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Dangers of fluoxetine
THE LANCET
SIR—Bundey1 concludes that predictive testing for Huntington’s disease is a success story. Admittedly, the test does bring relief from anxiety and allow prudent arrangements for the future and family planning, but 10 years’ experience has taught us the extent of the psychological consequences of a positive test result. Becoming identified as a carrier does not induce clinical depressive symptoms,2 but leads to a more pessimistic view of the future. Two studies have shown that individuals who are married, childless, or close to the age of onset of Huntington’s disease experience the greatest distress among carriers.2,3 Carriers and their partners must find a balance between confronting the future and living as normal a life as possible. The partners of carriers who have children show more hopelessness about the future than those without children.3 Furthermore, the threat that their children may develop the disease may not only cause feelings of anxiety and hopelessness, but also of resentment and hostility. Such parents face the difficult task of explaining to their children their genetic risk and helping them to cope with this information. Partners who are aware of the difficult future commonly put on a brave face and do not seek professional support.3 In addition, acceptance of a favourable test result is not an easy process.4,5 Feelings of guilt, expressed as excessive attention for affected relatives, incomplete experienced relief, and avoidance of affected relatives, are common. This process, which may take several years, is usually complicated by events among family members such as the death of a parent, onset of symptoms in a carrier, admission of affected relatives to a psychiatric hospital, or unfavourable test results in siblings. Careful attention to the benefit for the whole family is important when an adult child applies for the test— indeed, the unaffected parent at 50% risk may not wish to know about his or her genetic status. Before any ethical or legal discussion about testing, psychological counselling for all individuals involved is needed to hasten understanding and appreciation of each other’s interests.4 One feature of testing for Huntington’s disease that can be regarded as a success story is the worldwide collaboration of professionals and patient organisations which has resulted in guidelines and balanced testing programmes.4 For the Vancouver group’s worldwide survey on catastrophic events after predictive testing, 107 centres from 20 countries provided data on 5781 individuals tested since 1986.5 Of the 40 catastrophic events reported, five people committed suicide and 16
Vol 349 • March 15, 1997
attempted suicide, mostly within 5 years after the test. But the small number of catastrophes does not imply “a success story” for the Huntington’s disease programme. Dissemination of knowledge and experience for the benefit of the Huntington population and for all other families with late onset genetic diseases remains a continuing task. Predictive testing for Huntington’s disease is an important model for other genetic disorders, and the most important success may be the willingness in health care to learn about the far-reaching implications of such testing. *A Tibben, R A C Roos, M F Niermeijer Departments of *Clinical Genetics, and Medical Psychology and Psychotherapy, Erasmus University, and University Hospital Dijkzigt, PO Box 1738, 3000 DR Rotterdam, Netherlands; and Leiden University Medical Centre, Leiden
1
2
3
4
5
Bundey S. Few psychological consequences of presymptomatic testing for Huntington disease. Lancet 1997; 349: 4. Codori AM, Slavney RS, Young C, Miglioretti DL, Brandt J. Predictors of psychological adjustment to genetic testing for Huntington’s disease. Health Psychol 1997; 16: 36–50. Tibben A, Timman RT, Bannink EC, Duivenvoorden HJ. 3-year follow-up after presymptomatic testing for Huntington disease in tested individuals and partners. Health Psychol 1997; 16: 20–35. International Huntington Association and the World Federation of Neurology Research Group on Huntington’s disease. J Med Genet 1994; 31: 555–59. Almqvist E, Bloch M. World-wide survey on catastrophic events following predictive testing for Huntington disease. Poster presented at the American Society of Human Genetics meeting, 1996.
Dangers of fluoxetine SIR—Bourguignon (Jan 18, p 214)1 raises issues about Eli Lilly and Company’s post-marketing surveillance of adverse events with respect to fluoxetine. Since its introduction more than a decade ago, fluoxetine has become the most widely studied and prescribed branded antidepressant. More than 90 independent regulatory bodies have approved its use, affirming its safety and efficacy. Worldwide, more than 24 million patients have been treated with fluoxetine, and the drug is the subject of more than 2000 scientific publications. In 1983, Lilly established a computerised system for the worldwide collection, storage, and reporting of spontaneous adverse events for all Lilly products. This database and the extensive clinical trial database for fluoxetine have been scrutinised by Lilly and have served as the basis for numerous regulatory submissions and publications.
Each of the concerns mentioned by Bourguignon 1 have been addressed previously by Lilly. For example, on the subject of aggressive behaviour, Fuller2 concluded that, consistent with work in animals, human aggressive behaviour is reduced with fluoxetine treatment. With respect to suicide, Tollefson and colleagues3 concluded that fluoxetine reduces suicidal ideation and might protect against the emergence of substantial suicidal ideation. Suicide has also been addressed in publications by non-Lilly authors. Jick and colleagues4 estimated the rate and means of suicide among people taking ten commonly prescribed antidepressants. They showed that several factors (ie, age; sex; antidepressant dose, therapy duration, and indication; number of antidepressants prescribed before suicide; and history of suicidal behaviour) correlated with the risk of suicide in people taking antidepressants. After controlling for these factors, the risk of suicide was similar among the ten antidepressants; thus, the risk of suicide was not determined by the antidepressant prescribed. Warshaw and Keller5 found no evidence that fluoxetine was associated with an increased risk of suicidal behaviour in a study of patients with anxiety disorders. On the contrary, there was a much lower probability of suicide attempts in the patients who received fluoxetine than in those who did not receive fluoxetine during the study. Rajinder Judge Eli Lilly and Company, Lilly Research Centre Limited, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
1 2
3
4 5
Bourguignon RP. Dangers of fluoxetine. Lancet 1997; 349: 214. Fuller RW. The influence of fluoxetine on aggressive behavior. Neuropsychopharmacology 1996; 14: 77–81. Tollefson GD, Fawcett J, Winokur G, et al. Evaluation of suicidality during pharmacologic treatment of mood and nonmood disorders. Ann Clin Psychiatry 1993; 5: 209–24. Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ 1995; 310: 215–18. Warshaw MG, Keller MB. The relationship between fluoxetine use and suicidal behavior in 654 subjects with anxiety disorders. J Clin Psychiatry 1996; 57: 158–66.
Iron deficiency in benign duodenal ulcer SIR—Chua and colleagues’ (Jan 18, p 174)1 assertion that “iron deficiency is rarely the result of benign duodenal ulceration”, made in their case report, is not borne out by publications subsequent to the study by Sheppard and co-workers.2 These include the documentation of benign duodenal
809
SIR—Bundey1 concludes that predictive testing for Huntington’s disease is a success story. Admittedly, the test does bring relief from anxiety and allow prudent arrangements for the future and family planning, but 10 years’ experience has taught us the extent of the psychological consequences of a positive test result. Becoming identified as a carrier does not induce clinical depressive symptoms,2 but leads to a more pessimistic view of the future. Two studies have shown that individuals who are married, childless, or close to the age of onset of Huntington’s disease experience the greatest distress among carriers.2,3 Carriers and their partners must find a balance between confronting the future and living as normal a life as possible. The partners of carriers who have children show more hopelessness about the future than those without children.3 Furthermore, the threat that their children may develop the disease may not only cause feelings of anxiety and hopelessness, but also of resentment and hostility. Such parents face the difficult task of explaining to their children their genetic risk and helping them to cope with this information. Partners who are aware of the difficult future commonly put on a brave face and do not seek professional support.3 In addition, acceptance of a favourable test result is not an easy process.4,5 Feelings of guilt, expressed as excessive attention for affected relatives, incomplete experienced relief, and avoidance of affected relatives, are common. This process, which may take several years, is usually complicated by events among family members such as the death of a parent, onset of symptoms in a carrier, admission of affected relatives to a psychiatric hospital, or unfavourable test results in siblings. Careful attention to the benefit for the whole family is important when an adult child applies for the test— indeed, the unaffected parent at 50% risk may not wish to know about his or her genetic status. Before any ethical or legal discussion about testing, psychological counselling for all individuals involved is needed to hasten understanding and appreciation of each other’s interests.4 One feature of testing for Huntington’s disease that can be regarded as a success story is the worldwide collaboration of professionals and patient organisations which has resulted in guidelines and balanced testing programmes.4 For the Vancouver group’s worldwide survey on catastrophic events after predictive testing, 107 centres from 20 countries provided data on 5781 individuals tested since 1986.5 Of the 40 catastrophic events reported, five people committed suicide and 16
Vol 349 • March 15, 1997
attempted suicide, mostly within 5 years after the test. But the small number of catastrophes does not imply “a success story” for the Huntington’s disease programme. Dissemination of knowledge and experience for the benefit of the Huntington population and for all other families with late onset genetic diseases remains a continuing task. Predictive testing for Huntington’s disease is an important model for other genetic disorders, and the most important success may be the willingness in health care to learn about the far-reaching implications of such testing. *A Tibben, R A C Roos, M F Niermeijer Departments of *Clinical Genetics, and Medical Psychology and Psychotherapy, Erasmus University, and University Hospital Dijkzigt, PO Box 1738, 3000 DR Rotterdam, Netherlands; and Leiden University Medical Centre, Leiden
1
2
3
4
5
Bundey S. Few psychological consequences of presymptomatic testing for Huntington disease. Lancet 1997; 349: 4. Codori AM, Slavney RS, Young C, Miglioretti DL, Brandt J. Predictors of psychological adjustment to genetic testing for Huntington’s disease. Health Psychol 1997; 16: 36–50. Tibben A, Timman RT, Bannink EC, Duivenvoorden HJ. 3-year follow-up after presymptomatic testing for Huntington disease in tested individuals and partners. Health Psychol 1997; 16: 20–35. International Huntington Association and the World Federation of Neurology Research Group on Huntington’s disease. J Med Genet 1994; 31: 555–59. Almqvist E, Bloch M. World-wide survey on catastrophic events following predictive testing for Huntington disease. Poster presented at the American Society of Human Genetics meeting, 1996.
Dangers of fluoxetine SIR—Bourguignon (Jan 18, p 214)1 raises issues about Eli Lilly and Company’s post-marketing surveillance of adverse events with respect to fluoxetine. Since its introduction more than a decade ago, fluoxetine has become the most widely studied and prescribed branded antidepressant. More than 90 independent regulatory bodies have approved its use, affirming its safety and efficacy. Worldwide, more than 24 million patients have been treated with fluoxetine, and the drug is the subject of more than 2000 scientific publications. In 1983, Lilly established a computerised system for the worldwide collection, storage, and reporting of spontaneous adverse events for all Lilly products. This database and the extensive clinical trial database for fluoxetine have been scrutinised by Lilly and have served as the basis for numerous regulatory submissions and publications.
Each of the concerns mentioned by Bourguignon 1 have been addressed previously by Lilly. For example, on the subject of aggressive behaviour, Fuller2 concluded that, consistent with work in animals, human aggressive behaviour is reduced with fluoxetine treatment. With respect to suicide, Tollefson and colleagues3 concluded that fluoxetine reduces suicidal ideation and might protect against the emergence of substantial suicidal ideation. Suicide has also been addressed in publications by non-Lilly authors. Jick and colleagues4 estimated the rate and means of suicide among people taking ten commonly prescribed antidepressants. They showed that several factors (ie, age; sex; antidepressant dose, therapy duration, and indication; number of antidepressants prescribed before suicide; and history of suicidal behaviour) correlated with the risk of suicide in people taking antidepressants. After controlling for these factors, the risk of suicide was similar among the ten antidepressants; thus, the risk of suicide was not determined by the antidepressant prescribed. Warshaw and Keller5 found no evidence that fluoxetine was associated with an increased risk of suicidal behaviour in a study of patients with anxiety disorders. On the contrary, there was a much lower probability of suicide attempts in the patients who received fluoxetine than in those who did not receive fluoxetine during the study. Rajinder Judge Eli Lilly and Company, Lilly Research Centre Limited, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
1 2
3
4 5
Bourguignon RP. Dangers of fluoxetine. Lancet 1997; 349: 214. Fuller RW. The influence of fluoxetine on aggressive behavior. Neuropsychopharmacology 1996; 14: 77–81. Tollefson GD, Fawcett J, Winokur G, et al. Evaluation of suicidality during pharmacologic treatment of mood and nonmood disorders. Ann Clin Psychiatry 1993; 5: 209–24. Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ 1995; 310: 215–18. Warshaw MG, Keller MB. The relationship between fluoxetine use and suicidal behavior in 654 subjects with anxiety disorders. J Clin Psychiatry 1996; 57: 158–66.
Iron deficiency in benign duodenal ulcer SIR—Chua and colleagues’ (Jan 18, p 174)1 assertion that “iron deficiency is rarely the result of benign duodenal ulceration”, made in their case report, is not borne out by publications subsequent to the study by Sheppard and co-workers.2 These include the documentation of benign duodenal
809