Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, USA
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Correspondence: Dr Ramin Mojtabai, 200 Haven Avenue, Apt. 6P, New York, NY 10033, USA. Tel: (212) 7818413; Fax: (212) 7816345; E-mail: rm322{at}columbia.edu
Declaration of interest None. Partial support detailed in Acknowledgements.
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ABSTRACT |
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Aims To examine the long-term course and mortality of schizophrenia in patients with a poor 2-year course.
Method The report is based on two incidence cohorts of first-contact patients in urban and rural Chandigarh, India, originally recruited for the World Health Organization Determinants of Outcome of Severe Mental Disorders study. Patients were assessed using standardised instruments at 2- and 15-year follow-ups.
Results Ninety-two per cent of the patients with a poor 2-year course had a poor long-term course and 47% died a nine times higher mortality rate than among patients with other 2-year course types.
Conclusions In this developing country setting, a poor 2-year course was strongly predictive of poor prognosis and high mortality, raising questions about the adequacy of care for such patients.
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INTRODUCTION |
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METHOD |
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Patients were followed up and reinterviewed at 2 years as part of the DOSMeD study and at 15 years as part of another WHO-sponsored international study (Sartorius et al, 1996). At the 15-year follow-up, patient cohorts established in Chandigarh and a number of other sites in the DOSMeD and other WHO studies were reassessed using a comprehensive set of standardised instruments in addition to instruments used in the original DOSMeD study. The key instrument for rating the course of illness at the 15-year follow-up was the Life Chart Schedule (LCS; Susser et al, 2000). An abbreviated form of this instrument, the Broad Rating Schedule (BRS; Sartorius et al, 1996), was used to rate the course of illness for deceased patients and patients lost after the 2-year follow-up.
Sample
Two hundred and nine patients were originally recruited into the urban and
rural sites combined. Of these, 171 (82%) had a rating of course of illness at
the 2-year follow-up. Ninety-one (53%) of the 171 were male and 80 (47%) were
female; 118 (69%) were from the urban site and 53 (31%) from the rural site;
the average age of these patients at baseline was 26.7 years (s.d.=9.4).
One hundred and eleven (65%) of the 171 patients could be interviewed directly at the 15-year follow-up using the LCS. Twenty-four (14%) of the 171 had died by that time; a rating of the course of illness up to the time of death was made using the BRS. For another 19 (11%) patients who could not be located for the 15-year follow-up interview, information on the course of illness for up to an average of 10.5 (s.d.=3.3) years was available. For these patients too, a rating of course of illness was made using the BRS. In summary, information on the long-term course of illness was available for 154 (90%) of the 171 patients. Long-term course information was not available for 17 patients. Five of these were located but refused a follow-up interview, and another 12 were lost to follow-up with no information on the course of illness after the 2-year follow-up.
The sample for examining the association of the 2-year course and mortality comprised all 171 patients for whom information on the 2-year course, vital status and time of death was available. Of these, 15 had a poor 2-year course and 156 had other course types. The sample for examining the association of the 2-year and the long-term course comprised 154 of the 171, namely those for whom information on the long-term course was available. Of these, 13 had a poor 2-year course and 141 had other course types.
Ratings of course
Course in the first 2 years of follow-up was assessed using ratings of
pattern of course on the Psychiatric and Personal History Schedule (PPHS;
Jablensky et al,
1992). The PPHS was administered by a mental health professional,
often a psychiatric social worker or a psychiatrist who usually also
interviewed a key informant. Ratings of pattern of course had excellent
interrater reliability (Jablensky et
al, 1992). The ratings included seven patterns of course in
addition to continuous course (see
Jablensky et al,
1992). For the purpose of this study, a poor 2-year course was
operationalised as a rating of continuous psychotic illness (no remission)
with psychotic symptoms present most of the time. A poor 2-year course was
contrasted with other 2-year course types that included all other course
patterns.
Course of illness for subjects who participated in the 15-year follow-up
was assessed using the LCS (Susser et
al, 2000) a standardised instrument that provides
detailed ratings on the course of illness in multiple domains, including
residence, work, symptoms and treatment. The instrument was administered by a
mental health professional, often a psychiatric social worker or psychiatrist.
The LCS ratings have shown good interrater reliability
(Susser et al, 2000),
with excellent reliability for course of illness ratings (=0.90). The
course ratings covered the period since intake and included three course types
in addition to the continuous course type. For the purpose of this study, poor
long-term course was operationalised as a rating of psychotic over most of the
period. If there were any remissions, these were brief (not longer than 6
months). A poor long-term course was contrasted with other long-term course
types that included all other course patterns.
Ratings for the deceased and patients with partial follow-up were made using the BRS. The format of the items used for rating the course of illness on this abbreviated instrument was identical to that used in the LCS. All available information, including medical records and interviews with relatives (for deceased patients), were used to make these ratings.
Rating, time and cause of death
Rating of death and its time and cause were based on personal interviews
with the patient's survivors and supplemented by a review of medical records,
where available. No death register is available for this region.
Data analysis
Association of the 2-year course with the long-term course was examined in
two steps. First the risk for poor long-term course was compared between
patients with a poor 2-year course and those with other 2-year course types by
computing relative risks. Next, to control for the effect of potential
confounding variables, the association between 2-year and long-term course was
assessed using logistic regression in which the long-term course was the
dependent variable and the 2-year course was the independent variable. The
following variables were also included in the model to control for their
effects: gender, urban v. rural setting, narrow (S+) v.
broad (Non-S+) definitions of schizophrenia
(Wing et al, 1974;
Jablensky et al, 1992)
and the interval between onset and intake into the study
(Jablensky et al,
1992).
Association of the 2-year course with mortality was examined by two different methods. First, mortality rates were compared among patients with a poor 2-year course v. other 2-year course types. Age-standardised mortality rate ratios and 95% confidence intervals were computed using the age distribution of the group with other 2-year course types as the standard. The numerator for computation of mortality rate was the number who died, and the denominator was the number of person-years. Patients who were followed up to 15 years contributed 15 person-years, and those who died or were lost to follow-up before the 15-year follow-up contributed up to the time of death or loss to followup (the time-point when the research team last had any information about the patient). The Epitab routine of the Stata 6.0 computer program for Windows (StataCorp, 1999) was used for computation of the age-standardised rate ratio. Next, Kaplan-Meier survival curves were used to display visually the mortality risk among patients with a poor 2-year course v. other course types. The log-rank test was used to assess the statistical significance of differences in the survival rates of the two groups.
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RESULTS |
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Association of the 2-year course with mortality
As noted above, the sample for examining the association of the 2-year
course with mortality comprised 171 patients 15 with a poor 2-year
course and 156 with other 2-year course types. Of the 15 with a poor 2-year
course, 7 (47%) had died before the 15-year follow-up. Of the 156 with other
course types, on the other hand, only 17 (11%) had died by that time. The
difference in the proportion of patients who had died was statistically
significant (2=14.5, d.f.=1, P<0.001). The
age-standardised mortality rate ratio for patient groups with a poor 2-year
course over the other 2-year course types was 9.4 (95% CI 3.8-23.7)
(Table 2, column 7). As the
age-specific mortality rate ratios reported in column 6 of
Table 2 show, the increased
mortality was evident in all age groups. After excluding suicides, the
agestandardised mortality rate ratio was 8.7 (95% CI 3.0-25.4).
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The increased risk of mortality among patients with a poor 2-year course is illustrated visually by KaplanMeier survival curves in Fig. 1. Similar to the incidence rate ratio, the log-rank test indicated a statistically significant difference in the risk of mortality for the two groups (test statistic=4.0, P<0.001).
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For subjects who died the median time to death was 4.8 years after intake (3.3 years for the group with the poor 2-year course and 5.4 years for the group with other 2-year course types). Out of the seven deaths among patients with a poor 2-year course, the specific causes of death in six patients were known. These were suicide (two cases), acute nephrotic syndrome superimposed on malnutrition (one case), infectious gastroenteritis superimposed on malnutrition (one case), respiratory arrest associated with asthma (one case) and viral pneumonia (one case). The specific cause of one death was not known but the available information indicated a natural cause.
Out of the 17 deaths among patients with other 2-year course types, the specific causes of death in 11 were known. These were suicide (three cases), traffic accident (one case), renal failure (one case), stroke (two cases), heart failure (one case), acute myocardial infarction (one case), septicaemia (one case) and heat stroke (one case). In five of the six remaining deaths for which the specific causes were not known, the available information indicated natural causes. In one case, it could not be ascertained whether death was due to a natural cause or suicide.
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DISCUSSION |
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Long-term course
Of patients with a poor 2-year course, defined as a rating of continuous
psychotic illness at the 2-year follow up, 92% had a poor course in long-term
follow-up, which in most cases extended up to 15 years. This finding is
consistent with the 13-year follow-up study in the Nottingham site of the
DOSMeD project (Harrison et al,
1996), which reported a poor long-term prognosis for patients with
continuous psychotic course at the 2-year follow-up. Although fewer patients
in developing country settings compared to industrialised settings have a poor
2-year course (Jablensky et al,
1992), this course pattern appears to be highly persistent across
vastly different settings.
This finding might also have implications for aetiological research. The great diversity in the course and outcome of psychoses classified under the general rubric of schizophrenia is highly suggestive of aetiological heterogeneity (Tsuang & Farone, 1995). Findings from this study, as well as our earlier work (Susser et al, 1998) in which we examined the long-term course of psychoses with remitting course and acute onset, lend validity to the differentiation of some course patterns that are evident even in the early stages of illness.
Mortality
The high rate of mortality among patients with a poor 2-year course is
alarming. Most studies of mortality in schizophrenia have been conducted in
industrialised settings (e.g. Simpson
& Tsuang, 1996; Brown,
1997;
Ringbäck
Weitoft et al, 1998) and we were not able to locate any
previous mortality studies in an incidence cohort from a developing country
setting. In his 10-year follow-up study of a cohort of 101 patients in the
Colombian site of the International Pilot Study of Schizophrenia,
León
(1989) reported only two
deaths. However, that setting might be better classified as
semi-industrialised (Leff et al,
1992). Furthermore, the cohort was not an incidence cohort and the
duration of follow-up was shorter than in our study. Previous studies in
industrialised settings generally compared subtypes or categories based on
cross-sectional symptomatology and produced conflicting and overall weak
effects (Black et al,
1985; Wood et al,
1985; Allebeck & Wistedt,
1986; Black & Fisher,
1992). The magnitude of the effect for the schizophrenia subtypes
in those studies was much smaller than the effect of early poor course of
illness in the present study. Westermeyer et al
(1991) conducted one of the
few studies that examined the relationship of early course with long-term
mortality. In a 13-year follow-up study from Chicago, these authors compared
the suicide rates of patients with chronic and sub-chronic v. acute
and sub-acute schizophrenia, diagnosed according to the Research Diagnostic
Criteria (Spitzer et al,
1978). All of the suicides in this group of patients occurred in
the subgroup with a chronic or sub-chronic illness.
Implications for services
The high mortality rate among patients with a poor 2-year course raises
questions about the adequacy of care for this group of patients. In at least
two cases of death, the terminal illness was superimposed on malnutrition,
indicating that the unmet needs of these patients for such basic necessities
as food had contributed to their deaths. The better overall course and outcome
of schizophrenia in developing countries should not distract us from the
special needs of this small but highly vulnerable group of poor-prognosis
patients. The endemic poverty of many developing country settings might affect
this group of patients to a much greater extent than other patient groups
(Desjaralais et al,
1995). Because long-term residential care is scarce or
non-existent in most developing country settings, the burden of caring for
these patients often falls entirely upon the shoulders of their families
(Susser et al, 1996).
A daunting challenge facing mental health professionals and policy makers in
such settings is to recognise and accommodate the special needs of the
families of poor-prognosis patients.
Some information was available on the course of medication treatment for 7 out of 15 patients with a poor 2-year course in the sample for examining the association of course with mortality. Of these, only three had received treatment for most or all of the follow-up period. These data raise concerns about the continuity of treatment in this setting for patients with a poor course of illness.
Limitations
The findings from this study need to be considered in the context of its
limitations. First, not all of the members of the 2-year cohort could be
interviewed for the 15-year follow-up. For the deceased patients and those who
were lost to follow-up, the long-term course rating was based on a review of
medical records and/or interview with relatives. Ratings based on these
sources might not be as reliable as a direct and detailed follow-up interview.
It is reassuring, however, that the findings with regard to the association of
2-year course with long-term course were similar for patients with a complete
15-year followup (data not shown).
Second, the term developing country is often applied to settings with very different sociocultural, economic and care provision characteristics. Across these settings, one might expect differences with regard to association of short-term course with long-term course and mortality. Therefore, in generalising from this study to other developing country settings, great caution is called for. It is noteworthy, however, that we detected no meaningful differences between the urban and rural settings with regard to the association of short-term course with long-term course and mortality (data not shown). As noted earlier, urban and rural Chandigarh represent different sociocultural settings.
Third, in this setting, as in most other developing settings, no death register is available. Therefore, information on death, its timing and its cause was obtained from relatives and medical records, where available. Data obtained from these sources are less standardised than data from a death register, although perhaps more detailed.
Finally, the number of patients with a poor 2-year course was limited to 13 for examining the association of the 2-year with the long-term course and to 15 for examining the association of the 2-year course and mortality. Before replication in other studies with larger samples, the results of this study need to be interpreted with caution.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication February 28, 2000. Revision received July 10, 2000. Accepted for publication July 10, 2000.