User login
METHODS: We performed a literature search to identify relevant papers published between 1970 and 1999 on original long-term follow-up studies of depression in community and primary care populations. The included studies were of adult populations with depression based on diagnostic criteria and a follow-up of at least 5 years. Data about recurrences, relapses, psychopathology, disability, or quality of life at follow-up were examined.
RESULTS: We found 8 studies that fulfilled our criteria. The reported rates of recurrence or depression at follow-up were between 30% and 40%. Higher rates were found in the younger and older age groups. Data about other predictors of outcome, health status, and the relation between treatment and outcome did not justify any hard conclusions.
CONCLUSIONS: The long-term outcome of depression in the community and in primary care is rarely studied. The results of available studies are difficult to compare because of the large differences in populations and methods. Nevertheless, these studies suggest that the long-term prognosis of depression in the community and in primary care is not as poor as in psychiatry.
Depression is regarded as a chronic illness with a high prevalence and a large impact on quality of life.1-6 Nevertheless, the long-term outcome of depression in primary care and in the community is not clear. Most long-term outcome studies of depression have been performed with populations of patients who have been referred to psychiatric specialists.7-11 However, not everyone with depression in the community consults a physician, and usually only the more severe and lasting cases—approximately 5% to 15% of all patients who seek medical attention and have received a diagnosis of depression in primary care—are referred for secondary care.12,13 It is unlikely that the outcome in the community and in primary care is identical to that of referred cases, because of the difference in the prevalence of the various severity levels of depression between these populations.14
The follow-up periods of most studies of depression performed in the community and in primary care have been relatively short.15-17 From these studies we know that patients experience disability during depressive episodes, but we do not have a clear picture of the long-term consequences from the patient perspective.2,4,5 Also, in short-term studies, rates of depression measured at follow-up are not conclusive in determining recurrence rates.
Concerning treatment, it has been established in many short-term studies that antidepressants are effective for the treatment of major depressive disorder11,18,19 and perhaps also for minor depression20-23 (with a high prevalence in community and primary care).24-27
However, papers can be found describing a totally different picture for the long-term outcome of chronic diseases.28,29 These studies demonstrate that short-term effectiveness and safety do not automatically predict long-term outcome. Therefore, we think that knowledge about the long-term course of depression in the community and in primary care, naturalistic as well as treated, is indispensable for determining what treatment strategy is justified. Studies about the negative effects of antidepressants have been published,30-33 and some suggest that these drugs might influence the course of depression in a negative way.34 Long-term outcome information should be available for all levels of depression, including cases for which no medical attention is sought, and differences between naturalistic outcome and outcome after treatment should be clear. We reviewed the literature for long-term outcome studies of depression in the community and in primary care, looking for answers to the following 3 research questions: What is the recurrence rate of depression? Can a relation be found between long-term outcome and treatment? What are the long-term consequences for the health status of the patients involved?
Methods
Retrieval of the Literature
We performed a computerized search of studies from 1970 to 1999 using MEDLINE, Psychlit, Current Contents, and The Cochrane Library. We chose 1970 as our starting point, because at that time modern classification systems were introduced and research diagnostic criteria became available to investigators.
Thesaurus and free text words were combined for “depression/depressive disorder” with “general practice/family practice/primary care” or “community” and “follow-up/course/outcome/prognosis.”
Selection of the Literature
Two reviewers (H.J.S., E.M.vW-B.) made a selection by screening titles and abstracts. If an abstract had been selected by only one of the reviewers it was discussed until consensus was reached.
Our inclusion criteria were: original longitudinal follow-up studies in English of adult populations in the community or primary care with at least 25 patients in the follow-up. In the included studies diagnosis of depression was according to: the International Classification of Primary Care or the International Classification of Health Problems in Primary Care (ICHPPC-2) in general practice studies; the Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition, third edition revised, or fourth edition; the research diagnostic criteria (RDC) or immediate predecessor (St Louis); or the International Classification of Diseases (ICD)-9th Revision-Clinical Modification or the ICD-10th Revision.35,36 As inclusion criteria for outcome of depression we included studies reporting on recurrences, relapses, psychopathology, disability, or quality of life at follow-up. We defined long-term as a follow-up of at least 5 years, because recurrences usually occur within this time frame.9,13,37 A follow-up of at least 5 years should give an indication of percentages of single-episode depression and recurrence rates, and should provide more of an opportunity for distinguishing recurrence from relapse and no recovery (yet) than a shorter follow-up.
When abstracts met the inclusion criteria or remained unclear, full articles were retrieved for further evaluation. We also retrieved relevant reviews. All of these studies were screened with the ancestry approach. Additionally, a number of experts in the field from the Netherlands, the United Kingdom, and the United States were asked for additional references.
Data Abstraction and Presentation
Because of the wide variety of study designs, we limited ourselves to a qualitative evaluation. We abstracted data about design, setting, diagnostic criteria, number and specific diagnosis of depressive patients in the follow-up, age and sex, length of follow-up, treatment, and outcomes.
We calculated a total rate of recurrence or depression at follow up for all patients still alive and present at the end of the follow-up of each study. For that purpose we combined the rates for minor and major depression. This gave us the opportunity to compare the outcome results of depression diagnosed with family practice criteria with DSM cases and cases meeting RDC.
Results
Selection of Articles
The computer search supplied 421 potentially relevant articles. We selected 56 papers on the basis of that search, the reference lists of 4 review articles, and the suggestions of experts. Eight of those studies met all our inclusion criteria: 6 of these were community studies, and 2 were in primary care. Studies were excluded for 1 or more of the following reasons: no longitudinal follow-up (13), long-term follow-up shorter than 5 years (35), no diagnostic criteria mentioned in the article (4), population not from community or primary care (5) or too small (1), or outcome results of depression were mixed with other diagnoses (2).
Design, Aim, and Outcomes
Table 1 provides an overview of the included studies with outcomes as presented in the original articles. There was only one study from the 1970s38 meeting our criteria; all others were published in the last 10 years.
Initially there had either been a community survey with screening instruments, followed by diagnostic interviews or the whole population had been interviewed to identify cases of depression. Then there had been a follow up with the depressed subjects. In 4 of the 6 community studies the outcome was presented as depression at follow-up,39-42 and in the other 2 studies as recurrences.43,44 In 2 studies the results of depression at follow-up were based on 3 follow-up interviews: in the third, fourth, and fifth year after the initial assessment in the first study,41 and one every 5 years in the other.42 Three studies were performed on the elderly,39-41 one on young adults living in the community,42 and 2 in community samples in which all ages were represented.43,44 In one of these latter studies44 the population consisted of family members and relatives of affectively ill probands.
Both family practice studies had a historic cohort design13,38 and referred to patients recognized with depression in family practice. A cohort of depressed patients had been identified from a morbidity registry13 or practice,38 and was followed up longitudinally using the patients’ records (and registry13). The follow-up started on the date the diagnosis was made for the first time13 or the first time in the practice.38 Outcome in both studies was based on the reference to recurrences on the patients’ records over the entire study period.
The Diagnosis of Depression and Diagnostic Criteria
There was only one study using specific family practice criteria. For that study E-list criteria (the first classification for general practice, developed in the United Kingdom and derived from the ICD) was used initially and was later replaced with ICHPPC-2 criteria.45,13 In all the other studies DSM,40,42,43 RDC,38,42-44 or criteria derived from the RDC for use in elderly populations39,41 (obtained with GMS-AGECAT, a computerized diagnostic system for elderly subjects derived from the Geriatric Mental State46) were used. In the family practice study by Widmer and Cadoret38 the symptoms on the records were incorporated in the RDC retrospectively.
Length of Follow-up of Depression
In one study44 the length of the follow-up from the onset of depression was not clear because it did not mention when the depressive episodes occurred. In all other studies the follow-up began with a depressive episode. One study started the follow-up at first episodes only.13 That is the only study in which a time relation between the initial diagnosis and recurrences is presented longitudinally. One other study started at initial episodes in the practice38; all others start at index and recurrent episodes, but the proportions are not clear.
Recurrence or Depression at Follow-up
There were differences in levels of depression included in the outcome results Table 1. The rates of recurrence presented in the community studies ranged between 26% and 47%, and the rates of depression at follow-up were between 9% and 44%. Recurrence rates in the family practice studies ranged from 35% to 40%. The recurrence rate of 35% was calculated retrospectively, relying on the symptoms mentioned on the case records. The recurrence rate of 40% was found by extracting data from a morbidity registry and checking those data against symptoms on the patient records.13 Both studies also presented the number of recurrences. In one study 27% of the followed-up patients had 2 episodes; 6%, 3; and 3%, 4 or more38; in the other the percentages were 16% with 2, 12% with 3, and 12% with 4 or more.13
Treatment
The authors of 4 studies38-40,42 reported on treatment. None described the nature and length of treatment clearly, and treatment was not related to recurrence or depression at follow-up.
Mortality
Data for mortality were given in 4 studies13,39-41 (range of rates=14%-44%). The higher mortality rates refer to the elderly. In 2 studies mortality was similar to the expected rates (compared with a control group in one13 and with the National Mortality Statistics in the other39); in another study41 the rates were significantly higher than in a control group of nondepressed individuals; and in the last study13 the results of a comparison were not discussed. Data on suicide attempts and suicide can be found in only one study.13
Health Status
Two studies reported on disability or self-perceived physical health, but none of the studies used any of the well-known health status measurement instruments. One study39 reported on disability levels (with a modified version of the American Resources and Services) There was significantly more moderate to severe impairment among the depressed than among the recovered cases, as rated by a clinician; also, it is not clear whether this rating refers to the initial assessment or the follow-up. In the other study40 46% of the elderly patients reported poor health status, but it is not clear which instrument was used; no relation was found between outcome and perceived health status.
Total Rates of Recurrence or Depression at Follow-up
Table 2 shows the total rates of recurrence or depression at follow-up, adding up the results of minor and major depression when possible. The recurrence rates of the populations in which no specific age group was followed-up ranged from 30% to 40%. These studies had indications for higher recurrence rates in the younger age groups. The community studies of depression in the elderly and young adults reported outcome as depression at follow-up. The rates of depression at follow-up in 2 of the studies of the elderly39,41 were relatively high. One of these studies41 only reported on major depression at follow-up. This was also the case in the study with young adults.42
Discussion
Studies of the long-term outcome of depression in the community and in primary care are scarce and difficult to compare, and methodologic shortcomings hamper their generalizability.
Our data suggest that overall recurrence rates in the community and in family practice vary between 30% and 40%. The relationship between treatment and long-term outcome remains unclear, because none of the studies were controlled trials for treatment or looked into this matter adequately. This also applies to the patient’s qualitative experience. Almost all studies exclusively report physician-diagnosed recurrence or positive scores on diagnostic instruments of depression at follow-up.
Recurrence rates of 30% to 40% indicate that the prognosis for depression in community and family practice is not as poor as in psychiatry. In psychiatric settings much higher recurrence rates are found, with percentages of up to almost 90% depending on the length of follow-up and the setting.9,10,37 Prognosis seems to be related to age, with young adults and the elderly having poorer prognoses. In the study on young adults, between 30% and 40% of the patients had a major depressive disorder at follow-up, but those results did not include rates of minor depression. They also did not include recurrences between the follow-up interviews, and thus it is likely that recurrence rates were higher. Higher recurrence rates were also found in the younger age groups in 2 of the community studies.43,44 All the studies performed exclusively with the elderly reported depression at follow-up and gave a poor prognosis.39-41 This was not confirmed in the 2 community studies involving various ages and one general practice study.13,43,44 The higher rates in studies on the elderly might be explained by the use of diagnostic instruments more sensitive to detect depression specifically in that age group. Another explanation might be that differences were not found because of the relatively small number of elderly persons present in the other studies.
Limitations of the Studies
In the community studies subjects were identified with screening instruments. Therefore, a number of false-positive diagnoses may have been included in these studies that biased outcome results.47 This risk was minimized by using interviews in addition to the screening instruments. Another important limitation is the risk of missing part of the information about recurrences in the intervals between assessments. This risk is less in studies that include more than one follow-up assessment, as was done in 2 of the included studies,41,42 and also in studies where data about the interval are retrieved using information based on patients’ recall.40,43 Recall is known to introduce bias by not always giving sufficient details after longer periods of time.48
In the family practice studies where the specificity of the diagnosis is usually high,49,50 outcome results may have been biased because the results of undetected or misdiagnosed patients with depression are missing. In both studies the information was retrieved from the case records. Thus, accuracy depended on the completeness of the physicians’ notes. In one of the studies the case records were used in addition to data from a morbidity registry in which physicians were trained regularly to use criteria for diagnosis. Although suicide data can be found in this study, patients who left the practices or died within 10 years were excluded, and outcome results should be viewed taking that into consideration.
An important shortcoming is that most studies started at first or recurrent episodes, so it is not possible to give an exact percentage of single-episode depression versus recurrent illness. A description of the longitudinal course starting at first diagnosis is also not possible. Even in the one study starting at the first episode we can only draw conclusions about recurrence rates after diagnosis, because we have no certainty that the first diagnosis was in fact related to the first depressive episode. Other shortcomings are the small number of patients in the follow-up in 2 studies39,43 and uncertainty about the representativeness of the samples in one of the community studies.39,41,42,44 Since a family history of depression is a risk factor in an individual,51 the population of family members of affectively ill probands cannot be regarded as a representative community sample.44
The validity of the recurrence rates mentioned in the articles is difficult to assess because only one author gave confidence intervals of recurrence rates or depression at follow-up.13
Limitations of Our Review
Although we made our choice of inclusion criteria to ensure reasonable comparability, older studies52,53 and those in which data on depression could not be extracted from a broader variety of mental illness in family practice54 were excluded. We also made the choice to describe a limited number of outcomes, but the small number of studies included and the variety within the studies did not allow a review of more outcome results.
Although the calculation of a total recurrence rate may be criticized, we think that the fluctuating nature of depression justifies this procedure.
Conclusions
There are large gaps in the available knowledge about long-term outcome of depression in primary care, and future studies are required to fill in these gaps. We recommend the following:
- The outcome of all types of depression should be evaluated in prospective studies, with a follow-up of at least 5 years, of representative samples in both community and primary care.
- Continuous morbidity registration should be used. With this aim, data meeting fixed criteria that have been established beforehand should be collected longitudinally.
- Studies should include naturalistic follow-up and relate treatment to outcome.
- Quality-of-life assessment should be included.
Recommendations for clinical practice
Family physicians can reassure patients with depression by telling them that although the long-term outcome of the illness is not completely clear, there are indications that the majority of patients with depression do not have a poor prognosis. As the long term risk of recurrence seems to be approximately 40%, most patients in primary care settings only have 1 episode of depression. This information might aid a patient’s recovery.
1. Froom J, Aoyama H, Hermoni D, et al. Depressive disorders in three primary care populations: United States, Israel, Japan. Fam Pract 1995;12:274-78
2. Ormel J, VonKorff M, Ustun TB, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA 1994;272:1741-48
3. Robins LN. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984;41:949-58
4. Williams JW, Kerber CA, Mulrow CD, et al. Depressive disorders in primary care: prevalence, functional disability, and identification. J Gen Intern Med 1995;10:7-12
5. Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients: results from the Medical Outcomes Study. JAMA 1989;262:914-19
6. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992;14:237-47
7. Coryell W, Turvey C, Endicott J, et al. Bipolar I affective disorder: predictors of outcome after 15 years. J Affect Disord 1998;50:109-16
8. Paykel ES. Historical overview of outcome of depression. Br J Psychiatry Suppl 1994;26:6-8
9. Angst J, Preisig M. Course of a clinical cohort of unipolar, bipolar and schizoaffective patients: results of a prospective study from 1959 to 1985. Schweiz Archiv Neurol Psychiatr 1995;146:5-16
10. Piccinelli M, Wilkinson G. Outcome of depression in psychiatric settings. Br J Psychiatry 1994;164:297-304
11. Lavori PW, Keller MB, Mueller TI, et al. Recurrence after recovery in unipolar MDD: an observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatric Res 1994;4:211-29
12. Blacker CV, Clare AW. Depressive disorder in primary care. Br J Psychiatry 1987;150:737-51
13. van Weel-Baumgarten E, van den Bosch W, van den Hoogen H, et al. Ten year follow-up of depression after diagnosis in general practice. Br J Gen Pract 1998;48:1643-46
14. Watts CA. Depressive disorders in the community: the scene in Great Britain, 1965. J Clin Psychiatry 1984;45:70-77
15. Klinkman MS, Schwenk TL, Coyne JC. Depression in primary care—more like asthma than appendicitis: the Michigan Depression Project. Can J Psychiatry 1997;42:966-73.
16. Lin EH, Simon GE, Katon WJ, et al. Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care. Am J Psychiatry 1999;156:643-45
17. Ormel J, Oldehinkel T, Brilman E, et al. Outcome of depression and anxiety in primary care: a three-wave 3 1/2-year study of psychopathology and disability. Arch Gen Psychiatry 1993;50:759-66
18. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52 (suppl):28-34.
19. Prien RF. Efficacy of continuation drug therapy of depression and anxiety: issues and methodologies. J Clin Psychopharmacol 1990;10:86S-90S.
20. Tan RS, Barlow RJ, Abel C, et al. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Br J Clin Pharmacol 1994;37:321-24
21. Thompson C, Thompson CM. The prescribing of antidepressants in general practice: II. A placebo-controlled trial of low-dose dothiepin. Human Psychopharma 1989;191-204.
22. Wernicke JF, Dunlop SR, Dornseif BE, et al. Low-dose fluoxetine therapy for depression. Psychopharmacol Bull 1988;24:183-88
23. Paykel ES, Freeling P, Hollyman JA. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Pharmacopsychiatry 1988;21:15-18
24. Hollyman JA, Freeling P, Paykel ES, et al. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. J R Coll Gen Pract 1988;38:393-97
25. Mynors WL, Gath D. Predictors of treatment outcome for major depression in primary care. Psychol Med 1997;27:731-36
26. Scott AI, Freeman CP. Edinburgh primary care depression study: treatment outcome, patient satisfaction, and cost after 16 weeks. BMJ 1992;304:883-87
27. Schulberg HC, Block MR, Madonia MJ, et al. Treating major depression in primary care practice: eight-month clinical outcomes. Arch Gen Psychiatry 1996;53:913-19
28. Pincus T, Stein CM. Why randomized controlled clinical trials do not depict accurately long-term outcomes in rheumatoid arthritis: some explanations and suggestions for future studies. Clin Exp Rheumatol 1997;15 (suppl):S27-38.
29. Wolfe F, Hawley DJ, Cathey MA. Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis. J Rheumatol 1991;18:1290-97.
30. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106-09
31. Po AL. Antidepressants and upper gastrointestinal bleeding. BMJ 1999;319:1081-82
32. Mackay FR, Dunn NR, Martin RM, et al. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract 1999;49:892-96
33. Sampson E, Warner JP. Serotonin syndrome: potentially fatal but difficult to recognize. Br J Gen Pract 1999;49:867-68
34. Tondo L, Laddomada P, Serra G, et al. Rapid cyclers and antidepressants. Int Pharmacopsychiatry 1981;16:119-23
35. Classification committee of WONCA. ICHPPC-2-defined (International classification of Health Problems in Primary Care). 3rd ed. Oxford, England: Oxford University Press; 1983.
36. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 1994.
37. Van Londen L, Molenaar RP, Goekoop JG, et al. Three- to 5-year prospective follow-up of outcome in major depression. Psychol Med 1998;28:731-35
38. Widmer RB, Cadoret RJ. Depression in primary care: changes in pattern of patient visits and complaints during a developing depression. J Fam Pract 1978;7:293-302
39. Kua EH. The depressed elderly Chinese living in the community: a five-year follow-up study. Int J Geriatr Psychiatry 1993;8:427-30
40. Kivela SL, Kongas SP, Kesti E, et al. Five-year prognosis for depression in old age. Int Psychogeriatr 1994;6:69-78
41. Sharma VK, Copeland JR, Dewey ME, et al. Outcome of the depressed elderly living in the community in Liverpool: a 5-year follow-up. Psychol Med 1998;28:1329-37
42. Angst J, Merikangas K. The depressive spectrum: diagnostic classification and course. J Affect Disord 1997;45:31-39
43. Eaton WW, Anthony JC, Gallo J, et al. Natural history of Diagnostic Interview Schedule/DSM-IV major depression: the Baltimore Epidemiologic Catchment Area follow-up. Arch Gen Psychiatry 1997;54:993-99
44. Coryell W, Endicott J, Keller MB. Predictors of relapse into major depressive disorder in a nonclinical population. Am J Psychiatry 1991;148:1353-58
45. Logan WPD, Cushion A. Morbidity statistics from general practice. Vol 1. London, England: Her Majesty’s Stationary Office; 1954.
46. Copeland JR, Dewey ME, Griffiths-Jones HM. A computerized psychiatric diagnostic system and case nomenclature for elderly subjects: GMS and AGECAT. Psychol Med 1986;16:89-99
47. Nagel R, Lynch D, Tamburrino M. Validity of the medical outcomes study depression screener in family practice training centers and community settings. Fam Med 1998;30:362-65
48. Andrews G, Anstey K, Brodaty H, et al. Recall of depressive episode 25 years previously. Psychol Med 1999;29:787-91
49. Wright AF. Should general practitioners be testing for depression? Br J Gen Pract 1994;44:132-35
50. Van Weel C. Validating long term morbidity recording. J Epidemiol Community Health 1995;49 (suppl):29-32.
51. Merikangas KR, Wicki W, Angst J. Heterogeneity of depression: classification of depressive subtypes by longitudinal course. Br J Psychiatry 1994;164:342-48
52. Murphy JM, Olivier DC, Sobol AM, et al. Diagnosis and outcome: depression and anxiety in a general population. Psychol Med 1986;16:117-26
53. Hagnell O, Lanke J, Rorsman B. Suicide and depression in the male part of the Lundby study: changes over time during a 25-year observation period. Neuropsychobiology 1982;8:182-87
54. Lloyd KR, Jenkins R, Mann A. Long-term outcome of patients with neurotic illness in general practice. BMJ 1996;313:26-28
METHODS: We performed a literature search to identify relevant papers published between 1970 and 1999 on original long-term follow-up studies of depression in community and primary care populations. The included studies were of adult populations with depression based on diagnostic criteria and a follow-up of at least 5 years. Data about recurrences, relapses, psychopathology, disability, or quality of life at follow-up were examined.
RESULTS: We found 8 studies that fulfilled our criteria. The reported rates of recurrence or depression at follow-up were between 30% and 40%. Higher rates were found in the younger and older age groups. Data about other predictors of outcome, health status, and the relation between treatment and outcome did not justify any hard conclusions.
CONCLUSIONS: The long-term outcome of depression in the community and in primary care is rarely studied. The results of available studies are difficult to compare because of the large differences in populations and methods. Nevertheless, these studies suggest that the long-term prognosis of depression in the community and in primary care is not as poor as in psychiatry.
Depression is regarded as a chronic illness with a high prevalence and a large impact on quality of life.1-6 Nevertheless, the long-term outcome of depression in primary care and in the community is not clear. Most long-term outcome studies of depression have been performed with populations of patients who have been referred to psychiatric specialists.7-11 However, not everyone with depression in the community consults a physician, and usually only the more severe and lasting cases—approximately 5% to 15% of all patients who seek medical attention and have received a diagnosis of depression in primary care—are referred for secondary care.12,13 It is unlikely that the outcome in the community and in primary care is identical to that of referred cases, because of the difference in the prevalence of the various severity levels of depression between these populations.14
The follow-up periods of most studies of depression performed in the community and in primary care have been relatively short.15-17 From these studies we know that patients experience disability during depressive episodes, but we do not have a clear picture of the long-term consequences from the patient perspective.2,4,5 Also, in short-term studies, rates of depression measured at follow-up are not conclusive in determining recurrence rates.
Concerning treatment, it has been established in many short-term studies that antidepressants are effective for the treatment of major depressive disorder11,18,19 and perhaps also for minor depression20-23 (with a high prevalence in community and primary care).24-27
However, papers can be found describing a totally different picture for the long-term outcome of chronic diseases.28,29 These studies demonstrate that short-term effectiveness and safety do not automatically predict long-term outcome. Therefore, we think that knowledge about the long-term course of depression in the community and in primary care, naturalistic as well as treated, is indispensable for determining what treatment strategy is justified. Studies about the negative effects of antidepressants have been published,30-33 and some suggest that these drugs might influence the course of depression in a negative way.34 Long-term outcome information should be available for all levels of depression, including cases for which no medical attention is sought, and differences between naturalistic outcome and outcome after treatment should be clear. We reviewed the literature for long-term outcome studies of depression in the community and in primary care, looking for answers to the following 3 research questions: What is the recurrence rate of depression? Can a relation be found between long-term outcome and treatment? What are the long-term consequences for the health status of the patients involved?
Methods
Retrieval of the Literature
We performed a computerized search of studies from 1970 to 1999 using MEDLINE, Psychlit, Current Contents, and The Cochrane Library. We chose 1970 as our starting point, because at that time modern classification systems were introduced and research diagnostic criteria became available to investigators.
Thesaurus and free text words were combined for “depression/depressive disorder” with “general practice/family practice/primary care” or “community” and “follow-up/course/outcome/prognosis.”
Selection of the Literature
Two reviewers (H.J.S., E.M.vW-B.) made a selection by screening titles and abstracts. If an abstract had been selected by only one of the reviewers it was discussed until consensus was reached.
Our inclusion criteria were: original longitudinal follow-up studies in English of adult populations in the community or primary care with at least 25 patients in the follow-up. In the included studies diagnosis of depression was according to: the International Classification of Primary Care or the International Classification of Health Problems in Primary Care (ICHPPC-2) in general practice studies; the Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition, third edition revised, or fourth edition; the research diagnostic criteria (RDC) or immediate predecessor (St Louis); or the International Classification of Diseases (ICD)-9th Revision-Clinical Modification or the ICD-10th Revision.35,36 As inclusion criteria for outcome of depression we included studies reporting on recurrences, relapses, psychopathology, disability, or quality of life at follow-up. We defined long-term as a follow-up of at least 5 years, because recurrences usually occur within this time frame.9,13,37 A follow-up of at least 5 years should give an indication of percentages of single-episode depression and recurrence rates, and should provide more of an opportunity for distinguishing recurrence from relapse and no recovery (yet) than a shorter follow-up.
When abstracts met the inclusion criteria or remained unclear, full articles were retrieved for further evaluation. We also retrieved relevant reviews. All of these studies were screened with the ancestry approach. Additionally, a number of experts in the field from the Netherlands, the United Kingdom, and the United States were asked for additional references.
Data Abstraction and Presentation
Because of the wide variety of study designs, we limited ourselves to a qualitative evaluation. We abstracted data about design, setting, diagnostic criteria, number and specific diagnosis of depressive patients in the follow-up, age and sex, length of follow-up, treatment, and outcomes.
We calculated a total rate of recurrence or depression at follow up for all patients still alive and present at the end of the follow-up of each study. For that purpose we combined the rates for minor and major depression. This gave us the opportunity to compare the outcome results of depression diagnosed with family practice criteria with DSM cases and cases meeting RDC.
Results
Selection of Articles
The computer search supplied 421 potentially relevant articles. We selected 56 papers on the basis of that search, the reference lists of 4 review articles, and the suggestions of experts. Eight of those studies met all our inclusion criteria: 6 of these were community studies, and 2 were in primary care. Studies were excluded for 1 or more of the following reasons: no longitudinal follow-up (13), long-term follow-up shorter than 5 years (35), no diagnostic criteria mentioned in the article (4), population not from community or primary care (5) or too small (1), or outcome results of depression were mixed with other diagnoses (2).
Design, Aim, and Outcomes
Table 1 provides an overview of the included studies with outcomes as presented in the original articles. There was only one study from the 1970s38 meeting our criteria; all others were published in the last 10 years.
Initially there had either been a community survey with screening instruments, followed by diagnostic interviews or the whole population had been interviewed to identify cases of depression. Then there had been a follow up with the depressed subjects. In 4 of the 6 community studies the outcome was presented as depression at follow-up,39-42 and in the other 2 studies as recurrences.43,44 In 2 studies the results of depression at follow-up were based on 3 follow-up interviews: in the third, fourth, and fifth year after the initial assessment in the first study,41 and one every 5 years in the other.42 Three studies were performed on the elderly,39-41 one on young adults living in the community,42 and 2 in community samples in which all ages were represented.43,44 In one of these latter studies44 the population consisted of family members and relatives of affectively ill probands.
Both family practice studies had a historic cohort design13,38 and referred to patients recognized with depression in family practice. A cohort of depressed patients had been identified from a morbidity registry13 or practice,38 and was followed up longitudinally using the patients’ records (and registry13). The follow-up started on the date the diagnosis was made for the first time13 or the first time in the practice.38 Outcome in both studies was based on the reference to recurrences on the patients’ records over the entire study period.
The Diagnosis of Depression and Diagnostic Criteria
There was only one study using specific family practice criteria. For that study E-list criteria (the first classification for general practice, developed in the United Kingdom and derived from the ICD) was used initially and was later replaced with ICHPPC-2 criteria.45,13 In all the other studies DSM,40,42,43 RDC,38,42-44 or criteria derived from the RDC for use in elderly populations39,41 (obtained with GMS-AGECAT, a computerized diagnostic system for elderly subjects derived from the Geriatric Mental State46) were used. In the family practice study by Widmer and Cadoret38 the symptoms on the records were incorporated in the RDC retrospectively.
Length of Follow-up of Depression
In one study44 the length of the follow-up from the onset of depression was not clear because it did not mention when the depressive episodes occurred. In all other studies the follow-up began with a depressive episode. One study started the follow-up at first episodes only.13 That is the only study in which a time relation between the initial diagnosis and recurrences is presented longitudinally. One other study started at initial episodes in the practice38; all others start at index and recurrent episodes, but the proportions are not clear.
Recurrence or Depression at Follow-up
There were differences in levels of depression included in the outcome results Table 1. The rates of recurrence presented in the community studies ranged between 26% and 47%, and the rates of depression at follow-up were between 9% and 44%. Recurrence rates in the family practice studies ranged from 35% to 40%. The recurrence rate of 35% was calculated retrospectively, relying on the symptoms mentioned on the case records. The recurrence rate of 40% was found by extracting data from a morbidity registry and checking those data against symptoms on the patient records.13 Both studies also presented the number of recurrences. In one study 27% of the followed-up patients had 2 episodes; 6%, 3; and 3%, 4 or more38; in the other the percentages were 16% with 2, 12% with 3, and 12% with 4 or more.13
Treatment
The authors of 4 studies38-40,42 reported on treatment. None described the nature and length of treatment clearly, and treatment was not related to recurrence or depression at follow-up.
Mortality
Data for mortality were given in 4 studies13,39-41 (range of rates=14%-44%). The higher mortality rates refer to the elderly. In 2 studies mortality was similar to the expected rates (compared with a control group in one13 and with the National Mortality Statistics in the other39); in another study41 the rates were significantly higher than in a control group of nondepressed individuals; and in the last study13 the results of a comparison were not discussed. Data on suicide attempts and suicide can be found in only one study.13
Health Status
Two studies reported on disability or self-perceived physical health, but none of the studies used any of the well-known health status measurement instruments. One study39 reported on disability levels (with a modified version of the American Resources and Services) There was significantly more moderate to severe impairment among the depressed than among the recovered cases, as rated by a clinician; also, it is not clear whether this rating refers to the initial assessment or the follow-up. In the other study40 46% of the elderly patients reported poor health status, but it is not clear which instrument was used; no relation was found between outcome and perceived health status.
Total Rates of Recurrence or Depression at Follow-up
Table 2 shows the total rates of recurrence or depression at follow-up, adding up the results of minor and major depression when possible. The recurrence rates of the populations in which no specific age group was followed-up ranged from 30% to 40%. These studies had indications for higher recurrence rates in the younger age groups. The community studies of depression in the elderly and young adults reported outcome as depression at follow-up. The rates of depression at follow-up in 2 of the studies of the elderly39,41 were relatively high. One of these studies41 only reported on major depression at follow-up. This was also the case in the study with young adults.42
Discussion
Studies of the long-term outcome of depression in the community and in primary care are scarce and difficult to compare, and methodologic shortcomings hamper their generalizability.
Our data suggest that overall recurrence rates in the community and in family practice vary between 30% and 40%. The relationship between treatment and long-term outcome remains unclear, because none of the studies were controlled trials for treatment or looked into this matter adequately. This also applies to the patient’s qualitative experience. Almost all studies exclusively report physician-diagnosed recurrence or positive scores on diagnostic instruments of depression at follow-up.
Recurrence rates of 30% to 40% indicate that the prognosis for depression in community and family practice is not as poor as in psychiatry. In psychiatric settings much higher recurrence rates are found, with percentages of up to almost 90% depending on the length of follow-up and the setting.9,10,37 Prognosis seems to be related to age, with young adults and the elderly having poorer prognoses. In the study on young adults, between 30% and 40% of the patients had a major depressive disorder at follow-up, but those results did not include rates of minor depression. They also did not include recurrences between the follow-up interviews, and thus it is likely that recurrence rates were higher. Higher recurrence rates were also found in the younger age groups in 2 of the community studies.43,44 All the studies performed exclusively with the elderly reported depression at follow-up and gave a poor prognosis.39-41 This was not confirmed in the 2 community studies involving various ages and one general practice study.13,43,44 The higher rates in studies on the elderly might be explained by the use of diagnostic instruments more sensitive to detect depression specifically in that age group. Another explanation might be that differences were not found because of the relatively small number of elderly persons present in the other studies.
Limitations of the Studies
In the community studies subjects were identified with screening instruments. Therefore, a number of false-positive diagnoses may have been included in these studies that biased outcome results.47 This risk was minimized by using interviews in addition to the screening instruments. Another important limitation is the risk of missing part of the information about recurrences in the intervals between assessments. This risk is less in studies that include more than one follow-up assessment, as was done in 2 of the included studies,41,42 and also in studies where data about the interval are retrieved using information based on patients’ recall.40,43 Recall is known to introduce bias by not always giving sufficient details after longer periods of time.48
In the family practice studies where the specificity of the diagnosis is usually high,49,50 outcome results may have been biased because the results of undetected or misdiagnosed patients with depression are missing. In both studies the information was retrieved from the case records. Thus, accuracy depended on the completeness of the physicians’ notes. In one of the studies the case records were used in addition to data from a morbidity registry in which physicians were trained regularly to use criteria for diagnosis. Although suicide data can be found in this study, patients who left the practices or died within 10 years were excluded, and outcome results should be viewed taking that into consideration.
An important shortcoming is that most studies started at first or recurrent episodes, so it is not possible to give an exact percentage of single-episode depression versus recurrent illness. A description of the longitudinal course starting at first diagnosis is also not possible. Even in the one study starting at the first episode we can only draw conclusions about recurrence rates after diagnosis, because we have no certainty that the first diagnosis was in fact related to the first depressive episode. Other shortcomings are the small number of patients in the follow-up in 2 studies39,43 and uncertainty about the representativeness of the samples in one of the community studies.39,41,42,44 Since a family history of depression is a risk factor in an individual,51 the population of family members of affectively ill probands cannot be regarded as a representative community sample.44
The validity of the recurrence rates mentioned in the articles is difficult to assess because only one author gave confidence intervals of recurrence rates or depression at follow-up.13
Limitations of Our Review
Although we made our choice of inclusion criteria to ensure reasonable comparability, older studies52,53 and those in which data on depression could not be extracted from a broader variety of mental illness in family practice54 were excluded. We also made the choice to describe a limited number of outcomes, but the small number of studies included and the variety within the studies did not allow a review of more outcome results.
Although the calculation of a total recurrence rate may be criticized, we think that the fluctuating nature of depression justifies this procedure.
Conclusions
There are large gaps in the available knowledge about long-term outcome of depression in primary care, and future studies are required to fill in these gaps. We recommend the following:
- The outcome of all types of depression should be evaluated in prospective studies, with a follow-up of at least 5 years, of representative samples in both community and primary care.
- Continuous morbidity registration should be used. With this aim, data meeting fixed criteria that have been established beforehand should be collected longitudinally.
- Studies should include naturalistic follow-up and relate treatment to outcome.
- Quality-of-life assessment should be included.
Recommendations for clinical practice
Family physicians can reassure patients with depression by telling them that although the long-term outcome of the illness is not completely clear, there are indications that the majority of patients with depression do not have a poor prognosis. As the long term risk of recurrence seems to be approximately 40%, most patients in primary care settings only have 1 episode of depression. This information might aid a patient’s recovery.
METHODS: We performed a literature search to identify relevant papers published between 1970 and 1999 on original long-term follow-up studies of depression in community and primary care populations. The included studies were of adult populations with depression based on diagnostic criteria and a follow-up of at least 5 years. Data about recurrences, relapses, psychopathology, disability, or quality of life at follow-up were examined.
RESULTS: We found 8 studies that fulfilled our criteria. The reported rates of recurrence or depression at follow-up were between 30% and 40%. Higher rates were found in the younger and older age groups. Data about other predictors of outcome, health status, and the relation between treatment and outcome did not justify any hard conclusions.
CONCLUSIONS: The long-term outcome of depression in the community and in primary care is rarely studied. The results of available studies are difficult to compare because of the large differences in populations and methods. Nevertheless, these studies suggest that the long-term prognosis of depression in the community and in primary care is not as poor as in psychiatry.
Depression is regarded as a chronic illness with a high prevalence and a large impact on quality of life.1-6 Nevertheless, the long-term outcome of depression in primary care and in the community is not clear. Most long-term outcome studies of depression have been performed with populations of patients who have been referred to psychiatric specialists.7-11 However, not everyone with depression in the community consults a physician, and usually only the more severe and lasting cases—approximately 5% to 15% of all patients who seek medical attention and have received a diagnosis of depression in primary care—are referred for secondary care.12,13 It is unlikely that the outcome in the community and in primary care is identical to that of referred cases, because of the difference in the prevalence of the various severity levels of depression between these populations.14
The follow-up periods of most studies of depression performed in the community and in primary care have been relatively short.15-17 From these studies we know that patients experience disability during depressive episodes, but we do not have a clear picture of the long-term consequences from the patient perspective.2,4,5 Also, in short-term studies, rates of depression measured at follow-up are not conclusive in determining recurrence rates.
Concerning treatment, it has been established in many short-term studies that antidepressants are effective for the treatment of major depressive disorder11,18,19 and perhaps also for minor depression20-23 (with a high prevalence in community and primary care).24-27
However, papers can be found describing a totally different picture for the long-term outcome of chronic diseases.28,29 These studies demonstrate that short-term effectiveness and safety do not automatically predict long-term outcome. Therefore, we think that knowledge about the long-term course of depression in the community and in primary care, naturalistic as well as treated, is indispensable for determining what treatment strategy is justified. Studies about the negative effects of antidepressants have been published,30-33 and some suggest that these drugs might influence the course of depression in a negative way.34 Long-term outcome information should be available for all levels of depression, including cases for which no medical attention is sought, and differences between naturalistic outcome and outcome after treatment should be clear. We reviewed the literature for long-term outcome studies of depression in the community and in primary care, looking for answers to the following 3 research questions: What is the recurrence rate of depression? Can a relation be found between long-term outcome and treatment? What are the long-term consequences for the health status of the patients involved?
Methods
Retrieval of the Literature
We performed a computerized search of studies from 1970 to 1999 using MEDLINE, Psychlit, Current Contents, and The Cochrane Library. We chose 1970 as our starting point, because at that time modern classification systems were introduced and research diagnostic criteria became available to investigators.
Thesaurus and free text words were combined for “depression/depressive disorder” with “general practice/family practice/primary care” or “community” and “follow-up/course/outcome/prognosis.”
Selection of the Literature
Two reviewers (H.J.S., E.M.vW-B.) made a selection by screening titles and abstracts. If an abstract had been selected by only one of the reviewers it was discussed until consensus was reached.
Our inclusion criteria were: original longitudinal follow-up studies in English of adult populations in the community or primary care with at least 25 patients in the follow-up. In the included studies diagnosis of depression was according to: the International Classification of Primary Care or the International Classification of Health Problems in Primary Care (ICHPPC-2) in general practice studies; the Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition, third edition revised, or fourth edition; the research diagnostic criteria (RDC) or immediate predecessor (St Louis); or the International Classification of Diseases (ICD)-9th Revision-Clinical Modification or the ICD-10th Revision.35,36 As inclusion criteria for outcome of depression we included studies reporting on recurrences, relapses, psychopathology, disability, or quality of life at follow-up. We defined long-term as a follow-up of at least 5 years, because recurrences usually occur within this time frame.9,13,37 A follow-up of at least 5 years should give an indication of percentages of single-episode depression and recurrence rates, and should provide more of an opportunity for distinguishing recurrence from relapse and no recovery (yet) than a shorter follow-up.
When abstracts met the inclusion criteria or remained unclear, full articles were retrieved for further evaluation. We also retrieved relevant reviews. All of these studies were screened with the ancestry approach. Additionally, a number of experts in the field from the Netherlands, the United Kingdom, and the United States were asked for additional references.
Data Abstraction and Presentation
Because of the wide variety of study designs, we limited ourselves to a qualitative evaluation. We abstracted data about design, setting, diagnostic criteria, number and specific diagnosis of depressive patients in the follow-up, age and sex, length of follow-up, treatment, and outcomes.
We calculated a total rate of recurrence or depression at follow up for all patients still alive and present at the end of the follow-up of each study. For that purpose we combined the rates for minor and major depression. This gave us the opportunity to compare the outcome results of depression diagnosed with family practice criteria with DSM cases and cases meeting RDC.
Results
Selection of Articles
The computer search supplied 421 potentially relevant articles. We selected 56 papers on the basis of that search, the reference lists of 4 review articles, and the suggestions of experts. Eight of those studies met all our inclusion criteria: 6 of these were community studies, and 2 were in primary care. Studies were excluded for 1 or more of the following reasons: no longitudinal follow-up (13), long-term follow-up shorter than 5 years (35), no diagnostic criteria mentioned in the article (4), population not from community or primary care (5) or too small (1), or outcome results of depression were mixed with other diagnoses (2).
Design, Aim, and Outcomes
Table 1 provides an overview of the included studies with outcomes as presented in the original articles. There was only one study from the 1970s38 meeting our criteria; all others were published in the last 10 years.
Initially there had either been a community survey with screening instruments, followed by diagnostic interviews or the whole population had been interviewed to identify cases of depression. Then there had been a follow up with the depressed subjects. In 4 of the 6 community studies the outcome was presented as depression at follow-up,39-42 and in the other 2 studies as recurrences.43,44 In 2 studies the results of depression at follow-up were based on 3 follow-up interviews: in the third, fourth, and fifth year after the initial assessment in the first study,41 and one every 5 years in the other.42 Three studies were performed on the elderly,39-41 one on young adults living in the community,42 and 2 in community samples in which all ages were represented.43,44 In one of these latter studies44 the population consisted of family members and relatives of affectively ill probands.
Both family practice studies had a historic cohort design13,38 and referred to patients recognized with depression in family practice. A cohort of depressed patients had been identified from a morbidity registry13 or practice,38 and was followed up longitudinally using the patients’ records (and registry13). The follow-up started on the date the diagnosis was made for the first time13 or the first time in the practice.38 Outcome in both studies was based on the reference to recurrences on the patients’ records over the entire study period.
The Diagnosis of Depression and Diagnostic Criteria
There was only one study using specific family practice criteria. For that study E-list criteria (the first classification for general practice, developed in the United Kingdom and derived from the ICD) was used initially and was later replaced with ICHPPC-2 criteria.45,13 In all the other studies DSM,40,42,43 RDC,38,42-44 or criteria derived from the RDC for use in elderly populations39,41 (obtained with GMS-AGECAT, a computerized diagnostic system for elderly subjects derived from the Geriatric Mental State46) were used. In the family practice study by Widmer and Cadoret38 the symptoms on the records were incorporated in the RDC retrospectively.
Length of Follow-up of Depression
In one study44 the length of the follow-up from the onset of depression was not clear because it did not mention when the depressive episodes occurred. In all other studies the follow-up began with a depressive episode. One study started the follow-up at first episodes only.13 That is the only study in which a time relation between the initial diagnosis and recurrences is presented longitudinally. One other study started at initial episodes in the practice38; all others start at index and recurrent episodes, but the proportions are not clear.
Recurrence or Depression at Follow-up
There were differences in levels of depression included in the outcome results Table 1. The rates of recurrence presented in the community studies ranged between 26% and 47%, and the rates of depression at follow-up were between 9% and 44%. Recurrence rates in the family practice studies ranged from 35% to 40%. The recurrence rate of 35% was calculated retrospectively, relying on the symptoms mentioned on the case records. The recurrence rate of 40% was found by extracting data from a morbidity registry and checking those data against symptoms on the patient records.13 Both studies also presented the number of recurrences. In one study 27% of the followed-up patients had 2 episodes; 6%, 3; and 3%, 4 or more38; in the other the percentages were 16% with 2, 12% with 3, and 12% with 4 or more.13
Treatment
The authors of 4 studies38-40,42 reported on treatment. None described the nature and length of treatment clearly, and treatment was not related to recurrence or depression at follow-up.
Mortality
Data for mortality were given in 4 studies13,39-41 (range of rates=14%-44%). The higher mortality rates refer to the elderly. In 2 studies mortality was similar to the expected rates (compared with a control group in one13 and with the National Mortality Statistics in the other39); in another study41 the rates were significantly higher than in a control group of nondepressed individuals; and in the last study13 the results of a comparison were not discussed. Data on suicide attempts and suicide can be found in only one study.13
Health Status
Two studies reported on disability or self-perceived physical health, but none of the studies used any of the well-known health status measurement instruments. One study39 reported on disability levels (with a modified version of the American Resources and Services) There was significantly more moderate to severe impairment among the depressed than among the recovered cases, as rated by a clinician; also, it is not clear whether this rating refers to the initial assessment or the follow-up. In the other study40 46% of the elderly patients reported poor health status, but it is not clear which instrument was used; no relation was found between outcome and perceived health status.
Total Rates of Recurrence or Depression at Follow-up
Table 2 shows the total rates of recurrence or depression at follow-up, adding up the results of minor and major depression when possible. The recurrence rates of the populations in which no specific age group was followed-up ranged from 30% to 40%. These studies had indications for higher recurrence rates in the younger age groups. The community studies of depression in the elderly and young adults reported outcome as depression at follow-up. The rates of depression at follow-up in 2 of the studies of the elderly39,41 were relatively high. One of these studies41 only reported on major depression at follow-up. This was also the case in the study with young adults.42
Discussion
Studies of the long-term outcome of depression in the community and in primary care are scarce and difficult to compare, and methodologic shortcomings hamper their generalizability.
Our data suggest that overall recurrence rates in the community and in family practice vary between 30% and 40%. The relationship between treatment and long-term outcome remains unclear, because none of the studies were controlled trials for treatment or looked into this matter adequately. This also applies to the patient’s qualitative experience. Almost all studies exclusively report physician-diagnosed recurrence or positive scores on diagnostic instruments of depression at follow-up.
Recurrence rates of 30% to 40% indicate that the prognosis for depression in community and family practice is not as poor as in psychiatry. In psychiatric settings much higher recurrence rates are found, with percentages of up to almost 90% depending on the length of follow-up and the setting.9,10,37 Prognosis seems to be related to age, with young adults and the elderly having poorer prognoses. In the study on young adults, between 30% and 40% of the patients had a major depressive disorder at follow-up, but those results did not include rates of minor depression. They also did not include recurrences between the follow-up interviews, and thus it is likely that recurrence rates were higher. Higher recurrence rates were also found in the younger age groups in 2 of the community studies.43,44 All the studies performed exclusively with the elderly reported depression at follow-up and gave a poor prognosis.39-41 This was not confirmed in the 2 community studies involving various ages and one general practice study.13,43,44 The higher rates in studies on the elderly might be explained by the use of diagnostic instruments more sensitive to detect depression specifically in that age group. Another explanation might be that differences were not found because of the relatively small number of elderly persons present in the other studies.
Limitations of the Studies
In the community studies subjects were identified with screening instruments. Therefore, a number of false-positive diagnoses may have been included in these studies that biased outcome results.47 This risk was minimized by using interviews in addition to the screening instruments. Another important limitation is the risk of missing part of the information about recurrences in the intervals between assessments. This risk is less in studies that include more than one follow-up assessment, as was done in 2 of the included studies,41,42 and also in studies where data about the interval are retrieved using information based on patients’ recall.40,43 Recall is known to introduce bias by not always giving sufficient details after longer periods of time.48
In the family practice studies where the specificity of the diagnosis is usually high,49,50 outcome results may have been biased because the results of undetected or misdiagnosed patients with depression are missing. In both studies the information was retrieved from the case records. Thus, accuracy depended on the completeness of the physicians’ notes. In one of the studies the case records were used in addition to data from a morbidity registry in which physicians were trained regularly to use criteria for diagnosis. Although suicide data can be found in this study, patients who left the practices or died within 10 years were excluded, and outcome results should be viewed taking that into consideration.
An important shortcoming is that most studies started at first or recurrent episodes, so it is not possible to give an exact percentage of single-episode depression versus recurrent illness. A description of the longitudinal course starting at first diagnosis is also not possible. Even in the one study starting at the first episode we can only draw conclusions about recurrence rates after diagnosis, because we have no certainty that the first diagnosis was in fact related to the first depressive episode. Other shortcomings are the small number of patients in the follow-up in 2 studies39,43 and uncertainty about the representativeness of the samples in one of the community studies.39,41,42,44 Since a family history of depression is a risk factor in an individual,51 the population of family members of affectively ill probands cannot be regarded as a representative community sample.44
The validity of the recurrence rates mentioned in the articles is difficult to assess because only one author gave confidence intervals of recurrence rates or depression at follow-up.13
Limitations of Our Review
Although we made our choice of inclusion criteria to ensure reasonable comparability, older studies52,53 and those in which data on depression could not be extracted from a broader variety of mental illness in family practice54 were excluded. We also made the choice to describe a limited number of outcomes, but the small number of studies included and the variety within the studies did not allow a review of more outcome results.
Although the calculation of a total recurrence rate may be criticized, we think that the fluctuating nature of depression justifies this procedure.
Conclusions
There are large gaps in the available knowledge about long-term outcome of depression in primary care, and future studies are required to fill in these gaps. We recommend the following:
- The outcome of all types of depression should be evaluated in prospective studies, with a follow-up of at least 5 years, of representative samples in both community and primary care.
- Continuous morbidity registration should be used. With this aim, data meeting fixed criteria that have been established beforehand should be collected longitudinally.
- Studies should include naturalistic follow-up and relate treatment to outcome.
- Quality-of-life assessment should be included.
Recommendations for clinical practice
Family physicians can reassure patients with depression by telling them that although the long-term outcome of the illness is not completely clear, there are indications that the majority of patients with depression do not have a poor prognosis. As the long term risk of recurrence seems to be approximately 40%, most patients in primary care settings only have 1 episode of depression. This information might aid a patient’s recovery.
1. Froom J, Aoyama H, Hermoni D, et al. Depressive disorders in three primary care populations: United States, Israel, Japan. Fam Pract 1995;12:274-78
2. Ormel J, VonKorff M, Ustun TB, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA 1994;272:1741-48
3. Robins LN. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984;41:949-58
4. Williams JW, Kerber CA, Mulrow CD, et al. Depressive disorders in primary care: prevalence, functional disability, and identification. J Gen Intern Med 1995;10:7-12
5. Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients: results from the Medical Outcomes Study. JAMA 1989;262:914-19
6. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992;14:237-47
7. Coryell W, Turvey C, Endicott J, et al. Bipolar I affective disorder: predictors of outcome after 15 years. J Affect Disord 1998;50:109-16
8. Paykel ES. Historical overview of outcome of depression. Br J Psychiatry Suppl 1994;26:6-8
9. Angst J, Preisig M. Course of a clinical cohort of unipolar, bipolar and schizoaffective patients: results of a prospective study from 1959 to 1985. Schweiz Archiv Neurol Psychiatr 1995;146:5-16
10. Piccinelli M, Wilkinson G. Outcome of depression in psychiatric settings. Br J Psychiatry 1994;164:297-304
11. Lavori PW, Keller MB, Mueller TI, et al. Recurrence after recovery in unipolar MDD: an observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatric Res 1994;4:211-29
12. Blacker CV, Clare AW. Depressive disorder in primary care. Br J Psychiatry 1987;150:737-51
13. van Weel-Baumgarten E, van den Bosch W, van den Hoogen H, et al. Ten year follow-up of depression after diagnosis in general practice. Br J Gen Pract 1998;48:1643-46
14. Watts CA. Depressive disorders in the community: the scene in Great Britain, 1965. J Clin Psychiatry 1984;45:70-77
15. Klinkman MS, Schwenk TL, Coyne JC. Depression in primary care—more like asthma than appendicitis: the Michigan Depression Project. Can J Psychiatry 1997;42:966-73.
16. Lin EH, Simon GE, Katon WJ, et al. Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care. Am J Psychiatry 1999;156:643-45
17. Ormel J, Oldehinkel T, Brilman E, et al. Outcome of depression and anxiety in primary care: a three-wave 3 1/2-year study of psychopathology and disability. Arch Gen Psychiatry 1993;50:759-66
18. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52 (suppl):28-34.
19. Prien RF. Efficacy of continuation drug therapy of depression and anxiety: issues and methodologies. J Clin Psychopharmacol 1990;10:86S-90S.
20. Tan RS, Barlow RJ, Abel C, et al. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Br J Clin Pharmacol 1994;37:321-24
21. Thompson C, Thompson CM. The prescribing of antidepressants in general practice: II. A placebo-controlled trial of low-dose dothiepin. Human Psychopharma 1989;191-204.
22. Wernicke JF, Dunlop SR, Dornseif BE, et al. Low-dose fluoxetine therapy for depression. Psychopharmacol Bull 1988;24:183-88
23. Paykel ES, Freeling P, Hollyman JA. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Pharmacopsychiatry 1988;21:15-18
24. Hollyman JA, Freeling P, Paykel ES, et al. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. J R Coll Gen Pract 1988;38:393-97
25. Mynors WL, Gath D. Predictors of treatment outcome for major depression in primary care. Psychol Med 1997;27:731-36
26. Scott AI, Freeman CP. Edinburgh primary care depression study: treatment outcome, patient satisfaction, and cost after 16 weeks. BMJ 1992;304:883-87
27. Schulberg HC, Block MR, Madonia MJ, et al. Treating major depression in primary care practice: eight-month clinical outcomes. Arch Gen Psychiatry 1996;53:913-19
28. Pincus T, Stein CM. Why randomized controlled clinical trials do not depict accurately long-term outcomes in rheumatoid arthritis: some explanations and suggestions for future studies. Clin Exp Rheumatol 1997;15 (suppl):S27-38.
29. Wolfe F, Hawley DJ, Cathey MA. Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis. J Rheumatol 1991;18:1290-97.
30. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106-09
31. Po AL. Antidepressants and upper gastrointestinal bleeding. BMJ 1999;319:1081-82
32. Mackay FR, Dunn NR, Martin RM, et al. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract 1999;49:892-96
33. Sampson E, Warner JP. Serotonin syndrome: potentially fatal but difficult to recognize. Br J Gen Pract 1999;49:867-68
34. Tondo L, Laddomada P, Serra G, et al. Rapid cyclers and antidepressants. Int Pharmacopsychiatry 1981;16:119-23
35. Classification committee of WONCA. ICHPPC-2-defined (International classification of Health Problems in Primary Care). 3rd ed. Oxford, England: Oxford University Press; 1983.
36. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 1994.
37. Van Londen L, Molenaar RP, Goekoop JG, et al. Three- to 5-year prospective follow-up of outcome in major depression. Psychol Med 1998;28:731-35
38. Widmer RB, Cadoret RJ. Depression in primary care: changes in pattern of patient visits and complaints during a developing depression. J Fam Pract 1978;7:293-302
39. Kua EH. The depressed elderly Chinese living in the community: a five-year follow-up study. Int J Geriatr Psychiatry 1993;8:427-30
40. Kivela SL, Kongas SP, Kesti E, et al. Five-year prognosis for depression in old age. Int Psychogeriatr 1994;6:69-78
41. Sharma VK, Copeland JR, Dewey ME, et al. Outcome of the depressed elderly living in the community in Liverpool: a 5-year follow-up. Psychol Med 1998;28:1329-37
42. Angst J, Merikangas K. The depressive spectrum: diagnostic classification and course. J Affect Disord 1997;45:31-39
43. Eaton WW, Anthony JC, Gallo J, et al. Natural history of Diagnostic Interview Schedule/DSM-IV major depression: the Baltimore Epidemiologic Catchment Area follow-up. Arch Gen Psychiatry 1997;54:993-99
44. Coryell W, Endicott J, Keller MB. Predictors of relapse into major depressive disorder in a nonclinical population. Am J Psychiatry 1991;148:1353-58
45. Logan WPD, Cushion A. Morbidity statistics from general practice. Vol 1. London, England: Her Majesty’s Stationary Office; 1954.
46. Copeland JR, Dewey ME, Griffiths-Jones HM. A computerized psychiatric diagnostic system and case nomenclature for elderly subjects: GMS and AGECAT. Psychol Med 1986;16:89-99
47. Nagel R, Lynch D, Tamburrino M. Validity of the medical outcomes study depression screener in family practice training centers and community settings. Fam Med 1998;30:362-65
48. Andrews G, Anstey K, Brodaty H, et al. Recall of depressive episode 25 years previously. Psychol Med 1999;29:787-91
49. Wright AF. Should general practitioners be testing for depression? Br J Gen Pract 1994;44:132-35
50. Van Weel C. Validating long term morbidity recording. J Epidemiol Community Health 1995;49 (suppl):29-32.
51. Merikangas KR, Wicki W, Angst J. Heterogeneity of depression: classification of depressive subtypes by longitudinal course. Br J Psychiatry 1994;164:342-48
52. Murphy JM, Olivier DC, Sobol AM, et al. Diagnosis and outcome: depression and anxiety in a general population. Psychol Med 1986;16:117-26
53. Hagnell O, Lanke J, Rorsman B. Suicide and depression in the male part of the Lundby study: changes over time during a 25-year observation period. Neuropsychobiology 1982;8:182-87
54. Lloyd KR, Jenkins R, Mann A. Long-term outcome of patients with neurotic illness in general practice. BMJ 1996;313:26-28
1. Froom J, Aoyama H, Hermoni D, et al. Depressive disorders in three primary care populations: United States, Israel, Japan. Fam Pract 1995;12:274-78
2. Ormel J, VonKorff M, Ustun TB, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA 1994;272:1741-48
3. Robins LN. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984;41:949-58
4. Williams JW, Kerber CA, Mulrow CD, et al. Depressive disorders in primary care: prevalence, functional disability, and identification. J Gen Intern Med 1995;10:7-12
5. Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients: results from the Medical Outcomes Study. JAMA 1989;262:914-19
6. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992;14:237-47
7. Coryell W, Turvey C, Endicott J, et al. Bipolar I affective disorder: predictors of outcome after 15 years. J Affect Disord 1998;50:109-16
8. Paykel ES. Historical overview of outcome of depression. Br J Psychiatry Suppl 1994;26:6-8
9. Angst J, Preisig M. Course of a clinical cohort of unipolar, bipolar and schizoaffective patients: results of a prospective study from 1959 to 1985. Schweiz Archiv Neurol Psychiatr 1995;146:5-16
10. Piccinelli M, Wilkinson G. Outcome of depression in psychiatric settings. Br J Psychiatry 1994;164:297-304
11. Lavori PW, Keller MB, Mueller TI, et al. Recurrence after recovery in unipolar MDD: an observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatric Res 1994;4:211-29
12. Blacker CV, Clare AW. Depressive disorder in primary care. Br J Psychiatry 1987;150:737-51
13. van Weel-Baumgarten E, van den Bosch W, van den Hoogen H, et al. Ten year follow-up of depression after diagnosis in general practice. Br J Gen Pract 1998;48:1643-46
14. Watts CA. Depressive disorders in the community: the scene in Great Britain, 1965. J Clin Psychiatry 1984;45:70-77
15. Klinkman MS, Schwenk TL, Coyne JC. Depression in primary care—more like asthma than appendicitis: the Michigan Depression Project. Can J Psychiatry 1997;42:966-73.
16. Lin EH, Simon GE, Katon WJ, et al. Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care. Am J Psychiatry 1999;156:643-45
17. Ormel J, Oldehinkel T, Brilman E, et al. Outcome of depression and anxiety in primary care: a three-wave 3 1/2-year study of psychopathology and disability. Arch Gen Psychiatry 1993;50:759-66
18. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52 (suppl):28-34.
19. Prien RF. Efficacy of continuation drug therapy of depression and anxiety: issues and methodologies. J Clin Psychopharmacol 1990;10:86S-90S.
20. Tan RS, Barlow RJ, Abel C, et al. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Br J Clin Pharmacol 1994;37:321-24
21. Thompson C, Thompson CM. The prescribing of antidepressants in general practice: II. A placebo-controlled trial of low-dose dothiepin. Human Psychopharma 1989;191-204.
22. Wernicke JF, Dunlop SR, Dornseif BE, et al. Low-dose fluoxetine therapy for depression. Psychopharmacol Bull 1988;24:183-88
23. Paykel ES, Freeling P, Hollyman JA. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Pharmacopsychiatry 1988;21:15-18
24. Hollyman JA, Freeling P, Paykel ES, et al. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. J R Coll Gen Pract 1988;38:393-97
25. Mynors WL, Gath D. Predictors of treatment outcome for major depression in primary care. Psychol Med 1997;27:731-36
26. Scott AI, Freeman CP. Edinburgh primary care depression study: treatment outcome, patient satisfaction, and cost after 16 weeks. BMJ 1992;304:883-87
27. Schulberg HC, Block MR, Madonia MJ, et al. Treating major depression in primary care practice: eight-month clinical outcomes. Arch Gen Psychiatry 1996;53:913-19
28. Pincus T, Stein CM. Why randomized controlled clinical trials do not depict accurately long-term outcomes in rheumatoid arthritis: some explanations and suggestions for future studies. Clin Exp Rheumatol 1997;15 (suppl):S27-38.
29. Wolfe F, Hawley DJ, Cathey MA. Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis. J Rheumatol 1991;18:1290-97.
30. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106-09
31. Po AL. Antidepressants and upper gastrointestinal bleeding. BMJ 1999;319:1081-82
32. Mackay FR, Dunn NR, Martin RM, et al. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract 1999;49:892-96
33. Sampson E, Warner JP. Serotonin syndrome: potentially fatal but difficult to recognize. Br J Gen Pract 1999;49:867-68
34. Tondo L, Laddomada P, Serra G, et al. Rapid cyclers and antidepressants. Int Pharmacopsychiatry 1981;16:119-23
35. Classification committee of WONCA. ICHPPC-2-defined (International classification of Health Problems in Primary Care). 3rd ed. Oxford, England: Oxford University Press; 1983.
36. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 1994.
37. Van Londen L, Molenaar RP, Goekoop JG, et al. Three- to 5-year prospective follow-up of outcome in major depression. Psychol Med 1998;28:731-35
38. Widmer RB, Cadoret RJ. Depression in primary care: changes in pattern of patient visits and complaints during a developing depression. J Fam Pract 1978;7:293-302
39. Kua EH. The depressed elderly Chinese living in the community: a five-year follow-up study. Int J Geriatr Psychiatry 1993;8:427-30
40. Kivela SL, Kongas SP, Kesti E, et al. Five-year prognosis for depression in old age. Int Psychogeriatr 1994;6:69-78
41. Sharma VK, Copeland JR, Dewey ME, et al. Outcome of the depressed elderly living in the community in Liverpool: a 5-year follow-up. Psychol Med 1998;28:1329-37
42. Angst J, Merikangas K. The depressive spectrum: diagnostic classification and course. J Affect Disord 1997;45:31-39
43. Eaton WW, Anthony JC, Gallo J, et al. Natural history of Diagnostic Interview Schedule/DSM-IV major depression: the Baltimore Epidemiologic Catchment Area follow-up. Arch Gen Psychiatry 1997;54:993-99
44. Coryell W, Endicott J, Keller MB. Predictors of relapse into major depressive disorder in a nonclinical population. Am J Psychiatry 1991;148:1353-58
45. Logan WPD, Cushion A. Morbidity statistics from general practice. Vol 1. London, England: Her Majesty’s Stationary Office; 1954.
46. Copeland JR, Dewey ME, Griffiths-Jones HM. A computerized psychiatric diagnostic system and case nomenclature for elderly subjects: GMS and AGECAT. Psychol Med 1986;16:89-99
47. Nagel R, Lynch D, Tamburrino M. Validity of the medical outcomes study depression screener in family practice training centers and community settings. Fam Med 1998;30:362-65
48. Andrews G, Anstey K, Brodaty H, et al. Recall of depressive episode 25 years previously. Psychol Med 1999;29:787-91
49. Wright AF. Should general practitioners be testing for depression? Br J Gen Pract 1994;44:132-35
50. Van Weel C. Validating long term morbidity recording. J Epidemiol Community Health 1995;49 (suppl):29-32.
51. Merikangas KR, Wicki W, Angst J. Heterogeneity of depression: classification of depressive subtypes by longitudinal course. Br J Psychiatry 1994;164:342-48
52. Murphy JM, Olivier DC, Sobol AM, et al. Diagnosis and outcome: depression and anxiety in a general population. Psychol Med 1986;16:117-26
53. Hagnell O, Lanke J, Rorsman B. Suicide and depression in the male part of the Lundby study: changes over time during a 25-year observation period. Neuropsychobiology 1982;8:182-87
54. Lloyd KR, Jenkins R, Mann A. Long-term outcome of patients with neurotic illness in general practice. BMJ 1996;313:26-28