Fortnightly review: A regular review of the long term follow up of depression
BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7116.1143 (Published 01 November 1997) Cite this as: BMJ 1997;315:1143
- J Angst, professor of psychiatrya
- Accepted 19 May 1997
Introduction
Depression is a common and disabling psychiatric disorder with a lifetime prevalence in the community estimated at 17%.1 Outcome studies show that depressive disorders often recur and may become chronic in up to 25% of patients. For these patients the issue is whether they can reasonably expect to recover completely, while the challenge for clinicians is to recognise the course of the disorder and to manage it appropriately. I have reviewed data from long term outcome studies to clarify the issues surrounding recovery from depression and to help identify appropriate management. Studies were selected from a literature search of the full Medline database (1966 to date) and my own collection of publications.
Depression and disability
The medical outcomes study collated data from 11 242 outpatients in the United States.2 3 It showed that depressive symptoms, with or without major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, DSM-III-R), impaired functional ability and wellbeing as much as the most common chronic medical conditions such as diabetes, chronic lung disease, hypertension, and heart disease. After two years' follow up approximately 40% of patients with major depression were still affected and functionally impaired, while those with chronic minor depression (dysthymia) had the worst outcome—54% had had a major depressive episode during this period.3 Partial recovery of functional capacity was the rule.3
Summary points
Depression limits daily functioning and wellbeing considerably
It often recurs
Up to 25% of patients develop chronic depression
Prophylaxis has been recommended for patients who have had several episodes of major depression
Many depressed patients receive either no treatment or inadequate treatment after an initial episode
Increased attention must be paid to maintenance treatment
The World Health Organisation collaborative study, a cross national study of over 5000 outpatients, examined the relationship between psychiatric status and functional disability in different countries.4 The results showed that psychiatric disorder is common in primary care and is associated with substantial functional disability. One of the strongest associations overall was functional disability with major depression (as assessed by the World Health Organisation's primary care version of the composite international diagnostic interview). The relationship between psychopathology and disability was not explained by physical health status.
These studies indicate that many depressed patients have functional disability for some years after an index episode. What then is the prognosis for recovery from depression?
Lifetime prognosis
Recovery rates
Before examining recovery, it is important to define the terms commonly used to describe the course of depressive illness. These are adapted from Frank et al 5 and are presented in table 1.
Definition of the terms usedaccording to the Hamilton depression rating scale (HAM-D), the Beck depressioninventory(BDI), and the schedule for affective disorders and schizophrenia (SADS)
Two comprehensive reviews have considered recovery in follow up studies in psychiatric settings.6 7 Piccinelli and Wilkinson reviewed 51 follow up studies of depressed adults treated in inpatient or outpatient psychiatric services, and noted outcome in terms of recovery, recurrence, and persistent depression.7 Average recovery rates were calculated after one year and more than 10 years of follow up, and figures for each study were weighted in relation to the sample size. The authors estimated that 50-60% of patients with major depression recovered at least briefly over the short term (one year) and that up to 90% showed recovery for at least a short time at up to five years.7 However, rates fell when sustained recovery was considered—a weighted average of 43% had recovered at one year but only 24% at 10 or more years.7
In an earlier review of 29 studies up to the mid 1980s, I considered the clinical course of depressive disorder in relation to diagnostic subgroups.6 Bipolar and unipolar affective disorders seemed to show similar rates of recovery.6 Depression did not seem to have a worse outcome in the elderly than in younger adults, and 35 to 60% of elderly patients showed good recovery.6 In a recent community study 31% of elderly patients without dementia were considered recovered at five year follow up, a figure which agrees broadly with rates reported from clinical studies.8
Double depression
An estimated 25% of patients with acute major depression have an underlying chronic minor depression (dysthymia), a condition which has been termed double depression.9 10 In these patients it is important to distinguish between recovery from an acute depressive episode to a state of chronic minor depression and recovery to a state with no affective symptoms. Fewer than 40% of patients with double depression became free of symptoms after one or two years of follow up, although recovery from the acute episode of major depression was reported as 83% at one year and 97% at two years.10 Moreover, dysthymic patients had a higher rate and frequency of relapse than patients with major depression alone and their recovery from the chronic minor depression was slow.10
Recurrence
Piccinelli and Wilkinson estimated that approximately 25% of patients had a recurrence of major depression within one year of an index episode, and the proportion increased to around 75% at 10 or more years7. Numerous authors have investigated the duration of intervals between successive episodes of depression. There is wide agreement that the first interval between episodes is longer than subsequent ones6 11 and that a later age of onset of depression correlates with shorter first and subsequent intervals.6
Chronicity
Chronicity (defined as non-remitting episodes of major depression of at least two years' duration) is well documented, and most large studies report that this occurs in 10-25% of depressed patients.6 7 12 Similar rates have been reported in both unipolar depression and bipolar disorder.131415
A prospective five year follow up study of patients with chronic major depression reported that almost 25% had not had two or more symptom free months in this period, and that recovery was substantially delayed in chronic depression.16 Data from the National Institute of Mental Health collaborative study on the psychobiology of depression indicated that the rate of recovery from an index episode of depression declined over time. It was approximately 70% within one year but 81%, 87%, and 88% in years 2, 4, and 5, respectively.17
Dysthymia is, by definition, chronic, and DSM-IV criteria for the disorder require the presence of depressed mood for at least two years, although with symptoms less severe than those of major depressive disorder (subsyndromal depression). Despite the reduced severity of symptoms, the functional impairment caused by dysthymia was comparable to that of major depressive disorder,18 19 underlining the clinical importance of this condition.
Treatment
Clearly, appropriate treatment strategies are needed. When medication for an acute episode of major depression is stopped too soon after an initial response, symptoms reappear in about 50% of patients (relapse of depression). Most investigators recommend that medication should be continued after remission, until the patient has been free of major symptoms for at least four to six months.20212223 A longer course of maintenance treatment is strongly recommended for patients with residual symptoms and a history of chronic disorder or several depressive episodes, or both. In patients with double depression, intensive treatment after recovery from the acute episode of major depression is necessary, as continued chronic minor depression in these people seems to predispose them to rapid relapse.10
Maintenance treatment
The World Health Organisation Mental Health Collaborating Centres have recommended prophylactic maintenance treatment in patients who have had several episodes of major depression over five years24 but the optimum duration of maintenance treatment is still under debate. There are study data supporting two or three years of maintenance treatment,2526 but information on which to base recommendations for longer periods is limited.
The efficacy of medication plus psychotherapy in prophylactic maintenance treatment of depression has been established in a number of controlled studies, and examples of the rate of recurrence reported at up to three years of follow up are given in table 2.272829303132 Maintenance treatment with antidepressants produces a substantial reduction in the recurrence of depression, and even patients with chronic disorder (chronic major depression, dysthymia and double depression) respond to appropriate medication.30
Rates of recurrence of depression during controlled trials of maintenance treatment
Psychotherapy
Interpersonal psychotherapy as maintenance treatment was investigated in a three year outcome study in depressed patients with repeated episodes of depression (Pittsburgh maintenance therapies in recurrent depression study).2831 Monthly interpersonal psychotherapy sessions designed specifically to improve social adjustment were clearly shown to be a useful adjunct to medication in prolonging the interval between recurrent episodes of depression.
Electroconvulsive treatment
Maintenance electroconvulsive therapy may be practised reasonably regularly but it is rarely reported.33 In a small study of nine patients with thought or mood disorders, maintenance electroconvulsive therapy given for longer than six months was shown to be effective in producing full or partial remission and was well tolerated in all patients.34 Few clinicians support long term electroconvulsive therapy, although it may prove a useful alternative for patients who cannot tolerate psychotropic medication.35
Psychotherapy versus pharmacotherapy
Interpersonal psychotherapy and cognitive behavioural therapy have been successful in treating acute episodes of major depression but they make heavy demands on resources and are therefore costly options for long term treatment. Scott and Freeman considered treatment outcome and economic costs in outpatients with non-psychotic major depression and concluded that the cost savings of treatment based in primary care outweighed the advantages of specialist treatment.36 Furthermore, the introduction of the selective serotonin reuptake inhibitors, which are as effective as the older tricyclic antidepressants but are often better tolerated by patients, has widened the choice of acceptable drug treatments available to the primary care physician.32
Duration of maintenance
Investigators agree that maintenance treatment with antidepressants can reduce the risk of recurrence. Therefore, patients at greatest risk need to be identified and prescribed an adequate level of medication. Studies indicate that even three years of treatment with a full dose of an antidepressant may be insufficient to prevent depression recurring when treatment is stopped in these patients, and they may need prophylaxis for five years or longer.29
Indications for maintenance treatment
Highly recurrent depressive disorder:
Longstanding history of yearly episodes of depression
Short illness cycle length (less than three years)
Several episodes over a five year period
Severe incapacitating episodes of depression
History of protracted episodes of depression
Chronic major depression
Double depression
Residual dysthymia
Effective treatment
Although depression is common and disabling, the naturalistic, collaborative study of depression and the depression patient research in European society study showed that depressed patients consistently received either no medication or ineffective dosages of medication.37383940 More attention must also be paid to maintenance treatment, and the advent of antidepressants that are better tolerated by patients means that patient's compliance with long term treatment strategies has improved.
The serious consequences of depressive disorders indicate the need for swift and effective intervention by doctors. Moreover, they need to consider the recovery of depressed patients in broader terms, paying attention to assessing the effect of depression on the patients' daily functioning as well as the improvement in symptoms.
Acknowledgments
I thank Dr Christine McKillop for help with a literature search and editorial support.