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Current Medical Research and Opinion
Vol. 12, No. 6,1991
Temazepam ‘Planpak’: a multicentre general practice trial in planned benzodiazepine hypnotic withdrawal
J. Drake, M.B., Ch.B.
Curr. Med. Res. Opin., (1991), 12,390.
Received: 30th January 1991
Medical Department, Farmitalia Carlo Erba Ltd., St. Albans, England
Summary A trial was carried out in 44 patients to demonstrate the efficacy of planned
withdrawal of benzodiazepine hypnotics in general practice using Temazepam ‘Planpak’. The withdrawal period was 6 weeks during which time the dose of temazepam was reduced every 2 weeks from 10 mg to 5 mg to 2 mg. Patients were followed up f or between 3 and 6 months after withdrawal. Four patients failed to complete the withdrawalphase due to sleep disturbance. Adverse events reported were minor: Twenty-six (.59%)patients were able to sleep without a hypnotic after the Withdrawal phase. Patients on I0 mg temazepam on. entry into the trial had a higher success rate than those on 15 mg or20 mg nightly (p = 0.002). A t follow-up I2 to 3.5 weeks after completion of the trial, 52%of the patients who entered were sleeping without the use of a hypnotic. A patient management plan fo r hypnotic withdrawal is proposed. Key words: Temazepam - benzodiazepines - drug withdrawal symptoms general practice
Introduction Psychoactive compounds have been used by societies for numerous years in the promotion of better sleep and dependency has invariably been associated with their use. Benzodiazepine hypnotics have a favourable benefit-to-risk ratio and this may have led to overuse. Experience has taught prescribers to rationalize their use and patients to evaluate both the advantages and disadvantages of treatment with a hypnotic. King et aL4 in a study funded by the U.K. Department of Health found that 56% of patients taking a benzodiazepine liked taking them, described them as helpful and stated they “could not do without them”. The majority of patients were taking a hypnotic for sleep disturbance. It is unlikely, therefore, that ‘Pharmacological Calvini~m’~ is a practical solution to possible benzodiazepine dependency. Patients rightly demand a more holistic solution. Patients want their sleep disturbances treated without the risk of dependence. A solution could be Temazepam ‘Planpak‘ (‘Planpak’),a specially designed pack containing capsules of 10 mg, 5 mg and 2 mg temazepam which allow a single nightly dose for 14 days at each dose level, after which the patient receives no further medication. Correspondence to: Dr. John Drake, Medical Director, Farmitalia Carlo Erba (U.K.) Ltd., Italia House. 23 Grosvenor Road, St. Albans, Herts. ALl3AW, England
J. Drake
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 12/31/14 For personal use only.
This trial was designed to assess the efficacy in general practice of the fixed dose reduction scheme offered by ‘Planpak’ in benzodiazepine withdrawal. An open study was chosen because it was considered unethical to compare the use of ‘Planpak’ with abrupt withdrawal in view of the fact that 1 in 3 patients on benzodiazepines are at risk of experiencing a withdrawal reaction.6
Patients and methods Patients who wished to stop hypnotic therapy were eligible for the study if they had been taking a benzodiazepine hypnotic for at least 3 months of which at least 1 month must have been with temazepam in a dose range of 10 mg to 20 mg nightly prior to entering the study. Patients were excluded if they had a serious medical or active psychiatric condition, a history of benzodiazepine or alcohol abuse in the previous year, were taking centrally active drugs other than temazepam within 28 days of entry, or were taking a nightly dose of temazepam in excess of 20 mg. Eight general practitioners treated 44 patients (27 females and 17 males) of median age 56 years (range 21 to 78 years) with a 42-day course of a fixed dose reduction of temazepam (‘Planpak’) after which time the patients were followed up for a period of between 3 to 6 months. Sixteen of the patients were retired, 13 were housewives, 11 were in employment and 4 were unemployed. Twenty-three patientsdid not takealcohol, 16drank alittle,2drank moderately and the statusof 3 was not recorded. Thirty patients did not smoke, 4 smoked less than 10cigarettes per day, 7 smoked 10 to 20 per day and 3 smoked more than 20 per day. Patients gave informed consent to participate in the study after an explanation of the trial and were then given a booklet explaining ‘Planpak’ and giving sleep hygiene information. Patients were free to withdraw from the trial at any time and they were given a 24-hour telephone number where advice would be available if needed. At the first visit (Day 0), demographic data and information on duration and quality of sleep were recorded. ‘Planpak’ treatment was started on the night of Day 0. During the trial each patient returned to the surgery for four assessments. Visits 2 to 4 coincided with the end of the first week of each new dose of temazepam, and Visit 5 with the end of treatment. On Visits 2 (7 days),3 (21 days) and 4 (35 days), sleep and mood during the previous week were assessed to detect any significant withdrawal symptoms. The assessments were made on a 5-point scale and graded as much better than usual, better than usual, same as usual, worse than usual, much worse than usual. On Visit 5 (42 days) the patients were asked to rate ‘Planpak’ as helpful or unhelpful, whether they had changed their smoking or drinking pattern, and whether they were prepared to sleep without medication. The investigators were asked to assess ‘Planpak’ as successful or unsuccessful and to state whether any additional hypnotic medication was to be prescribed. Adverse events were solicited and compliance checked at each visit. A follow-up questionnaire for each patient was completed by the investigators between 3 and 6 months after Visit 5 to establish the current status of the patient with regard to hypnotic taking for any reason. 39 1
Temazepam ‘Planpak’: a multi-centre general practice trial in planned benzodiazepine hypnotic withdrawal
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Results The group of 44 heterogeneous patients had a median time of benzodiazepine usage of 19.5 months (range 3 months to 20 years) and a median time of temazepam usage of 12 months (range 2 months to 8 years). The dose distribution of temazepam on entry was 27 patients taking 10 mg nightly, 4 taking 15 mg, and 13 taking 20 mg. All patients had a sleep disturbance. Forty-one patients slept for 6 hours or more and 37 patients were satisfied with the quality of their sleep. At Visit 2,38 patients rated their sleep as much better, better or the same as the previous week. At Visits 3 and 4, the respective numbers were 29 and 26. Daytime mood was rated as much better, better or the same at Visit 2 by 40 patients and by 39 and 33, respectively. at Visits 3 and 4. On the final visit, 29 (66%)of patients rated ‘Planpak’ as helpful while 15 did not. Of the 29 who rated ‘Planpak’ as helpful, only 3 had experienced a minor sleep disturbance during the withdrawal phase whereas of the 15 who were not helped, 4 withdrew because of sleep disturbance and the other 11 all experienced a change in sleep pattern. Twenty-six (59%)patients were not given a prescription for a hypnotic at the end of the 6 weeks. Fourteen (32%)were given a prescription for temazepam in the range of 10 to 20 mg nightly. Only 6 (22%)of the 27 patients taking 10 mg nightly on entry were given a prescription whereas 12 (71%)of the 17 on 15 to 20 mg nightly were given a prescription. This difference is statistically significant (p =0.002, ?I 2-test). Three patients changed their smoking or alcohol pattern during the 6 weeks. One patient stopped smoking, another reduced the number of cigarettes smoked and the third stopped drinking. Twelve patients reported an adverse event during the treatment phase, namely;. 8 reported sleep disturbances of whom 4 withdrew, 1 had an urinary tract infection, I an asthma attack, 1 felt ‘shaky in the day’ and 1 experienced a sore throat in the mornings. Follow-up questionnaires were returned for all patients. five of the 26 who had successfully completed ‘Planpak’ required further treatment with a hypnotic for t h e following reasons; 2 inability to sleep, 1 bereavement, 1 anxious about husband’s health, and the other was unable to cope after a holiday. Two patients who had been ’Planpak’ failures managed to stop, a further 2 tried to give up and failed and 5, including the 2 who had tried, were willing to try and stop at a future date. Overall, 23 (52%)of those patients who entered the study were hypnotic-free at a period of between 3 and 6 months after the end of ‘Planpak’treatment.
Discussion The success rate in this multi-centre general practice trial was 52% of patients free of hypnotics, after the planned dose reduction using Temazepam ‘Planpak’, at between 3 to 6 months following completion of the withdrawal phase. These data support the findings of Hopkins et aL2 who, in a single practice, obtained a success 392
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J. Drake
rate of 58% at 3 months after a 6-week dose reduction. However, Patterson5 in a single practice obtained a success rate of 92% at 6 months after using Temazepam ‘Planpak’. Cormack et al.’ in a benzodiazepine withdrawal study with many patients taking high doses, and not using a planned dose reduction, obtained only a 23% success rate but this was a ‘minimal intervention’ study in which the patients were merely asked by letter or interview to reduce their medication. In the present study, 9% of patients experienced a significant withdrawal reaction even though the entry dose of 20 mg temazepam was not exceeded in the 28 days prior to entry. This figure is considerably lower than abrupt withdrawal in which Tyrer6 has estimated 1 in 3 patients will experience withdrawal effects. However, like Cormack et al.’ these data support the view that the dose of benzodiazepine should be reduced to as low as possible before withdrawal is started. Withdrawal of benzodiazepine in this trial did not switch dependency to alcohol or smoking. The data would support the view that agreed goal setting with the patient and support is beneficial in achieving successful withdrawal. The findings in this trial lead to the following recommendations. Erst, patients taking temazepam for long periods in doses above 20 mg nightly should reduce gradually to a dose of between 10 to 20 mg before starting the ‘Planpak’ regimen. Secondly, ‘Planpak’ is likely to be successful if the patient and doctor are committed to stopping benzodiazepine medication, and thirdly that support with planned regular short visits and open access to advice during the withdrawal period may be helpful. This management plan is likely to achieve a success rate of over 50%, leading to a cost saving of about 25% per year of the hypnotic drugs bill and an improved quality of life for the patients. Acknowledgements The following general practitioners participated in the trial: Drs. P. Bernard, West Kirby; C. Chandani, Rothwell, Leeds; N. Chapman, Saxilby, Lincoln; A. Garrow, Newark; B. Hamilton, Stanstead; D. Haworth. Blackpool; H. Richards, Brighton; and D. Wheatcroft, Letchworth. The trial was co-ordinated by Medical Monitoring & Research Ltd., Hertford and data statistical analysis was carried out by S. Kimber, M.I.S. References 1. Cormack, M. A., Owens, R. G., and Dewey, M. E., (1989). The effect of minimal interventions by general practitioners on long-term benzodiazepine use. J. R. Coll. Gen. Pract., 39, 408-411. 2. Hopkins, D. R., Sethi, K. B., and Mucklow, J. C., (1982). Benzodiazepine withdrawal in general practice. J. R. Coll. Gen. Pract., 32,758-762. 3. Klerman, G. L., (1971). Drugs and social values. f n t . J. Addict., 5,313-319. 4. King, M. B., Gabe, J., Williams, P., and Rodrigo, E. K., (1990). Long term use of benzodiazepines: the view of patients. BEJ. Gen. Pract., 40, 194-196. 5. Patterson, R., (1989).Using a commercial reduction pack. Mod. Med., 34,2930. 6 . Tyrer, P. J., (1988). Dependence as a limitingfactor in the clinical use of minor tranquillisers. Pharrnacol. Ther:.36, 173-188.
393
Current Medical Research and Opinion
Vol. 12, No. 6,1991
Temazepam ‘Planpak’: a multicentre general practice trial in planned benzodiazepine hypnotic withdrawal
J. Drake, M.B., Ch.B.
Curr. Med. Res. Opin., (1991), 12,390.
Received: 30th January 1991
Medical Department, Farmitalia Carlo Erba Ltd., St. Albans, England
Summary A trial was carried out in 44 patients to demonstrate the efficacy of planned
withdrawal of benzodiazepine hypnotics in general practice using Temazepam ‘Planpak’. The withdrawal period was 6 weeks during which time the dose of temazepam was reduced every 2 weeks from 10 mg to 5 mg to 2 mg. Patients were followed up f or between 3 and 6 months after withdrawal. Four patients failed to complete the withdrawalphase due to sleep disturbance. Adverse events reported were minor: Twenty-six (.59%)patients were able to sleep without a hypnotic after the Withdrawal phase. Patients on I0 mg temazepam on. entry into the trial had a higher success rate than those on 15 mg or20 mg nightly (p = 0.002). A t follow-up I2 to 3.5 weeks after completion of the trial, 52%of the patients who entered were sleeping without the use of a hypnotic. A patient management plan fo r hypnotic withdrawal is proposed. Key words: Temazepam - benzodiazepines - drug withdrawal symptoms general practice
Introduction Psychoactive compounds have been used by societies for numerous years in the promotion of better sleep and dependency has invariably been associated with their use. Benzodiazepine hypnotics have a favourable benefit-to-risk ratio and this may have led to overuse. Experience has taught prescribers to rationalize their use and patients to evaluate both the advantages and disadvantages of treatment with a hypnotic. King et aL4 in a study funded by the U.K. Department of Health found that 56% of patients taking a benzodiazepine liked taking them, described them as helpful and stated they “could not do without them”. The majority of patients were taking a hypnotic for sleep disturbance. It is unlikely, therefore, that ‘Pharmacological Calvini~m’~ is a practical solution to possible benzodiazepine dependency. Patients rightly demand a more holistic solution. Patients want their sleep disturbances treated without the risk of dependence. A solution could be Temazepam ‘Planpak‘ (‘Planpak’),a specially designed pack containing capsules of 10 mg, 5 mg and 2 mg temazepam which allow a single nightly dose for 14 days at each dose level, after which the patient receives no further medication. Correspondence to: Dr. John Drake, Medical Director, Farmitalia Carlo Erba (U.K.) Ltd., Italia House. 23 Grosvenor Road, St. Albans, Herts. ALl3AW, England
J. Drake
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 12/31/14 For personal use only.
This trial was designed to assess the efficacy in general practice of the fixed dose reduction scheme offered by ‘Planpak’ in benzodiazepine withdrawal. An open study was chosen because it was considered unethical to compare the use of ‘Planpak’ with abrupt withdrawal in view of the fact that 1 in 3 patients on benzodiazepines are at risk of experiencing a withdrawal reaction.6
Patients and methods Patients who wished to stop hypnotic therapy were eligible for the study if they had been taking a benzodiazepine hypnotic for at least 3 months of which at least 1 month must have been with temazepam in a dose range of 10 mg to 20 mg nightly prior to entering the study. Patients were excluded if they had a serious medical or active psychiatric condition, a history of benzodiazepine or alcohol abuse in the previous year, were taking centrally active drugs other than temazepam within 28 days of entry, or were taking a nightly dose of temazepam in excess of 20 mg. Eight general practitioners treated 44 patients (27 females and 17 males) of median age 56 years (range 21 to 78 years) with a 42-day course of a fixed dose reduction of temazepam (‘Planpak’) after which time the patients were followed up for a period of between 3 to 6 months. Sixteen of the patients were retired, 13 were housewives, 11 were in employment and 4 were unemployed. Twenty-three patientsdid not takealcohol, 16drank alittle,2drank moderately and the statusof 3 was not recorded. Thirty patients did not smoke, 4 smoked less than 10cigarettes per day, 7 smoked 10 to 20 per day and 3 smoked more than 20 per day. Patients gave informed consent to participate in the study after an explanation of the trial and were then given a booklet explaining ‘Planpak’ and giving sleep hygiene information. Patients were free to withdraw from the trial at any time and they were given a 24-hour telephone number where advice would be available if needed. At the first visit (Day 0), demographic data and information on duration and quality of sleep were recorded. ‘Planpak’ treatment was started on the night of Day 0. During the trial each patient returned to the surgery for four assessments. Visits 2 to 4 coincided with the end of the first week of each new dose of temazepam, and Visit 5 with the end of treatment. On Visits 2 (7 days),3 (21 days) and 4 (35 days), sleep and mood during the previous week were assessed to detect any significant withdrawal symptoms. The assessments were made on a 5-point scale and graded as much better than usual, better than usual, same as usual, worse than usual, much worse than usual. On Visit 5 (42 days) the patients were asked to rate ‘Planpak’ as helpful or unhelpful, whether they had changed their smoking or drinking pattern, and whether they were prepared to sleep without medication. The investigators were asked to assess ‘Planpak’ as successful or unsuccessful and to state whether any additional hypnotic medication was to be prescribed. Adverse events were solicited and compliance checked at each visit. A follow-up questionnaire for each patient was completed by the investigators between 3 and 6 months after Visit 5 to establish the current status of the patient with regard to hypnotic taking for any reason. 39 1
Temazepam ‘Planpak’: a multi-centre general practice trial in planned benzodiazepine hypnotic withdrawal
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 12/31/14 For personal use only.
Results The group of 44 heterogeneous patients had a median time of benzodiazepine usage of 19.5 months (range 3 months to 20 years) and a median time of temazepam usage of 12 months (range 2 months to 8 years). The dose distribution of temazepam on entry was 27 patients taking 10 mg nightly, 4 taking 15 mg, and 13 taking 20 mg. All patients had a sleep disturbance. Forty-one patients slept for 6 hours or more and 37 patients were satisfied with the quality of their sleep. At Visit 2,38 patients rated their sleep as much better, better or the same as the previous week. At Visits 3 and 4, the respective numbers were 29 and 26. Daytime mood was rated as much better, better or the same at Visit 2 by 40 patients and by 39 and 33, respectively. at Visits 3 and 4. On the final visit, 29 (66%)of patients rated ‘Planpak’ as helpful while 15 did not. Of the 29 who rated ‘Planpak’ as helpful, only 3 had experienced a minor sleep disturbance during the withdrawal phase whereas of the 15 who were not helped, 4 withdrew because of sleep disturbance and the other 11 all experienced a change in sleep pattern. Twenty-six (59%)patients were not given a prescription for a hypnotic at the end of the 6 weeks. Fourteen (32%)were given a prescription for temazepam in the range of 10 to 20 mg nightly. Only 6 (22%)of the 27 patients taking 10 mg nightly on entry were given a prescription whereas 12 (71%)of the 17 on 15 to 20 mg nightly were given a prescription. This difference is statistically significant (p =0.002, ?I 2-test). Three patients changed their smoking or alcohol pattern during the 6 weeks. One patient stopped smoking, another reduced the number of cigarettes smoked and the third stopped drinking. Twelve patients reported an adverse event during the treatment phase, namely;. 8 reported sleep disturbances of whom 4 withdrew, 1 had an urinary tract infection, I an asthma attack, 1 felt ‘shaky in the day’ and 1 experienced a sore throat in the mornings. Follow-up questionnaires were returned for all patients. five of the 26 who had successfully completed ‘Planpak’ required further treatment with a hypnotic for t h e following reasons; 2 inability to sleep, 1 bereavement, 1 anxious about husband’s health, and the other was unable to cope after a holiday. Two patients who had been ’Planpak’ failures managed to stop, a further 2 tried to give up and failed and 5, including the 2 who had tried, were willing to try and stop at a future date. Overall, 23 (52%)of those patients who entered the study were hypnotic-free at a period of between 3 and 6 months after the end of ‘Planpak’treatment.
Discussion The success rate in this multi-centre general practice trial was 52% of patients free of hypnotics, after the planned dose reduction using Temazepam ‘Planpak’, at between 3 to 6 months following completion of the withdrawal phase. These data support the findings of Hopkins et aL2 who, in a single practice, obtained a success 392
Curr Med Res Opin Downloaded from informahealthcare.com by Washington University Library on 12/31/14 For personal use only.
J. Drake
rate of 58% at 3 months after a 6-week dose reduction. However, Patterson5 in a single practice obtained a success rate of 92% at 6 months after using Temazepam ‘Planpak’. Cormack et al.’ in a benzodiazepine withdrawal study with many patients taking high doses, and not using a planned dose reduction, obtained only a 23% success rate but this was a ‘minimal intervention’ study in which the patients were merely asked by letter or interview to reduce their medication. In the present study, 9% of patients experienced a significant withdrawal reaction even though the entry dose of 20 mg temazepam was not exceeded in the 28 days prior to entry. This figure is considerably lower than abrupt withdrawal in which Tyrer6 has estimated 1 in 3 patients will experience withdrawal effects. However, like Cormack et al.’ these data support the view that the dose of benzodiazepine should be reduced to as low as possible before withdrawal is started. Withdrawal of benzodiazepine in this trial did not switch dependency to alcohol or smoking. The data would support the view that agreed goal setting with the patient and support is beneficial in achieving successful withdrawal. The findings in this trial lead to the following recommendations. Erst, patients taking temazepam for long periods in doses above 20 mg nightly should reduce gradually to a dose of between 10 to 20 mg before starting the ‘Planpak’ regimen. Secondly, ‘Planpak’ is likely to be successful if the patient and doctor are committed to stopping benzodiazepine medication, and thirdly that support with planned regular short visits and open access to advice during the withdrawal period may be helpful. This management plan is likely to achieve a success rate of over 50%, leading to a cost saving of about 25% per year of the hypnotic drugs bill and an improved quality of life for the patients. Acknowledgements The following general practitioners participated in the trial: Drs. P. Bernard, West Kirby; C. Chandani, Rothwell, Leeds; N. Chapman, Saxilby, Lincoln; A. Garrow, Newark; B. Hamilton, Stanstead; D. Haworth. Blackpool; H. Richards, Brighton; and D. Wheatcroft, Letchworth. The trial was co-ordinated by Medical Monitoring & Research Ltd., Hertford and data statistical analysis was carried out by S. Kimber, M.I.S. References 1. Cormack, M. A., Owens, R. G., and Dewey, M. E., (1989). The effect of minimal interventions by general practitioners on long-term benzodiazepine use. J. R. Coll. Gen. Pract., 39, 408-411. 2. Hopkins, D. R., Sethi, K. B., and Mucklow, J. C., (1982). Benzodiazepine withdrawal in general practice. J. R. Coll. Gen. Pract., 32,758-762. 3. Klerman, G. L., (1971). Drugs and social values. f n t . J. Addict., 5,313-319. 4. King, M. B., Gabe, J., Williams, P., and Rodrigo, E. K., (1990). Long term use of benzodiazepines: the view of patients. BEJ. Gen. Pract., 40, 194-196. 5. Patterson, R., (1989).Using a commercial reduction pack. Mod. Med., 34,2930. 6 . Tyrer, P. J., (1988). Dependence as a limitingfactor in the clinical use of minor tranquillisers. Pharrnacol. Ther:.36, 173-188.
393
