Br. J. clin. Pharmac. (1979), 8, 69S-72S
DOUBLE-BLIND EVALUATION OF THE SAFETY AND HYPNOTIC EFFICACY OF TEMAZEPAM IN INSOMNIAC OUTPATIENTS W.A. HEFFRON & P. ROTH Department of Family, Community and Emergency Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131
1 Efficacy of temazepam 30 mg at night as an hypnotic was compared with placebo in 55 out-patients with insomnia. The study was double blind, with two comparable groups of patients established by random allocation. Placebo and medication were taken for 4 consecutive nights and sleep questionnaires were completed the next day. 2 Patients reported that temazepam was more effective than placebo in reducing the difficulty of falling asleep and improving sleep maintenance. They also indicated that they awoke less and were less disturbed by early morning awakenings and reported as a group that the average duration of sleep was increased by 1 hour. 3 The patients receiving temazepam reported being more alert in the morning and for the entire day than with placebo.
Introduction THE objective of this study was to evaluate the efficacy and safety of temazepam as an hypnotic compared with placebo in outpatients with insomnia.
Methods The study involved 55 patients in a double-blind, parallel group design, patients being randomly assigned to either placebo at night (26 patients) or temazepam 30 mg at night (29 patients). Treatment was taken at bedtime for 4 consecutive nights and sleep questionnaires were completed by the patients the following day. Efficacy was based on the evaluation by the patients of the drug effect on the following variables: (1) Sleep induction was determined by answers to two questions: "How long did it take you to fall asleep last night?" and "Estimate the time it took to fall asleep." (2) Nocturnal awakenings were estimated by the question: "How often did you wake up last night after you fell asleep?". (3) An improvement in sleep maintenance was indicated by a reduction in nocturnal awakenings after the patient had fallen asleep. (4) The duration of sleep was based on the interval between the actual time of waking up in the morning and the actual time the patient went to bed the night before minus the time estimated by the patient taken to fall asleep after he went to bed. (5) Early morning awakenings were determined by the answers to the question: "Did you wake up earlier in 0306-5251/79/160069-04 $01.00
the morning than you had to and could not fall back to sleep again?" (6) For quality of sleep the patient answered the question: "How well did you sleep last night as compared to when you do not take any sleep medicine?" Both the patient and physician evaluated the general effectiveness of the study treatments compared with previous sleep medications used by the patient. The patient answered the question: "In general, is this medicine better or not better than the medicine you took before to help you sleep?". The physician at the end of the study gave an overall impression of the effect of the study medication on the insomnia of each patient, and also compared study medication with no previous medication and with the most effective previous medication used by the patient. Responses by the patients to two separate questions determined any possible residual effects ('hangover') of the study treatments: "How awake do you feel this morning as compared to when you do not take any sleep medicine?" and "How alert did you feel today as compared to when you do not take any sleep medicine?". Safety was assessed by initial and final evaluations of (1) physical and ophthalmological examinations; (2) changes in vital signs (blood pressure, radial pulse, temperature); and (3) laboratory investigations (haematology, CBC, platelets, blood chemistry and urinalysis). The incidence, type severity and duration of any possible adverse reaction encountered was recorded. © Macmillan Journals Ltd. 1979
70S
W.A. HEFFRON & P. ROTH
Results
severity of the insomnia was considered moderate in the majority of the patients (62%), severe in 29% and mild in 9%. There were no significant statistical differences between the treatment groups in the above characteristics except in the total sleep time per night. All patients had taken medication previously for their sleep disturbances. Thirty-one different substances had been used previously by the patients, the most frequent being diazepam and flurazepam. Generally, most patients using these drugs reported a fair to good effect on their insomnia. Temazepam improved sleep induction on all four study nights. This result correlated with the actual estimate of time to fall asleep, a mean of 44 min for temazepam and 82 min for placebo (Tables 1 and 2). Temazepam treatment was significantly more effective (P < 0.01 ) than placebo in reducing noctural awakenings on each of the four individual study
There was no significant statistical difference between the treatment groups for age, height, weight, sex or race based on a one-way analysis of variance. Twenty males and 35 females entered the study. Before treatment, patients reported sleeping for a mean of 4.4 h per night and all indicated not having sufficient sleep and feeling tired the following morning. Most of the patients (76%) reported a problem falling asleep which was associated with a mean induction of 1.8 hours. Frequent nocturnal awakenings were reported by 82% of the patients. Most of the patients reported awakenings one to three times per night; 82% were classified as having chronic insomnia, whereas only 13% were considered as having sporadic and 6% acute insomnia. The
Table 1 Mean values for sleep induction (patients asked to "estimate" the time taken to fall asleep by assigning a number) Treatment Groups
N 1
Placebo Temazepam *
P< 0.05;
* *
26 29
3.85 2.93*
2
3.92 2.76**
Mean valuest Study nights 3
3.58 2.93
4
3.96 2.76**
1-4
3.83 2.84**
P
DOUBLE-BLIND EVALUATION OF THE SAFETY AND HYPNOTIC EFFICACY OF TEMAZEPAM IN INSOMNIAC OUTPATIENTS W.A. HEFFRON & P. ROTH Department of Family, Community and Emergency Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131
1 Efficacy of temazepam 30 mg at night as an hypnotic was compared with placebo in 55 out-patients with insomnia. The study was double blind, with two comparable groups of patients established by random allocation. Placebo and medication were taken for 4 consecutive nights and sleep questionnaires were completed the next day. 2 Patients reported that temazepam was more effective than placebo in reducing the difficulty of falling asleep and improving sleep maintenance. They also indicated that they awoke less and were less disturbed by early morning awakenings and reported as a group that the average duration of sleep was increased by 1 hour. 3 The patients receiving temazepam reported being more alert in the morning and for the entire day than with placebo.
Introduction THE objective of this study was to evaluate the efficacy and safety of temazepam as an hypnotic compared with placebo in outpatients with insomnia.
Methods The study involved 55 patients in a double-blind, parallel group design, patients being randomly assigned to either placebo at night (26 patients) or temazepam 30 mg at night (29 patients). Treatment was taken at bedtime for 4 consecutive nights and sleep questionnaires were completed by the patients the following day. Efficacy was based on the evaluation by the patients of the drug effect on the following variables: (1) Sleep induction was determined by answers to two questions: "How long did it take you to fall asleep last night?" and "Estimate the time it took to fall asleep." (2) Nocturnal awakenings were estimated by the question: "How often did you wake up last night after you fell asleep?". (3) An improvement in sleep maintenance was indicated by a reduction in nocturnal awakenings after the patient had fallen asleep. (4) The duration of sleep was based on the interval between the actual time of waking up in the morning and the actual time the patient went to bed the night before minus the time estimated by the patient taken to fall asleep after he went to bed. (5) Early morning awakenings were determined by the answers to the question: "Did you wake up earlier in 0306-5251/79/160069-04 $01.00
the morning than you had to and could not fall back to sleep again?" (6) For quality of sleep the patient answered the question: "How well did you sleep last night as compared to when you do not take any sleep medicine?" Both the patient and physician evaluated the general effectiveness of the study treatments compared with previous sleep medications used by the patient. The patient answered the question: "In general, is this medicine better or not better than the medicine you took before to help you sleep?". The physician at the end of the study gave an overall impression of the effect of the study medication on the insomnia of each patient, and also compared study medication with no previous medication and with the most effective previous medication used by the patient. Responses by the patients to two separate questions determined any possible residual effects ('hangover') of the study treatments: "How awake do you feel this morning as compared to when you do not take any sleep medicine?" and "How alert did you feel today as compared to when you do not take any sleep medicine?". Safety was assessed by initial and final evaluations of (1) physical and ophthalmological examinations; (2) changes in vital signs (blood pressure, radial pulse, temperature); and (3) laboratory investigations (haematology, CBC, platelets, blood chemistry and urinalysis). The incidence, type severity and duration of any possible adverse reaction encountered was recorded. © Macmillan Journals Ltd. 1979
70S
W.A. HEFFRON & P. ROTH
Results
severity of the insomnia was considered moderate in the majority of the patients (62%), severe in 29% and mild in 9%. There were no significant statistical differences between the treatment groups in the above characteristics except in the total sleep time per night. All patients had taken medication previously for their sleep disturbances. Thirty-one different substances had been used previously by the patients, the most frequent being diazepam and flurazepam. Generally, most patients using these drugs reported a fair to good effect on their insomnia. Temazepam improved sleep induction on all four study nights. This result correlated with the actual estimate of time to fall asleep, a mean of 44 min for temazepam and 82 min for placebo (Tables 1 and 2). Temazepam treatment was significantly more effective (P < 0.01 ) than placebo in reducing noctural awakenings on each of the four individual study
There was no significant statistical difference between the treatment groups for age, height, weight, sex or race based on a one-way analysis of variance. Twenty males and 35 females entered the study. Before treatment, patients reported sleeping for a mean of 4.4 h per night and all indicated not having sufficient sleep and feeling tired the following morning. Most of the patients (76%) reported a problem falling asleep which was associated with a mean induction of 1.8 hours. Frequent nocturnal awakenings were reported by 82% of the patients. Most of the patients reported awakenings one to three times per night; 82% were classified as having chronic insomnia, whereas only 13% were considered as having sporadic and 6% acute insomnia. The
Table 1 Mean values for sleep induction (patients asked to "estimate" the time taken to fall asleep by assigning a number) Treatment Groups
N 1
Placebo Temazepam *
P< 0.05;
* *
26 29
3.85 2.93*
2
3.92 2.76**
Mean valuest Study nights 3
3.58 2.93
4
3.96 2.76**
1-4
3.83 2.84**
P
