Netherlands Institute of Mental Health and Addiction, Utrecht and De Galderse Roos, Institute for Mental Health Care, Arnhem
Netherlands Institute of Mental Health and Addiction, Utrecht
Research and Documentation Center of the Ministry of Justice, The Hague
Netherlands Institute of Mental Health and Addiction, Utrecht and Department of Psychiatry, University of Amsterdam
Department of Psychiatry, University of Groningen
University Medical Centre, Utrecht and Altrecht Institute for Mental Health Care, Utrecht, The Netherlands
Correspondence: Jan Spijker, Netherlands Institute of Mental Health and Addiction (Trimbos Institute), PO Box 725, 3500 AS Utrecht, The Netherlands. Tel: +31 302971100; fax: +31 302971111; e-mail: JSpijker{at}trimbos.nl
Declaration of interest The study was supported by The Netherlands Ministry of Health, Welfare and Sport, the Medical Sciences Department of The Netherlands Organisation for Scientific Research and the National Institute for Public Health and Environment.
See editorial, pp.
181183, this issue.
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ABSTRACT |
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Aims To assess the duration of MDE and its clinical and socio-demographic determinants in a study group drawn from the general population with newly originated episodes of major depression.
Method The Netherlands Mental Health Survey and Incidence Study is a prospective epidemiological survey in the adult population (n=7076), using the Composite International Diagnostic Interview. Duration of MDE over 2 years was assessed with a Life Chart Interview.
Results The median duration of MDE was 3.0 months; 50% of participants recovered within 3 months, 63% within 6 months, 76% within 12 months and nearly 20% had not recovered at 24 months. Determinants of persistence were severity of depression and comorbid dysthymia. A recurrent episode predicted shorter duration.
Conclusions Although half of those affected with MDE recovered rapidly, the risk of chronicity (duration 24 months or more) was considerable. This underlines the necessity of diagnosing and treating those at risk.
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INTRODUCTION |
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The primary aims of our study were (a) to investigate duration of major depressive episodes in detail over a period of 2 years in a cohort with newly originated episodes (first or recurrent) from the general population, and (b) to study potential socio-demographic and clinical determinants of episode duration. A secondary aim was to assess the effect of referral filter bias (by comparing episode duration across levels of care).
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METHOD |
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Psychopathology over the preceding 12-month period did not have a strong impact on attrition: at T1 agoraphobia (odds ratio 1.96) and social phobia (OR 1.37), and at T2 major depression (OR 1.37), dysthymia (OR 1.80) and alcohol dependence (OR 1.83), adjusted for demographic factors, were associated with attrition (de Graaf et al, 2000a, b).
Diagnostic instrument
Diagnoses of psychiatric disorders according to DSMIIIR
(American Psychiatric Association,
1987) were based on the Composite International Diagnostic
Interview (CIDI), version 1.1 (computerised version;
Smeets & Dingemans, 1993).
The CIDI is a structured interview developed by the World Health Organization
(1990) and has been found to
have acceptable interrater reliability and testretest reliability for
most diagnoses, including major depression
(Wittchen, 1994). The
following DSMIIIR diagnoses are recorded in the NEMESIS
data-set: schizophrenia and other non-affective psychotic disorders; mood
disorders (bipolar disorder, major depression, dysthymia); anxiety disorders
(panic disorder, agoraphobia, simple phobia, social phobia, generalised
anxiety disorder, obsessivecompulsive disorder); eating disorders; and
psychoactive substance use disorders (alcohol or drug misuse and dependence,
including use of sedatives, hypnotics and anxiolytics).
Study cohort
In order to include only newly originated episodes of major depression
(first or recurrent cases), respondents with a diagnosis of 2-year prevalence
of major depression at T2 but no diagnosis of 1-month prevalence at
T1 were identified (n=273). Those diagnosed with bipolar
disorder or a primary psychotic disorder were excluded.
Characteristics of participants with depression
Socio-demographic variables
Variables recorded at T0 were gender, age, educational
attainment, cohabitation status and employment status.
Clinical factors
Based on the CIDI, the following information on the index episode of
DSMIIIR major depression was obtained:
Care utilisation
At T2 respondents were asked whether they had received help for
mental problems within the past 24 months. We distinguished three levels of
care:
Duration of major depressive episode
The duration of major depressive episodes was assessed retrospectively at
T2, using the LCI (Lyketsos
et al, 1994). To improve recall, we used memory cues such
as personal events, birthdays or holidays in the past 2 years. Psychopathology
was assessed over periods of 3 months, and for each period we recorded:
Using this information on duration and severity, each 3-month period was
scored as follows: i, no or minimal depressive symptoms; ii, at least mild
severity with brief duration ( 6 weeks); iii, at least mild severity with
longer duration (> 6 weeks). Recovery was defined as no or minimal
depressive symptoms in a 3-month period, thereby extending the US National
Institute for Mental Health (NIMH) definition of recovery
(Keller et al, 1992)
by 1 month. No distinction was made between remission and recovery
(Frank et al, 1991)
because the data did not allow for such precision. The duration of major
depressive episodes was calculated by summing the 3-month periods until
recovery. A single period ii or a period ii at the beginning or at the end of
a major depressive episode was counted as 1.5 months; all other periods were
counted as 3 months.
Because administration of the LCI was time-consuming and not relevant for the entire NEMESIS sample, and because interviewers were not aware of DSMIIIR diagnoses derived from the CIDI, the use of the LCI was made dependent on a probe question about whether the respondent had felt depressed for any period of more than 2 weeks since T0. In the study cohort, 23 (8.4%) of the 273 respondents did not respond affirmatively to the probe question. No significant differences were found between probe-question-positive responders and probe-question-negative responders on socio-demographic and clinical variables. The duration of major depressive episodes was determined for the first depressive episode recorded in the LCI. Ten respondents responded affirmatively to the probe question but reported no 3-month period of depressive symptoms; they were classified as having had a major depressive episode of brief duration, set arbitrarily at 0.5 month.
Analyses
Duration of major depressive episodes was calculated using survival
analysis. The cumulative probability of recovery was estimated with the
KaplanMeier product limit (Hosmer
& Lemeshow, 1999). This technique describes all respondents
over time, either to the event of interest (in this case, recovery) or until
they are lost to further follow-up (censoring). The effect of censored data is
minimised by including all respondents who began the observation period,
regardless of whether they finished it. Median survival time is the first
recovery at which cumulative survival reaches 0.5 (50%) or less. Mean survival
time is not the arithmetic mean but is equal to the area under the survival
curve for the uncensored cases. We used the statistical package SPSS for
Windows, version 8.0 (SPSS,
1998). Survival curves for cohorts selected from different levels
of care were compared using the log rank test.
A stepwise Cox proportional hazards model was used to test the association between socio-demographic and clinical variables and duration of major depressive episodes. The hazard ratio is the increase (or decrease) in risk of the event of interest, incurred by the presence or absence of a variable.
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RESULTS |
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Determinants of episode duration
More than two-thirds of the respondents were female. In 43.2% the index
major depressive episode was a recurrent episode and comorbid dysthymia was
infrequent (Table 1).
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None of the socio-demographic variables predicted the outcome. Of the clinical variables, the presence of comorbid dysthymia and severity of the index episode predicted longer episode duration, and the index episode being a recurrent episode predicted shorter episode duration (Table 2). Entering these three variables into a multivariate Cox regression model (method backwards) did not alter the hazard ratios substantially but the presence of comorbid dysthymia was only just statistically significant.
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We also performed survival analyses for these three clinical variables (Fig. 2). Severe depression lengthens the median duration from 3.0 months (95% CI 2.5-3.5) to 7.5 months (95% CI 5.1-10.0) and the mean duration from 7.5 months (95% CI 6.2-8.8) to 10.5 months (95% CI 8.5-12.5). The presence of comorbid dysthymia lengthens the mean duration from 7.7 months (95% CI 6.6-8.8) to 13.7 months (95% CI 9.5-18.0). No median duration with comorbid dysthymia was determined, as cumulative survival did not reach 0.5 (50%). A recurrent episode shortens the median duration from 6.0 months (95% CI 4.3-7.7) to 3.0 months (95% CI 2.4-3.6) and the mean duration from 10.2 months (95% CI 8.6-11.8) to 6.1 months (95% CI 4.7-7.5).
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Duration of episode across different levels of care
Of all the respondents, 67.2% had received professional help for their
mental problems within the past 24 months
(Table 1). The survival curves
for respondents stratified for different levels of care are shown in
Fig. 3. In those without
professional care the median duration of major depressive episodes was 3.0
months (95% CI 2.1-3.9) and the mean duration (with the upper limit of 24
months) was 8.1 months (95% CI 6.0-10.1). In respondents with only primary
care the median duration of major depressive episodes was 4.5 months (95% CI
3.4-5.6) and the mean duration (with the upper limit of 24 months) was 7.8
months (95% CI 6.3-9.4). In those with mental health system care the median
duration of major depressive episodes was 6.0 months (95% CI 3.9-8.1) and the
mean duration (with the upper limit of 24 months) was 9.5 months (95% CI
3.9-8.1). Statistically, the differences in time to recovery in the different
modalities of care were not significant (log rank 1.79, d.f.=2,
P=0.41).
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DISCUSSION |
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The high rate of chronicity in the general population is the most conspicuous and unexpected finding of our study. In both treated and untreated people with depression the risk of a chronic course (duration 24 months or more) was considerable. Referral filter bias could not be demonstrated, as no association was found between level of care and episode duration. This is remarkable since we found level of care to be associated with more severe depression earlier (Spijker et al, 2001). An explanation for the lack of association between episode duration and level of care could be that hospitalised patients with the most severe forms of psychopathology were probably underrepresented in NEMESIS.
The strength of our design is that it enabled us to study the duration of major depressive episodes in a cohort with newly originated episodes from the general population, avoiding lead time and referral filter bias. A limitation of the method employed is that duration of episodes was retrospectively assessed using the LCI. We believe, however, that this method of assessment of duration, with a combination of prospectively (CIDI) and retrospectively (LCI) obtained data, is the best in practice for general population surveys. The LCI proved practicable and useful (Eaton et al, 1997) and the testretest and interrater reliability of a similar life chart instrument was satisfactory (Hunt & Andrews, 1995). We recognise that the reliability of retrospectively assessed psychopathological data is questionable owing to recall problems, but this improves with shorter time intervals (Lyketsos et al, 1994), as in our design.
It was not possible using the LCI to determine whether a period with depressive complaints continuously met the DSM-III-R criteria for a major depressive episode. Therefore, in our analyses of duration we included both the major depressive episode and its preceding and succeeding sub-threshold depressive syndromes. Also, cases of comorbid dysthymia were included (10% of the respondents), somewhat increasing the chronicity rate. However, the inclusion of sub-threshold depressive syndromes and dysthymia reflects the naturalistic course of major depressive episodes better and may have more clinical relevance (Judd et al, 1998).
In conclusion, the natural course of major depressive episodes in the general population has remarkable characteristics: although half of those affected recovered rapidly (within 3 months), the rate of recovery slowed towards 12 months, virtually coming to a standstill after 12 months. Almost 20% of the participants with depression had not recovered at 24 months. These findings have important implications for prevention and treatment. Both in treated and in non- treated participants the risk of persistence was considerable. For untreated individuals it is essential that the depressive condition is detected and that treatment is offered. For treated individuals it is essential to identify lack of treatment response and adjust the therapy accordingly. The clinical characteristics of the index episode seem to be the best clue to identifying people at risk of non-recovery; but a more detailed risk profile is certainly needed.
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Clinical Implications and Limitations |
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LIMITATIONS
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Received for publication November 6, 2001. Accepted for publication January 26, 2002.
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