Mortality and late-onset affective disorder

Journal of Affectroe Disorders, 5 Elsevier

Mortality

(I 983) 297-304

297

and Late-Onset

Affective Disorder

N.J.R. Evans ‘,* and F.A. Whitlock

2,*a

’ Department of Psychiatry, Unioersrty of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ (Great Britarn) and ’ University of Queensland, Brisbane (Australia) (Received 23 December, (Accepted 15 February.

1982) 1983)

Summary Psychiatric illness is associated with increased morbidity and mortality from physical illness. A particular association between depression and reduced expectation of life in males has been previously noted. If depression is a manifestation of incipient fatal illness, it might be predicted that those who had not previously been depressed would be at greater risk of dying in the next few years. This was not confirmed in a j-year follow-up study, which found a higher overall mortality from natural causes in male patients with both late and early onset of depression.

Introduction Numerous studies (for review see Rorsman 1974) have demonstrated that psychiatric patients have higher mortality than the general population. Most of the evidence has come from following-up inpatients, but Innes and Millar (1970) and Rorsman (1974) report similar findings from total groups of outpatients and inpatients referred over a period to their respective psychiatric services. The mortality is highest amongst elderly patients with organic syndromes (Kay 1962; Varsamis et al. 1972) as might be expected, although Rorsman found that the excess was most marked in younger age groups where the background mortality was very low. Suicide and other unnatural deaths make a substantial contribution, but most investigators have found a significant excess of deaths from natural causes in many different psychiatric disorders. A notable exception to this is the work of Tsuang and

N.J.R.E. is supported by an M.R.C. Project Grant to Professor Roth. * Present address: Consultant Psychiatrist, Coney Hill Hospital, Coney Hill, Gloucester. ** Professor Emeritus.

0165-0327/83/$03.00

0 1983 Elsevier Science Publishers

B.V.

298

his colleagues who in a series of papers (1977, 1978, 1980a. b) examined mortality over 30-40 years in patients suffering from schizophrenia, mania and depression. They considered that each of these diagnostic groups had raised death rates, particularly in the first 10 years of follow-up, but when suicide and accidental death were excluded, there was no significant excess of deaths in males with mania and males and females with depression (Tsuang et al. 1978). Mortality is likely to be a reflection of morbidity and several investigators have found a high prevalence of physical illness in psychiatric populations (recently reviewed by Kathol and Petty 1981). Of the various possible explanations for this association, the one with which the present study is most concerned is that physical illness may be an aetiological factor in psychiatric illness. In the absence of direct methods of proving a causal link, few authors have offered evidence for one. However, Roth and Kay (1956) compared late and early onset cases of affective disorder with respect to physical illness: in the case of males aged 60 and over the late onset group has a higher prevalence of chronic physical illness than the early onset group, and it was considered an important aetiological factor. A more specific association, that between cancer and affective disorders, has also been the subject of many investigations, most recently reviewed by Petty and Noyes (1981). Kerr et al. (1969) and Whitlock and Siskind (1979) in 4-year follow-up studies of depressed patients found a higher than expected mortality from cancer among males but not among females. Most of these patients had suffered their first attack of depression in middle age or later. Varsamis et al. (1972) studying elderly patients found that those with affective disorders had a normal survival rate, but malignant disease was a relatively common cause of death. Evans et al. (1974) did not find that cancer contributed disproportionately to the increased mortality which they observed in both sexes. Niemi and Jaaskelainen (1978) sought for a differential cancer morbidity in unipolar and bipolar depressives, but found no significant increase in either group. Tsuang et al. (1980a, b) discussed some of the methodological problems of determining cancer rates in groups of patients whose illness patterns differ from those of the general population, and concluded that the incidence of cancer in the Iowa series was not significantly abnormal. If late onset depression is a forerunner of fatal illness within the next few years one might anticipate that older patients with recurrent depression would have no greater than expected death rates. Hence one needs to look at patients aged 40 and over and compare those with first attacks of illness with those whose first affective disturbances had occurred earlier in life. With this problem in mind we attempted to follow-up a number of patients who had been admitted to hospital suffering from a depressive illness so see how many had died over the subsequent 5 years.

Method The cohort was assembled by examining the hospital records of all patients aged 40 and over admitted to Fulbourn Hospital in 1973. The case notes of those in whom depression was recorded as a prominent symptom were collected, whether or

299

not the clinician’s primary diagnosis was depression. Further scrutiny resulted in the exclusion of those in whom the depressive syndrome was judged to be secondary to, or had occurred in, a setting of another identifiable disorder such as dementia or schizophrenia. This left 67 females and 47 males with clear-cut depression but no attempt was made to subdivide the group into different depressive syndromes. Basic demographic information was extracted from the notes and particular attention was given to details of date of onset of the index illness and previous psychiatric illnesses and admissions. Usually there was clear evidence on whether the index admission was for a first or a recurrent illness. In most examples of the latter there were written records of previous admissions. The follow-up was conducted primarily by a short postal questionnaire to the patient’s last recorded general practitioner, and then by inquiries to other general practitioners and hospitals, local Registrars, and the central index of the Office of Population Censuses and Surveys. Searches were also made of case notes in general hospitals in Cambridge, and of post-mortem records. We obtained information on physical and psychiatric illness, and death up to the end of 1978, giving a minimum follow-up period of 5 years from admission. Mortality data for the general population of the East Anglian Hospital Region were supplied by the Information Services of the Cambridgeshire Area Health Authority (Teaching).

Results

Sample We were able to obtain adequate data for the all 47 males and for 65 out of 67 females. One emigrated soon after discharge from hospital, and by the general practitioner to have died, we certificate. The follow-up findings are summarized

whole of the follow-up period for of the two untraced patients had in the case of 1 male patient said were unable to trace the death in Table 1.

Overall mortality Table 2 shows the mortality in the years 1974- 1978; three deaths occurred during 1973, but mortality calculations have not been done for this year during which the cohort was continually enlarging as the patients were admitted to hospital. The observed mortality is compared with expected figures, standardised for age, derived from the general population data. The males show a significant excess of deaths, most marked in the first 3 years, but continuing even into the 5th year of follow-up. Five out of the 15 deaths in 1974- 1978 were suicides, the anticipated highly significant excess, but the remaining deaths from natural causes are still significantly more numerous than in the general population. In contrast, the females show only a small excess of deaths, which does not reach significance; when deaths from natural causes alone are considered by excluding the single suicide, the excess is of course even smaller.

300

TABLE

1

SUMMARY

OF FOLLOW-UP

Females Total sample: 67 traced: 65 2 untraced: 55 alive: 21 well 29 had further psychiatric illness 12 had further physical illness (7 had both)

10 dead: 1 suicide 1 cancer 8 other natural

deaths

17 dead: 5 suicides 2 cancer 10 other natural

deaths

Males

Total sample: traced:

47 47

30 alive 6 well 21 had further psychiatric illness 7 had further physical illness (4 had both)

Middle-aged and elderly men admitted to hospital with depression have once more been found to have an excessive mortality in subsequent years. The findings support the usual contention that not only are suicides more frequent, but also deaths from natural causes. Suicide noted here is the verdict recorded by the Coroner concerned. The practice of individual Coroners in assessing the evidence of suicidal intent is known to vary. In fact in this sample there were no other unnatural deaths which might have been regarded medically though not legally as suicide. Because the numbers are small, no conclusions are offered about separate natural causes of death. It must also be remembered that, apart from the suicide cases, no necropsies had been performed, and, therefore, the certified cause of death would have been based on clinical information at the time, and the results of any investigations previously performed. It is known that post-mortem examination is likely to lead to a different diagnosis of cause of death in a proportion of cases. For these reasons we are unable to shed any more light on the reported association between depression and occult malignant disease. It was a great merit of the study of Kerr et al. that a post-mortem was performed on most of their subjects, but equally it created the problem of finding a comparable control group, as the general population had a low post-mortem rate and tumours may go undetected. This question is discussed more fully by Whitlock (1978) where a comparison was made between previously undetected tumours found in two necropsy series, suicides and age-matched accident victims. The specific question which the present study aimed to answer is whether mortality is excessive only in those patients who are depressed for the first time.

1974 1975 1976 1977 1978

2

1

3 2 2

4 6 11 13 15 ***

1.08 0.99 0.93 0.79 0.79

3 5 7 8 IO *

I .07 0.98 0.92 0.78 0.78

tables (Biometrika)

4 5 5 ***

0.007 0.007 0.007 0.005 0.006

1 I

Observed

2.05 2.97 3.75 4.53

1.07

0.007 0.014 0.02 1 0.026 0.032

1 1

2 2 2

_ _

_

I **

1

3 2 2 1

1.08 2.07 3.00 3.79 4.58

Females Observed

’

Expected

Totals cumulated Expected

+ One death cause unknown, assumed to be natural. * P < 0.05; ** P < 0.01; ***P < 0.001from Poisson a Significance tested only for 1978.

suicide

Deaths excluding

-

1 **

1 ** 3 ***

1974 1975 1976 1977 1978

Observed

Males

Suicides

Year

4* 2+ 5 ** 2 2

1974-1978

1974 1975 1976 1977 1978

2

All deaths

DEATHS

TABLE

1.34 1.34 I .29 I .25 I .26

0.008 0.006 0.005 0.006 0.007

1.26 1.27

1.35 1.35 1.30

Expected

2 4 6 7 8

I I I I*

1

3 5 7 8 9

Observed

a

I .34 2.68 3.97 5.23 6.49

0.008 0.014 0.019 0.025 0.032

2.70 4.00 5.26 6.53

1.35

Expected

Total cumulated

302

TABLE

3

A. DEATHS DEPRESSION

1973-1978 - MALES

Age on admission

First attack

(yr)

No.

BY

35-44 45-54

1 3

1

55-64 65-74 75+

9 3 1

B. TAKING

FIRST

Late onset

(YU

No.

FIRST

OR

SUBSEQUENT

Suicides

NO.

ATTACK

Natural deaths

Suicides

5 8

_ 1

1 _

1 1 _

1 1 _

10 6 1

4 3 1

1 1 _

3 (17.6%)

2

30

9 (30%)

3

IN 1969 AS LATE/EARLY

OF

attack

_

ATTACK

Age on admission

AND

Subsequent Natural deaths

17

AGE

DIVIDING

LINE

Early onset Natural deaths

Suicides

No.

Natural deaths

Suicides

35-44 45-54

3 9

_ 2

_

2 3

_

1

55-64 65-74 75 +

13 I 2

2 3 1

2 2 _

6 2 _

3 1 _

_ _

34

8 (23.5%)

4

13

4 (30.8%)

1

Table 3 shows the findings for all the deaths including those which occurred in 1973, in standard age groups. The sample is divided in 2 ways first (A) by whether the index admission was occasioned by the first attack of depression and secondly (B) by whether there was a long or short history of affective disorder. The division here is placed in 1969, not arbitrarily, but from the observed distribution of dates of first attack. This was highly skewed: 17 of the men had their first attack in 1973 and a further 17 between 1969 and 1972; the remaining 13 were widely scattered with first illnesses between 1939 and 1966. Possibly in some of the later onset patients there were not two or more discrete episodes in a relatively short time, but one episode including partial remission and relapse. Alternatively, previously healthy individuals might have experienced repeated episodes of depression associated with deteriorating physical health. The natural history of affective disorders is very variable. In Table 3 (A) the suicide rate is little different between those having first or subsequent attacks, but the natural deaths are seen to have occurred at almost twice the rate amongst those who were not ill for the first time. However, this difference is

303

TABLE

4

SUMMARY Initials

OF MALE

DEATHS

Age on admission

Cause of death

Psychiatric

features

1st attack 1st attack Manic and depressive Recurrent 2nd attack: 1st attack 2nd attack; Manic and 1st attack 1st attack Recurrent Manic and

Recurrent depression since 1970 Manic and depressive attacks since 1959 2nd attack; 1st in 1948 1st attack 1st attack

(Yr)

KE RH JMcK

52 53 62

BM SM LM EM wo LP AR AS GW

66 62 69 78 68 69 63 62 64

Diabetes Carcinoma of lung Pulmonary embolism and intestinal obstruction Myocardial infarction Pulmonary embolism Cerebrovascular accident Bronchopneumonia Cardiac failure Renal failure Carcinoma of lung Cerebrovascular accident Uncertain

68 41 64 70 58

Multiple injuries Aspirin poisoning Barbiturate poisoning Drowning Extensive burns

attacks

since 1959

depression since 195 1 1st in 1971 1969 1st in 1971 depressive attacks since 1971

depression since 1954 depressive attacks since 1956

Surcide

JG HM GM AR EW

much

smaller

in (B)

where

the patients

are grouped

mortality rates by date of first onset 1969- 1973 - 5/ 17; pre 1969 ~ 4/13. Age confounding

in the way proposed.

The

of depression are: 1973 ~ 3/ 17; does not appear to be a significant

factor.

More details of the patients who died are given in Table 4, and the lack of any distinctive pattern is clear. We conclude then that, contrary to expectation, the appearance of depression for the first time is no more sinister than its re-appearance in a previously an increased

affected

subject,

risk of premature

but that any attack in middle and later life indicates death.

Acknowledgements We are grateful to Mr. R. Mitchell and Miss R. Thomas, Records Officers at Fulbourn Hospital, and their staff, for their help, to the Division of Psychiatry for permission to use their records, and to Sir Martin Roth for discussion of this work.

304

References Evans, N.J.R., Baldwin, J.A. and Gath, D., The incidence of cancer among inpatients with affective disorders, Brit. J. Psychiat., 124 (1974) 518-525. Innes, G. and Millar, W.M., Mortality among psychiatric patients, Scot. Med. J.. 15 (1970) 143- 148. Kathol, R.G. and Petty, F., Relationship of depression to medical illness, J. Affect. Dis.. 3 (1981) 111-121. Kay, D.W.K., Outcome and cause of death in mental disorders of old age - A long-term follow-up of functional and organic psychoses, Acta Psychiat. Stand., 38 (1962) 249-276. Kerr, T.A., Schapira. K. and Roth, M.. The relationship between premature death and affective disorders. Brit. J. Psychiat., 115 (1969) 1277-1282. Niemi, T. and Jllskelainen, J., Cancer morbidity in depressive persons. J. Psychosom. Res.. 22 (1978) 117-120. Petty, F. and Noyes, R., Depression secondary to cancer, Biol. Psychiat.. 16 (1981) 1203-1220. Rorsman, B., Mortality among psychiatric patients, Acta Psychiat. Stand., 50 (1974) 3544375. Roth, M. and Kay, D.W.K., Affective disorders arising in the senium. Part 2 (Physical disability as an aetiological factor), J. Ment. Sci., 102 (1956) 141-150. Tsuang, M.T. and Woolson, R.F., Mortality in patients with schizophrenia, mania, depression and surgical conditions, Brit. J. Psychiat., 130 (1977) 162-166. Tsuang, M.T. and Woolson, R.F., Excess mortality in schizophrenia and affective disorders - Do suicides and accidental deaths solely account for this excess? Arch. Gen. Psychiat., 35 (1978) 1181-1185. Tsuang, M.T., Woolson, R.F. and Fleming, J.A., Premature deaths in schizophrenia and affective disorders - An analysis of survival curves and variables affecting the shortened survival. Arch. Gen. Psychiat., 37 (1980a) 979-983. Tsuang, M.T., Woolson, R.F. and Fleming, J.A., Causes of death in schizophrenia and manic depression. Brit. J. Psychiat., 136 (1980b) 239-242. Varsamis, J., Zuchowski, T. and Maini, K.K., Survival rates and causes of death in geriatric psychiatric patients, Can. Psychiat. Asso. J., 17 (1972) 17-22. Whitlock, F.A., Suicide, cancer and depression, Brit. J. Psychiat., 132 (1978) 269-274. Whitlock, F.A. and Siskind, M., Depression and cancer - A follow-up study, Psychol. Med.. 9 (1979) 747-752.