Sleep, morning alertness and quality of life in subjects treated with zopiclone and in good sleepers. Study comparing 167 patients and 381 good sleepers

Eur fsychiarq~ (1995) 0 Elsevier, Paris

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Sleep, morning alertness and quality of life in subjects treated with zopiclone and in good sleepers. Study comparing 167 patients and 381 good sleepers D LCgerl, C Jam&, A Pellois2, MA Quera-Salva3, JP Dreyfus4 ’ UnitP de Sommeil,

HGtel-Dieu de Pun’s, I place du Parvis-Notre-Dame, 75181 Paris cedex 04: z The’ruplix 46-.52 rue Alberr, z Unit6 de Sommeil, HCpiial Raymond-Poincark 104 boulevard Raymond Poincark 92380 Garches; 4 D@artement MPdical, Sofres. I6 rue Barbt?. 92129 Montrouge cedex. France

75OI3 Paris;

Summary-From 20,000 households regularly surveyed by a national survey institute (Sofres), two groups were selected and questioned (using a 23-item questionnaire) about sleep vigilance and quality of life. The first group was composed of insomniacs using zopiclone for the last 12 months and no other CNS treatments ( I67 subjects). The second group was composed of 38 I “good sleepers” selected as having no or occasionally one sleep disturbance in the last 12 months. No difference was found between the two groups in average total sleep time. Sleep disturbances were statistically equal in the two groups except for difficulties in initiating sleep which is more present for zopiclone users (13% vs 3%). Vigilance was mostly comparable in both groups.Five aspects of quality of life explored by the questionnaires (the professional, relational and sentimental, domestic, leisure and safety aspects) appeared to be comparable in the two groups.

insomnia / zopiclone I quality of life I alertness / sleep

INTRODUCTION Insomnia is not only a trouble of sleepincluding difficulty initiating sleep,frequent awakeningsfrom sleep, short sleep time or non restorative sleep. It also has daytime consequencessuch asfatigue, sleepiness,impaired daytime functioning, depression, anxiety or other mood changes. In fact without daytime consequences, insomnia would not have severe consequencesexcept for a bad perception of sleep(Mendelson et al, 1984). This is why the perception of individuals regarding their own daytime life is so important when speakingabout insomnia(Addison et al, 1991). Treatments of insomniacan have a beneficial effect on insomniawith no efficiency or sideeffects on daytime functioning. A good treatment hasto be effective both in improving symptomsof insomniaand in maintaining good vigilance (Gillin et al. 1990). Except for very recently, the quality of life aspectsof insomnia had not beentaken into account to a great degreewhen studying new treatmentsor comparing insomniacsand good sleepers(Kelly et al, 1993; Jenkinset al. 1988).

Furthermore, moststudieswhich observethe effects of a treatmentagainstinsomniause only medicalmeans such asdoctor interviews or studiesin a medical environment. This introducesa lot of bias by first considering insomniaasa medical disease,then by taking into account the complex relationship between the patient and the practician. Moreover, the selectionof patients is made by insomniacswho consult a doctor. These insomniacsrepresentonly a small percentage of the total number. Controls areordinarily selectedin populationswhich are related to the medical environment and are available for studies,It is difficult to obtain for example a group of good sleeperswith respectto ageand sex distribution in the generalpopulation. We wanted to exclude the medical track from this study and to consider insomnia by way of a general national survey institute which is not specialisedin medical surveys alone, ashasbeenmadeby the gallop institute in the USA (Gallop, 1991). Zopiclone which is a non benzodiazepine hypnotic, hasshown to be effective and well tolerated. It is also free from residualeffects on performance and psycho-

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logical function during the day after treatment. In a double blind randomised multinational study, 458 insomniac patients received either zopiclone 7.5 mg or placebo nightly for 14 days and for an extended 6 weeks on demand. In the zopiclone group, significant improvement was observed in some aspects of quality of life (ie daily activities, social life etc) compared to placebo, both after 14 days and at the end of the trial (Goldenberg et al, 1994). The aim of the study was to compare sleep, diurnal performance and daily activity, in terms of quality of life in a population as close as possible to the general population. The population was divided into two groups: a group of insomniac subjects taking zopiclone and a group of good sleepers, METHOD From 20,000 households regularly surveyed by a national survey institute (Sofres), two groups of subjects were selected: insomniacs who had been using zopiclone for the last 12 months (group I ; 296 subjects); subjects with no hypnotic treatment for the last I2 months (group 2; 528 subjects). The two groups were questioned about their sleep, vigilance and quality of life using a self-administered 23-item questionnaire devised for the study by sleep specialists. The first part of the questionnaire (items one to five) concerned all the treatments taken by the patient at the time of the study: dosages, duration, frequency. Item 6 to item I5 were devoted to sleep, the average duration for getting asleep, night awakenings, morning awakening and form, sleep duration, sleep quality, etc. Items 16 to 23 explored the five aspects concerning quality of life: professional, relational and sentimental, domestic, leisure and safety aspects. The questionnaire was returned by post to the survey company. In the two groups, only those subjects not taking other treatments with known effects on vigilance were retained: 167 subjects in group 1 and 462 in group 2. From group 2 we obtained a group of good sleepers by selecting only those individuals who claimed no or occasionally one sleep disturbance in the last I2 months, from the following list: difficulty in falling asleep, waking up during the night or waking up too early in the morning. Difficulty in falling asleep was defined as having a sleep latency greater than 30 minutes. Waking up during the night meant having more than two awakenings lasting more than 45 minutes. Waking up too early was taken as waking up in the morning one hour before usual with no return to sleep. A remainder of 381 subjects of the previous group 2 (73%) were considered as good sleepers. The two groups were matched resulting in two groups composed

according to sex and age, of 6 I % females and 39%

et al males.

The distribution among ages was the same in the two from 15 to 24 years old, 15% from 25 to 34 years old, 19% from 35 to 44 years old, 19% from 45 to 54 years old, 17% from 55 to 64 years old and 26% aged over 65. The answers to the questionnaire from the two groups were compared using a “parametric test” according to standardised normal distribution (Laplace Gauss).

groups: 4%

RESULTS Characteristics of sleep, alertness and live aspects conceming the quality of life were studied by the questionnaire. Characteristics

of sleep

No difference was found between the two groups concerning the average total of sleep time: 7 hours 25 minutes in the group with zopiclone and 7 hours 40 minutes in the good sleepers group. However the distribution of the average sleep time within the two groups was not the same. The zopiclone users (68%) had between 6 and 8 hours of sleep per night, against 84% of the good sleepers (fig 1). Occasional sleep disturbances were found in the two groups. The good sleepers were defined as having had no or occasionally one sleep disturbance in the last 12 months. Zopiclone users had more difficulties in falling asleep than good sleepers: 13% vs 3% in respective groups 0, < 0.05). Good sleepers had more occasional awakenings during the night than zopiclone users: 61% vs 52% (p < 0.05). However there was no difference between the two groups in either the percentage of awakenings lasting more than 45 minutes per night (13% of zopiclone users vs 11% for good sleepers). There was no significant difference in occasional awakenings too early in the morning which were asserted by 34% of the zopiclone group and 27% of the good sleeper group. Alertness

and performance

Alertness just after waking up in the morning was assessed in the two groups: 63% of the zopiclone users said they had no problem shaking off sleep in the morning vs 44% of good sleepers (,v c 0.05); 66% of the zopiclone users vs 74% of good sleepers claimed to be in good form upon awakening @ < 0.05). However, there was no difference between the two groups in the following items: having clear ideas just after sleep: 76% of zopiclone users vs 75% of good sleepers; being sleepy in the morning (21% vs 26%).

Sleep,

morning

alertness

and quality

“I feel bizarre, uneasy, for no reason” was denied by more zopiclone users (90%) than by good sleepers (85%) (NS). “I had difficulties in coping with my daily tasks; I feel tired” was denied by 85% of zopiclone users and 70% of good sleepers @ < 0.05). “I am physically tired, I have difficulties doing continuous work” was asserted by 16% of zopiclone users and 34% of good sleepers (p < 0.05). “I have difficulties concentrating, memorising and maintaining my attention” concerned 25% of zopiclone users vs 38% of good sleepers (p < 0.05). Quality of life Five aspects of the quality of life of participants were studied by the questionnaire. Professional aspect No significant difference was found in the appreciation of the quality of working life between good sleepers who worked (230 people) and working insomniacs using zopiclone (75). 14% of zopiclone users and 18% of good sleepers had difficulties carrying out their work. 93% of zopiclone usersand97% of goodsleepers felt good in their jobs. Relational and sentimental aspects We obtainedin the two groupshigh percentagesof subjects satisfied with their sentimentallife. This must be carefully considered.One only questionwith two items was devoted to this aspect. In fact, 91% of patients taking zopiclone were content with their sentimental life (57% very content and 34% reasonablycontent). They were statistically equal to the goodsleepergroup, 94% of whom were content with their sentimentallife (58% very content and 36% reasonablycontent). Furthermore, 59% of patients treated with zopiclone as opposedto 64% of good sleeperswent out in the evening. There were 77% of insomniacstreated by zopiclone vs 83% of good sleeperswho received visitors at home. However treated patients were lesslikely to go out during the day than the control group (87% vs 93%, p < 0.05). Domestic aspect The patientshad a domesticactivity comparableto that of good sleepers:69% vs 67% did their houseworknormally, 88% vs 81% went shopping, 61% vs 62% did odd jobs around the home or did gardening. L&sure aspect Although asmany patientstreated by zopiclone walked

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or played sport as good sleepers,77% vs 72%, fewer watched television, 90% vs 95%. Safety aspect Finally, with regardto driving: 6% of zopiclone usersvs 14% of good sleepersexperiencedproblemsof drowsinesswhile driving. 5% of zopicloneusersvs 10%of control subjectshadhad nearaccidentsdue to sleepiness. DISCUSSION In this epidemiologicalstudy, the methodsof the wellknown Gallop poll institute were used (Sofres, France). This was particularly important in obtaining objective and complete answers from a population which is mainly unconcernedby sleepdisorders:the good sleepers(Johnson, 1983). Moreover, the group of zopiclone users was selected without any intervention or biason the part of medical practitioners. The answerswere, therefore, probably independentof any relationship between patients and doctors or medical staff. On the other hand, we madea questionnairesurvey which is not the best way to assertgood or bad sleep and to affirm the good resultsof a treatment. It may be consideredasa subjectiveappreciationof peopleabout their sleep(Carskadonef al, 1976).Our questionsabout quality of life simply tried to appreciatevarious tendenciesof ordinary life without adopting any generalscale for quality of life. However, we observed five trends generally adoptedin evaluating quality of life which is also an almost subjective component of well being. These trends were the professional,domestic, relational, leisureand safety aspectsof daily life. As good sleepersare generally an unsurveyed category, a further major interest of this study wasthe comparisonof sucha large control group with a group of treated insomniacs.We decided to include in the good sleepergroup, people who had no or occasionally only one sleepdisturbance. This is becausewe think that peoplewho assertedthat they had no sleepdisturbances at all in the last 12 months(very good sleepers)did not reflect the general population of good sleepers,especially in the ageing population. Thus, when comparing the sleepobtained with zopiclone in insomniacs,with the sleepassertedby good sleepers,it wasinterestingto observethat there was no difference betweenthe two groups,apart from occasional difficulties falling asleep.Moreover, good sleepers seemedto have moreoccasionalawakeningsduring the night than zopiclone users.However this could be due to the fact that zopiclone users overestimated their

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sleep, in comparison with their previous situation without treatment. Concerning daytime alertness, the results of our study confirm the results of previous studies which showed that there was very little effect of the treatment on vigilance the day after and that alertness after treatment was comparable with that of placebo users. What was surprising was the prevalence of sleepiness and difficulties coping with alertness in the general population of good sleepers: 34% of good sleepers said they had difficulties doing continuous work and that they were tired; 30% that they had difficulties coping with daily tasks and that they felt lazy; and 38% had difficulties concentrating, memorising and maintaining their attention. These results cannot be related to bad sleep as a high percentage of people in the group asserted that their average total sleep time was at least 7 hours per night. Thus sleep deprivation could not be a cause of these symptoms of sleepiness and fatigue. We observed that in most cases, patients and good sleepers were equivalent in terms of quality of life, as far as we may conclude with a limited questionnaire. Some very important aspects such as sentimental life or professional life were not modified by the treatment. Insomnia, when it is treated appeared not to be prejudicial for patients regarding their own feeling about quality of life. It is, of course, important for daily tasks such as domestic ones or for professional activities. It is in addition more important for more sensitive aspects such as sentimental relations or fulability to meeting other people. One fear of patients about central nervous system treatments is, in fact, to have modified perceptions of their usual environment. Apparently, these first results showed that there was no difference between good sleepers and insomniacs treated by zopiclone. Quality of life obtained with the treatment has to be an important goal of new hypnotics. We analysed five aspects of the quality of life. It is of primary concern, to both patients and practitioners to know if these aspects are affected by zopiclone treatment. The risk of accidents related to sleepiness has been very well documented over these last years (Aldrich, 1989). Consequently sleepiness has not only individual consequences but also economical implications (Leger, 1994). One unanswered question is how hypnotics

er ul

could have an impact on the risk of accidents the day after. Some studies found a high percentage of injured drivers with benzodiazepines in their blood samples. On the other hand our study found that, when driving, zopiclone users appeared to relate less sleepiness at the wheel and fewer near accidents than good sleepers. This should be carefully interpreted and could be explained by a greater concern vis a vis sleepinessfrom insomniacsthan from good sleepers.However, it goes againstthe general point of view that insomniacsand people taking sleepingpills stand a greater risk of accidents (Balter er al, 1992). Finally, we mustinsiston the necessityof developing this type of study in order to appreciatethe real impact of neuropsychiatric treatmentson the quality of life of patients.From now on treatmentscannot be evaluated independently of daytime life. REFERENCES Addison RG, Thorpy MJ, Rochrs TA. Sleep: wake complaints in the general population. Sleep Res 199 I ;20: I I2 Aldrich MS. Automobile accidents in patients with sleep disorders. Sleep 1989; 12:487-94 Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its tteatment. J C[in Psychiurry 1992;53(suppl I2):34-9 Carskadon MA, Dement WC, Mitler MM. Self reports versu.r sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia. Am J Psychiutry 1976; 133: 1382-88 Gallop organization, Slee/r Lr Amerku. Princeton, NJ: The Gallop Organization. 199 I : I-30 Gillin JC, Byerley WF. Drug therapy: The diagnosis and management of insomnia. N I%$ J Med 1990;322:239-48 Goldenberg F, Hindmarch J. Joyce CRB, Le Gal M, Partinen M, Pilate C. Zopiclone, sleep and health-related quality of life. Hunun P.~ychophatmucol I994;9:245-52 Jenkins CD, Stanton BA, Niemcryk S, Rose RM. A scale for the estimation of sleep problems in clinical research. J Clin Epidemiol 1988;41:313-21 Johnson LC, Spinweber CL. Quality of sleep and performance in the Navy: a longitudinal study of good sleepers and poor sleepers. In: Guilleminault C. Lugaresi E. eds. Sleep-wclke Disorders: Nafurul History. Epidemiology. utld Long Term Evolution. New York: Raven Press, 1983; I3- I8 Kelly F, Delahaye C, Le Gal M. Quality of life and insomnia. Results of the validation studies for a specifically designed questionnaire. JAMA SE4 January 1993;suppl:21-6 tiger D. The cost of sleep-related accidents: a report for the National Commission on Sleep Disorders Research. Sleep 1994; 17:84-93 Mendelson WB, Gamett D, Linnoila M. Do insomniacs have impaired daytime functioning? Biol Psychicrfry 1984; 19: 1261-63