Anxiolytic effects of serotoninergic psychedelics on patients with psychiatric disorders
R. Freire1, C. Chaves2, M. Cabo3, J. Mojgani1, E. Brietzke1, C. Svab4, F. Buono5, A. Garakani5
1Queen's University, Department of Psychiatry, Kingston, Canada, 2McMaster University, Department of Psychiatry & Behavioural Neurosciences, Hamilton, Canada, 3Federal University of Rio de Janeiro, Laboratory of Panic and Respiration, Rio de Janeiro, Brazil, 4Queen's University, Bracken Health Sciences Library, Kingston, Canada, 5Yale University, Department of Psychiatry and Behavioral Health, New Haven, United States
Background: Anxiety disorders are among the most prevalent psychiatric disorders worldwide, causing significant impacts on physical and emotional health and substantial functional impairment. Not only individuals with anxiety disorders have severe and debilitating anxiety symptoms; patients with PTSD, OCD and mood disorders often present with anxiety. The term classic psychedelics refers to substances that act as agonists or partial agonists of 5-hydroxytryptamine receptor type 2A (5-HT2A). These serotonergic psychedelics have also been shown to interact with other receptors such as 5-HT1A, 5-HT2B, and 5-HT2C. Although the exact mechanism of action is not fully elucidated yet, these drugs probably affect neuronal connections directly, modulate brain activity and produce neuroplasticity. Recent studies demonstrated that serotonergic psychedelics produce significant improvements in depressive disorders. They are also promising in the treatment of anxiety symptoms.
Aims & Objectives: The objective of this systematic review and meta-analysis is to ascertain if serotoninergic psychedelics improve anxiety symptoms in individuals with psychiatric disorders, with especial emphasis on anxiety disorders, OCD, PTSD and mood disorders.
Method: This was a systematic review with meta-analysis. Searches were conducted in Ovid MEDLINE, EMBASE, Cochrane Central, PsychINFO, clinicaltrials.gov, WHO International Clinical Trials Registry Platform, EU Clinical Trials Register, from 1980 to the current date. Articles in English were considered. Searches will be re-run prior to the final analysis. Unpublished studies were sought to access publication bias.
Inclusion criteria: Randomized controlled trials (RCT). Studies with adults with any psychiatric disorders except substance use disorder according to DSM-III, DSM-IV or DSM-5 diagnostic criteria. Studies with participants with comorbid medicals conditions (e.g. cancer) were not excluded as long as all participants met diagnostic criteria for a primary psychiatric diagnosis. The study intervention was administration of serotoninergic (classic) psychedelics. Both macro and microdosing studies were included.
The main analyzed outcome was anxiety symptoms in adults with psychiatric disorders. Placebo was the comparator for the active treatment. Acceptable outcomes were change in anxiety symptoms from baseline to the last follow-up using a formal assessment of anxiety symptoms. Clinical scales for assessment of anxiety symptoms included anxiety disorder specific scales (e.g. GAD-7, PAS) or general scales (e.g. Beck Anxiety Inventory). Frequency of panic attacks was also acceptable as an outcome measure. Standardized mean differences in clinical scales’ scores was the main measure of effect.
Inclusion criteria: Randomized controlled trials (RCT). Studies with adults with any psychiatric disorders except substance use disorder according to DSM-III, DSM-IV or DSM-5 diagnostic criteria. Studies with participants with comorbid medicals conditions (e.g. cancer) were not excluded as long as all participants met diagnostic criteria for a primary psychiatric diagnosis. The study intervention was administration of serotoninergic (classic) psychedelics. Both macro and microdosing studies were included.
The main analyzed outcome was anxiety symptoms in adults with psychiatric disorders. Placebo was the comparator for the active treatment. Acceptable outcomes were change in anxiety symptoms from baseline to the last follow-up using a formal assessment of anxiety symptoms. Clinical scales for assessment of anxiety symptoms included anxiety disorder specific scales (e.g. GAD-7, PAS) or general scales (e.g. Beck Anxiety Inventory). Frequency of panic attacks was also acceptable as an outcome measure. Standardized mean differences in clinical scales’ scores was the main measure of effect.
Results: The initial search yielded 3,608 references. There were 2,340 references after exclusion of duplicates. There were 225 references after title/abstract screening. A large number of references were excluded in the full text review, because results were missing (138), lack of adequate measurement of anxiety symptoms (38), it was not double blind (10), there were less than 10 participants per arm (9) or other reasons (25). Only 9 studies were included for the final analysis. The authors are still finalizing the data extraction and analysis.
Discussion & Conclusions: Data on effectiveness and safety of serotonergic psychedelics in the treatment of anxiety symptoms is still scarce. These drugs are promising, but more research must be done on anxiety symptoms and anxiety disorders.
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