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Mapping review

Long-term treatment with antidepressants – evidence and gap map

The Norwegian Institute of Public Health has mapped existing research on long-term treatment with antidepressants.

Forside antidep kart.jpg

The Norwegian Institute of Public Health has mapped existing research on long-term treatment with antidepressants.

Key message

Depression is the fourth leading cause of lost quality of life and lost years lived according to the World Health Organization. The Norwegian Institute of Public Health has mapped existing research on long-term treatment with antidepressants.

  • We included 189 research articles.
  • A large part of this research has been performed on patients who had previously responded well to antidepressants
  • Few studies had registered their research protocol prior to publication
  • Most studies had authors with conflicts of interest

Links to evidence and gap maps:



Depression is one of the major contributors to the burden of disease in society. One out of five persons will experience depression during their lives.

The national guideline on the diagnosis and treatment of adults with depression in primary and specialty care states that patients who have taken antidepressants for six months after remission of the disease should be considered for treatment discontinuation. We have tried to map studies that have investigated effects and side effects of long-term use of antidepressants compared to no use (i.e., the effect of using). Another aim was to investigate what happens if a group that has used antidepressants with good effect continues to use the drugs compared to a group that abruptly discontinues antidepressants (i.e., the effect of quitting).


We have mapped existing research on long-term treatment with antidepressants exceeding six months.


We ran a systematic literature search for studies with persons diagnosed with depression who have used antidepressants over a period of more than six months. Two team members evaluated titles and abstracts independently of one another and agreed on which articles to include for full text screening. Two team members then evaluated full text publications independently of one another and agreed which articles to include in the final selection of studies.

Because this is a research mapping review, we did not analyse results from the included studies. We used a coding handbook and extracted data on the study design, patient populations, types and doses of antidepressants, duration of treatment, control groups, research hypotheses, methodology, among other aspects of each included study.


Our literature search resulted in 12 320 hits. Following title and abstract screening, we ordered full text versions of 1428 articles. Of these, we included 189 in the final selection of studies. Most of the studies were undertaken in North America and Europe. Women between 18 and 64 years of age were the largest patient group. The most studied group of antidepressives were selective serotonin reuptake inhibitors (SSRI). In 84 per cent of studies, the authors declared a conflict of interest. Eighty percent of studies did not report a study protocol. In almost half (47 percent) of the studies, a lead-in period was used in order to select patients who responded positively to an antidepressant. Links to evidence and gap maps: www.nornesk.no/forskningskart-antidepressiv/forskningskart-over-type-antidepressiv-og-utfall.html




Without analysing the results, we found that a large number of included studies had methodological weaknesses that would suggest a lower level of confidence in their results. Much of the research has been conducted on patients who already had responded positively to antidepressants. Relatively few authors have registered a protocol before starting the study. Most of the studies have authors who have conflicts of interest.

Authors ought to pre-register future studies in clinical trial databases. One should also follow guidelines for reporting of results, including flow charts for participation and attrition, e.g. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, http://www.prisma-statement.org), CONSORT (Consolidated Standards of Reporting Trials, http://www.consort-statement.org) and STROBE (Strengthening the Reporting of Observational Studies in Epidemiology, https://www.strobe-statement.org).

Use of lead-in periods can make drug therapies appear more effective than they will be in clinical practice.


We found 189 studies on patients with depression who had used antidepressants for six months or more. Although we have not summarized the results of the included studies, we have pointed to some aspects that might weaken the confidence in these results (e.g. conflicts of interest and lack of protocol registration).

Downloadable as PDF. In Norwegian. English summary.

About this publication

  • Year: 2020
  • By: Norwegian Institute of Public Health
  • Authors Smedslund G, Holte HH, Zinöcker S, Vist GE.
  • ISBN (digital): 978-82-8406-073-6