This 6-month follow-up of a Phase II, double-blind, randomized controlled trial (n=59) finds sustained improvements in depressive symptoms for both psilocybin therapy (PT) and escitalopram treatment (ET) for moderate-to-severe major depressive disorder (MDD). PT shows greater improvements in psychosocial functioning, meaning in life, and psychological connectedness compared to ET at the 6-month follow-up.
Abstract of Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder
“Background Psilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination.
Methods This is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD. Participants were recruited from a hospital in the UK. Male or female patients with major depressive disorder (DSM-IV), moderate to severe depression (HAM-D ≥17), no MRI or SSRI contraindications, confirmed diagnosis by a GP or mental healthcare professional, aged 18–80, and competent in English were eligible. Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and bookended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET). The primary outcome measure was change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, which has been reported previously. Herein, we present results at the 6-month follow-up time point. Measures of social functioning, connectedness, and meaning in life constituted the study’s secondary outcomes during follow-up. Safety in the follow-up period was not assessed. This trial is registered at ClinicalTrials.gov, NCT03429075.
Findings Between January 15th, 2019 and March 20th, 2020, 59 patients were enrolled and 30 (11 females [37%] and 19 males [63%]) were assigned to the psilocybin group and 29 (9 females [31%] and 20 males [69%]) to the escitalopram group. 25 participants in the PT group and 21 in the ET group completed the 6-month follow-up. At the 6-month follow-up, both PT and ET conditions yielded sustained improvements in depressive symptom severity. The mean between-condition difference in QIDS-SR-16 scores at 6-months was 1.51 (95% CI: −1.35, 4.38; p = 0.311). Secondary outcomes demonstrated that PT had greater mean between-condition differences in functioning (WSAS: −7.46; 95% CI: −12.4, −2.47; p < 0.001), psychological connectedness (WCS: 11.02; 95% CI: 1.25, 20.83; p = 0.033), and meaning in life (MLQ: 4.86; 95% CI: 0.67, 9.05; p = 0.021) compared to ET.
Interpretation Six-week intensive treatments with either psilocybin or escitalopram (with psychological support) for MDD were associated with long-term improvements in depressive symptom severity. The greater degree of improvement in the PT arm at follow-up on psychosocial functioning, meaning in life, and psychological connectedness suggests warrant future research. However, these results are descriptive and should be interpreted with caution. Key limitations of the study include its suboptimal power to detect small but meaningful differences between treatments, missing data, the potential use of additional interventions during the follow-up period, and reliance on self-reported treatment assessments. These factors may affect the interpretation of the study findings and should be considered when evaluating the results.“
Authors: David Erritzoe, Tommaso Barba, Kyle T. Greenway, Roberta Murphy, Jonny Martell, Bruna Giribaldi, Christopher Timmermann, Ashleigh Murphy-Beiner, Michelle Baker Jones, David J. Nutt, Brandon Weiss & Robin L. Carhart-Harris
Summary of Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder
Major Depressive Disorder (MDD) is one of the leading causes of disability worldwide, characterised by significant changes in mood, motivation, pleasure, and cognition. A key challenge in treating MDD is the high risk of relapse or recurrence, with approximately one-third of patients who achieve remission relapsing within a year. Therefore, a crucial consideration for any MDD treatment is its ability to produce sustained antidepressant response or remission.
This study investigated the sustained effects of Psilocybin Therapy (PT) versus Escitalopram Treatment (ET) in MDD over a six-month follow-up period. The research builds upon a previous 6-week trial involving 59 patients randomised to either PT or ET. The PT condition consisted of two high-dose (25 mg) psilocybin treatment sessions with psychological support, while the ET condition involved daily doses of escitalopram, a selective serotonin reuptake inhibitor (SSRI), along with equivalent psychological support and placebo-like doses of psilocybin.
The researchers aimed to address the limitations of conventional antidepressant treatments, such as SSRIs and psychotherapy. While these treatments are generally effective, they often require long-term daily dosing, can have adverse side effects, and may take weeks or months to achieve clinical response. PT is being increasingly investigated as a rapid-acting treatment for MDD and treatment-resistant depression, with previous trials demonstrating that one or two doses of psilocybin, administered with psychological support, can produce almost immediate reductions in depressive symptoms that may persist for months.
Methods
Study Design and Participants
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https://doi.org/10.1016/j.eclinm.2024.102799
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Cite this paper (APA)
Erritzoe, D., Barba, T., Greenway, K. T., Murphy, R., Martell, J., Giribaldi, B., Timmermann, C., Murphy-Beiner, A., Baker Jones, M., Nutt, D., Brandon Weiss, & Carhart-Harris, R. (2024). Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. eClinicalMedicine. https://doi.org/10.1016/j.eclinm.2024.102799
Study details
Compounds studied
Psilocybin
Topics studied
Depression
Study characteristics
Original Re-analysis
Placebo-Controlled
Active Placebo
Double-Blind
Randomized
Follow-up
Participants
59
Humans
Compound Details
The psychedelics given at which dose and how many times
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