Ulla Knorr1, Lars Vedel Kessing. 1. Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. ulla.knorr@rh.regionh.dk
Abstract
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) show antidepressant properties in many patients with a diagnosis of depression. An understanding of the underlying mechanisms of the effect of SSRIs in healthy patients may lead to an understanding of the yet unclear pathophysiology of depression. Recent reviews of studies investigating the effect of SSRIs in healthy persons conclude that the results are inconsistent and that--in relation to a wide range of outcomes--the effect of SSRIs is limited; however, reasons for the inconsistencies are poorly studied. AIMS AND METHODS: To investigate whether methodological artefacts can explain the diverging findings, we conducted a systematic review of all randomized multiple-dose, placebo-controlled trials on the effect of treatment by SSRI for at least a week in healthy persons published before January 2009. RESULTS: We identified 33 trials, investigating six SSRIs and 163 outcome tests. The effect of SSRI showed divergence presumably related to methodological issues. Specifically, it is likely that the majority of studies included a mix of healthy persons with and without a family history of affective disorders. Few presented information on factors that may influence outcomes such as age, gender, family history of psychiatric disorder, drug levels and ethnicity. No study fulfilled principles of conducting and reporting randomized controlled trials, according to the CONSORT Statement guidelines. CONCLUSIONS: It is unclear whether the effect of SSRIs in healthy persons may lead to an understanding of the pathophysiology of depression, since the present evidence is divergent and may be severely influenced by a number of methodological drawbacks.
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) show antidepressant properties in many patients with a diagnosis of depression. An understanding of the underlying mechanisms of the effect of SSRIs in healthy patients may lead to an understanding of the yet unclear pathophysiology of depression. Recent reviews of studies investigating the effect of SSRIs in healthy persons conclude that the results are inconsistent and that--in relation to a wide range of outcomes--the effect of SSRIs is limited; however, reasons for the inconsistencies are poorly studied. AIMS AND METHODS: To investigate whether methodological artefacts can explain the diverging findings, we conducted a systematic review of all randomized multiple-dose, placebo-controlled trials on the effect of treatment by SSRI for at least a week in healthy persons published before January 2009. RESULTS: We identified 33 trials, investigating six SSRIs and 163 outcome tests. The effect of SSRI showed divergence presumably related to methodological issues. Specifically, it is likely that the majority of studies included a mix of healthy persons with and without a family history of affective disorders. Few presented information on factors that may influence outcomes such as age, gender, family history of psychiatric disorder, drug levels and ethnicity. No study fulfilled principles of conducting and reporting randomized controlled trials, according to the CONSORT Statement guidelines. CONCLUSIONS: It is unclear whether the effect of SSRIs in healthy persons may lead to an understanding of the pathophysiology of depression, since the present evidence is divergent and may be severely influenced by a number of methodological drawbacks.
Authors: Stephanie N Mullins-Sweatt; Christopher J Hopwood; Michael Chmielewski; Neil A Meyer; Jiwon Min; Ashley C Helle; Maggie D Walgren Journal: Personal Ment Health Date: 2019-07-31
Authors: Ulla Knorr; Maj Vinberg; Anders Gade; Per Winkel; Christian Gluud; Jørn Wetterslev; Ulrik Gether; Lars Kessing Journal: Ther Adv Psychopharmacol Date: 2011-10
Authors: Ulla Knorr; Maj Vinberg; Allan Hansen; Marianne Klose; Ulla Feldt-Rasmussen; Linda Hilsted; Jørgen Hasselstrøm; Ulrik Gether; Per Winkel; Christian Gluud; Jørn Wetterslev; Lars Vedel Kessing Journal: PLoS One Date: 2011-06-27 Impact factor: 3.240
Authors: Ulla Knorr; Maj Vinberg; Erik Lykke Mortensen; Per Winkel; Christian Gluud; Jørn Wetterslev; Ulrik Gether; Lars Vedel Kessing Journal: PLoS One Date: 2012-02-29 Impact factor: 3.240
Authors: Agorastos Agorastos; Michael Kellner; Oliver Stiedl; Christoph Muhtz; Klaus Wiedemann; Cüneyt Demiralay Journal: Int J Neuropsychopharmacol Date: 2014-12-11 Impact factor: 5.176