Clinical trials of psilocybin in treatment resistant major depression
| Patients | Psilocybin dose | Number of sessions | Primary outcome measure | Methodology | Outcome | Reference |
|---|---|---|---|---|---|---|
| Unipolar major depression | ||||||
| DSM-5 MDD; failure to respond to 2 to 4 treatments | 1 mg (n = 79)10 mg (n = 75)25 mg (n = 79) | Single session | MADRS | Multicentre, double-blind; MMRM for analysis of change from baseline to week 3 | 25 mg superior to 1 mg at week 3; patient-reported depression severity, anxiety, affect, and functioning improved at week 3 | [45, 59] |
| MDD confirmed by MINI; failure to respond to 2 treatments | 10 mg (n = 12)25 mg (n = 12) | Two dosing sessions separated by 1 week | QIDS | Single site, open label | Reduced depressive symptoms 1 week and 3 months after high dose | [57] |
| MDD confirmed by MINI; failure to respond to 2 treatments | 10 mg (n = 20)§25 mg (n = 20)§ | Two dosing sessions separated by 1 week | QIDS | Single site, open label | Reduced depressive symptoms at 1 week, 3- and 6-month follow-ups | [58] |
| DSM-5 MDD; failure to respond to 2 to 4 treatments | 25 mg (n = 19) | Single session | MADRS | Open label study; adjunct to SSRI treatment | Mean change from baseline to week 3 MADRS score 14.9; significant clinical improvement | [60] |
| DSM-5 MDD; insufficient response to at least five treatments | 25 mg (n = 12) | Single session | MADRS | Single site, open label | Statistically significant decline in MADRS scores from baseline to week 3, 12 (RMANOVA) | [61] |
| DSM-5 MDD; non-response to ≥ 5 treatments; military veterans | 25 mg (n = 15) | Single session | MADRS | Single site, open label | MADRS score decreased significantly from baseline across weeks 1, 3, and 12 (MMRM) | [62] |
| Bipolar II depression | ||||||
| Clinical assessment MDD or BPD II depression; multiple medication failures | 25 mg (n = 30) | 1, 2, or 3 sessions depending on response | MADRS | Randomised wait list controlled | Reduced depressive symptoms after one dose; further reductions after repeated doses | [63] |
| DSM-5 BPD II with insufficient response to two or more pharmacological treatments | 25 mg (n = 15) | Single session | MADRS | Single site, open label | Mean change of 24 points on MADRS from baseline to week 3 | [64] |
§ includes 12 patients from 2016 report [57]. DSM: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association; MDD: major depressive disorder; MADRS: Montgomery-Åsberg depression rating scale; MMRM: mixed models for repeated measures; MINI: Mini International Neuropsychiatric Interview; QIDS: Quick Inventory of Depressive Symptomatology; SSRI: selective serotonin reuptake inhibitor; RMANOVA: repeated measures analysis of variance; BPD II: bipolar disorder type II
TRN: Conceptualization, Investigation, Writing—original draft, Writing—review & editing.
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