Suicide and Patients With
Neurologic Diseases
Methodologic Problems Elsebeth
Nylev Stenager, MD, Egon Stenager,
Objective.\p=m-\Thesuicide risk in patients with many neurologic diseases has been reported to be greater than that in the general population. Studies on the subject are, however, often encumbered with methodologic problems. We appraised these problems and, based on an evaluation, reappraised knowledge of the suicide risk in patients with specific neurologic diseases. Data Source.\p=m-\Usingthe computerized database MEDLINE, we identified all published reports with the key words suicide, attempted suicide, and neurologic diseases. Study Selection.\p=m-\Weassessed and reviewed studies concerning the most common neurologic diseases for methodologic problems in the study design. Data Extraction.\p=m-\Thefollowing methodologic problems emerged during our review: (1) choice of study type, ie, autopsy study or follow-up study; (2) choice of study population; (3) choice of control groups; (4) epidemiologic/ statistical methods used; and (5) validity of statistics reported. Data Synthesis.\p=m-\Weanalyzed the methodologic problems in studies of patients with multiple sclerosis, epilepsy, Huntington's chorea, spinal cord lesions, cranial trauma, \s=b\
brain tumors, Parkinson's
disease, vascular disorders, and
migraine. In most of the studies, the methods used gave rise to uncertainty about the conclusion presented.
Conclusion.\p=m-\Anincreased suicide risk was found in patients suffering from multiple sclerosis and spinal cord lesions as well as in selected groups of patients with epilepsy. In other neurologic diseases, the suicide risk may be increased, but the results are uncertain due to the methodologic problems in the study design. (Arch Neurol. 1992;49:1296-1303) well known that the risk of suicide patients with It ismental disorders, such schizophrenia and manic de¬ than that in the is in
as
general pop-
pressive psychoses, greater
Accepted for publication June 26,
1992.
Research, Department of Psychiatry and Research Unit, Odense (Denmark) University. Presented in part as a poster at the Fourth European Symposium on Suicidal Behaviour, Odense, Denmark, June 12, 1992, and at the Third Meeting of the European Neurological Society, Lausanne, Switzerland, June 29, 1992. Reprint requests to the Neuropsychiatric Research Unit, Odense University Hospital, Odense, Denmark (Dr Stenager). From the Institute of Clinical
Neuropsychiatric
MD
ulation.1,2 We also know that the risk of developing a men¬ tal disorder in connection with a number of neurologic diseases is significantly greater than that in the healthy population. For example, patients with multiple sclerosis (MS), epilepsy, or cerebral insult are at greater risk of de¬ pression.3 The lifetime risk of suicide for patients with de¬ pression is estimated to be about 15%.1 However, in a re¬ cent follow-up study involving 4022 patients with affective disorders, the standardized mortality ratio (SMR) for sui¬ cide was 26 compared with the general population.4 It is known that patients with a neurologic disease are vulner¬ able to depression. It seems reasonable, therefore, to assume that they are also at greater risk of suicide than the
general population. In devising preventive measures against suicide for this patient group, it is imperative to know exactly which dis¬ eases are likely to involve an increased suicide risk and, if possible, when in the course of the particular disease and
for which age groups the risk is greatest. The literature concerning suicide among patients with neurologic diseases is extensive. The choice of method in earlier overview articles on neurologic diseases and sui¬ cide risk5"7 was rarely criticized. However, the diversity of methods used in the various investigations makes com¬ parison difficult. Moreover, the conclusions drawn are not always incontestible. Before reviewing the literature, it is therefore necessary to examine thoroughly the méthod¬ ologie weaknesses most frequently encountered. The purpose of this review is, therefore, to describe the errors most likely to occur in research on the méthodologie suicide risk for specific patient populations and to exam¬ ine the literature on the suicide risk for patients with neu¬ rologic diseases. METHODOLOGIC PROBLEMS THAT ARISE WHEN ASSESSING THE SUICIDE RISK The aspects examined include (1) type of investigation,
(2) investigation
populations, (3) suitability of control epidemiologie/statistical methods used, and (5) validity of suicide statistics presented.
groups, (4)
Type of Investigation As a rule, one of the following three types of investiga¬ tion is made: (1) autopsy investigations reporting the number of patients with a particular neurologic disease
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who committed suicide; (2) follow-up investigations on the number of patients who, in a defined period of time, were in specific specialized departments and com¬ hospitalized mitted suicide; or (3) epidemologic investigations based on registers recording clearly defined patient populations. Specific problems arise in connection with investigations based on autopsy studies. Their weakness lies in the dif¬ ficulty in finding a representative control group, as most autopsy studies consist of a selected patient population, partly composed of forensically examined cases and partly of selected hospitalized cases. Some investigations have sought to surmount this problem by making a comparison with the prevalence of the disease studied in the general population, ie, a comparison of the living with the dead. It can, therefore, hardly be expected that the composition of age and sex is the same in both populations. Therefore, the conclusions reached must be interpreted with great caution. The population
suitable for investigation registers covering large group of patients with a par¬ ticular disease in which both those who are severely ill and those with a mild form of the disease are recorded. Only in this way is it possible to assess the suicide risk present for all patients having the disease. Furthermore, only ex¬ tensive registration can form the basis of an optimal epidemiologie/statistical method by which an evaluation of the suicide risk can be made. There are, however, so few such registers available that optimal investigation by that method is hardly possible. are
sources
most
Epidemiologic/Statistical
Procedures A great variety of methods were used in the investiga¬ tions reviewed herein. A calculation may have been made of observed and expected deaths based on the suicide risk in the general population, or a percentagewise comparison may have been made of the number of patients with a par¬ ticular disease who have committed suicide relative to a control group. Finally, a few investigations include a cal¬ culation of an SMR for age and sex, and in addition con¬ trol of years at risk (ie, the period from disease onset/ diagnosis to suicide), which is the optimal method. The great diversity of methods makes it difficult to compare the investigations. Consequently, many of the authors of earlier overview articles compared diversely selected subjects, thereby reaching conclusions that were directly misleading. Finally, it should be mentioned that a small number of case histories are to be found, but general conclusions about the risk of suicide cannot be drawn from them.
a
Population Used Selection.—It is a serious problem that the populations investigated are often highly selected and that the popu¬ lation most often consists of patients who have been hos¬
pitalized in a specialized department. Consequently, they of the most seriously ill patients, which in turn means that the results are unlikely to be generally appli¬ cable to all patients suffering from the particular disease. There is, in addition, the question of dropouts resulting from selection bias, for example, those for whom it has been impossible to obtain information on the cause of are made up
death. Definition of Disease.—Many of the diseases in ques¬ tion are not always precisely defined in an investigation, nor are the criteria for the presence of the particular disease always sufficiently stringent. This applies particularly to
investigations concerning epilepsy. Small Populations.—In many investigations, the popu¬ lations used are small, often amounting to about 100 patients. As suicide is rare (in Denmark, 30 per 100000 population per year), the reliability of the results based on such small populations is questionable.
Selection of Control Groups When evaluating the risk of suicide for a specific group, it is usual to make a comparison with the general popula¬ tion. This has been done in many investigations but with¬ out taking into account that the suicide risk varies de¬ pending on age and sex. Therefore, overestimation or underestimation of the risk may occur in the absence of relativity to age and sex compositions in the patient pop¬ ulation. As the populations investigated generally are small, the danger of producing misleading results is great.
Validity of Suicide Statistics It is precisely in the case of the death of a patient who had had a serious physical disease that a tendency is seen to ignore the possibility of suicide as the cause. Instead, the event is accepted as the natural death of a seriously ill per¬ son.
The risk of suicide can in this way be underestimated.
Moreover, the suicide statistics in many countries
are
not
always likely to be reliable, especially when the cause of death is such a controversial issue as suicide. Thus, it is clear that investigations of the frequency of suicide for patients with a chronic disease should be
closely examined before significant conclusions are drawn on
the extent of the risk involved.
SUICIDE ATTEMPT The sources of error inherent in some investigations on the subject of attempted suicide are not described herein, but the pitfalls are in principle the same as those already mentioned. It is believed to be more relevant, however, to emphasize herein that the problems concerning the valid¬ ity of the investigations available on attempted suicide are significantly greater than in the case of suicide. AUTOPSY STUDIES A number of studies with large populations have sought to examine the suicide risk connected with a long list of diseases, including neurologic diseases. Whitlock7 exam¬ ined 1000 cases of suicide in England and Wales for the period from 1968 through 1972. He compared the number of suicides among persons with a specific disease with the prevalence of suicide in the general population. He found that the suicide risk for persons with epilepsy, MS, cranial trauma, and cerebral tumor was significantly greater than in the general population. In the same way, Stennsmann and Sundquist-Stensman8 examined 416 suicides for the period from 1977 to 1984 in Sweden and also found an increased suicide risk for per¬ sons with neurologic diseases. The methods used in both investigations, in which a comparison was made of the distribution of a disease in persons who had committed suicide with the frequency of the disease in the general population, can hardly defend the conclusions drawn in the investigations, as it cannot be presumed that distribu¬ tion by age and sex in the general population is identical
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Table 1.—Suicide Risk in Patients With No. of
Source, Study Period
Subjects
No. of Suicides
Multiple Sclerosis
Autopsy Follow-up Standardized Study Study Mortality Ratio
Increased Risk
Schwartz and Pierron,'2 1972
408
Yes
No
No
No
Sadovnick et al," 1 972-1 988
31 26
Yes
No
No
Yes
Kurtzke
al," 1942-1951 Stenager et al,18 1953-1 985 Leibowitz et al,14 1960-1966 et
Control group
not sex-
adjusted
476
1
No
Yes
No
No
No calculation of suicide risk
6088
58
No
Yes
1.83
Yes
Correct statistical method
295
8
No
Yes
No
Yes
that in the population committing suicide. In addition, the varying mortality rate of the disease is also of consequence. to
FOLLOW-UP STUDY Allgulander and Fisher" conducted a follow-up investi¬ gation in Sweden of a randomly selected group of all pa¬ tients admitted to the hospital following self-poisoning in the period from 1974 to 1985. An attempt was made to identify predictors of suicidal behavior (suicide and attempted suicide). With use of a Cox regression model, it was found that in men diseases of the central nervous system increased the risk of repeated suicide attempts. However, few men have diseases of the central nervous system, so the result may be explained by a chance occurrence (ie, spurious finding) and therefore the question should be examined in other populations for
confirmation.
MULTIPLE SCLEROSIS Several investigations have been conducted to assess the connection between the risk of suicide and MS (Table 1). Müller,10 McAlpine et al,11 Schwartz and Pierron,12 and Kurtzke et al13 did not find an increase in the suicide risk in their investigations, which were based on small patient groups. In an Israeli study,14 it was found that the suicide was 14 times greater for patients with MS. Sadovnick et al15 found that among 80 deceased patients with MS, 13 had committed suicide. In a Danish pilot investiga¬ tion16,17 of the period from 1973 to 1985, five of 56 deaths were found to be due to suicide. In all the investigations mentioned, no age or sex standardization was conducted in the comparison with the control population. To date, the most extensive and methodologically cor¬ rect investigation18 of the frequency of suicide in patients with MS involved 6088 patient entries in the Danish Scle¬ rosis Register. In this investigation, SMRs were calculated. The SMR for men diagnosed while younger than 40 years was determined to be 3.12 (95% confidence interval, 2.01 to 4.60) and for women diagnosed within the same age range it was determined to be 2.12 (95% confidence inter¬ val, 1.13 to 3.62). Patients diagnosed after the age of 40 were not found to be at greater risk for suicide. The period of greatest risk is, according to the investigation, the first 5 years after diagnosis. The cumulative lifetime risk of com¬ mitting suicide is 1.95%. In a recently published American investigation, Sadovnick et al19 found a significantly greater suicide risk than was found in the Danish study, ie, a risk that was 7.5 times greater. The SMR was not calculated, nor was sex standardization conducted. Therefore, the skewed sex
frequency
Comments
No adequate statistical method used
distribution of the disease may become a source of consid¬ erable error. It may be concluded, then, that patients with MS are at greater risk of committing suicide than the gen¬ eral population, but the risk involved is slight and is con¬ fined to younger patients. EPILEPSY correlation between disease and sui¬ cide risk, epilepsy has been most thoroughly investigated (Table 2). As early as 1941, Prudhomme20 published an in¬ vestigation in which he examined, over an extended period, 75 000 patients admitted with the diagnosis of ep¬ ilepsy and found 67 suicides. Because of the method used, the investigation could merely confirm that suicide oc¬ curred in that particular patient group, but its frequency could not be established on that basis. In a Danish study21 published in 1970, mortality in a representatively selected large group of epileptics was ex¬ amined. The purpose of the study was to register and dif¬ ferentiate the assessment of the epileptics' application for life insurance, which explains why the control group cho¬ sen was made up of the company's elite customers and not the general population. Cause of death, including suicide, was compared between the two groups, and it was found that the risk of suicide was three times higher for epilep¬ tics. No information on age and sex standardization was given. Furthermore, the control group selected may be presumed to be a low-risk group and therefore overestimation of the suicide risk is likely. Zielenski22 conducted a study of all the persons with ep¬ ilepsy in Warsaw, Poland, by examining all accessible pa¬ tient sources. In the period from 1967 to 1969, 239 deaths occurred. The mortality rate in 1969 was calculated and was found to be significantly high. The suicide risk was five times higher for men and 10 times higher for women. The results were not standardized for age, and the com¬ parison population was not described. A large follow-up investigation23 concerned 2099 epi¬ leptics who were admitted to Chalfont Centre, Chalfont St Peter, Buckinghamshire, England, because of epilepsy be¬ tween 1931 and 1971 and who were treated with anticon¬ vulsant drugs and followed up until 1977. The suicide rate was compared with that in the control population, age and sex standardization was conducted, and the risk span was taken into account. The investigation revealed a suicide increase that was 5.4 times greater (95% confidence inter¬ val, 3.3 to 8.2). The method used in the investigation is so far the most reliable one identified in our review. In a Finnish investigation24 of 179 deaths of previously admitted epileptics, 13 were found to be due to suicide, which is significantly more than in the general population In the context of
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a
Table 2.—Suicide Risk in Source,
Study
Period
Prudhomme,20
undefined Henriksen et al,2
No. of
No. of
Subjects Suicides Autopsy
Followup
Epileptic
Increased Risk
Patients
Standardized Ratio
Mortality No
75 000
67
No
Yes
2763
21
No
Yes
3 times
No
6710
12
Yes
Males, 5 times; females, 10 times
No
Yes
5.4 times
5.4
No
3 times
No
1950-1964
Comments
The study confirmed the presence of suicide In this patient group The control group selected from low-risk persons; no age or sex
adjustment Zielenski,22
1965-1969
White et al,23
2000
21
179
13
Undefined control group;
adjustment Age-adjusted
no
age
or
sex
1931-1971 Ivanainen and
Yes
Lehtimen,24
Strongly selected high-risk population; no age or sex adjustment
1900-1976
investigation dealt with a highly selected of epileptics, and neither age nor sex standardiza¬ group tion was performed. In their overview article published in 1981, Matthews and Barabas25 reviewed the literature on the correlation between suicide risk and epilepsy. They examined a num¬ ber of small investigations on deaths in selected epileptic populations in various countries and reached a total suicide frequency of 5%. This rate is in comparison with the frequency of 1.4% in the American general population, and Matthews and Barabas presented the result as evidence of a significantly higher suicide risk for epileptics. The valid¬ ity of the method used is disputable, and therefore the re¬ sults cannot be taken as documentation of a higher suicide risk among epileptics. Barraclough5 has published an extensive review of the literature available on the suicide risk for various groups of epileptics. He found that the risk for patients with tem¬ poral lobe epilepsy is five times higher and for those with a form of the disease that is difficult to treat it is 25 times higher. In this investigation as well, the number of observed and expected patients committing suicide is taken from a long list of variously selected materials from several countries, the sum total of which is used to reach a conclusion, the basis of which is methodologically unsound. In the context of method used in the investigations re¬ viewed herein, one is found to be above criticism,23 while the remainder are open to a great likelihood of error in the estimation of the risk of suicide for epileptics with varying degrees of disease severity. In the investigation in ques¬ tion, it was found that the risk of suicide was 5.4 times greater for patients receiving medicinal treatment for ep¬ ilepsy. No recent investigations of the suicide risk for ep¬ ileptics could be found, but it could be expected that with the advent of the improved treatment options now avail¬ able for these patients, the suicide risk for the group has decreased. in Finland. The
EPILEPSY AND ATTEMPTED SUICIDE Hawton et al,26 during a 2-year period, examined the frequency of epilepsy among patients admitted to the hos¬ pital following attempted suicide. The number of at¬ tempted suicides among epileptics is compared with the prevalence in the general population and found to be five times greater. The patients had more often undergone psychiatric treatment and had previously attempted sui-
cide more often than people in the control population. Méndez et al27 compared epileptics who had attempted suicide with a matched group of suicide attempters not suffering from epilepsy. The conclusion of the investiga¬ tion was that epileptics more frequently have borderline personality disturbances, psychotic disorders, and previ¬ ous suicide attempts. HUNTINGTON'S CHOREA Huntington's chorea (HC) is an autosomal dominant hereditary disease that is characterized by progressive de¬ generation of the central nervous system, personality changes, and dementia. Because of its course, the disease presents a special problem when assessing the suicide risk. As early as 1872, when describing the disease, Huntington28 pointed out that the tendency to mental illness, par¬ ticularly the form of disorder associated with suicide, was pronounced. There are distinct problems involved when assessing the suicide risk associated with HC. Because of its genetically dominant heredity, the patient is, from fam¬ ily experience (ie, parents, siblings suffering from the dis¬ ease), surely aware of the consequences of the disease. Awareness of the 50% risk of contracting the disease is something that must be lived with, particularly in the pe¬ riod in life when planning a family or choosing an educa¬ tion or occupation. For the majority of patients, the onset of the disease occurs at about the age of 40 years, and the average survival time from that point is 10 to 20 years. There has been great interest, therefore, in finding ways to identify the patients who are liable to contract the dis¬ ease, and new tools have been devised to identify disease carriers, ie, the DNA marker. Use of these tools, however, implies that serious consideration should be given to the humane and ethical aspects involved. It would naturally be a relief for some patients to learn that they were not in danger of contracting the disease, while at the same time the burden of being a genetic carrier is great. Interview in¬ vestigations have been conducted with relatives in the group at risk. In one such investigation,29 67 persons with a father or mother with HC were interviewed. Forty per¬ cent of them knew of suicidal behavior in their family, 78.8% wished to be tested for the disease if possible, 71% were prepared to undergo elective abortion on confirma¬ tion of the HC gene in their embryo, and 11 % mentioned suicide as a way out should the test result prove to be pos¬ itive. Such a test should have a high predictive value. Fur¬ thermore, there must be complete awareness of the conse-
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Table 3.—Suicide Risk in Patients With Source,
Study Period Reed and Chandler,30
Huntington's
No. of Patients
No. of Suicides
Autopsy
Study
Follow-up Study
Increased Risk*
203
3
No
Yes
No
et
al,3'
506
20
Yes
No
population, adjustment
Under 50:
OR=1.06;
over
50: OR=8.19
Saugstad and 0degârd,33
199
1
No
Yes
Farrer,35 undefined
452
25%
Yes
No
Comments
Small
1940-1956
Schoenfeld 1980-1983
Disease
No
1916-1975
Increased 4 times
no
age
or sex
Selection due to unsure cause of death for one third of the
population psychiatric population, use high-risk population as controls No age adjustment, a large number of dropouts
Selected
OR indicates odds ratio.
quences of
screening the group at risk, including the of possibility increased suicide risk. The investigations dealing with the risk of suicide for patients with HC and their relatives are reviewed in Table 3. Reed and Chandler30 examined patients who, with use of various sources, were found to have definite HC. The patients were followed up until 1956. Several examinations were performed, one on the occurrence of suicide in the family and one in a population of patients who were alive in April 1940. The first group showed an increased suicide risk compared with that in the healthy population, three times greater for men and five times greater for women. However, no increase was found for the second group examined. The selection of the patient population in the investigation poses some problems, as the sample is small and no age standardization was performed, which means that the increased suicide mor¬ tality in the family that is found should be interpreted with
including
caution.
Schoenfeld et al31 examined 506 patients, 403 of whom had a definite diagnosis and 103 of whom had a probable one. They found 20 suicides in the population, which cor¬ responds to an increase by five times for suicide risk for patients older than 50 years, while the risk for those younger than 50 years was not increased. Cause of death, however, could only be established with certainty for one third of those examined. This means that the suicide risk may have been underestimated. The authors therefore also investigated the population with known cause of death and found that the risk was three times greater for persons younger than 50 years and 23 times greater for persons older than 50 years. There are elements of uncertainty in the investigation concerning selection, and consequently uncertainty about the causes of death for two thirds of the patients. In a letter to the readers, Chiù and Aleksander32 stated that in their study population they did not find an increased suicide risk for patients with HC. Saugstad and 0degard33 examined all patients with HC who were admitted to psychiatric departments in Norway from 1916 to 1975. They found one suicide and one suicide attempt; compared with the yearly number of suicides in psychiatric patients, the expected number would have been two suicides. The population included only patients who had been admitted to a psychiatric department. On the other hand, it could have been expected that these pa¬ tients would constitute those at highest risk of suicide in the HC group. The control group used was also composed of psychiatric patients who, in an earlier investigation,34 were found to have a significantly higher mortality rate by unnatural causes. The conclusion must be that patients
with HC do not have a higher mortality rate than patients who have been admitted to psychiatric departments and not that which the authors contend, ie, that suicide is rare, as a high-risk group was used as a control group. Farrer35 examined 452 patients known to have HC and found that 5.7% of all deaths were due to suicide. This was correlated with the suicide frequency in the general Cana¬ dian and American populations, which was 1.5%, so that the conclusion was that the suicide risk for patients with HC was four times greater than that for the general pop¬ ulation. There was a dropout rate of about 20% in the pa¬ tients for whom the cause of death was not reported. No correlation was found for point of disease onset and prob¬ ability of suicide, nor was a connection with the particular clinical disease type found. Those who committed suicide had survived an average of at least half of the expected lifetime from onset. Most investigations30,31,33,35 reported an increased fre¬ quency of suicide for patients with HC, but they all con¬ tain sources of error that render conclusions on the extent of the suicide risk unreliable. TRAUMATIC SPINAL LESIONS and Bors36 examined 2011 patients who had Nyquist been admitted to an American hospital in the period from 1946 to 1965 (Table 4). Twenty-one patients committed suicide, which corresponds to 1.3% of all patients and 8.1% of all deaths. The frequency was almost equally distributed for all forms of sequelae of spinal lesions. The majority of the suicides were in young patients under 30 years. An evaluation of a possible increase in the mortality rate for suicide in the patient population was not made in the
investigation.
Geisler et al37,38 conducted two investigations on mortal¬ ity in patients with traumatic spinal lesions. One investi¬ gation covered the period from 1945 to 1973 and comprised 1501 patients; the other covered the period from 1973 to 1980. The investigations covered a representative group of patients who had survived the early period after the trauma, and information on causes of death was available for 98% of the patients. The investigation contains a com¬ parison with an age-standardized healthy population, but the mortality rates were not calculated. A higher suicide frequency than for the general population was found, however, and the risk increased as the general mortality for spinal lesions dropped. In another investigation, Le and Price39 examined 417 patients with spinal lesions in the period from 1963 to 1976. An exact calculation was made of the survival rate of pa¬ tients compared with that of a population matched for age
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Table 4.—Suicide Risk in Patients With Traumatic Source,
Study
No. of
Period
Nyquist and Bors,36
1946-1965
No. of
Subjects Suicides 2011
21
Spinal
Lesions
Follow-up Study
Increased Risk
Mortality Ratio
Yes
Yes
No
Standardized Comments
The
highest
number of suicides
among the young (
Neurologic Diseases
Methodologic Problems Elsebeth
Nylev Stenager, MD, Egon Stenager,
Objective.\p=m-\Thesuicide risk in patients with many neurologic diseases has been reported to be greater than that in the general population. Studies on the subject are, however, often encumbered with methodologic problems. We appraised these problems and, based on an evaluation, reappraised knowledge of the suicide risk in patients with specific neurologic diseases. Data Source.\p=m-\Usingthe computerized database MEDLINE, we identified all published reports with the key words suicide, attempted suicide, and neurologic diseases. Study Selection.\p=m-\Weassessed and reviewed studies concerning the most common neurologic diseases for methodologic problems in the study design. Data Extraction.\p=m-\Thefollowing methodologic problems emerged during our review: (1) choice of study type, ie, autopsy study or follow-up study; (2) choice of study population; (3) choice of control groups; (4) epidemiologic/ statistical methods used; and (5) validity of statistics reported. Data Synthesis.\p=m-\Weanalyzed the methodologic problems in studies of patients with multiple sclerosis, epilepsy, Huntington's chorea, spinal cord lesions, cranial trauma, \s=b\
brain tumors, Parkinson's
disease, vascular disorders, and
migraine. In most of the studies, the methods used gave rise to uncertainty about the conclusion presented.
Conclusion.\p=m-\Anincreased suicide risk was found in patients suffering from multiple sclerosis and spinal cord lesions as well as in selected groups of patients with epilepsy. In other neurologic diseases, the suicide risk may be increased, but the results are uncertain due to the methodologic problems in the study design. (Arch Neurol. 1992;49:1296-1303) well known that the risk of suicide patients with It ismental disorders, such schizophrenia and manic de¬ than that in the is in
as
general pop-
pressive psychoses, greater
Accepted for publication June 26,
1992.
Research, Department of Psychiatry and Research Unit, Odense (Denmark) University. Presented in part as a poster at the Fourth European Symposium on Suicidal Behaviour, Odense, Denmark, June 12, 1992, and at the Third Meeting of the European Neurological Society, Lausanne, Switzerland, June 29, 1992. Reprint requests to the Neuropsychiatric Research Unit, Odense University Hospital, Odense, Denmark (Dr Stenager). From the Institute of Clinical
Neuropsychiatric
MD
ulation.1,2 We also know that the risk of developing a men¬ tal disorder in connection with a number of neurologic diseases is significantly greater than that in the healthy population. For example, patients with multiple sclerosis (MS), epilepsy, or cerebral insult are at greater risk of de¬ pression.3 The lifetime risk of suicide for patients with de¬ pression is estimated to be about 15%.1 However, in a re¬ cent follow-up study involving 4022 patients with affective disorders, the standardized mortality ratio (SMR) for sui¬ cide was 26 compared with the general population.4 It is known that patients with a neurologic disease are vulner¬ able to depression. It seems reasonable, therefore, to assume that they are also at greater risk of suicide than the
general population. In devising preventive measures against suicide for this patient group, it is imperative to know exactly which dis¬ eases are likely to involve an increased suicide risk and, if possible, when in the course of the particular disease and
for which age groups the risk is greatest. The literature concerning suicide among patients with neurologic diseases is extensive. The choice of method in earlier overview articles on neurologic diseases and sui¬ cide risk5"7 was rarely criticized. However, the diversity of methods used in the various investigations makes com¬ parison difficult. Moreover, the conclusions drawn are not always incontestible. Before reviewing the literature, it is therefore necessary to examine thoroughly the méthod¬ ologie weaknesses most frequently encountered. The purpose of this review is, therefore, to describe the errors most likely to occur in research on the méthodologie suicide risk for specific patient populations and to exam¬ ine the literature on the suicide risk for patients with neu¬ rologic diseases. METHODOLOGIC PROBLEMS THAT ARISE WHEN ASSESSING THE SUICIDE RISK The aspects examined include (1) type of investigation,
(2) investigation
populations, (3) suitability of control epidemiologie/statistical methods used, and (5) validity of suicide statistics presented.
groups, (4)
Type of Investigation As a rule, one of the following three types of investiga¬ tion is made: (1) autopsy investigations reporting the number of patients with a particular neurologic disease
Downloaded From: http://archneur.jamanetwork.com/ by a Yale University User on 05/15/2015
who committed suicide; (2) follow-up investigations on the number of patients who, in a defined period of time, were in specific specialized departments and com¬ hospitalized mitted suicide; or (3) epidemologic investigations based on registers recording clearly defined patient populations. Specific problems arise in connection with investigations based on autopsy studies. Their weakness lies in the dif¬ ficulty in finding a representative control group, as most autopsy studies consist of a selected patient population, partly composed of forensically examined cases and partly of selected hospitalized cases. Some investigations have sought to surmount this problem by making a comparison with the prevalence of the disease studied in the general population, ie, a comparison of the living with the dead. It can, therefore, hardly be expected that the composition of age and sex is the same in both populations. Therefore, the conclusions reached must be interpreted with great caution. The population
suitable for investigation registers covering large group of patients with a par¬ ticular disease in which both those who are severely ill and those with a mild form of the disease are recorded. Only in this way is it possible to assess the suicide risk present for all patients having the disease. Furthermore, only ex¬ tensive registration can form the basis of an optimal epidemiologie/statistical method by which an evaluation of the suicide risk can be made. There are, however, so few such registers available that optimal investigation by that method is hardly possible. are
sources
most
Epidemiologic/Statistical
Procedures A great variety of methods were used in the investiga¬ tions reviewed herein. A calculation may have been made of observed and expected deaths based on the suicide risk in the general population, or a percentagewise comparison may have been made of the number of patients with a par¬ ticular disease who have committed suicide relative to a control group. Finally, a few investigations include a cal¬ culation of an SMR for age and sex, and in addition con¬ trol of years at risk (ie, the period from disease onset/ diagnosis to suicide), which is the optimal method. The great diversity of methods makes it difficult to compare the investigations. Consequently, many of the authors of earlier overview articles compared diversely selected subjects, thereby reaching conclusions that were directly misleading. Finally, it should be mentioned that a small number of case histories are to be found, but general conclusions about the risk of suicide cannot be drawn from them.
a
Population Used Selection.—It is a serious problem that the populations investigated are often highly selected and that the popu¬ lation most often consists of patients who have been hos¬
pitalized in a specialized department. Consequently, they of the most seriously ill patients, which in turn means that the results are unlikely to be generally appli¬ cable to all patients suffering from the particular disease. There is, in addition, the question of dropouts resulting from selection bias, for example, those for whom it has been impossible to obtain information on the cause of are made up
death. Definition of Disease.—Many of the diseases in ques¬ tion are not always precisely defined in an investigation, nor are the criteria for the presence of the particular disease always sufficiently stringent. This applies particularly to
investigations concerning epilepsy. Small Populations.—In many investigations, the popu¬ lations used are small, often amounting to about 100 patients. As suicide is rare (in Denmark, 30 per 100000 population per year), the reliability of the results based on such small populations is questionable.
Selection of Control Groups When evaluating the risk of suicide for a specific group, it is usual to make a comparison with the general popula¬ tion. This has been done in many investigations but with¬ out taking into account that the suicide risk varies de¬ pending on age and sex. Therefore, overestimation or underestimation of the risk may occur in the absence of relativity to age and sex compositions in the patient pop¬ ulation. As the populations investigated generally are small, the danger of producing misleading results is great.
Validity of Suicide Statistics It is precisely in the case of the death of a patient who had had a serious physical disease that a tendency is seen to ignore the possibility of suicide as the cause. Instead, the event is accepted as the natural death of a seriously ill per¬ son.
The risk of suicide can in this way be underestimated.
Moreover, the suicide statistics in many countries
are
not
always likely to be reliable, especially when the cause of death is such a controversial issue as suicide. Thus, it is clear that investigations of the frequency of suicide for patients with a chronic disease should be
closely examined before significant conclusions are drawn on
the extent of the risk involved.
SUICIDE ATTEMPT The sources of error inherent in some investigations on the subject of attempted suicide are not described herein, but the pitfalls are in principle the same as those already mentioned. It is believed to be more relevant, however, to emphasize herein that the problems concerning the valid¬ ity of the investigations available on attempted suicide are significantly greater than in the case of suicide. AUTOPSY STUDIES A number of studies with large populations have sought to examine the suicide risk connected with a long list of diseases, including neurologic diseases. Whitlock7 exam¬ ined 1000 cases of suicide in England and Wales for the period from 1968 through 1972. He compared the number of suicides among persons with a specific disease with the prevalence of suicide in the general population. He found that the suicide risk for persons with epilepsy, MS, cranial trauma, and cerebral tumor was significantly greater than in the general population. In the same way, Stennsmann and Sundquist-Stensman8 examined 416 suicides for the period from 1977 to 1984 in Sweden and also found an increased suicide risk for per¬ sons with neurologic diseases. The methods used in both investigations, in which a comparison was made of the distribution of a disease in persons who had committed suicide with the frequency of the disease in the general population, can hardly defend the conclusions drawn in the investigations, as it cannot be presumed that distribu¬ tion by age and sex in the general population is identical
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Table 1.—Suicide Risk in Patients With No. of
Source, Study Period
Subjects
No. of Suicides
Multiple Sclerosis
Autopsy Follow-up Standardized Study Study Mortality Ratio
Increased Risk
Schwartz and Pierron,'2 1972
408
Yes
No
No
No
Sadovnick et al," 1 972-1 988
31 26
Yes
No
No
Yes
Kurtzke
al," 1942-1951 Stenager et al,18 1953-1 985 Leibowitz et al,14 1960-1966 et
Control group
not sex-
adjusted
476
1
No
Yes
No
No
No calculation of suicide risk
6088
58
No
Yes
1.83
Yes
Correct statistical method
295
8
No
Yes
No
Yes
that in the population committing suicide. In addition, the varying mortality rate of the disease is also of consequence. to
FOLLOW-UP STUDY Allgulander and Fisher" conducted a follow-up investi¬ gation in Sweden of a randomly selected group of all pa¬ tients admitted to the hospital following self-poisoning in the period from 1974 to 1985. An attempt was made to identify predictors of suicidal behavior (suicide and attempted suicide). With use of a Cox regression model, it was found that in men diseases of the central nervous system increased the risk of repeated suicide attempts. However, few men have diseases of the central nervous system, so the result may be explained by a chance occurrence (ie, spurious finding) and therefore the question should be examined in other populations for
confirmation.
MULTIPLE SCLEROSIS Several investigations have been conducted to assess the connection between the risk of suicide and MS (Table 1). Müller,10 McAlpine et al,11 Schwartz and Pierron,12 and Kurtzke et al13 did not find an increase in the suicide risk in their investigations, which were based on small patient groups. In an Israeli study,14 it was found that the suicide was 14 times greater for patients with MS. Sadovnick et al15 found that among 80 deceased patients with MS, 13 had committed suicide. In a Danish pilot investiga¬ tion16,17 of the period from 1973 to 1985, five of 56 deaths were found to be due to suicide. In all the investigations mentioned, no age or sex standardization was conducted in the comparison with the control population. To date, the most extensive and methodologically cor¬ rect investigation18 of the frequency of suicide in patients with MS involved 6088 patient entries in the Danish Scle¬ rosis Register. In this investigation, SMRs were calculated. The SMR for men diagnosed while younger than 40 years was determined to be 3.12 (95% confidence interval, 2.01 to 4.60) and for women diagnosed within the same age range it was determined to be 2.12 (95% confidence inter¬ val, 1.13 to 3.62). Patients diagnosed after the age of 40 were not found to be at greater risk for suicide. The period of greatest risk is, according to the investigation, the first 5 years after diagnosis. The cumulative lifetime risk of com¬ mitting suicide is 1.95%. In a recently published American investigation, Sadovnick et al19 found a significantly greater suicide risk than was found in the Danish study, ie, a risk that was 7.5 times greater. The SMR was not calculated, nor was sex standardization conducted. Therefore, the skewed sex
frequency
Comments
No adequate statistical method used
distribution of the disease may become a source of consid¬ erable error. It may be concluded, then, that patients with MS are at greater risk of committing suicide than the gen¬ eral population, but the risk involved is slight and is con¬ fined to younger patients. EPILEPSY correlation between disease and sui¬ cide risk, epilepsy has been most thoroughly investigated (Table 2). As early as 1941, Prudhomme20 published an in¬ vestigation in which he examined, over an extended period, 75 000 patients admitted with the diagnosis of ep¬ ilepsy and found 67 suicides. Because of the method used, the investigation could merely confirm that suicide oc¬ curred in that particular patient group, but its frequency could not be established on that basis. In a Danish study21 published in 1970, mortality in a representatively selected large group of epileptics was ex¬ amined. The purpose of the study was to register and dif¬ ferentiate the assessment of the epileptics' application for life insurance, which explains why the control group cho¬ sen was made up of the company's elite customers and not the general population. Cause of death, including suicide, was compared between the two groups, and it was found that the risk of suicide was three times higher for epilep¬ tics. No information on age and sex standardization was given. Furthermore, the control group selected may be presumed to be a low-risk group and therefore overestimation of the suicide risk is likely. Zielenski22 conducted a study of all the persons with ep¬ ilepsy in Warsaw, Poland, by examining all accessible pa¬ tient sources. In the period from 1967 to 1969, 239 deaths occurred. The mortality rate in 1969 was calculated and was found to be significantly high. The suicide risk was five times higher for men and 10 times higher for women. The results were not standardized for age, and the com¬ parison population was not described. A large follow-up investigation23 concerned 2099 epi¬ leptics who were admitted to Chalfont Centre, Chalfont St Peter, Buckinghamshire, England, because of epilepsy be¬ tween 1931 and 1971 and who were treated with anticon¬ vulsant drugs and followed up until 1977. The suicide rate was compared with that in the control population, age and sex standardization was conducted, and the risk span was taken into account. The investigation revealed a suicide increase that was 5.4 times greater (95% confidence inter¬ val, 3.3 to 8.2). The method used in the investigation is so far the most reliable one identified in our review. In a Finnish investigation24 of 179 deaths of previously admitted epileptics, 13 were found to be due to suicide, which is significantly more than in the general population In the context of
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a
Table 2.—Suicide Risk in Source,
Study
Period
Prudhomme,20
undefined Henriksen et al,2
No. of
No. of
Subjects Suicides Autopsy
Followup
Epileptic
Increased Risk
Patients
Standardized Ratio
Mortality No
75 000
67
No
Yes
2763
21
No
Yes
3 times
No
6710
12
Yes
Males, 5 times; females, 10 times
No
Yes
5.4 times
5.4
No
3 times
No
1950-1964
Comments
The study confirmed the presence of suicide In this patient group The control group selected from low-risk persons; no age or sex
adjustment Zielenski,22
1965-1969
White et al,23
2000
21
179
13
Undefined control group;
adjustment Age-adjusted
no
age
or
sex
1931-1971 Ivanainen and
Yes
Lehtimen,24
Strongly selected high-risk population; no age or sex adjustment
1900-1976
investigation dealt with a highly selected of epileptics, and neither age nor sex standardiza¬ group tion was performed. In their overview article published in 1981, Matthews and Barabas25 reviewed the literature on the correlation between suicide risk and epilepsy. They examined a num¬ ber of small investigations on deaths in selected epileptic populations in various countries and reached a total suicide frequency of 5%. This rate is in comparison with the frequency of 1.4% in the American general population, and Matthews and Barabas presented the result as evidence of a significantly higher suicide risk for epileptics. The valid¬ ity of the method used is disputable, and therefore the re¬ sults cannot be taken as documentation of a higher suicide risk among epileptics. Barraclough5 has published an extensive review of the literature available on the suicide risk for various groups of epileptics. He found that the risk for patients with tem¬ poral lobe epilepsy is five times higher and for those with a form of the disease that is difficult to treat it is 25 times higher. In this investigation as well, the number of observed and expected patients committing suicide is taken from a long list of variously selected materials from several countries, the sum total of which is used to reach a conclusion, the basis of which is methodologically unsound. In the context of method used in the investigations re¬ viewed herein, one is found to be above criticism,23 while the remainder are open to a great likelihood of error in the estimation of the risk of suicide for epileptics with varying degrees of disease severity. In the investigation in ques¬ tion, it was found that the risk of suicide was 5.4 times greater for patients receiving medicinal treatment for ep¬ ilepsy. No recent investigations of the suicide risk for ep¬ ileptics could be found, but it could be expected that with the advent of the improved treatment options now avail¬ able for these patients, the suicide risk for the group has decreased. in Finland. The
EPILEPSY AND ATTEMPTED SUICIDE Hawton et al,26 during a 2-year period, examined the frequency of epilepsy among patients admitted to the hos¬ pital following attempted suicide. The number of at¬ tempted suicides among epileptics is compared with the prevalence in the general population and found to be five times greater. The patients had more often undergone psychiatric treatment and had previously attempted sui-
cide more often than people in the control population. Méndez et al27 compared epileptics who had attempted suicide with a matched group of suicide attempters not suffering from epilepsy. The conclusion of the investiga¬ tion was that epileptics more frequently have borderline personality disturbances, psychotic disorders, and previ¬ ous suicide attempts. HUNTINGTON'S CHOREA Huntington's chorea (HC) is an autosomal dominant hereditary disease that is characterized by progressive de¬ generation of the central nervous system, personality changes, and dementia. Because of its course, the disease presents a special problem when assessing the suicide risk. As early as 1872, when describing the disease, Huntington28 pointed out that the tendency to mental illness, par¬ ticularly the form of disorder associated with suicide, was pronounced. There are distinct problems involved when assessing the suicide risk associated with HC. Because of its genetically dominant heredity, the patient is, from fam¬ ily experience (ie, parents, siblings suffering from the dis¬ ease), surely aware of the consequences of the disease. Awareness of the 50% risk of contracting the disease is something that must be lived with, particularly in the pe¬ riod in life when planning a family or choosing an educa¬ tion or occupation. For the majority of patients, the onset of the disease occurs at about the age of 40 years, and the average survival time from that point is 10 to 20 years. There has been great interest, therefore, in finding ways to identify the patients who are liable to contract the dis¬ ease, and new tools have been devised to identify disease carriers, ie, the DNA marker. Use of these tools, however, implies that serious consideration should be given to the humane and ethical aspects involved. It would naturally be a relief for some patients to learn that they were not in danger of contracting the disease, while at the same time the burden of being a genetic carrier is great. Interview in¬ vestigations have been conducted with relatives in the group at risk. In one such investigation,29 67 persons with a father or mother with HC were interviewed. Forty per¬ cent of them knew of suicidal behavior in their family, 78.8% wished to be tested for the disease if possible, 71% were prepared to undergo elective abortion on confirma¬ tion of the HC gene in their embryo, and 11 % mentioned suicide as a way out should the test result prove to be pos¬ itive. Such a test should have a high predictive value. Fur¬ thermore, there must be complete awareness of the conse-
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Table 3.—Suicide Risk in Patients With Source,
Study Period Reed and Chandler,30
Huntington's
No. of Patients
No. of Suicides
Autopsy
Study
Follow-up Study
Increased Risk*
203
3
No
Yes
No
et
al,3'
506
20
Yes
No
population, adjustment
Under 50:
OR=1.06;
over
50: OR=8.19
Saugstad and 0degârd,33
199
1
No
Yes
Farrer,35 undefined
452
25%
Yes
No
Comments
Small
1940-1956
Schoenfeld 1980-1983
Disease
No
1916-1975
Increased 4 times
no
age
or sex
Selection due to unsure cause of death for one third of the
population psychiatric population, use high-risk population as controls No age adjustment, a large number of dropouts
Selected
OR indicates odds ratio.
quences of
screening the group at risk, including the of possibility increased suicide risk. The investigations dealing with the risk of suicide for patients with HC and their relatives are reviewed in Table 3. Reed and Chandler30 examined patients who, with use of various sources, were found to have definite HC. The patients were followed up until 1956. Several examinations were performed, one on the occurrence of suicide in the family and one in a population of patients who were alive in April 1940. The first group showed an increased suicide risk compared with that in the healthy population, three times greater for men and five times greater for women. However, no increase was found for the second group examined. The selection of the patient population in the investigation poses some problems, as the sample is small and no age standardization was performed, which means that the increased suicide mor¬ tality in the family that is found should be interpreted with
including
caution.
Schoenfeld et al31 examined 506 patients, 403 of whom had a definite diagnosis and 103 of whom had a probable one. They found 20 suicides in the population, which cor¬ responds to an increase by five times for suicide risk for patients older than 50 years, while the risk for those younger than 50 years was not increased. Cause of death, however, could only be established with certainty for one third of those examined. This means that the suicide risk may have been underestimated. The authors therefore also investigated the population with known cause of death and found that the risk was three times greater for persons younger than 50 years and 23 times greater for persons older than 50 years. There are elements of uncertainty in the investigation concerning selection, and consequently uncertainty about the causes of death for two thirds of the patients. In a letter to the readers, Chiù and Aleksander32 stated that in their study population they did not find an increased suicide risk for patients with HC. Saugstad and 0degard33 examined all patients with HC who were admitted to psychiatric departments in Norway from 1916 to 1975. They found one suicide and one suicide attempt; compared with the yearly number of suicides in psychiatric patients, the expected number would have been two suicides. The population included only patients who had been admitted to a psychiatric department. On the other hand, it could have been expected that these pa¬ tients would constitute those at highest risk of suicide in the HC group. The control group used was also composed of psychiatric patients who, in an earlier investigation,34 were found to have a significantly higher mortality rate by unnatural causes. The conclusion must be that patients
with HC do not have a higher mortality rate than patients who have been admitted to psychiatric departments and not that which the authors contend, ie, that suicide is rare, as a high-risk group was used as a control group. Farrer35 examined 452 patients known to have HC and found that 5.7% of all deaths were due to suicide. This was correlated with the suicide frequency in the general Cana¬ dian and American populations, which was 1.5%, so that the conclusion was that the suicide risk for patients with HC was four times greater than that for the general pop¬ ulation. There was a dropout rate of about 20% in the pa¬ tients for whom the cause of death was not reported. No correlation was found for point of disease onset and prob¬ ability of suicide, nor was a connection with the particular clinical disease type found. Those who committed suicide had survived an average of at least half of the expected lifetime from onset. Most investigations30,31,33,35 reported an increased fre¬ quency of suicide for patients with HC, but they all con¬ tain sources of error that render conclusions on the extent of the suicide risk unreliable. TRAUMATIC SPINAL LESIONS and Bors36 examined 2011 patients who had Nyquist been admitted to an American hospital in the period from 1946 to 1965 (Table 4). Twenty-one patients committed suicide, which corresponds to 1.3% of all patients and 8.1% of all deaths. The frequency was almost equally distributed for all forms of sequelae of spinal lesions. The majority of the suicides were in young patients under 30 years. An evaluation of a possible increase in the mortality rate for suicide in the patient population was not made in the
investigation.
Geisler et al37,38 conducted two investigations on mortal¬ ity in patients with traumatic spinal lesions. One investi¬ gation covered the period from 1945 to 1973 and comprised 1501 patients; the other covered the period from 1973 to 1980. The investigations covered a representative group of patients who had survived the early period after the trauma, and information on causes of death was available for 98% of the patients. The investigation contains a com¬ parison with an age-standardized healthy population, but the mortality rates were not calculated. A higher suicide frequency than for the general population was found, however, and the risk increased as the general mortality for spinal lesions dropped. In another investigation, Le and Price39 examined 417 patients with spinal lesions in the period from 1963 to 1976. An exact calculation was made of the survival rate of pa¬ tients compared with that of a population matched for age
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Table 4.—Suicide Risk in Patients With Traumatic Source,
Study
No. of
Period
Nyquist and Bors,36
1946-1965
No. of
Subjects Suicides 2011
21
Spinal
Lesions
Follow-up Study
Increased Risk
Mortality Ratio
Yes
Yes
No
Standardized Comments
The
highest
number of suicides
among the young (
