Research report
Mortality of patients with mood disorders: follow-up over 34–38 years

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Abstract

Background: All follow-up studies of causes of death in affective disordered patients have found they have markedly elevated suicide rates and a less reproducible increased mortality from other causes. The reported rates by gender, disorder type and treatment are more variable. Methods: Hospitalised affective disordered patients (n=406) were followed prospectively for 22 years or more. Later, mortality was assessed for 99% of them at which time 76% had died. Results: Standardised Mortality Rates (observed deaths/expected deaths) for patients were elevated especially for suicide and circulatory disorders in both men and women. Women actually had higher suicide rates but that did not take into account the twofold increase in general population rates for men. Unipolar patients had significantly higher rates of suicide than bipolar Is or IIs. In all groups long term medication treatment with antidepressants alone or with a neuroleptic, or with lithium in combination with antidepressants and/or neuroleptics significantly lowered suicide rates even though the treated were more severely ill. Although at the age of onset the suicide rates were most elevated, from ages 30 to 70 the rates were remarkably constant despite the different courses of illness. Limitations: The patients were identified as inpatients and followed prospectively. The treatments were uncontrolled and are not quantifiable but were documented during the follow-up. Conclusions: Men and women hospitalised for affective disorders have elevated mortality rates from suicide and circulatory disorders. Unipolars have higher suicide rates than bipolar Is or IIs. Long term medication treatment lowers the suicide rates, despite the fact that it was the more severely ill who were treated.

Introduction

It is well known that psychiatric patients have elevated mortality rates that vary between 36 and 100% compared to the general population (Rorsman, 1974, Martin et al., 1985a, Martin et al., 1985b, Schwalb and Schwalb, 1987, Murphy et al., 1989). This was also demonstrated specifically for patients with mood disorders (Table 1) in clinical and epidemiological samples (Murphy et al., 1987, Zheng et al., 1997). The elevated mortality is mainly explained by suicide, but a number of other causes contribute to this elevation: death by accidents (Tsuang and Woolson, 1978, Weeke and Vaeth, 1986, Murphy et al., 1987, Murphy et al., 1989), secondary substance abuse (Eastwood et al., 1982), coronary heart disease (Weeke and Vaeth, 1986, Murphy et al., 1989, Sharma and Markar, 1994), cerebrovascular disorders (Baldwin, 1980, Schwalb and Schwalb, 1987, Zheng et al., 1997), respiratory infections (Baldwin, 1980, Schwalb and Schwalb, 1987, Sharma and Markar, 1994), thyroid disorders (Baldwin, 1980) and homicide (Hoyer et al., 2000). Mortality from neoplasms was not found to be elevated (Rorsman, 1974, Baldwin, 1980, Schwalb and Schwalb, 1987, Murphy et al., 1989).

The true suicide mortality is difficult to evaluate because an unknown number of patients may commit suicide at the onset of their illness before a diagnosis can be made. In this context psychological autopsy studies of suicides in the general population are of great interest. A classic paper of Robins et al. (1959) found that of 194 suicides, 101 had psychotic diagnoses. The most common diagnosis was manic-depressive illness in 60%. Barraclough et al. (1974) reported a very high rate of 86% and Coppen (1994) found among all suicides, 70% were depressed. Other studies found considerably lower rates: among adolescents studied in Finland (Marttunen et al., 1991) and in the USA (Brent et al., 1993) 50% of suicides were explained by depression; in adults only 20–30% of suicides were reported to be a consequence of depression (Dorpat and Ripley, 1960, Arato et al., 1988, Henriksson et al., 1993, Dilsaver et al., 1994).

Traditionally follow-up studies on mortality and suicide of patients with mood disorders were from hospitalised samples. Since the classic review of such studies by Guze and Robins (1970) it was generally assumed that on the average about 15% (range 12–19%) of depressed patients would commit suicide. But doubts were recently raised by Blair-West et al. (1997) who stressed on the basis of the prevalence of depression in the general population that such high suicide rates would far exceed the observed incidence figures. They pointed out that studies of inpatients carried an inherent bias in favour of high suicide rates: inpatients cannot be representative of all depressives as suicidality is one of the primary indications for admission. They estimated a much lower theoretical suicide rate of 3.5% for patients with affective disorders. In a new analysis they estimated a lifetime suicide rate of 3.4%, with a high preponderance of male suicides (6.9%) over female suicides (1.1%) as a consequence of major depression (Blair-West et al., 1999). Based on hospitalised samples several long-term follow-up studies of major depressives were carried out over 10 or more years applying identical criteria (Table 2). The suicide rates varied between 4 and 7% (Lee and Murray, 1988, Kiloh et al., 1988) or 10.6% (Winokur and Tsuang, 1975). Our preliminary results (Angst and Preisig, 1995) showed 13% suicides.

Still uncertain is the question of whether suicides would occur more frequently among bipolar patients or unipolar patients (Morrison, 1982). Most studies found no differences (Stallone et al., 1980) or even a higher mortality among unipolar depressives (Brent et al., 1993), this was recently confirmed by the large meta-analysis of Harris and Barraclough (1997).

Prospective community studies are still very rare and long-term follow-up studies on suicides do not exist with the exception of two investigations. The 25-year follow-up Lundby study of Hagnell et al. (1982) found 28 suicides (23 m, 5 f) among 3563 persons. Of these, 15 who committed suicide had suffered from depression. The age-standardised suicide rate in men with depression was 13-fold higher than that of the total cohort. In a much more restricted (age, follow-up) study, in a 2-year follow-up of the Piedmont sample of the epidemiologic catchment area study only 2.7% of elderly subjects (60 years and older) with major depressive episodes had committed suicide (Fredman et al., 1989). Compared to the normal population the relative risk was not elevated [0.9 (95% CI: 0.5–1.4)]. Because the Lundby study counted treated depressives rather than relying on diagnoses made by interviews of community samples, the diagnoses of both subjects and controls seem more valid and the results more dependable even though the numbers were small.

A large outpatient random sample study of Martin et al., 1985a, Martin et al., 1985b found only five cases of unnatural deaths among 253 patients with mood disorders followed-up over 7 years. None of the 137 patients with primary depression had committed suicide, all were in treatment. A private practice study of 42 unipolar depressive outpatients followed over 8.5 years (Morrison, 1982) estimated that the suicide rate was only slightly higher than in the general population.

From these data it is obvious that studies of community and outpatient samples give much lower suicide rates than studies of hospitalised patients.

Our investigation on suicide in affective disorders is limited to severe depressed or manic hospitalised patients. The purpose of the long-term follow-up is to analyse the mortality of unipolar depressives and bipolar patients compared to the normal population and to analyse the impact of an interval medication, given under naturalistic conditions between episodes, on mortality. The present analysis is an extensive up-date of earlier analyses (Angst, 1998, Angst, 1999, Angst et al., 1998).

Section snippets

Sample

The sample consists of 186 unipolar and 220 bipolar depressive or manic patients who were hospitalised between 1959 and 1963 in the Psychiatric Hospital University of Zurich with a diagnosis of mania or endogenous depression, endo-reactive depression, manic-depressive disorder or affective disorder with mood-congruent or mood-incongruent psychotic features (hallucinations or delusions) including schizoaffectives. Sixty-one percent of patients met criteria for psychosis over lifetime. Bipolarity

Results

Of the 406 patients 99.3% could be followed-up to the end of 1997. Three persons were lost by emigration. Table 3 gives a summary of the deaths: 83% of males and 72% of females had died. Persons still alive had a median age of 70 years and those who died a median age of 74 years.

Discussion

The present study is the longest recorded prospective follow-up (over 34–38 years) of a large sample of hospitalised patients with mood disorders. There is no similar study, in which the majority of subjects (76%) were followed-up repeatedly until their deaths. Therefore the data on mortality are probably representative for a severely ill patient population, of which 61% had manifested psychotic symptoms (mood congruent or mood-incongruent delusions or hallucinations) at least once over

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