British Journal of Psychiatry (1992), 161, 633—637

Can We Predict the Persistence of Depression? JAN SCOTT, DONALD ECCLESTON and RICHARD BOYS

Fifty-five patients with primary major depression were followed up prospectively from time

of onsetof the indexillnessepisodeuntilrecovery.The courseof depressioninhospital-treated patients was protracted,

with a median length of episode of one year. Two factors significantly

predicted persistenceof symptoms: interval between onset and receipt of treatment, and premorbidneuroticism,which accountedfor 55% of the variance in length of episode.

It is estimated that the prevalence of major depressive disorder in the community is 2—3.5%, and of dysthymia 2—4%(Robins eta!, 1984). A substantial

et a!, 1986; Scott et a!, 1988), and those which

proportion of sufferers do not have the good prognosis we have come to expect (Scott, 1988). A four-year follow-up by Kerr et a! (1972) classified 40% of patients with affective disorder as having a poor outcome. Longer-term follow-up studies (Lee & Murray, 1988; Kiloh et a!, 1988) of the prognosis of two large cohorts of depressed patients 15—18 years after the index episode demonstrated that only 20Gb of patients remained well, while 30% had a very

Weissman eta!,1976;Kellereta!,1982, 1984, 1986).

prospectively follow a cohort of major depressives and analyse the pattern of recovery with time (e.g.

Akiskal et a! (1981) and Scott et a! (1988) found that chronic major depressives differed from depressives who recovered in that they were more likely to have a unipolar illness and to have more previous episodes of illness, a family history of affective disorder, higher levels of premorbid neur oticism, and increased prevalence of life events before and after the onset of the index episode.

poor outcome (Lee & Murray, 1988). Those with a

Hirschfeld et a! (1986) confirmed the prognostic

previous history of affective episodes at the psychotic

significance of premorbid personality.

end of the spectrum (Lee & Murray, 1988) and with endogenous depressive episodes (Kiloh et a!, 1988)

One difficulty in defining depressions as chronic and non-chronic is the arbitrary nature of the cut off point. Does a patient with an illness that remitted after 23 months (by definition a non-chronic illness)

had a worse prognosis overall. Further studies of the Maudsley

cohort

(Duggan

eta!,

1990, 1991) suggested

differ sufficiently from someone whose illness persisted for 25 months (i.e. chronic) to warrant a separate classification? Prospective studies which

that subtype of depression interacted with premorbid personality, such that melancholic individuals with

high index neuroticism scores were likely to have a poor outcome.

view length of illness as a continuous variable are

The above studies were well designed and con tributed important information to our understanding of the long-term prognosis of depression. However, as with previous studies, the patients with a poor outcome comprised a heterogeneous group of those with frequently recurring illnesses, with social impairment, with an atypical course (in which the

therefore important in furthering understanding of factors that may predict chronic symptoms. Weissman et a! (1976) followed a cohort of 150 women over four years and found that high levels of

premorbid neuroticism and lack of adequate mainten ance treatment were the key predictors of chronic symptoms.

Keller et a! (1982) reviewed a cohort

diagnostic category changed over time), and with

of 101 primary and secondary major depressives

persistent symptoms. The limited research on the latter group suggests that the median prevalence of chronic symptoms in major depression (defined as

recruitedfrom fiveteachingcentresin the USA, and entry

the persistence of the index episode for two or more

predictor of outcome at two years. Other predictors

years) is 12% (Scott, 1988). Only in the past 10 years have there been attempts to identify the characteristics

of protracted recovery in Keller et ats series(1982,

found that time between onset of symptoms and the

research

study

was

a significant

1984, 1986) were: in-patient status, low family income, intact marriage, treatment centre visited,

of chronic and non-chronic (recovered) depressives, and the pathways to chromcity. These studies fall

secondary subtype of depression, and a major depressive episode superimposed upon an underlying

into two broad categories: those which identify a group of operationally defmed chronic depressives

and compare and contrast them with non-chronic major depressives (e.g. Akiskal eta!, 1981;Hirschfeld

into

chronic minor depression (‘doubledepression'). The diversity of methods does not allow direct comparisons to be made between the various studies,

633

634

SCOTT ET AL

nor allow the relative importance of different predictive factors to be delineated. The aim of this study was to identify and weigh clinical factors predicting the persistence of symptoms in a cohort of primary major depressives referred to a general

determinedusingthe Schedulefor AffectiveDisordersand Schizophrenia(SADS; Endicott & Spitzer, 1978).(i) Age at onset of first RDC illnessepisode.(ii)RDC diagnosisof

adult psychiatry service and followed up prospectively until recovery.

admissions, polarity of the affective disorder. (iv) Incomplete

Method Patients aged 18—65years, referred routinely to three psychiatry departments in Newcastle with a presumptive diagnosis of depression, were asked if they would be

(c) Details of past psychiatric history - the following were

first illness episode. (in) Previous illness episodes - including

number of previous illnessepisodes, number of previous recovery between episodes was assessed for the period between the penultimate episode and the index depressive episode. It was recorded for patients who met criteria for minor or intermittent depressive disorder between major episodes or who had failed to meet RDC for recovery. (v) Secondary

psychiatric

complications

—¿ drug

or alcohol

willing to take part in a research study. Patients who

misuse or other non-affective problems were noted. (d) Brief details of medical history - previous medical

satisfied Research Diagnostic

history was supplemented

Criteria (RDC; Spitzer eta!,

1978)for primarymajor depressivedisorderwereincluded. Exclusion criteria were: receiving pharmacological

treatments

known to cause (or be suspected of causing) depression; evidence of organic brain disease; depression secondary to physical illness; and inability or unwillingness to give informed consent.

by examination

of case notes.

illnessesof a prolongednature,markedseverity,or requiring long-term medication were noted. Similar information was recorded about problems arising after the onset of

the depression. (e) Family history of psychiatric disorder in first-degree relatives was obtained using the Family History—Research

Screening interviews with 74 patients yielded a cohort of 61

DiagnosticCriteria(FH-RDC; Andreaseneta!, 1977).Case

patients with primary major depressivedisorders who met the

notes were examined when possible. (f) Premorbid personality was assessed using the Eysenck

inclusioncriteriaand whotook part in the initialinterview. Thecohortwasthen followedup prospectivelyuntilrecovery from the indexepisode.Whenthe individualhad beenwith out symptoms for at least eight weeks (the RDC definition of recovery) a further interview collated information

regarding

the course of the illness. Six patientswere excludedbecause they were not available to take part in the follow-up interview. The final sample was thus 55 patients. Through the semistructured follow-up interview the patient, and when possible a close relative, completed a clinical protocol designed to explore illness characteristics and psychosocial factors of relevance to their current presentation; details have been describedby Scott eta! (1988). Information was recorded under the following headings: (a) Sociodemographic characteristics. (b) Details of index depressive

episode.

(i) Length

of

illness episode —¿ the time between onset and recovery. Recovery was defined according to RDC as detailed by Kellereta! (1982):“¿no RDC symptomsfor majordepressive disorder for at least 8 consecutive weeks regardless of the presence or absence of somatic therapy―.(ii) Severity of episode was assessed using the 17-item Hamilton

Rating

Personality

Questionnaire

(EPQ;

Eysenck

& Eysenck,

1975).An additional sentence was added to the instructions (Kendell & Discipio, 1968)to ensure that the scores referred to how the patient regarded him/herself premorbidly. (g) Life events in the six months before onset of illness up until recovery were recorded for all patients using the Interviewfor Recent Life Events (Paykel, 1983). Reported events were included only if the occurrence,

independence,

and timing could be substantiated. (h) Vulnerability and predisposing factors - three aspects of vulnerability (Brown & Harris, 1978) were explored. (i) Developmental object loss —¿ loss of one or both parents or prolonged periods of separation before the age of 11 years. (ii) Social support - one aspect only was investigated, whether patients felt they had an available confidante. (iii) Children- numberand ages of childrenat time of onset of illness were recorded.

Statistical analysis Descriptive statistics were used to identify the characteristics

of the sample and to determine the sex differences. A multiple linear regression analysis was carried out using the statistical package MINITAB to assess the relationship between length of illness and the sociodemographic and Carney et a!, 1965) was used to classify patients as clinical factors measured. The predictor variables were endogenous/neurotic. (iv) ‘¿No-treatment interval' - therapies used duringthe illnessepisode (includingpharmacotherapy, selected to avoid multicolineanty (thereby making the electroconvulsivetherapy (EC@)and psychologicaltherapies) statistical analyses more stable) and were entered in a were recorded using the categories identified in the stepwise manner. The analysis was performed repeatedly LongitudinalIntervalFollow-upEvaluation(LIFE;Shapiro until the regression equation that best described the & Keller, 1979; Keller et a!, 1987). The ‘¿no-treatmentvariation in length of illness was found. interval' was defined as the interval between the date of onset of the illness episode and the date when it is Results documented that the patient was prescribed a recognised The 19 patients excluded from the study did not differ antidepressant treatment in a dosage of at least 75 mg of Scale for Depression (HRSD; Hamilton, 1960)and the Beck Depression Inventory (BDI; Beck et a!, 1961). (iii) Endogenicity- the Newcastle Diagnostic Instrument(ND!;

a tricydic

or its LIFE equivalent.

significantly on clinical or sociodemographic

variables from

635

THE PERSISTENCE OF DEPRESSION the final group of 55 patients. As shown in Table 1, the sample comprised 29 women and 26 men, most of whom were currentlymarried(62°bo) and came from social class III (54°bo). The age at onset of the index depressive episode ranged from 20 to 63 years (mean 43.6 (s.d. 10) years). The length of the currentepisode varied from 4 to 29 months (median 12 months). Forty-twopatients(76%)wereadmittedduring the episode, but they did not differ significantlyfrom those not admitted. The mean HRSD and BDI scores were 22.5

(range 14—35;s.d. 4) and 27 (range 19—38;s.d. 4) respectively.Thirty-one patients(56°bo) scored greaterthan

they had at least one confidante, and only four had three

or more children under the age of 14 years at the onset of illness. When the factors identified as possible predictors of chronicity were entered, only two contributed significantly

to the predictionof persistent symptoms(Table 2). Fifty five per cent of the variance (adjusted R@)in the length of the index depressive episode was accounted for by the ‘¿no-treatmentinterval'

6 on the ND!. The interval between onset of symptoms and

a tricyclic. Forty-six patients (24 women, 22 men) had a unipolar disorder, and the mean age of onset of first-ever episode of illness was 33.3 years (range 13—60, s.d. 10.4). For only 8 patients (15%) was the index depressive episode their first experience of psychiatric problems. The number of previous illness episodes ranged from 0 to 6 (mean 1.8, s.d. 1.3, median 2); the range for admissions was the same (mean 1.4, s.d. 1.2, median 1). Incomplete recovery between the penultimate

and the index

episode

of depression

was

reported by 15 patients (27°lo). Twenty-seven patients had first-degree relatives with affective disorders; 20 reported unipolar disorders, six reported bipolar disorders, and one

patient had relatives with both unipolar and bipolar illnesses. The past medical histories of the sample were unremarkable, and only four reported the development of

specific health problems after the onset of the index episode. Two reported secondary alcohol abuse. Premorbid neuroticism scores on the EPQ ranged from

level of neuroticism.

Discussion

start of antidepressant treatment varied from 1to 12months (mean 5.6, s.d. 2.8). While 38 (69%) of the patients eventually received at least 150 mg of a tricyclic anti depressant or its equivalent, at the time of referral to the hospital services 29 patients were on less than 75 mg of

and premorbid

The no-treatment interval contributed 47% of the variance, and the neuroticism score the other 8%.

In this prospective study of factors predicting persistence of symptoms in primary major depression, follow-up was from early in the episode until recovery; patients were not assigned to specific treatment categories, nor were interventions by the responsible clinical team encouraged or discouraged. In the hospital setting (where all the patients received at least 75 mg of a tricyclic antidepressant and about 70% received 150mg or its equivalent), recovery from depression was still a slow process. Only 50°bo of the sample recovered within one year of onset of a depressive syndrome (a similar rate to that reported by Keller et a! (1986)). At two years, the rate of chronicity was 9°bo. Although in keeping with previously reported prevalence rates (see Scott, 1988), the chronicity rate at this stage reported by Keller et aPs (1986) prospective study of primary and secondary

major

depressives

was 21%.

Two possible

events were reported by 34 patients. Fifteen patients had

explanations of the discrepancy are that this study focused on primary depressives only, and that the treatment received by patients in Keller et aPs study was less intense, only 20°bo receiving over 150 mg of

lost a parent through death or separation before the age of 11 years. Most of the sample (36, 65%) reported that

a tricycic or its equivalent. When sociodemographic and clinical factors pre

6 to 20 (mean 12.7,s.d. 4.4, median 12).Independentlife

Table 1 Characteristics of 55 patients with primary major depression

CharacteristicsSex 26Mean ratio (female: male)29: (10.1)Mean (s.d.) age: years43.6 (s.d.) length of illness: months12.2 (4.6)Mean (s.d.) no-treatment interval: months5.6 (2.8)Mean (s.d.) HRSDscore22.5 (4.1)Mean (s.d.) BDI score27 (4.0)No. NDI31Mean scoring >6 on (s.d.) age at first episode:years33.3 (10.4)Mean (s.d.) no. of previous episodes1.8 (1.3)Mean (1.2)No. (s.d.) no. of previous admissions1.4 disorder27Mean with a family history of affective EPQwomen14.1 (s.d.) premorbidneuroticismscoreon (4.4)men11.1

viously found to be important in distinguishing good and poor prognosis groups in depression were examined, only two significant predictors of persistent symptoms were found in this cohort. More import antly, these variables were not illness factors but related to premorbid personality and the length of time taken for a recognised antidepressant treatment to be prescribed after the onset of the depressive illness. It is worth reflecting on the methodological problems encountered in this study. The measurement

of premorbid neurotic traits during the course of a depressive episode is fraught with difficulties. Current mental state colours people's perception of their pre illness functioning, and while the technique used is valid (Kendell & Discipio, 1968), data on repeated self-ratings after recovery were not available to (3.9)

support its reliability. The measurement of the interval between onset of the illness and active

636

SCOTT

ET AL

Table 2 Stepwisemultiple illnessSourceDegrees

R2No-treatment

of freedomSum

interval 8%Regression on EPQ1 Neuroticismscore Error2

linear regression analysis of factorspredicting

1927.88

of squaresFPAdjusted 4.870.001

157.7528.58

521085.63

treatment is even more reliant on the accuracy of patients' self-reports, and the quality of case notes.

This cohort was interviewed at an early stage of the index episode, which should help ensure reliability of recall, but the technique is at best a crude estimate. Only a regular review of non-depressed patients followed up prospectively until onset of symptoms could give confidence that this interval

lengthof

0.00345% 0.7255%

827.5733.450.001

45%

possible variance in illness length accounted for by a score for premorbid neuroticism. Kerr et a! (1972) found that depressives with higher levels of neuroticism were significantly more likely to have a poor prognosis. This finding has been confirmed by studies comparing chronic and non-chronic depressive subgroups (Akiskal eta!, 1981; Scott eta!, 1988),

prospective

studies

of heterogeneous

poor

was measured accurately. The no-treatment interval is determined by both the behaviour of the individual after onset of

outcome groups (Duggan et a!, 1990), and studies of persistent symptoms (Weissman et a!, 1976). In Keller et as―s (1986) study, neuroticism was not

symptoms and the doctor's response to the patient after presentation. The treatment offered is dependent

measured,

upon the clinician's ability to recognise the affective disorder and prescribe appropriate treatment (and persuade the patient to comply). Inadequate or

but patients

were classified

as ‘¿double

depressives' if major depression was superimposed on underlying dysthymic disorder. These double depressives

recovered

at a slower rate than those with

an acute major depression. Symptoms of dysthymia

inappropriate initial treatment is a major contributing factor to chronicity (Akiskal et a!, 1981; Bridges,

(DSM—III—R; American

1983; Quitkin,

areas of overlap (Garside eta!, 1970), and this merits

1985), as is lack of adequate

continu

ation of treatment (Weissman et a!, 1976). While 85% of this cohort had at least one previous

episode of depression, more than half of those referred to the hospital services for the first time during the index episode were on less than 75 mg of a tricycic antidepressant. Keller eta! (1986) reported that severity of illness was a predictor of length of episode. That this study did not find this may seem surprising, be postulated that the no-treatment

but it could interval and

severity of illness are highly inter-related.

Illnesses

may become more severe over time, and a patient might not seek help until the symptoms are more intense, thus delaying the opportunity to receive

Psychiatric

Association,

1987) and so-called neurotic traits have important further exploration. Could double depression be similarto (or the same as) acute major depression

in a setting of neurotic premorbid personality? The latter combination has previously been identified by Duggan et a! (1990) as predicting poor long term outcome.

In this study, those with more previous episodes of depression also had high scores for neuroticism. Has their personality been affected by recurrent illness episodes? Akiskal eta! (1983) and Scott (1988)

have argued that affective disorders may not leave the premorbid personality unchanged. The interaction between neuroticism and depression may be a two-way process, with high premorbid neuroticism

treatment; or a doctor may fail to diagnose the depression or delay treatment until more severe

predicting poor outcome from an episode (Kerr et a!,

symptoms are manifested. Early intensive treatment is therefore strongly recommended to shorten the courseof the illness. One of the strongestpredictors

exaggerating premorbid neurotic traits (Hirschfeld et a!, 1989). Finally, the influence of premorbid neurotic traits on the assessment of the illness episode and the requirement for treatment should not be ignored.

of chronicity is prior length of index illness episode (Scott, 1988). Premorbid neurotic traits was the only other significant predictor of persistence of symptoms in this study. Premorbid neuroticism has previously been found to be a predictor of prognosis in depression, but this study is the first to identify the

1970; Frank eta!,

Recogrnsing

1987), but repeated

depression

illness episodes

in an individual

with high

neuroticism might be impeded, or the clinician may focus excessively on trait-related as opposed to state related

factors.

This may adversely

influence

diagnosis

and delay treatment. This study suggests that those

THE PERSISTENCE OF DEPRESSION with high neuroticism scores require intensive treat ment for major depression at an earlier stage if chronic symptoms are to be avoided. Earlier studies

(Akiskal et a!, 1981; Scott et a!, 1988; Scott & Eccleston,

1992) suggest this is especially true of

those with a family history of affective disorders and a high prevalence of life events before and after the onset of the illness episode.

637

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Victoria Infirmary, Newcast!e upon Tyne NEJ 4LP; Donald Eccleston, MB,PhD,DSc,FRCPsych,Professor, University Department of Psychiatry, Roya! Victoria Infirmary; Richard Boys, BSc,MSc,FSS,Lecturer, Department of Mathematics and Statistics, University of Newcast!e upon Tyne Correspondence

Can we predict the persistence of depression? J Scott, D Eccleston and R Boys BJP 1992, 161:633-637. Access the most recent version at DOI: 10.1192/bjp.161.5.633

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