- Email: [email protected]
Treatment of insomnia
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE
e-mail submissions to [email protected]
Insurance agreement to facilitate genetic testing Sir—A major objection to communitywide introduction of predictive genetic screening for serious diseases is the potential for discrimination by insurance companies.1 If discrimination is likely to result, many people will refuse genetic testing even if it is in their clinical interest. Most cases of haemochromatosis, a genetically inherited iron-overload disease, are due to homozygosity for one mutation, C282Y, in the HFE gene.2 People at high risk of developing the disease (up to one per 200 population in Australia)3 can be identified by DNA testing. In C282Y homozygous individuals, venesection prevents the iron accumulation that causes pathology, as well as providing donor blood to the community.4 Despite this successful treatment, concerns have been raised that if a person has this genetic predisposition, they may be subject to insurance premium loading.1,5 In Australia, unlike in the USA, insurance companies are bound by law to provide health insurance at one rate to all (community loading), and, therefore, only life insurance is open to discrimination. We were concerned about this issue when introducing a pilot genetic screening programme for haemochromatosis in Melbourne, Australia. We approached the umbrella organisation for life and disability insurance companies in Australia, the Investment and Financial Services Association. They agreed to the following assurances for life-insurance policies for people undergoing genetic screening for haemochromatosis. People who are not C282Y homozygous are guaranteed to have no insurance loadings on the basis of this genetic test. For C282Y homozygotes, those with normal iron indices will obtain insurance at baseline rates with no
conditions on the policy based on the genetic result; those with raised iron indices but no evidence of organ damage will be required to show evidence that steps are being taken to normalise iron indices and the policy will be issued at baseline rates when iron indices become normal; and those with raised iron indices and existing organ damage will be penalised if obtaining new policies, but insurance companies will comment that testing is desirable since treatment will keep disease progress to a minimum. We believe that this agreement represents a major step forward in dealing with the issue of genetic testing and insurance. Agreement between the medical and scientific community and the insurance industry is in the best interest of people who choose to have genetic testing and will be of increasing importance as more genetic markers that indicate predisposition to preventable disorders are described. *Martin Delatycki, Katrina Allen, Robert Williamson Murdoch Children’s Research Institute and Genetic Health Services Victoria, Royal Children’s Hospital, Parkville, Victoria 3052, Australia (e-mail: [email protected]) 1
2
3
4
5
Barash CI. Genetic discrimination and screening for hemochromatosis: then and now. Genet Test 2000; 4: 213–18. Powell LW, Subramaniam VN, Yapp TR. Haemochromatosis in the new millennium. J Hepatol 2000; 32: 48–62. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A populationbased study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341: 718–24. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996; 110: 1107–19. Motulsky AG, Beutler E. Population screening in hereditary hemochromatosis. Ann Rev Public Health 2000; 21: 65–79.
THE LANCET • Vol 359 • April 20, 2002 • www.thelancet.com
Treatment of insomnia Sir—In his review of insomnia, Charles George (Nov 10 p 1623)1 writes as if the disorder is a clinical entity in its own right; it may be, but only rarely. Pharmacological treatment has an important role, but that role is limited and, in my view, that should have been stated. George writes that insomnia may also be associated with tiredness, lack of energy, difficulty in concentrating, and irritability and mood change. In fact, insomnia with all these symptoms (any one of which may be more prominent than the others) constitutes a syndrome for which the cause must be sought before treatment can be given. The most common causes are mood disorders, either primary or the result of adverse events, or of excessive alcohol consumption, most frequently not amounting to alcohol abuse. It is these disorders that probably cost the quoted figure of US$13 billion per year and their treatment should be that of the cause, not of the insomnia. George states that pharmacological therapy in the treatment of insomnia is widely used, but he neither defends this practice nor criticises it. It should not be widely used if the cause is carefully considered. Later, George quotes a report in which an increased number of awakenings was reported on the second and third nights after discontinuation of zaleplon,2 and he goes on to say, as if to lessen this finding, that other symptoms of rebound insomnia were not seen. What other symptoms of rebound insomnia are there apart from awakenings? This is the only reference to rebound in the article although the difficulty of rebound arousal is central to the use of all sedative substances. Samuel I Cohen Department of Psychiatry, London Hospital Medical College, Jerusalem 93108, Israel
1433
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
1 2
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26. Elie R, Ruther E, Farr I, Emilien G, Salinas E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic: Zaleplon Clinical Study Group. J Clin Psychiatry 1999; 60: 536–44.
Sir—In the effects section of Charles George’s review of zaleplon to treat insomnia,1 he notes that patients given this drug have little or no next-day sedation, or impairment of memory or psychomotor performance. Furthermore, he says cognitive impairment is minimal. In the side-effects section, he notes that dose-dependent decrements occur on several performance tasks, including balance, digit symbol substitution test, picture recall, and recognition. Let us say that the purpose of sleep is to make us more awake and able to solve problems the next day. I think George should emphasise that no hypnotic, zalpelon included, makes people sleep in a way that produces improvement in alertness or cognitive function the next day; at best, things are no worse. These drugs seem merely to render patients unconscious for a decent length of time. The benefits of sleeping pills are only that patients do not lie in bed awake and worrying at night, and do not bother their physicians with complaints about insomnia. Thomas E Finucane Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA 1
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26.
Sir—Charles George reviews some hopes for the use of zaleplon in the treatment for insomnia.1 I am elderly and so are many of my patients, and insomnia is a frequent complaint. Why did he not say what amount of sleep is enough for people aged 60–70 years or more? When should treatment with sleeping pills be started? I always suggest to my patients who have difficulty sleeping that they keep a digital clock beside the bed with glowing digits. They are frequently surprised at how long they have actually slept. 5–6 h sleep is generally satisfactory, and the clock can work as a sleeping aid. All the zopiclones, zolpidems, and triazolams produce tolerance and perhaps should be taken only every second or third night.2 Dream deprivation and rebound may be another difficulty. What are the effects of zaleplon in these respects?
1434
Physicians should also counsel patients on what to do if she or he awakes at 0300–0400 h, after a sleep of, say, 4–6 h. V Schreiber IIIrd Medical Department, 1st School of Medicine, Charles University, Prague 12821 Czech Republic 1 2
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26. Stone T, Darlington G. Pills, potions, poisons. Oxford: Oxford University Press, 2000.
Author’s reply Sir—Samuel Cohen is correct when he points out that mood disorders, primary or secondary, are an important cause of insomnia. I agree with this view, but the point of the review was to highlight the actions and effectiveness of pyrazoloprymidines in the management of insomnia rather than provide a template or algorithm for clinical diagnosis. As such, the review should not be used in isolation by clinicians. Concerning rebound insomnia, increased number of awakenings is certainly one manifestation of this disorder, but difficulty with getting to sleep is also one. Insomnia is an important disorder that can clearly affect daytime performance. As Thomas Finucane points out, an hypnotic by itself cannot improve alertness or cognitive function in normal individuals with normal sleep. However, when patients are not sleeping, use of an hyponotic to pharmacologically provide a period of rest and recuperation allows them to improve their alertness over their previously diminished values. Sleeping pills can be a useful adjunct to allow patients some sleep and prevent them worrying at night, but in such patients hypnotic sedatives are not a substitute for dealing with the primary disorder. V Schreiber raises an age-old question about the amount of sleep required. Clearly there is no one amount of sleep for any person, irrespective of age, and simply not meeting your arbitrary quota for age 65 does not in itself mandate a prescription for sleeping medications. I believe that the use of any medications for promotion of sleep is generally accepted on a short-term or prognosis basis. Charles George Department of Medicine, University of Western Ontario; *Sleep Laboratory, London Health Sciences Centre, Victoria Campus, London, ON N6A 4G5, Canada (e-mail: [email protected] or [email protected])
Appropriateness ratings Sir—We were surprised that Geoffrey Anderson and Adalsteinn Brown, in their Nov 3 Commentary,l do not mention the most important result from the ACRE study,2 the doseresponse relation between the degree of appropriateness and the impact on clinical outcome. Thus, the increased hazard of death and non-fatal myocardial infarction was greatest among patients rated as the most appropriate candidates for coronary artery bypass grafting ([CABG] a rating of 9). Among patients to whom the expert panel assigned a rating of 5 or 6 (generally classified as uncertain), there were also significant effects, with hazard ratios intermediate in magnitude between that for patients rated as appropriate and that for patients rated as inappropriate. Therefore, the expert panel seems to provide more than a binary yes-no judgment of appropriateness and may offer insights when evidence is less than clear cut. Previous studies restricted the definition of underuse to the subgroup of patients for whom revascularisation is judged appropriate and necessary. The ACRE results suggest that this definition is too restricted. How should the clinical relevance of expert panel ratings of angiography appropriateness be assessed? Anderson and Brown focus on their test characteristics, the limitations of which we have already highlighted (eg, 11% of patients in whom angiography was deemed inappropriate had triple-vessel or left main stem disease).3 However, appropriateness ratings are not designed as a diagnostic test but to aid judgment about relative benefits in terms of clinical outcomes. Studies investigating patients eligible for angiography, suggest that clinical outcomes are better among appropriate candidates who undergo this procedure compared with those who do not.4 Although, as yet there are no such studies on primary care populations. We are not suggesting that appropriateness ratings are used as a mechanical filter for access to coronary angiography, but do suggest that ratings are clinically useful if they inform the referral decision. As far as we are aware, there is no better validated method of judging who should or should not undergo angiography. We agree with Anderson and Brown that appropriateness ratings can be improved. We agree that it would be feasible to link each indication more explicitly to the strength of evidence.
THE LANCET • Vol 359 • April 20, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
CORRESPONDENCE
e-mail submissions to [email protected]
Insurance agreement to facilitate genetic testing Sir—A major objection to communitywide introduction of predictive genetic screening for serious diseases is the potential for discrimination by insurance companies.1 If discrimination is likely to result, many people will refuse genetic testing even if it is in their clinical interest. Most cases of haemochromatosis, a genetically inherited iron-overload disease, are due to homozygosity for one mutation, C282Y, in the HFE gene.2 People at high risk of developing the disease (up to one per 200 population in Australia)3 can be identified by DNA testing. In C282Y homozygous individuals, venesection prevents the iron accumulation that causes pathology, as well as providing donor blood to the community.4 Despite this successful treatment, concerns have been raised that if a person has this genetic predisposition, they may be subject to insurance premium loading.1,5 In Australia, unlike in the USA, insurance companies are bound by law to provide health insurance at one rate to all (community loading), and, therefore, only life insurance is open to discrimination. We were concerned about this issue when introducing a pilot genetic screening programme for haemochromatosis in Melbourne, Australia. We approached the umbrella organisation for life and disability insurance companies in Australia, the Investment and Financial Services Association. They agreed to the following assurances for life-insurance policies for people undergoing genetic screening for haemochromatosis. People who are not C282Y homozygous are guaranteed to have no insurance loadings on the basis of this genetic test. For C282Y homozygotes, those with normal iron indices will obtain insurance at baseline rates with no
conditions on the policy based on the genetic result; those with raised iron indices but no evidence of organ damage will be required to show evidence that steps are being taken to normalise iron indices and the policy will be issued at baseline rates when iron indices become normal; and those with raised iron indices and existing organ damage will be penalised if obtaining new policies, but insurance companies will comment that testing is desirable since treatment will keep disease progress to a minimum. We believe that this agreement represents a major step forward in dealing with the issue of genetic testing and insurance. Agreement between the medical and scientific community and the insurance industry is in the best interest of people who choose to have genetic testing and will be of increasing importance as more genetic markers that indicate predisposition to preventable disorders are described. *Martin Delatycki, Katrina Allen, Robert Williamson Murdoch Children’s Research Institute and Genetic Health Services Victoria, Royal Children’s Hospital, Parkville, Victoria 3052, Australia (e-mail: [email protected]) 1
2
3
4
5
Barash CI. Genetic discrimination and screening for hemochromatosis: then and now. Genet Test 2000; 4: 213–18. Powell LW, Subramaniam VN, Yapp TR. Haemochromatosis in the new millennium. J Hepatol 2000; 32: 48–62. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A populationbased study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341: 718–24. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996; 110: 1107–19. Motulsky AG, Beutler E. Population screening in hereditary hemochromatosis. Ann Rev Public Health 2000; 21: 65–79.
THE LANCET • Vol 359 • April 20, 2002 • www.thelancet.com
Treatment of insomnia Sir—In his review of insomnia, Charles George (Nov 10 p 1623)1 writes as if the disorder is a clinical entity in its own right; it may be, but only rarely. Pharmacological treatment has an important role, but that role is limited and, in my view, that should have been stated. George writes that insomnia may also be associated with tiredness, lack of energy, difficulty in concentrating, and irritability and mood change. In fact, insomnia with all these symptoms (any one of which may be more prominent than the others) constitutes a syndrome for which the cause must be sought before treatment can be given. The most common causes are mood disorders, either primary or the result of adverse events, or of excessive alcohol consumption, most frequently not amounting to alcohol abuse. It is these disorders that probably cost the quoted figure of US$13 billion per year and their treatment should be that of the cause, not of the insomnia. George states that pharmacological therapy in the treatment of insomnia is widely used, but he neither defends this practice nor criticises it. It should not be widely used if the cause is carefully considered. Later, George quotes a report in which an increased number of awakenings was reported on the second and third nights after discontinuation of zaleplon,2 and he goes on to say, as if to lessen this finding, that other symptoms of rebound insomnia were not seen. What other symptoms of rebound insomnia are there apart from awakenings? This is the only reference to rebound in the article although the difficulty of rebound arousal is central to the use of all sedative substances. Samuel I Cohen Department of Psychiatry, London Hospital Medical College, Jerusalem 93108, Israel
1433
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
1 2
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26. Elie R, Ruther E, Farr I, Emilien G, Salinas E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic: Zaleplon Clinical Study Group. J Clin Psychiatry 1999; 60: 536–44.
Sir—In the effects section of Charles George’s review of zaleplon to treat insomnia,1 he notes that patients given this drug have little or no next-day sedation, or impairment of memory or psychomotor performance. Furthermore, he says cognitive impairment is minimal. In the side-effects section, he notes that dose-dependent decrements occur on several performance tasks, including balance, digit symbol substitution test, picture recall, and recognition. Let us say that the purpose of sleep is to make us more awake and able to solve problems the next day. I think George should emphasise that no hypnotic, zalpelon included, makes people sleep in a way that produces improvement in alertness or cognitive function the next day; at best, things are no worse. These drugs seem merely to render patients unconscious for a decent length of time. The benefits of sleeping pills are only that patients do not lie in bed awake and worrying at night, and do not bother their physicians with complaints about insomnia. Thomas E Finucane Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA 1
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26.
Sir—Charles George reviews some hopes for the use of zaleplon in the treatment for insomnia.1 I am elderly and so are many of my patients, and insomnia is a frequent complaint. Why did he not say what amount of sleep is enough for people aged 60–70 years or more? When should treatment with sleeping pills be started? I always suggest to my patients who have difficulty sleeping that they keep a digital clock beside the bed with glowing digits. They are frequently surprised at how long they have actually slept. 5–6 h sleep is generally satisfactory, and the clock can work as a sleeping aid. All the zopiclones, zolpidems, and triazolams produce tolerance and perhaps should be taken only every second or third night.2 Dream deprivation and rebound may be another difficulty. What are the effects of zaleplon in these respects?
1434
Physicians should also counsel patients on what to do if she or he awakes at 0300–0400 h, after a sleep of, say, 4–6 h. V Schreiber IIIrd Medical Department, 1st School of Medicine, Charles University, Prague 12821 Czech Republic 1 2
George CFP. Pyrazolopyrimidines. Lancet 2001; 358: 1623–26. Stone T, Darlington G. Pills, potions, poisons. Oxford: Oxford University Press, 2000.
Author’s reply Sir—Samuel Cohen is correct when he points out that mood disorders, primary or secondary, are an important cause of insomnia. I agree with this view, but the point of the review was to highlight the actions and effectiveness of pyrazoloprymidines in the management of insomnia rather than provide a template or algorithm for clinical diagnosis. As such, the review should not be used in isolation by clinicians. Concerning rebound insomnia, increased number of awakenings is certainly one manifestation of this disorder, but difficulty with getting to sleep is also one. Insomnia is an important disorder that can clearly affect daytime performance. As Thomas Finucane points out, an hypnotic by itself cannot improve alertness or cognitive function in normal individuals with normal sleep. However, when patients are not sleeping, use of an hyponotic to pharmacologically provide a period of rest and recuperation allows them to improve their alertness over their previously diminished values. Sleeping pills can be a useful adjunct to allow patients some sleep and prevent them worrying at night, but in such patients hypnotic sedatives are not a substitute for dealing with the primary disorder. V Schreiber raises an age-old question about the amount of sleep required. Clearly there is no one amount of sleep for any person, irrespective of age, and simply not meeting your arbitrary quota for age 65 does not in itself mandate a prescription for sleeping medications. I believe that the use of any medications for promotion of sleep is generally accepted on a short-term or prognosis basis. Charles George Department of Medicine, University of Western Ontario; *Sleep Laboratory, London Health Sciences Centre, Victoria Campus, London, ON N6A 4G5, Canada (e-mail: [email protected] or [email protected])
Appropriateness ratings Sir—We were surprised that Geoffrey Anderson and Adalsteinn Brown, in their Nov 3 Commentary,l do not mention the most important result from the ACRE study,2 the doseresponse relation between the degree of appropriateness and the impact on clinical outcome. Thus, the increased hazard of death and non-fatal myocardial infarction was greatest among patients rated as the most appropriate candidates for coronary artery bypass grafting ([CABG] a rating of 9). Among patients to whom the expert panel assigned a rating of 5 or 6 (generally classified as uncertain), there were also significant effects, with hazard ratios intermediate in magnitude between that for patients rated as appropriate and that for patients rated as inappropriate. Therefore, the expert panel seems to provide more than a binary yes-no judgment of appropriateness and may offer insights when evidence is less than clear cut. Previous studies restricted the definition of underuse to the subgroup of patients for whom revascularisation is judged appropriate and necessary. The ACRE results suggest that this definition is too restricted. How should the clinical relevance of expert panel ratings of angiography appropriateness be assessed? Anderson and Brown focus on their test characteristics, the limitations of which we have already highlighted (eg, 11% of patients in whom angiography was deemed inappropriate had triple-vessel or left main stem disease).3 However, appropriateness ratings are not designed as a diagnostic test but to aid judgment about relative benefits in terms of clinical outcomes. Studies investigating patients eligible for angiography, suggest that clinical outcomes are better among appropriate candidates who undergo this procedure compared with those who do not.4 Although, as yet there are no such studies on primary care populations. We are not suggesting that appropriateness ratings are used as a mechanical filter for access to coronary angiography, but do suggest that ratings are clinically useful if they inform the referral decision. As far as we are aware, there is no better validated method of judging who should or should not undergo angiography. We agree with Anderson and Brown that appropriateness ratings can be improved. We agree that it would be feasible to link each indication more explicitly to the strength of evidence.
THE LANCET • Vol 359 • April 20, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.