A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression

Summary & key facts

Researchers gave one single 10 mg intranasal dose of BPL-003 (a form of 5-methoxy-N,N-dimethyltryptamine) to 12 people with treatment-resistant major depression and followed them for 12 weeks. Most people showed a quick drop in depressive symptoms that lasted across the three months of follow-up. About three out of four people had side effects, usually mild or moderate like nausea or nasal discomfort, and one person had a temporary high blood pressure spike. Because this was a very small, open study without a comparison group, the results look promising but do not prove the treatment works for everyone and need testing in larger controlled trials.

Key facts:

• Twelve people with treatment-resistant major depression took part in a 12-week open study and everyone finished the trial.
• Each person received a single 10 mg dose of intranasal BPL-003 and was watched for safety and depressive symptoms for about three months.
• About three out of four people had treatment-related side effects; most of these were mild or moderate, and the most common were nausea and nasal discomfort.
• One person had a severe, temporary increase in blood pressure that returned to normal during monitoring.
• Most people were judged ready to leave the clinic about 98 minutes after dosing.
• Across the follow-up checks, the average drop on the depression rating scale was about 12 to 13 points, which the researchers described as a rapid and sustained improvement.
• Roughly 10 out of 11 assessed participants met the study's definition of a treatment response at one or more timepoints, and 7 people reached remission at least once during follow-up.
• The study was small, had no placebo or comparison group, and mostly included men aged about 30 to mid-50s, so the findings need confirmation in larger, controlled trials before we can know how well the treatment works in general.

Abstract

AIMS: -dimethyltryptamine, in patients with moderate-to-severe major depressive disorder (MDD) with treatment-resistant depression (TRD). METHODS: Twelve participants with TRD were enrolled in a 12-week, open-label, phase 2a trial. Safety of a single intranasal dose of 10 mg BPL-003 was assessed through clinical evaluations, treatment-emergent adverse events (TEAEs) and Readiness for Discharge Questionnaire (RDQ). Key depression-related assessments were Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline, percentage of responders, and participants in remission on Days 2, 8, 29, 57 and 85 post-dose. RESULTS: All participants completed the trial; 2 females, 10 males, aged 31-55 years. Nine (75.0%) participants had 18 treatment-related TEAEs; 8 mild, 9 moderate and 1 severe (increased blood pressure, which returned to baseline within the observation period), with nausea and nasal discomfort the most frequently reported. Ten participants were ready after their first RDQ (nominal time 90 minutes post-dose). Median time from dosing to discharge readiness was 98 minutes (range 95-167). There was a mean decrease in MADRS total score from baseline of 12.2-13.0 points across all timepoints between Days 2 and 85; most participants (10/11) were responders, and 7 were in remission at ⩾1 post-dose timepoint. CONCLUSION: Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.

Topics

Neurotransmitter Receptor Influence on Behavior Phosphodiesterase function and regulation Psychedelics and Drug Studies

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

Adverse effect Affect (linguistics) Anesthesia Clinical trial Depression (economics) Internal medicine Major depressive disorder Medicine Nasal administration Pathophysiology Pharmacology Phase (matter) Phases of clinical research Psychiatry Randomized controlled trial Reduction (mathematics) Safety profile Treatment-resistant depression

Substances

Other

Conditions & symptoms

Depression Sadness or low mood