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Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center
Epilepsy & Behavior 9 (2006) 632–635 www.elsevier.com/locate/yebeh
Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center Sigmund Jenssen a,*, Edward Gracely b, Tariq Mahmood c, Joseph I. Tracy c, Michael R. Sperling c a
Department of Neurology, Drexel Medical College, Broad and Vine Streets, Hahnemann University Hospital, Mail Stop 308, Philadelphia, PA 19107, USA b Department of Preventive Health, Drexel Medical College, Hahnemann University Hospital, Philadelphia, PA, USA c Department of Neurology, Jefferson Medical College, Philadelphia, PA, USA Received 21 July 2006; revised 16 August 2006; accepted 17 August 2006 Available online 25 September 2006
Abstract Many patients with epilepsy complain of decreased energy and somnolence. There is increased awareness that comorbidity, especially depression, plays an important role in determining the quality of life for patients with epilepsy. We set out to determine how subjective somnolence is affected by depression, age, hours of sleep, sleep apnea, seizure frequency, and numbers of antiepileptic drugs and central nervous system drugs. A questionnaire and chart review were used to investigate patients in a tertiary referral center. We found that subjective somnolence was prominent and that it relates mainly to depression, less to obstructive sleep apnea, and not to the other variables. Further investigation is needed into the relationship between depression and subjective somnolence in patients with epilepsy. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Comorbidity; Somnolence; Sleep disorder; Depression; Antiepileptic medication; Adverse effect; Seizure frequency; Obstructive sleep apnea; Quality of life
1. Introduction Vigilance and somnolence are in constant flux and affected by multiple external and internal causes. As a result, it can be difficult to point to one cause of excessive somnolence. Sleep disorders, lack of sleep, medical illnesses, and medications all may cause excessive daytime somnolence (EDS), defined as a sustained lack of alertness and tendency to fall asleep during daytime hours. Clinicians treating epilepsy frequently hear patients complain of sleepiness. In several previous studies, sleepiness in patients with epilepsy has been examined by use of questionnaires and with objective tests like the Multiple Sleep Latency Test [1]. Some researchers have found that patients with epilepsy have increased somnolence as compared with *
Corresponding author. Fax: +1 215 762 8613. E-mail address: [email protected] (S. Jenssen).
1525-5050/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2006.08.010
the general population. In addition, depression is prevalent among patients with epilepsy and an important determinant of quality of life [2]. As both these conditions frequently occur in persons with epilepsy, we investigated if there is any interaction between EDS and depression and which other factors affect EDS. We assessed factors that are particular to epilepsy and those that are not particular to epilepsy and can affect all adults. 2. Methods 2.1. Subjects After obtaining approval from the institutional review board, we recruited subjects who attended the Comprehensive Epilepsy Center at Thomas Jefferson University in Philadelphia, a tertiary care referral center. Patients older than 16 with epilepsy were randomly asked to answer the surveys, and their charts were reviewed. We excluded patients unable to answer the survey by themselves, patients who did not have
S. Jenssen et al. / Epilepsy & Behavior 9 (2006) 632–635 abnormal EEGs consistent with epilepsy, patients with psychogenic seizures, patients with significant concomitant medical diseases, and pregnant women.
2.2. Surveys The survey elicited the following information regarding sleep habits: mean hours of sleep per night, number of daytime naps per week, shift work. Only mean hours of sleep was included. Also, there were questions regarding the use of alcohol and caffeine. Three previously validated questionnaires were included: 1. The Epworth Sleepiness Scale (ESS) is a self-reported eight-item test that gauges the propensity of falling asleep in different hypothetical situations; scores range from a minimum of 0 to a maximum of 24 [3,4]. We considered a score of P10 as indicating excessive daytime somnolence. ESS scores have not correlated well with objective tests like the Multiple Sleep Latency Test, but have correlated better with the severity of the condition in patients with narcolepsy than in patients with obstructive sleep apnea [5]. 2. The Beck Depression Inventory-II (BDI) [6] is a self-reported 21-item scale that measures the degree of depressive thought content; scores range from a minimum of 0 to a maximum of 61. Moderate depression is set at a score between 15 and 30 and severe depression at >30. 3. The Sleep Apnea section of the Sleep Disorder Questionnaire (SA) is a 12-item self reported questionnaire that inquires about risk factors for and symptoms of obstructive sleep apnea (OSA), for example, smoking, weight gain, load snoring, abrupt awakening [7]. Although high scores correlate well with the presence of sleep-disordered breathing on the polysomnogram, no cutoff values have been defined.
2.3. Chart review Each subject’s medical chart was reviewed by a physician. We recorded body mass index (BMI), mean number of seizures per month over the preceding year, number of current antiepileptic drugs (AEDs) used, and total number of drugs with effects on the central nervous system (CNS), including AEDs, antidepressants, neuroleptics, anxiolytics, and sleep medications.
2.4. Statistical analysis The SSPS Version 11 software package was used. The following continuous variables were analyzed: ESS score, BDI score, SA score, age, BMI, hours of sleep, number of AEDs, number of CNS drugs, and seizure frequency. ESS was the dependent variable; and the remaining variables were independent. Dependent and the independent variables were analyzed for skewness and transformed when skewness was P0.6, using logarithmic or square root transformation approximating skewness as close as possible to 0.0. Univariate analysis consisted of Spearman correlations with ESS. After appropriate transformations, multiple linear regression was used with ESS as the dependent variable.
3. Results One hundred and fifty patients participated, 136 of whom had complete ESS scores and were therefore eligible for analysis. Forty-eight (35%) were males. Table 1 summarizes the descriptive statistics for the variables of interest. Mean ESS score was 7.9 (SD 4.6, range 0–23, median 7). This is significantly higher than what has been described for normal individuals not at risk for EDS (mean ESS 4.6, SD 2.8) [8]. Forty-six patients (35%) had ESS scores of P10 and, therefore, had EDS according to this scale.
633
Table 1 Descriptive statisticsa Variable
Number of subjects
Mean
Range
SD
Epworth score Hours of sleep Age (years) Body mass index Sleep apnea score Beck Depression Inventory-II score Seizure frequency (monthly) Number of AEDs Number of CNS drugs
136 132 136 131 130 131 136 136 136
7.9 8.1 38.3 27.5 14.5 12.6 3.2 1.6 1.8
0–23 3–12.5 17–75 16–51 9–37 0–43 0–60 0–4 0–5
4.6 1.7 12 6.8 5.3 10.2 4.5 0.7 0.5
a
All variables are continuous. See text for a more in-depth description.
Mean hours of sleep per day was not below what has been shown to be common in the general population. The SA score has no abnormal cutoff values. About one-third (31.9%) had at least moderate depression, and 13 patients (9.9%) had severe depression. Mean number of AEDs was 1.6 (range 0–4), and mean number of CNS drugs was 1.8 (range 0–5). In addition to AEDs, CNS drugs included antidepressant medications for 30 patients, anxiolytic medications for 3, and sedating neuroleptics for 2 patients. Table 2 summarizes the results of the analysis. Univariate analysis with the Spearman correlation coefficients revealed that age was inversely associated with ESS (P = 0.049), whereas BDI (P = 0.001) as well as number of CNS drugs (P = 0.036), was positively associated. The SA score revealed a trend toward association with elevated ESS (P = 0.075, two-tailed). All variables except ESS scores, age, and hours of sleep had a large amount of skewness, and had to be submitted to transformation as described above. In the multivariate analysis, only BDI (P = 0.036) was significant; the SA score (P = 0.089) was marginally significant. All of the
Table 2 Univariate and multivariate analysisa Variable
Spearman correlation P value
q Hours of sleep Age Body mass index Sleep apnea score Beck Depression Inventory-II score Seizure frequency Number of AEDs Number of CNS drugs a
Multivariate regression P value
b
0.050 0.170 0.074 0.166
0.595 0.049 0.426 0.075
0.50 0.150 0.086
0.180 0.435
0.299 0.025 0.129 0.180
0.001 0.778 0.146 0.036
0.317 0.010 0.130 0.111
0.004 0.930 0.239 0.324
For the multiple regression, the logarithms of sleep apnea score, seizure frequency, and body mass index and the square root of Beck Depression Inventory-II score were used. Anyone taking four AEDs was counted as having ‘‘three or more.’’ The other variables did not require transformation. Also see text.
634
S. Jenssen et al. / Epilepsy & Behavior 9 (2006) 632–635
factors taken together could only account for approximately 10% of the variance of ESS scores. Of this, BDI scores accounted for nearly all of the effect (r2 for BDI alone was 0.088); SA scores had only a minor independent effect. CNS drugs were no longer significant in the multivariate model (b = 0.085, P = 0.47), as this effect was totally explained by depression. Hours of sleep, number of anticonvulsant drugs, age, BMI, and seizure frequency had no effect on ESS scores in the multivariate model. 4. Discussion The main findings of this study are that excessive daytime somnolence is a frequent complaint of people with epilepsy and depression is the main factor correlating with EDS. It should be noted that EDS can be estimated with different scales and physiological tests, and the results differ according to which tool is being used [5]. Most previous studies have not reported an increased prevalence of EDS in persons with epilepsy as compared with a control population. Two other studies [9,10] reported considerably lower mean ESS scores for patients with epilepsy (3.5 and 5.6, respectively, compared with our 7.9), and none of them noted a difference from their own control group [9] or from historical controls [10]. Another study reported a nonsignificant increase in EDS (P < 0.10) as compared with neurological patients without epilepsy [11], and a recent article reported no increase as compared with healthy controls [12]. It is uncertain why our results differ. It is possible that this difference is related to patient selection bias—most of our patients had longstanding refractory epilepsy—or perhaps differences in treatment. On the other hand, several studies have determined that patients with epilepsy have more sleep complaints as compared with controls [9,12], but often there is no good explanation, because there are no differences in the prevalence of specific sleep disorders. The amount of sleep, as seen in our study, as well as sleep–wake habits, is not altered in patients with epilepsy [12]. This is the first study to find a correlation between EDS and depression in patients with epilepsy. The high prevalence of depression in our study is not surprising as this has been described previously in numerous studies [13,14]. There are indications that depression in epilepsy is at least in part caused by biological factors. For example, differences in seizure characteristics differed in patients with and without depression according to one report [15], and if seizures are stopped with epilepsy surgery, depression and anxiety improve [16]. Epilepsy could cause both depression and disordered sleep. Depression is associated with changes in REM sleep; epileptic seizures cause a short-term decrease in the amount of REM sleep during the night following a seizure [17]. Epilepsy could be associated with changes in stress hormones [18]. Increased cortisol is associated with insomnia [19], and patients with epilepsy have been found to have sleep maintenance insomnia [12], which again could cause EDS and sleep complaints.
Notably, depression was not related to seizure frequency in this study, similar to previous reports [2,20], so although having seizures may cause difficulties, the rate of seizure occurrence appears unrelated to the magnitude of the problem. On this basis, one would not expect somnolence to correlate very closely with seizure frequency, and although one study has reported such a correlation [10], our study, as well as another [21], did not. The difference here could be due to patient selection bias. The number of AEDs taken did not correlate with EDS, similar to previous findings [10]. It is possible that EDS is more of a problem with older-generation AEDs. This, however, remains speculative [22]. As many patients were taking a combination of older- and newer-generation medications, it is unlikely that further analysis of the data will distinguish the effect of each type of AED on EDS. Further analysis of AED levels and EDS may yield different results. Medications with effects on the central nervous system had only mild influence on EDS. The effect disappears after discounting depression, and the cause is unknown. There was a modest trend for the SA score to correlate with EDS [11]. This score assesses the risk of sleep apnea [7], which has also been found to correlate with disturbed breathing in polysomnograms of patients with epilepsy [23]. Sleep apnea in patients with epilepsy has been reported to be more frequent in older, male patients with a higher SA score, who are more likely to have seizures during sleep, even with normal scores on the ESS [23]. It is important to diagnose obstructive sleep apnea because it is treatable, and seizures are sometimes dramatically improved with treatment of sleep apnea using breathing devices [24]. In conclusion, this study confirms that excessive daytime somnolence is common in patients with epilepsy seen in a tertiary care center and that depression is the main predictor of EDS. Still, the factors investigated accounted for only small fraction of possible causes of EDS (similar to another study recently published [12]). We still know little of other factors that are probably important in determining EDS. Because quality of life relates to sleepiness [9], this area bears further investigation. The effect of aggressive treatment of depression on sleep complaints and EDS could, for example, be further investigated. References [1] Drake Jr ME, Weate SJ, Newell SA, Padamadan H, Pakalnis A. Multiple sleep latency tests in epilepsy. Clin Electroencephalogr 1994;25(2):59–62. [2] Boylan LS, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O. Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy [see comment]. Neurology 2004;62:258–61. [3] Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540–5. [4] Johns MW. Sleepiness in different situations measured by the Epworth Sleepiness Scale. Sleep 1994;17:703–10.
S. Jenssen et al. / Epilepsy & Behavior 9 (2006) 632–635 [5] Sangal RB, Mitler MM, Sangal JAM. US modafinil in narcolepsy multicenter study group. MSLT, MWT and ESS: indices of sleepiness in 522 drug-free patients with narcolepsy. Sleep Res 1997;26:492. [6] Beck AT, Steer RA, Brown GK. Beck Depression Inventory manual. San Antonio: TX: Psychological Corp.; 1996. [7] Douglass AB, Bornstein R, Nino-Murcia G, et al. The Sleep Disorders Questionnaire: I. Creation and multivariate structure of SDQ. Sleep 1994;17:160–7. [8] Johns M, Hocking B. Daytime sleepiness and sleep habits of Australian workers. Sleep 1997;20:844–9. [9] De Weerd A, de Haas S, Otte A, et al. Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life. Epilepsia 2004;45:1397–404. [10] Manni R, Politini L, Sartori I, Ratti MT, Galimberti CA, Tartara A. Daytime sleepiness in epilepsy patients: evaluation by means of the Epworth Sleepiness Scale. J Neurol 2000;247:716–7. [11] Malow BA, Bowes RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997;20:1105–10. [12] Khatami R, Zutter D, Siegel A, Mathis J, Donati F, Bassetti CL. Sleep–wake habits and disorders in a series of 100 adult epilepsy patients: a prospective study. Seizure 2006/7;15:299–306. [13] Mendez MF, Cummings JL, Benson DF. Depression in epilepsy: significance and phenomenology. Arch Neurol 1986;43:766–70. [14] Gilliam F, Hecimovic H, Sheline Y. Psychiatric comorbidity, health, and function in epilepsy [review]. Epilepsy Behav 2003;4(Suppl. 4):S26–30.
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[15] Schmitz EB, Robertson MM, Trimble MR. Depression and schizophrenia in epilepsy: social and biological risk factors. Epilepsy Res 1999;35:59–68. [16] Devinsky O, Barr WB, Vickrey BG, et al. Changes in depression and anxiety after resective surgery for epilepsy. Neurology 2005;65:1744–9. [17] Bazil CW, Castro LH, Walczak TS. Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy. Arch Neurol 2000;57:363–8. [18] Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000;57:925–35. [19] Buckley TM, Schatzberg AF. On the interactions of the hypothalamic–pituitary–adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 2005;90:3106–14. [20] Smith DF, Baker GA, Dewey M, Jacoby A, Chadwick DW. Seizure frequency, patient-perceived seizure severity and the psychosocial consequences of intractable epilepsy. Epilepsy Res 1991;9:231–41. [21] Malow BA, Fromes GA, Aldrich MS. Usefulness of polysomnography in epilepsy patients. Neurology 1997;48:1389–94. [22] Bazil CW. Effects of antiepileptic drugs on sleep structure: are all drugs equal? [review]. CNS Drugs 2003;17:719–28. [23] Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002–7. [24] Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome [see comment]. Neurology 1994;44:2060–4.
Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center Sigmund Jenssen a,*, Edward Gracely b, Tariq Mahmood c, Joseph I. Tracy c, Michael R. Sperling c a
Department of Neurology, Drexel Medical College, Broad and Vine Streets, Hahnemann University Hospital, Mail Stop 308, Philadelphia, PA 19107, USA b Department of Preventive Health, Drexel Medical College, Hahnemann University Hospital, Philadelphia, PA, USA c Department of Neurology, Jefferson Medical College, Philadelphia, PA, USA Received 21 July 2006; revised 16 August 2006; accepted 17 August 2006 Available online 25 September 2006
Abstract Many patients with epilepsy complain of decreased energy and somnolence. There is increased awareness that comorbidity, especially depression, plays an important role in determining the quality of life for patients with epilepsy. We set out to determine how subjective somnolence is affected by depression, age, hours of sleep, sleep apnea, seizure frequency, and numbers of antiepileptic drugs and central nervous system drugs. A questionnaire and chart review were used to investigate patients in a tertiary referral center. We found that subjective somnolence was prominent and that it relates mainly to depression, less to obstructive sleep apnea, and not to the other variables. Further investigation is needed into the relationship between depression and subjective somnolence in patients with epilepsy. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Comorbidity; Somnolence; Sleep disorder; Depression; Antiepileptic medication; Adverse effect; Seizure frequency; Obstructive sleep apnea; Quality of life
1. Introduction Vigilance and somnolence are in constant flux and affected by multiple external and internal causes. As a result, it can be difficult to point to one cause of excessive somnolence. Sleep disorders, lack of sleep, medical illnesses, and medications all may cause excessive daytime somnolence (EDS), defined as a sustained lack of alertness and tendency to fall asleep during daytime hours. Clinicians treating epilepsy frequently hear patients complain of sleepiness. In several previous studies, sleepiness in patients with epilepsy has been examined by use of questionnaires and with objective tests like the Multiple Sleep Latency Test [1]. Some researchers have found that patients with epilepsy have increased somnolence as compared with *
Corresponding author. Fax: +1 215 762 8613. E-mail address: [email protected] (S. Jenssen).
1525-5050/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2006.08.010
the general population. In addition, depression is prevalent among patients with epilepsy and an important determinant of quality of life [2]. As both these conditions frequently occur in persons with epilepsy, we investigated if there is any interaction between EDS and depression and which other factors affect EDS. We assessed factors that are particular to epilepsy and those that are not particular to epilepsy and can affect all adults. 2. Methods 2.1. Subjects After obtaining approval from the institutional review board, we recruited subjects who attended the Comprehensive Epilepsy Center at Thomas Jefferson University in Philadelphia, a tertiary care referral center. Patients older than 16 with epilepsy were randomly asked to answer the surveys, and their charts were reviewed. We excluded patients unable to answer the survey by themselves, patients who did not have
S. Jenssen et al. / Epilepsy & Behavior 9 (2006) 632–635 abnormal EEGs consistent with epilepsy, patients with psychogenic seizures, patients with significant concomitant medical diseases, and pregnant women.
2.2. Surveys The survey elicited the following information regarding sleep habits: mean hours of sleep per night, number of daytime naps per week, shift work. Only mean hours of sleep was included. Also, there were questions regarding the use of alcohol and caffeine. Three previously validated questionnaires were included: 1. The Epworth Sleepiness Scale (ESS) is a self-reported eight-item test that gauges the propensity of falling asleep in different hypothetical situations; scores range from a minimum of 0 to a maximum of 24 [3,4]. We considered a score of P10 as indicating excessive daytime somnolence. ESS scores have not correlated well with objective tests like the Multiple Sleep Latency Test, but have correlated better with the severity of the condition in patients with narcolepsy than in patients with obstructive sleep apnea [5]. 2. The Beck Depression Inventory-II (BDI) [6] is a self-reported 21-item scale that measures the degree of depressive thought content; scores range from a minimum of 0 to a maximum of 61. Moderate depression is set at a score between 15 and 30 and severe depression at >30. 3. The Sleep Apnea section of the Sleep Disorder Questionnaire (SA) is a 12-item self reported questionnaire that inquires about risk factors for and symptoms of obstructive sleep apnea (OSA), for example, smoking, weight gain, load snoring, abrupt awakening [7]. Although high scores correlate well with the presence of sleep-disordered breathing on the polysomnogram, no cutoff values have been defined.
2.3. Chart review Each subject’s medical chart was reviewed by a physician. We recorded body mass index (BMI), mean number of seizures per month over the preceding year, number of current antiepileptic drugs (AEDs) used, and total number of drugs with effects on the central nervous system (CNS), including AEDs, antidepressants, neuroleptics, anxiolytics, and sleep medications.
2.4. Statistical analysis The SSPS Version 11 software package was used. The following continuous variables were analyzed: ESS score, BDI score, SA score, age, BMI, hours of sleep, number of AEDs, number of CNS drugs, and seizure frequency. ESS was the dependent variable; and the remaining variables were independent. Dependent and the independent variables were analyzed for skewness and transformed when skewness was P0.6, using logarithmic or square root transformation approximating skewness as close as possible to 0.0. Univariate analysis consisted of Spearman correlations with ESS. After appropriate transformations, multiple linear regression was used with ESS as the dependent variable.
3. Results One hundred and fifty patients participated, 136 of whom had complete ESS scores and were therefore eligible for analysis. Forty-eight (35%) were males. Table 1 summarizes the descriptive statistics for the variables of interest. Mean ESS score was 7.9 (SD 4.6, range 0–23, median 7). This is significantly higher than what has been described for normal individuals not at risk for EDS (mean ESS 4.6, SD 2.8) [8]. Forty-six patients (35%) had ESS scores of P10 and, therefore, had EDS according to this scale.
633
Table 1 Descriptive statisticsa Variable
Number of subjects
Mean
Range
SD
Epworth score Hours of sleep Age (years) Body mass index Sleep apnea score Beck Depression Inventory-II score Seizure frequency (monthly) Number of AEDs Number of CNS drugs
136 132 136 131 130 131 136 136 136
7.9 8.1 38.3 27.5 14.5 12.6 3.2 1.6 1.8
0–23 3–12.5 17–75 16–51 9–37 0–43 0–60 0–4 0–5
4.6 1.7 12 6.8 5.3 10.2 4.5 0.7 0.5
a
All variables are continuous. See text for a more in-depth description.
Mean hours of sleep per day was not below what has been shown to be common in the general population. The SA score has no abnormal cutoff values. About one-third (31.9%) had at least moderate depression, and 13 patients (9.9%) had severe depression. Mean number of AEDs was 1.6 (range 0–4), and mean number of CNS drugs was 1.8 (range 0–5). In addition to AEDs, CNS drugs included antidepressant medications for 30 patients, anxiolytic medications for 3, and sedating neuroleptics for 2 patients. Table 2 summarizes the results of the analysis. Univariate analysis with the Spearman correlation coefficients revealed that age was inversely associated with ESS (P = 0.049), whereas BDI (P = 0.001) as well as number of CNS drugs (P = 0.036), was positively associated. The SA score revealed a trend toward association with elevated ESS (P = 0.075, two-tailed). All variables except ESS scores, age, and hours of sleep had a large amount of skewness, and had to be submitted to transformation as described above. In the multivariate analysis, only BDI (P = 0.036) was significant; the SA score (P = 0.089) was marginally significant. All of the
Table 2 Univariate and multivariate analysisa Variable
Spearman correlation P value
q Hours of sleep Age Body mass index Sleep apnea score Beck Depression Inventory-II score Seizure frequency Number of AEDs Number of CNS drugs a
Multivariate regression P value
b
0.050 0.170 0.074 0.166
0.595 0.049 0.426 0.075
0.50 0.150 0.086
0.180 0.435
0.299 0.025 0.129 0.180
0.001 0.778 0.146 0.036
0.317 0.010 0.130 0.111
0.004 0.930 0.239 0.324
For the multiple regression, the logarithms of sleep apnea score, seizure frequency, and body mass index and the square root of Beck Depression Inventory-II score were used. Anyone taking four AEDs was counted as having ‘‘three or more.’’ The other variables did not require transformation. Also see text.
634
S. Jenssen et al. / Epilepsy & Behavior 9 (2006) 632–635
factors taken together could only account for approximately 10% of the variance of ESS scores. Of this, BDI scores accounted for nearly all of the effect (r2 for BDI alone was 0.088); SA scores had only a minor independent effect. CNS drugs were no longer significant in the multivariate model (b = 0.085, P = 0.47), as this effect was totally explained by depression. Hours of sleep, number of anticonvulsant drugs, age, BMI, and seizure frequency had no effect on ESS scores in the multivariate model. 4. Discussion The main findings of this study are that excessive daytime somnolence is a frequent complaint of people with epilepsy and depression is the main factor correlating with EDS. It should be noted that EDS can be estimated with different scales and physiological tests, and the results differ according to which tool is being used [5]. Most previous studies have not reported an increased prevalence of EDS in persons with epilepsy as compared with a control population. Two other studies [9,10] reported considerably lower mean ESS scores for patients with epilepsy (3.5 and 5.6, respectively, compared with our 7.9), and none of them noted a difference from their own control group [9] or from historical controls [10]. Another study reported a nonsignificant increase in EDS (P < 0.10) as compared with neurological patients without epilepsy [11], and a recent article reported no increase as compared with healthy controls [12]. It is uncertain why our results differ. It is possible that this difference is related to patient selection bias—most of our patients had longstanding refractory epilepsy—or perhaps differences in treatment. On the other hand, several studies have determined that patients with epilepsy have more sleep complaints as compared with controls [9,12], but often there is no good explanation, because there are no differences in the prevalence of specific sleep disorders. The amount of sleep, as seen in our study, as well as sleep–wake habits, is not altered in patients with epilepsy [12]. This is the first study to find a correlation between EDS and depression in patients with epilepsy. The high prevalence of depression in our study is not surprising as this has been described previously in numerous studies [13,14]. There are indications that depression in epilepsy is at least in part caused by biological factors. For example, differences in seizure characteristics differed in patients with and without depression according to one report [15], and if seizures are stopped with epilepsy surgery, depression and anxiety improve [16]. Epilepsy could cause both depression and disordered sleep. Depression is associated with changes in REM sleep; epileptic seizures cause a short-term decrease in the amount of REM sleep during the night following a seizure [17]. Epilepsy could be associated with changes in stress hormones [18]. Increased cortisol is associated with insomnia [19], and patients with epilepsy have been found to have sleep maintenance insomnia [12], which again could cause EDS and sleep complaints.
Notably, depression was not related to seizure frequency in this study, similar to previous reports [2,20], so although having seizures may cause difficulties, the rate of seizure occurrence appears unrelated to the magnitude of the problem. On this basis, one would not expect somnolence to correlate very closely with seizure frequency, and although one study has reported such a correlation [10], our study, as well as another [21], did not. The difference here could be due to patient selection bias. The number of AEDs taken did not correlate with EDS, similar to previous findings [10]. It is possible that EDS is more of a problem with older-generation AEDs. This, however, remains speculative [22]. As many patients were taking a combination of older- and newer-generation medications, it is unlikely that further analysis of the data will distinguish the effect of each type of AED on EDS. Further analysis of AED levels and EDS may yield different results. Medications with effects on the central nervous system had only mild influence on EDS. The effect disappears after discounting depression, and the cause is unknown. There was a modest trend for the SA score to correlate with EDS [11]. This score assesses the risk of sleep apnea [7], which has also been found to correlate with disturbed breathing in polysomnograms of patients with epilepsy [23]. Sleep apnea in patients with epilepsy has been reported to be more frequent in older, male patients with a higher SA score, who are more likely to have seizures during sleep, even with normal scores on the ESS [23]. It is important to diagnose obstructive sleep apnea because it is treatable, and seizures are sometimes dramatically improved with treatment of sleep apnea using breathing devices [24]. In conclusion, this study confirms that excessive daytime somnolence is common in patients with epilepsy seen in a tertiary care center and that depression is the main predictor of EDS. Still, the factors investigated accounted for only small fraction of possible causes of EDS (similar to another study recently published [12]). We still know little of other factors that are probably important in determining EDS. Because quality of life relates to sleepiness [9], this area bears further investigation. The effect of aggressive treatment of depression on sleep complaints and EDS could, for example, be further investigated. References [1] Drake Jr ME, Weate SJ, Newell SA, Padamadan H, Pakalnis A. Multiple sleep latency tests in epilepsy. Clin Electroencephalogr 1994;25(2):59–62. [2] Boylan LS, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O. Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy [see comment]. Neurology 2004;62:258–61. [3] Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540–5. [4] Johns MW. Sleepiness in different situations measured by the Epworth Sleepiness Scale. Sleep 1994;17:703–10.
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