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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A systematic review of long-term studies of drug treated and non-drug treated depression

S Hughes and D Cohen.

Review published: 2009.

Link to full article: [Journal publisher]

CRD summary

This review concluded that long-term outcomes in depression appeared to be generally poor and there was no clear relationship between drug treatment and positive outcomes. Limitations, including the possibility of language and publication bias, the unclear quality of the included studies, and the lack of numerical and statistical data, mean that these conclusions should be interpreted with caution.

Authors' objectives

To determine the long-term outcomes of antidepressant treatment for depression during the modern pharmacological era (since 1988).


MEDLINE, PsycINFO, EMBASE and the Cochrane Library were searched from 1988 to April 2007 and search terms were reported. Reference lists of included studies were screened. The review was restricted to studies published in English since 1988.

Study selection

Studies that included at least one group, or a subset, of adults with unipolar depressive disorder treated with antidepressants or not treated with antidepressants were eligible for inclusion provided that they had at least 10 years of follow-up, with at least one follow-up after 1988 (for antidepressant studies only), and reported at least one clinical or psychosocial outcome, other than suicide or mortality. Studies that fulfilled the inclusion criteria for both antidepressant and non-antidepressant treatment were only included in the analysis for antidepressant treatment.

The included studies for antidepressant treatment were conducted in seven countries; the earliest began in 1947 and the follow-up ranged from 10 to 50 years. The number of follow-up assessments ranged from one to 25, and duration between follow-up assessments ranged from six months to 25 years. Participants had symptoms of unipolar depression, dysthymic disorder, mood disorder, or were hospitalised as former in-patients with a depressive disorder. Eight studies enrolled consecutive patients from psychiatric or medical clinics, one study reviewed patient records, and the remaining three studies recruited community samples. Data on antidepressant treatment was limited; most participants had received antidepressants during the index episode or later. Most participants in the included studies were white women with at least one in-patient stay. The primary outcomes were symptom status including recurrence, relapse, remission, or recovery.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

One reviewer extracted the data.

Methods of synthesis

A narrative synthesis was presented.

Results of the review

Twelve studies, with at least 3,901 participants at final follow-up, were reported in 24 publications and assessed antidepressant treatment. Three studies assessed non-antidepressant treatment (1,160 participants).

Overall 40% to 85% of patients experienced a recurrence during follow-up. Average time to recurrence was around 3.2 years across eight studies that provided data on this outcome. Around 25% of patients achieved a global rating of well or improved at the end of the study and a similar number had a poor outcome marked by multiple recurrences or continuous impairment. Most participants recovered from the index episode, but experienced multiple recurrences. The probability of recovery was highest in the first few years after the index episode and declined in later years (two studies). Episode duration and symptom severity were inconsistent across multiple episodes experienced by the same individual (two studies). Around 25% of participants never had an asymptomatic week during follow-up (two studies).

The outcomes for non-antidepressant treatment were no worse than those for antidepressant treatment.

Authors' conclusions

Long-term outcomes in depression appeared to be generally poor and there was no clear relationship between drug treatment and positive outcomes.

CRD commentary

This review addressed a clear objective supported by defined inclusion criteria. The literature search was appropriate for published studies, but this restriction to published studies in English means that there was a possibility of language and publication bias. Only one reviewer performed the data extraction increasing the possibility of reviewer error and bias; it was unclear whether appropriate steps were taken to reduce reviewer error and bias in the selection of studies. Study quality was not formally assessed and so the reliability of the included studies is unclear. A narrative synthesis was appropriate given the differences between studies, but only limited statistical and numerical data were reported making it difficult to draw conclusions. The authors' conclusions were supported by the data presented, but should be interpreted with some caution due to the limitations highlighted.

Implications of the review for practice and research

Practice: The authors stated that a lack of evidence from these long-term naturalistic studies of depression precluded any recommendations for maintenance antidepressant pharmacotherapy.

Research: The authors stated that studies designed to reflect real-world treatment conditions, that assess outcomes important to patients, and that explore factors that may influence outcomes, were needed to determine whether antidepressants are associated with long-term benefits. Studies should also assess the timing of drug use, duration, type, dose, observed and subjective effects, and details of previous drug-use, to assess whether antidepressants are associated with long-term benefits in specific patient subgroups.


Florida International University; State Attorneys General Consumer and Prescriber Grant Program.

Bibliographic details

Hughes S, Cohen D. A systematic review of long-term studies of drug treated and non-drug treated depression. Journal of Affective Disorders 2009; 118(1-3): 9-18. [PubMed: 19249104]

Indexing Status

Subject indexing assigned by NLM


Adult; Antidepressive Agents /adverse effects /therapeutic use; Cohort Studies; Controlled Clinical Trials as Topic; Depressive Disorder, Major /drug therapy /psychology; Evidence-Based Medicine; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Middle Aged; Recurrence /prevention & control; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19249104


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