The Combination of Oxytocin with Mindfulness-Based Group Therapy Reduces Negative Symptoms in Schizophrenia Spectrum Disorders: A Triple-Blind, Placebo-Controlled, Randomized, Controlled Clinical Pilot Trial (OXYMIND)
Marco Zierhut, Max Alt, Inge Maria Hahne, Niklas Bergmann, Felix Opper, Kristin Braun, Alice Braun, Julia Kraft, Thi Minh Tam Ta, Stephan Ripke, Malek Bajbouj, Eric Hahn, Kerem Boege
medRxiv July 4, 2026 preprint DOI: 10.64898/2026.07.01.26356996 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Pilot study |
|---|---|
| Sample size | 47 |
| Population | Participants with schizophrenia spectrum disorders (34% female) |
| Interventions | Intranasal oxytocin Mindfulness-based group therapy |
| Dose | 24 IU |
| Duration | 4 sessions of group therapy, with post-intervention and 4-week follow-up |
| Topics | Meditation |
| Keywords | Oxytocin Blinding Placebo Schizophrenia object-oriented programming Context archaeology Randomized controlled trial Adverse effect Clinical trial Clinical psychology Salience neuroscience Physical therapy Dropout neural networks |
| Registration | NCT06136390 |
| Key findings | Oxytocin combined with mindfulness-based group therapy may improve negative symptoms in schizophrenia spectrum disorders, with significant within-group improvements and small between-group effects at follow-up. |
Abstract
Abstract Background Negative symptoms in schizophrenia spectrum disorders (SSD) remain insufficiently treated and require novel therapeutic approaches. Oxytocin may improve negative symptoms, although its effects appear highly context-dependent according to the social salience hypothesis. We conducted a randomized, triple-blind, placebo-controlled pilot study combining intranasal oxytocin with mindfulness-based group therapy (MBGT), hypothesizing that the positive social context of MBGT would enhance oxytocin-related effects.
Methods: 47 participants with SSD (34% female) were randomized to receive either 24 IU oxytocin (MBGT+OXT; n = 26) or placebo (MBGT+PLA; n = 21) before four MBGT sessions. Primary outcome was negative symptoms assessed with the Positive and Negative Syndrome Scale negative subscale (PANSS-N) at post-intervention and 4-week follow-up. Secondary outcomes included the Brief Negative Symptom Scale (BNSS), Self-Evaluation of Negative Symptoms Scale (SNS), and additional clinical measures. Linear mixed models estimated within- and between-group effects.
Results: Overall dropout rate was 14.89%, with one dropout potentially treatment-related. Blinding was successful. Participants completed 95.63% of sessions. Only the MBGT+OXT group showed significant improvements in PANSS-N from baseline to post-intervention (d = −0.74) and follow-up (d = −0.77), with a small between-group effect at follow-up (d = 0.39). BNSS total improved significantly only in the MBGT+OXT group from baseline to post-intervention ( d = −0.88) and follow-up ( d = −0.91), with between-group effects favoring MBGT+OXT at follow-up (d = −0.38). No serious adverse events occurred.
Conclusions: These findings suggest, oxytocin combined with MBGT may improve negative symptoms in SSD and support further large-scale trials. Clinical Trials Registration https://clinicaltrials.gov/study/NCT06136390 , Registration number: NCT06136390
Comparable studies
Other randomized controlled trials on meditation, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Alterations in Brain and Immune Function Produced by Mindfulness Meditation Healthy employees in a work environment | 2003 | Randomized controlled trial | n = 41 |
| Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. Recovered recurrently depressed patients | 2000 | Randomized controlled trial | n = 145 |
| Open hearts build lives: Positive emotions, induced through loving-kindness meditation, build consequential personal resources. Working adults | 2008 | Randomized controlled trial | n = 139 |
| Short-term meditation training improves attention and self-regulation Undergraduate Chinese students | 2007 | Randomized controlled trial | n = 40 |
| Mindfulness-Based Cognitive Therapy for Depression: Replication and Exploration of Differential Relapse Prevention Effects. Recovered recurrently depressed patients | 2004 | Randomized controlled trial | n = 73 |