entirely. While tricyclic antidepressants control the REM-sleep symptoms fairly effectively, many of them have atropinic effects (eg, dry mouth, impotence) which patients may have difficulty tolerating.
Clinical guidelines on the appropriate use of stimulant medication in the treatment of narcolepsy address appropriate drug doses, tolerance development, potential adverse reactions and drug abuse.[4,19] The United States Food and Drug Administration (FDA) has approved only methylphenidate hydrochloride (Ritalin) and dextroamphetamine sulfate (Dexedrine) for the treatment of narcolepsy.[4,18] Clinically, however, physicians prescribe many other stimulant medications, often exceeding the FDA's recommended doses.[4,14] Caffeine, despite its alerting effects, is thought to have limited use in the treatment of narcolepsy. Table 1 lists the CNS stimulant medications available in the United States that are currently recommended by the Standards of Practice Committee of American Sleep Disorders Association (ASDA) for treating the EDS of narcolepsy.
Table 1. Oral Medications Used in the Treatment of Narcolepsy Medications Dose Range CNS stimulants:(1) pemoline (Cylert) 37.5-150 mg/day methylphenidate (Ritalin) 30-100 mg/day dextroamphetamine (Dexedrine) 15-100 mg/day methamphetamine (Desoxyn) 15-80 mg/day Tricyclic antidepressants:(2) protriptyline (Vivactil) 2.5-30 mg/day imipramine (Tofranil) 2.5-250 mg/day nortriptyline (Pamelor) 50-200 mg/day desipramine (Norpramine) 25-200 mg/day fluoxetine (Prozac) 20-60 mg/day
(1.) Source:American Sleep Disorders Association [ASDA], Standards of Practice Committee: Practice parameters for the use of stimulants in the treatment of narcolepsy. Sleep 1994; 17(4):348-351.
(2.) Sources:Aldrich MS: Narcolepsy Neurology 1992, 42(suppl 6): 34-43; Guillefninault C: Narcolepsy syndrome. Pages 549-561 in: Principles and Practice of Sleep Medicine, 2nd ed., Kryger MH, Roth T, Dement WC (editors). WB Saunders, 1994.
These recommended drugs are in a class of psychomotor stimulants known as indirect acting sympathomimetics. These stimulants act to increase the amount of monoamines (epinephrine, norepinephrine, dopamine and serotonin) available within the synaptic cleft of synapses located primarily in the dopamine systems of the CNS. Indirect sympathomimetic drugs are potent CNS stimulants. The stimulating effects include increased wakefulness, alertness, decreased fatigue, elevation of mood, increased motor activity and reduced proportion of REM sleep. While chemically similar, the relative effects of these stimulant drugs are highly variable in humans. Therefore, the narcolepsy treatment guidelines suggest that clinicians begin drug therapy with low doses and gradually increase the dose to maximum recommended levels based on the individual's response and lifestyle needs.
While CNS stimulant drugs are prescribed to control the EDS associated with narcolepsy, tricyclic antidepressant drugs are prescribed to control cataplexy, sleep paralysis and hypnagogic hallucinations. Tricyclic antidepressants suppress REM sleep activity and increase NREM sleep. The neuropharmacological function of these drugs is not well understood. The suspected biochemical actions are inhibition of norepinephrine and serotonin reuptake, acting along with the anticholinergic effects. Table 1 also lists the commonly prescribed tricyclic antidepressants available in the United States for treating the REM sleep-related symptoms of narcolepsy.[2,14] These antidepressants are usually prescribed in conjunction with the CNS stimulants. Fluoxetine (Prozac), a tricyclic antidepressant, usually exhibits fewer anticholinergic side effects compared to imipramine (Tofranil) and protriptyline (Vivactil).[2,14,21]
Other types of medications help control cataplexy, sleep paralysis and hypnagogic hallucinations, but for various reasons are not widely used. Monoamine oxidase (MAO) inhibitors, such as phenelzine (Nardil), effectively curb cataplexy by suppressing REM sleep. However, due to severe adverse effects and necessary dietary restrictions, MAO inhibitors are no longer commonly prescribed.[5,14] Gamma-hydroxybutyrate (GHB), an experimental drug derived from a CNS metabolite, improves nocturnal sleep.[2,14]
Activity, a basic human need, refers to the quality or process of exerting energy or of accomplishing an effect. Activity cycles, marked by time and corresponding to environmental schedules, may include work and related social routines as well as activities specific to other social roles and personal care. Thus, daily living activities (also known as activities of daily living or ADLs) may be defined as those activities a person performs within a 24-hour period which are perceived as necessary for living.
The impact narcolepsy has on a person's life and ability to perform ADLs has been investigated over the past 15 years, most notably by Ferrans et al, Broughton et al[6-8] and Rogers. Ferrans conceptualized the construct quality of life as a person's sense of well-being originating from the satisfaction or dissatisfaction with the areas of life important to him/her. Using the Narcolepsy Version of the Quality of Life Index (QLI), Ferrans et al measured the subjective quality of life for 539 people with narcolepsy. These participants reported the lowest quality of life in the domain of health and functioning, with a large percentage of participants still bothered by their narcoleptic symptoms even while taking medication. Ferrans et al suggested that these participants had extensively modified their normal ADL routines in an attempt to control their symptoms.
With 180 narcoleptic participants, Broughton et al also documented narcolepsy's adverse affects on an individual's life and sense of wellbeing.[6-8] Rogers, meanwhile, examined the coping strategies twenty narcoleptics used to manage their symptoms and minimize illness-related problems. The participants in these studies considered EDS and/or sleep attacks the most interfering of all narcoleptic symptoms on lifestyle.[6,23] While the majority (75-82%) of these narcoleptics held full-time jobs, problems such as reduced performance (due to sleepiness), fear of job loss and decreased promotional opportunities were reported.[6-23] Participants also reported difficulties with interpersonal relationships among family members and friends. The participants in the study by Broughton and colleagues described sleep attacks or cataplexy occurring during conversations, meals and sexual intercourse. Thirty-five percent of Rogers' participants verbalized a reluctance to experience strong emotions, preventing them from disciplining their children or expressing feelings to their spouses.
While these studies exhibited how narcolepsy can adversely affect a person's quality of life, Rogers suggested that the socio-economic problems associated with narcolepsy may not be as numerous as those otherwise reported. She proposed that the adverse effects of narcolepsy on daily living activities were minimized by a variety of practical behavioral strategies. Examples of coping strategies used by her subjects included: taking extra stimulant medication prior to driving a car, limiting the distance driven, taking a nap and/or drinking coffee when they felt drowsy. Common strategies at work included: frequently walking around, taking a nap during lunch, determining their own work schedule, or becoming self-employed. Rogers found most participants held jobs where quality, more than quantity, was valued by the company.
In addition to documenting the life-effects of narcolepsy, Broughton and colleagues also examined the influence of medication upon those life-effects. Surprisingly, the presence or absence of treatment (ie, medication) did not significantly affect narcoleptics' perception of their symptoms nor quality of life. This finding is disturbing considering that pharmacological therapy aims to control narcoleptic symptoms and allow optimal functioning during ADLs. No other study was found in the literature which investigated this topic. Therefore this investigation sought to examine whether drug therapy made a subjective difference in the lives of people with narcolepsy. The analyses addressed the research question: Is there a difference in the perceived severity of symptoms and the ability to perform ADLs as reported by narcoleptics taking medication versus those not taking medication?
Procedure and Instrumentation
Participants for this retrospective descriptive study were randomly chosen from the membership registry of the American Narcolepsy Association (ANA). A five-part questionnaire, the Narcolepsy Information Questionnaire (NIQ, originally developed by Sharon Merritt, RN, EdD and Felissa Cohen, RN, PhD) was prepared by the Center for Narcolepsy Research staff and then sent to the ANA, whose staff members addressed and mailed it. Names of the study participants were unknown to the investigators. A reminder post card (two weeks after initial mailing) and a second questionnaire (one month later) were sent to non-respondents. Signatures documenting informed consent were not required since the NIQ was returned voluntarily and anonymously. Of the 1200 participants originally selected, 1140 were actually eligible for this study. The sixty non-eligible participants had moved leaving no forwarding address, had died, or were persons interested in this disorder but not narcoleptic themselves. A final response rate of 61.4% was obtained (N=700). This sample represented the largest known survey of narcoleptics' symptom experiences at the time it was conducted.
The following items from the NIQ - Part I were examined for this inquiry. The respondents rated how frequently they experienced 31 symptoms chosen from a review of narcolepsy literature:[6,7,9,16,23] 1 -Not at all; 2 -Occasionally - about 1/4 of the time or less; 3 -Moderately - about 1/2 of the time; 4 -Frequently - about 3/4 of the time or more. Seven items representing the classic symptoms were chosen for this analysis: 3 day-time sleep attacks, daytime sleepiness (EDS), attacks of extreme weakness (cataplexy), paralysis at sleep onset, paralysis on awakening, restless night sleep, vivid sensory experiences upon falling asleep or awakening (hypnagogic or hypnopompic hallucinations).
The respondents were asked to list all the medications with their dosages that they were taking. The drug classes used for analysis included: CNS stimulants, caffeine stimulants, tricyclic antidepressants and experimental drugs.
The respondents rated how much narcolepsy interfered with their ability to carry out ADLs on a scale from 1 to 4 as follows: 1 -Does not interfere; 2 -Mildly interferes - about 1/4 of the time or less; 3 -Moderately interferes -about 1/2 of the time; 4 -Severely interferes -about 3/4 of the time or more.
One limitation of the NIQ was that respondents were not asked to rate their symptoms both on and off narcoleptic medication. Consequently, symptom severity comparing these two circumstances could not be analyzed.
The Crunch computer software package was used for statistical analysis. Frequencies were obtained for all variables. Chi-square analysis of symptom prevalence and ADL rating were examined to determine if significant differences existed between medicated and nonmedicated respondents. The level of significance was set at 0.05.
A sample size of 567 respondents who provided complete data for the symptom ratings, ADL ratings and medication information was used for this analysis (49.7% of the returned questionnaires). Within this sample, 419 respondents (74%) reported taking medications to treat their narcolepsy. Most respondents were female (62%), Caucasian (94%), married (65%) and educated (57% had attended some college or graduated from a 4-year college program). The respondents ranged in age from 15-85 years with a mean of 53.3 years (SD = 13.8 years). Fifty percent of the respondents were employed, with 33% of those employed working full-time (40 hours/week or more). A statistically significant association was found between employment levels and medication status ([chi square] = 14.987, df = 4, p = 0.0047). The group differences were: 57% of the respondents not taking narcoleptic medication versus 47% of those taking medication were unemployed; and 22% of the respondents not taking narcoleptic medication versus 36% of those taking medication worked full-time. No other significant association was found between the other demographic data and medication status.
EDS (98%), sleep attacks (92%) and restless night sleep (86%) were the most common classic narcoleptic symptoms reported by the NIQ respondents. Seventy-four percent of these narcoleptics reported hypnagogic hallucinations, 71% cataplexy, 53% sleep onset paralysis and 44% awakening paralysis. Table 2 shows the prevalence (frequency distribution) of the classic narcoleptic symptoms for these narcoleptics. Table values represent the number of respondents reporting how often the specific symptom occurred, sorted by the appropriate medication used to treat that particular symptom.
Table 2. Classic Narcoleptic Symptom Prevalence Ratings by Medication Status as per NIQ Respondents (N= 567)(*)
Symptom Prevalence Rating Not at all Occasional Excessive daytime sleepiness: not taking CNS stimulants 4 65 taking CNS stimulants 10 109 Sleep attacks: not taking CNS stimulants 20 78 taking CNS stimulants 27 163 Hypnagogic hallucinations: not taking tricyclic antidepressants 128 160 taking tricyclic antidepressants 21 37 Cataplexy: not taking tricyclic antidepressants 141 225 taking tricyclic antidepressants 21 63 Sleep onset paralysis: not taking tricyclic antidepressants 231 149 taking tricyclic antidepressants 38 52 Awakening paralysis: not taking tricyclic antidepressants 268 129 taking tricyclic antidepressants 51 45 Restless night sleep: non-medicated narcoleptics 21 36 medicated narcoleptics 61 98 Symptom Prevalence Rating Moderate Frequent Excessive daytime sleepiness: not taking CNS stimulants 55 66 taking CNS stimulants 114 144 Sleep attacks: not taking CNS stimulants 51 41 taking CNS stimulants 110 77 Hypnagogic hallucinations: not taking tricyclic antidepressants 89 74 taking tricyclic antidepressants 30 28 Cataplexy: not taking tricyclic antidepressants 59 26 taking tricyclic antidepressants 20 12 Sleep onset paralysis: not taking tricyclic antidepressants 46 25 taking tricyclic antidepressants 15 11 Awakening paralysis: not taking tricyclic antidepressants 36 18 taking tricyclic antidepressants 12 8 Restless night sleep: non-medicated narcoleptics 36 55 medicated narcoleptics 98 162
(*) 419 respondents reported taking some type of narcoleptic medication; 377 and 116 respondents were taking CNS stimulants and tricyclic antidepressants, respectively.
Ratings of restless night sleep were grouped between those respondents taking or not taking narcoleptic medication in general since investigating the specific medications treating this particular symptom was beyond the scope of this analysis. Due to a small number of respondents in the caffeine and experimental medication groups, chi-square analysis was performed only with the CNS stimulant and tricyclic antidepressant medication groups.
Chi-square analysis showed no statistically significant association between EDS symptom ratings and whether or not respondents were taking CNS stimulant medication ([chi square] = 1.776, df = 3, p = 0.6201). Likewise, no significant association was found between daytime sleep attacks symptom ratings and CNS stimulant medication status ([chi square] = 2.13, df = 3, p = 0.5458). A statistically significant association was found between respondents taking or not taking tricyclic antidepressant therapy and cataplexy symptom ratings ([chi square] = 10.253, df = 3, p = 0.0165), as well as the remaining REM-sleep symptom ratings (hypnagogic hallucinations: [chi square] = 8.814, df = 3, p = 0.0319; sleep onset paralysis: [chi square] = 13.301, df = 3, p = 0.0040; awakening paralysis: [chi square] = 9.214, df = 3, p = 0.0266). However, different results were obtained when these chi-square analyses were repeated with only the 405 respondents who reported having cataplexy. With the exception of hypnagogic hallucinations ([chi square] = 8.251, df = 3, p = 0.0411), no statistically significant association was found between tricyclic antidepressant therapy and the REM-sleep symptom ratings in these cataplectic narcoleptics (cataplexy: [chi square] = 1.860, df = 2, p = 0.3945; sleep onset paralysis: [chi square] = 6.799, df = 2, p = 0.0786; awakening paralysis: [chi square] = 4.727, df = 2, p = 0.1929). The hypnagogic hallucination group differences were: 21% of the respondents not taking tricyclic antidepressant medication reported no hypnagogic hallucinations versus 12% of those taking tricyclic antidepressants reported no hypnagogic hallucinations; and 19% of the respondents not taking tricyclic antidepressant medication reported having frequent hypnagogic hallucinations versus 28% of those taking tricyclic antidepressant medication reported having frequent hypnagogic hallucinations. No significant association was found between restless night sleep and drug therapy ([chi square] = 0.156, df = 3, p = 0.9844).
There were 419 respondents (74%) taking some type of narcoleptic medication. Three hundred and seventy-seven respondents were taking CNS stimulant medication, 116 respondents took tricyclic antidepressants, 18 respondents took caffeine stimulants and 3 respondents took the experimental drug GHB. There were 85 respondents taking both CNS stimulant and tricyclic antidepressant medication. The most common CNS stimulants used by these medicated narcoleptics were methylphenidate (50%), dextroamphetamine (29%) and pemoline (12%). The most common tricyclic antidepressants used were imipramine (15%) and protriptyline (8%). The remaining individual prescription drugs listed were each used by 3% or less of the medicated respondents. Examples of other CNS stimulants reportedly taken included diethylpropion (Tenuate), phenmetrazine (Preludin), benzphetamine (Didrex) and phentermine (Ionamin). Examples of other tricyclic antidepressants used include amitriptyline (Elavil), amoxapine (Asendin) and fluoxetine. The caffeine stimulants used were coffee, No Doz [R] or Vivarin. GHB was the only experimental drug reportedly taken by the medicated respondents. Table 3 shows the pattern of pharmacological therapy used by these medicated narcoleptics. Table values represent the number of respondents taking a particular type of narcoleptic medication and how many different medications they used to control their narcoleptic symptoms.
Table 3. Types of Narcolepsy Drugs Used and the Number of Drugs Taken by NIQ Respondents (N = 419)
Drug type Number of drugs taken 1 drug 2 drugs (n = 306) (n = 101) CNS stimulants: 1 stimulant 267 82 2 stimulants 0 16 3 stimulants 0 0 Caffeine stimulants: 1 stimulant 8 6 2 stimulants 0 2 Tricyclic antidepressants: 1 antidepressant 30 74 2 antidepressants 0 1 Experimental: GHB(*) 1 2 Number of drugs taken 3 drugs 4 drugs (n = 9) (n = 3) CNS stimulants: 1 stimulant 4 0 2 stimulants 5 1 3 stimulants 0 2 Caffeine stimulants: 1 stimulant 1 1 2 stimulants 0 0 Tricyclic antidepressants: 1 antidepressant 6 1 2 antidepressants 3 1 Experimental: GHB(*) 0 0
(*) GHB is gamma-hydroxybutyrate.
The NIQ respondents were asked to rate how much narcolepsy interfered with the ability to perform their ADLs. Eight percent of the respondents reported that narcolepsy did not interfere with the ability to carry out ADLs, while it mildly interfered for 40%, moderately interfered for 32% and severely interfered for 20%. Chi-square analysis revealed no significant association between ADL interference ratings and CNS stimulant therapy ([chi square] = 5.601, df = 3, p = 0.1327). As before, a statistically significant association was initially found between ADL interference ratings and tricyclic antidepressant therapy ([chi square] = 13.013, df = 3, p = 0.0046). However, when chi-square analysis was repeated with only the 405 respondents having cataplexy, no statistically significant association was found between ADL interference ratings and tricyclic antidepressant therapy ([chi square] = 5.632, df = 3, p = 0.1309). Chi-square analyses showed a significant association between ADL interference and all of the individual classic narcoleptic symptoms (EDS: [chi square] = 178.74, df = 9, p [is less than] 0.0001; daytime sleep attacks: [chi square] = 151.326, df = 9, p [is less than] 0.0001; cataplexy: [chi square] = 145.269, df = 9, p [is less than] 0.0001; hypnagogic hallucinations: [chi square] = 61.564, df = 9, p [is less than] 0.0001; sleep onset paralysis: [chi square = 75.155, df = 9, p [is less than] 0.0001; awakening paralysis: [chi square] = 60.562, df = 9, p [is less than] 0.0001; restless night sleep: [chi square] = 39.099, df = 9, p [is less than] 0.0001).
A multiple linear regression analysis was performed to determine which symptom(s) were significant predictors of ADL interference. The mathematically best-fitting model is shown in Table 4. The adjusted [R.sup.2] value shows that 39.6% of the ADL interference variability is explained by this regression model. EDS contributed 25% of the model variance, while cataplexy contributed 10%, sleep attack about 2%, sleep onset paralysis about 2% and hypnagogic hallucinations about 1%. Awakening paralysis and restless night sleep were not significant contributors to this model and therefore not significant predictors of ADL interference variance.
Table 4. Multiple Linear Regression Analysis of Contributing Perceived Classic Narcoleptic Symptoms to Perceived ADL Interference
Variable Regression Standard Beta coefficient error Entire model(*) 0.6912 EDS(**) 0.26862 0.04188 0.266 Cataplexy 0.28264 0.03904 0.265 Sleep attacks 0.16747 0.04050 0.170 Sleep onset paralysis 0.11617 0.03757 0.115 Hypnagogic hallucinations 0.07506 0.03126 0.089 Constant 0.45813 0.11900 Variable Multiple R [R.sup.2] Adjusted [R.sup.2] Entire model(*) 0.6335 0.4013 0.3960 EDS(**) 0.25 Cataplexy 0.10 Sleep attacks 0.02 Sleep onset paralysis 0.02 Hypnagogic hallucinations 0.01 Constant
(*) F (4,562) = 91.797, p [is less than] 0.0001.
(**) For all symptoms contributing to this model, p [is less than] 0.0001.
The NIQ respondents reported experiencing the somnolent symptoms more frequently than the REM-related symptoms. This was an expected finding, since EDS and daytime sleep attacks are the defining symptoms for narcolepsy.[14,21,22] No significant association was found between the somnolent narcoleptic symptoms and the CNS stimulant medication status of the NIQ respondents. With no proportional differences found in the somnolent symptom ratings between the CNS stimulant medicated and non-medicated groups, it is suggested that CNS stimulant medications may not influence the narcoleptic person's perception of his/her somnolent symptoms. Objective guidelines with which to measure and classify the severity of narcolepsy currently do not exist. Despite this lack of a severity classification system, pharmacologic therapy attempts to relieve the symptoms and make the severe narcoleptic more like a non-narcoleptic person. This investigation supports the notion that this may not currently be the case with CNS stimulant therapy. While it is known that EDS is the most refractory to treatment of all the narcoleptic symptoms, this finding may be also affected by limited drug availability due to governmental rules regulating the prescription practices for CNS stimulant medication.[7,22]
Initially, a statistically significant association was found between the REM-sleep related narcoleptic symptoms and the tricyclic antidepressant medication status of the NIQ respondents. However, when this analysis was repeated with only the cataplectic respondents, no statistically significant association was found (except with hypnagogic hallucinations). These results may possibly due to the influence of the large "not at all" frequency group found with each of the REM-sleep related symptoms. It is interesting to note that over half of the respondents with cataplexy reported only an occasional occurrence of the symptom and that they were not taking tricyclic antidepressant medication. This may be due to the intensity of cataplexy and the other REM sleep-related symptoms not being bothersome enough to take medication and warrant tolerating the adverse effects, either from the physician's recommendation or the patient's own choice. Hence, these results support the thought that most people learn to live with the symptoms by coping via behavioral strategies, versus taking medication, as Rogers had suggested. It is important to note that the NIQ did not ask participants to rate their symptoms while on and off medication. In a follow-up questionnaire, Cohen et al did collect this information along with investigating the pre- and posttreatment symptom experiences of narcoleptics.
The majority of medicated narcoleptic respondents were taking a CNS stimulant, as expected, considering the pervasiveness of EDS. For those respondents taking two or more medications, most were taking a combination of CNS stimulants and tricyclic antidepressants as recommended when EDS and the REM-related symptoms occur together.[14,19,21] The infrequent caffeine usage may be due to the underreporting of these products since the NIQ did not specifically ask for this information. Previous data suggested that narcoleptics frequently integrate some type of caffeine product into their diet via coffee, caffeine tablets or soft drinks to control their EDS and sleep attacks.
The majority of NIQ respondents reported that narcolepsy mildly to moderately interferes with the perceived ability to perform ADLs. As with the symptoms, no significant association was found between ADL interference and the various narcoleptic medications. However, it is surprising that 297 respondents (73%) with cataplexy reporting mild to severe ADL interference, were not on tricyclic antidepressant medication (114 respondents reported mild interference, 107 reported moderate interference and 76 reported severe interference in this nontricyclic antidepressant medicated group). Once again, it is suggested that many people with narcolepsy cope with their symptoms via behavioral strategies and that for many narcoleptics, medication may not be perceived as being completely effective in treating their symptoms. The regression model revealed that EDS contributed to about one fourth, and cataplexy to one tenth, the variation in ADL interference ratings. This model supports anecdotal information that these two narcoleptic symptoms interfere the most with ADL performance.
Limitations to this study need to be recognized. How much this sample represents the general narcoleptic population is unknown. Surveying ANA members may have introduced a bias towards an older, more motivated group of narcoleptics. It is also unknown whether or not the NIQ respondents were formally diagnosed with narcolepsy via polysomnography and the Multiple Sleep Latency Test (MSLT) as recommended by current medical standards.[4,14] As previously discussed, some sleep disorders experts have suggested that cataplexy be present to positively diagnose narcolepsy. Using the same statistical procedures, symptom and ADL ratings were compared between those narcoleptics reporting cataplexy and those that did not. No differences in the ratings were found.
In conclusion, this study found that medication therapy did not modify the symptom experience and ability to perform ADLs as perceived and reported by people with narcolepsy. However, it is unknown if the NIQ respondents rated their symptoms on or off medication. Despite the limited findings, people with narcolepsy probably should use a combination of behavioral strategies and medication regimens to cope effectively with this disorder's adverse effects on daily life. In many ways nurses can be instrumental in assisting this patient population to achieve the highest quality of life possible. By teaching and promoting healthy lifestyle habits (eg, eating a nutritional diet, practicing proper sleep hygiene), nurses can help narcoleptics manage their symptoms. Nurses can also teach narcoleptics how to observe their responses to medication and the behavior strategies they use in order to evaluate treatment effectiveness. With well-designed controlled studies using various quality-of-life measures, nurses can investigate more thoroughly the specific ancillary medication practices of narcoleptics (eg, the use of caffeine products), along with behavior strategies (eg, diet, naps and exercise) to find those practices most beneficial for individuals with narcolepsy.
Narcolepsy is a chronic neurological disorder resulting from an inappropriate expression of REM sleep and its components during wakefulness. Current medical treatment consists of CNS stimulants to control the somnolent symptoms (EDS and sleep attacks) and tricyclic antidepressants to control the REM sleep-related symptoms (cataplexy, sleep paralysis, hypnagogic hallucinations). This study was a secondary analysis which examined if drug therapy made a perceived difference in the subjective symptom experience and the ability to perform ADLs as reported by people with narcolepsy. No significant association was found between the narcoleptic symptoms, or the ability to perform ADLs, and drug therapy. However, this study did not examine symptom ratings on and off drug therapy. Narcoleptics may utilize behavioral strategies with their medication regimens to effectively cope with narcolepsy's adverse effects on daily life. This suggests through teaching current narcolepsy-related information and promoting healthful behaviors, nurses can help their narcoleptic patients attain the highest quality of life possible.
The authors wish to thank the staff at the Center for Narcolepsy Research, College of Nursing, University of Illinois at Chicago, for their assistance. The NIQ study was supported in part by Mr. J. A. Piscopo.
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Questions or comments about this article may be directed to. Sharon L. Merritt, RN, EdD Center for Narcolepsy Research, College of Nursing (M/C 802), University of Illinois at Chicago, 845 S. Damen Avenue, Chicago, Illinois 60612. She is Director of the Center for Narcolepsy Research and faculty at the Medical-Surgical Department in the College of Nursing at the University of Illinois at Chicago.
Autumn Schumacher, RN, MS, is currently a nursing doctorate student at the University of Illinois at Chicago. Felissa L. Cohen, RN, PhD is Dean of the School of Nursing, Southern Illinois University at Edwardsville.
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|Title Annotation:||activities of daily living|
|Author:||Schumacher, Autumn; Merritt, Sharon L.; Cohen, Felissa L.|
|Publication:||Journal of Neuroscience Nursing|
|Date:||Feb 1, 1997|
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