The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective
Abstract The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02285-2 |
| _version_ | 1797945691897593856 |
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| author | Lynn Boschloo Fredrik Hieronymus Alexander Lisinski Pim Cuijpers Elias Eriksson |
| author_facet | Lynn Boschloo Fredrik Hieronymus Alexander Lisinski Pim Cuijpers Elias Eriksson |
| author_sort | Lynn Boschloo |
| collection | DOAJ |
| description | Abstract The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice. |
| first_indexed | 2024-04-10T21:00:15Z |
| format | Article |
| id | doaj.art-ad14c02ec3e24461b91091258625d626 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-10T21:00:15Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-ad14c02ec3e24461b91091258625d6262023-01-22T12:25:55ZengNature Publishing GroupTranslational Psychiatry2158-31882023-01-011311710.1038/s41398-022-02285-2The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspectiveLynn Boschloo0Fredrik Hieronymus1Alexander Lisinski2Pim Cuijpers3Elias Eriksson4Department of Clinical Psychology, Utrecht UniversityDepartment of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Clinical, Neuro, and Developmental Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit AmsterdamDepartment of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgAbstract The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice.https://doi.org/10.1038/s41398-022-02285-2 |
| spellingShingle | Lynn Boschloo Fredrik Hieronymus Alexander Lisinski Pim Cuijpers Elias Eriksson The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective Translational Psychiatry |
| title | The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective |
| title_full | The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective |
| title_fullStr | The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective |
| title_full_unstemmed | The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective |
| title_short | The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective |
| title_sort | complex clinical response to selective serotonin reuptake inhibitors in depression a network perspective |
| url | https://doi.org/10.1038/s41398-022-02285-2 |
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