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Current Medical Research and Opinion
Vol. 6, No. 4, 1979
Treatment of anxietyrelated insomnia with chlormezanone
G . Ali-Khan, M.B., B.S.
Cum. Med. Res. Opin., (1979). 6,259.
Gravesend, England
Received : 25th January 1979
Summary Twenty-nine patients seen in general practice suffering from sleep disturbance due to mild neurotic anxiety were treated with 400 mg chlormezanone per night for 2 weeks. Patients' and doctors' assessments of quality of sleep and Hamilton anxiety rating scores were carried out initially andajier 1 and 2 weeks. Patients also completeda daily record card assessing their sleep. The results suggest that chlormezanone produced prompt improvement within 2 nights of the start of treatment, and by the end of the study periodonly 2 (7 %)patientsstill reported their sleep as being poor compared with 80 % initially, and I9 (66 %>rated their sleep as good or excellent. There was a steady reduction in anxiety rating scores throughout treatment. Only I patient reported a fransient mild side-effect. Key words: Chlormezanone - insomnia - neuroses, anxiety
Introduction One of the commonest causes of insomnia is anxiety. In some cases this is an acute normal reaction to a situation of stress. However, many patients with a permanent worrying, anxious type of personality become chronic sufferers from insomnia and in this type of patient it is important to steer them away from habituation to hypnotic drugs. It was decided, therefore, to carry out a multicentre open evaluation in general practice to assess the efficacy of chlormezanonet, a drug with anxiolytic and muscle relaxant properties,' in relieving anxiety and associated insomnia.
Patients and methods Informed consentingadults of either sex sufferingfrom sleep disturbance due to mild neurotic anxietywho were not receivingcurrent treatment were included in the study. The followingpatients were excluded :those under 18or over 80 years, those weighing less than 50 kg or more than 110 kg, pregnant patients, those with known renal or hepatic impairment, cardiovascular disease, confusional states or other psychiatric conditions,those taking monoamine oxidase inhibitors,phenothiazines,tranquillizers or hypnotics, and those unwilling to abstain from alcohol during the study period. Patients received 2 chlormezanone tablets (200 mg chlormezanone) nightly for 2 weeks. Assessments were carried out initially and after 1 and 2 weeks of treatment. T'Trancopal', trade mark Winthrop 259
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
Treatment of anxiety-relatedinsomnia with chlormezanone
The Hamilton rating scale was used to assess anxiety and patients rated their sleep on a 4-point scale (0 =poor, 1 =fair, 2 =good, and 3 =excellent). At the follow-up assessments, both patient and doctor recorded the effectiveness of treatment on a similar 4-point scale and any side-effects volunteered in response to the standard question “How is the treatment suiting you ?” were recorded. In addition to these weekly assessments, the patient completed a daily record of the quality of sleep using the same scale as above. Statistical comparisons were made using the non-parametric Mann Whitney U-test.
Results A total of 32 patients entered the study but 3 were excluded from analysis as they were found not to have fulfilled the criteria for entry. There were 19 females and 10 males with a mean age of 49.5 years (range 24 to 72 years). Table I shows the patients’ weekly sleep ratings during the course of the study. It Table I. Patients’ assessment of quality of sleep before and after treatment with chlomezanone: 29 patients Assessment
Poor
Fair
Good
Excellent
Initial Day 7 Day 14
23 2 2
4 14 8
10 16
3 3
Not stated
Mean rating score
2
0.15
1.48 1.69
Figure 1. Patimts’ nightly assessment of sleep: mean rating scores for 24 patients
-1 r
c
/.
-
Female (n
Time (d;l>s) Note: 5 patients did not complete their daily diary for the complete trial period
260
16)
: -
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
G. Ali-Khan
can be seen that by Day 14, only 2 (7 %) patients still reported poor sleep compared with 80 % initially and 19 (66 %) patients rated their sleep as good or excellent. Patients’ nightly sleep assessments are shown in Figure 1. It can be seen that the response to treatment was rapid, occurring within the first 2 nights of treatment. The mean values for the Hamilton anxiety rating scale are shown in Figure 2. There was a steady reduction in anxiety throughout the course of the study. Figure 2. Hamiiton rating scale for anxiety: mean scores for 29 patients 14.0-
12.010.0-
;
x.0-
,J
-
0.0-
/
.4.0-
I
x -- - - x
Male (n = 10)
x----K
Female (11 = 19)
I Day 7
Initial
I
Day 14
Time o f assessment
Patients’ and doctors’ ratings of effectivenessare shown in Table 11. In the majority of cases the treatment was rated as good or excellent by both patient and doctor. Table II. Docton’ and patients’overall assessment of effectiveness of treatment: 29 patknts Assessment
Poor
Fair
Good
Excellent
Mean rating
score Doctors Day 7 Day 14
1 2
16 12
11 13
1 2
1.41 1.52
3 4
12
11 15
3 3
1.48 1.59
Patients
Day 7 Day 14
7
Only 1 patient reported a side-effect during treatment, stating that she ‘felt a little high after the first 2 days of taking the tablets’. 261
Treatment of anxiety-related insomnia with chlormezanone
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
Discussion The results of this study in a small group of patients seen in general practice suggests that chlormezanone is effective in reducing anxiety and improving sleep in patients with anxiety-related insomnia. It was found to be effective within the first 2 nights of treatment and, in more than half the cases treated, both doctor and patient rated effectiveness as good or excellent. Whilst we appreciate the limitations of open assessments such as this and realize that this study does not identify any placebo component in the response, our findings support those of a recently published double-blind, placebo controlled study2 which found that chlormezanone was effective and well tolerated, significantly improving sleep and daytime anxiety in patients with sleep disturbances due to neurotic anxiety. Anxiety states with related insomnia are seen all too frequently by most general practitioners, and we would suggest that chlormezanone has a useful role to play in the treatment of such patients.
Acknowledgements Thanks are due to the following doctors who contributed to this study: D. W. Baldwin, Brighouse; R.Hully, Stoke-on-Trent ;and G. Khan, Skelmersdale.
References 1. Ganz, S. E., (1959). Clinical evaluation of a new muscle relaxant (chlorrnezanone). J. Indiana State Med. Assoc., 52, 1134. 2. Warnock, J. M. T., (1978). A controlled study of Trancopal in the treatment of sleep disturbances due to anxiety. J. Znt. Med. Res., 6, 115.
262
Current Medical Research and Opinion
Vol. 6, No. 4, 1979
Treatment of anxietyrelated insomnia with chlormezanone
G . Ali-Khan, M.B., B.S.
Cum. Med. Res. Opin., (1979). 6,259.
Gravesend, England
Received : 25th January 1979
Summary Twenty-nine patients seen in general practice suffering from sleep disturbance due to mild neurotic anxiety were treated with 400 mg chlormezanone per night for 2 weeks. Patients' and doctors' assessments of quality of sleep and Hamilton anxiety rating scores were carried out initially andajier 1 and 2 weeks. Patients also completeda daily record card assessing their sleep. The results suggest that chlormezanone produced prompt improvement within 2 nights of the start of treatment, and by the end of the study periodonly 2 (7 %)patientsstill reported their sleep as being poor compared with 80 % initially, and I9 (66 %>rated their sleep as good or excellent. There was a steady reduction in anxiety rating scores throughout treatment. Only I patient reported a fransient mild side-effect. Key words: Chlormezanone - insomnia - neuroses, anxiety
Introduction One of the commonest causes of insomnia is anxiety. In some cases this is an acute normal reaction to a situation of stress. However, many patients with a permanent worrying, anxious type of personality become chronic sufferers from insomnia and in this type of patient it is important to steer them away from habituation to hypnotic drugs. It was decided, therefore, to carry out a multicentre open evaluation in general practice to assess the efficacy of chlormezanonet, a drug with anxiolytic and muscle relaxant properties,' in relieving anxiety and associated insomnia.
Patients and methods Informed consentingadults of either sex sufferingfrom sleep disturbance due to mild neurotic anxietywho were not receivingcurrent treatment were included in the study. The followingpatients were excluded :those under 18or over 80 years, those weighing less than 50 kg or more than 110 kg, pregnant patients, those with known renal or hepatic impairment, cardiovascular disease, confusional states or other psychiatric conditions,those taking monoamine oxidase inhibitors,phenothiazines,tranquillizers or hypnotics, and those unwilling to abstain from alcohol during the study period. Patients received 2 chlormezanone tablets (200 mg chlormezanone) nightly for 2 weeks. Assessments were carried out initially and after 1 and 2 weeks of treatment. T'Trancopal', trade mark Winthrop 259
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
Treatment of anxiety-relatedinsomnia with chlormezanone
The Hamilton rating scale was used to assess anxiety and patients rated their sleep on a 4-point scale (0 =poor, 1 =fair, 2 =good, and 3 =excellent). At the follow-up assessments, both patient and doctor recorded the effectiveness of treatment on a similar 4-point scale and any side-effects volunteered in response to the standard question “How is the treatment suiting you ?” were recorded. In addition to these weekly assessments, the patient completed a daily record of the quality of sleep using the same scale as above. Statistical comparisons were made using the non-parametric Mann Whitney U-test.
Results A total of 32 patients entered the study but 3 were excluded from analysis as they were found not to have fulfilled the criteria for entry. There were 19 females and 10 males with a mean age of 49.5 years (range 24 to 72 years). Table I shows the patients’ weekly sleep ratings during the course of the study. It Table I. Patients’ assessment of quality of sleep before and after treatment with chlomezanone: 29 patients Assessment
Poor
Fair
Good
Excellent
Initial Day 7 Day 14
23 2 2
4 14 8
10 16
3 3
Not stated
Mean rating score
2
0.15
1.48 1.69
Figure 1. Patimts’ nightly assessment of sleep: mean rating scores for 24 patients
-1 r
c
/.
-
Female (n
Time (d;l>s) Note: 5 patients did not complete their daily diary for the complete trial period
260
16)
: -
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
G. Ali-Khan
can be seen that by Day 14, only 2 (7 %) patients still reported poor sleep compared with 80 % initially and 19 (66 %) patients rated their sleep as good or excellent. Patients’ nightly sleep assessments are shown in Figure 1. It can be seen that the response to treatment was rapid, occurring within the first 2 nights of treatment. The mean values for the Hamilton anxiety rating scale are shown in Figure 2. There was a steady reduction in anxiety throughout the course of the study. Figure 2. Hamiiton rating scale for anxiety: mean scores for 29 patients 14.0-
12.010.0-
;
x.0-
,J
-
0.0-
/
.4.0-
I
x -- - - x
Male (n = 10)
x----K
Female (11 = 19)
I Day 7
Initial
I
Day 14
Time o f assessment
Patients’ and doctors’ ratings of effectivenessare shown in Table 11. In the majority of cases the treatment was rated as good or excellent by both patient and doctor. Table II. Docton’ and patients’overall assessment of effectiveness of treatment: 29 patknts Assessment
Poor
Fair
Good
Excellent
Mean rating
score Doctors Day 7 Day 14
1 2
16 12
11 13
1 2
1.41 1.52
3 4
12
11 15
3 3
1.48 1.59
Patients
Day 7 Day 14
7
Only 1 patient reported a side-effect during treatment, stating that she ‘felt a little high after the first 2 days of taking the tablets’. 261
Treatment of anxiety-related insomnia with chlormezanone
Curr Med Res Opin Downloaded from informahealthcare.com by Wake Forest University School of Medicine on 01/07/15 For personal use only.
Discussion The results of this study in a small group of patients seen in general practice suggests that chlormezanone is effective in reducing anxiety and improving sleep in patients with anxiety-related insomnia. It was found to be effective within the first 2 nights of treatment and, in more than half the cases treated, both doctor and patient rated effectiveness as good or excellent. Whilst we appreciate the limitations of open assessments such as this and realize that this study does not identify any placebo component in the response, our findings support those of a recently published double-blind, placebo controlled study2 which found that chlormezanone was effective and well tolerated, significantly improving sleep and daytime anxiety in patients with sleep disturbances due to neurotic anxiety. Anxiety states with related insomnia are seen all too frequently by most general practitioners, and we would suggest that chlormezanone has a useful role to play in the treatment of such patients.
Acknowledgements Thanks are due to the following doctors who contributed to this study: D. W. Baldwin, Brighouse; R.Hully, Stoke-on-Trent ;and G. Khan, Skelmersdale.
References 1. Ganz, S. E., (1959). Clinical evaluation of a new muscle relaxant (chlorrnezanone). J. Indiana State Med. Assoc., 52, 1134. 2. Warnock, J. M. T., (1978). A controlled study of Trancopal in the treatment of sleep disturbances due to anxiety. J. Znt. Med. Res., 6, 115.
262
