Introduction Loneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo- controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA loneliness scale ≥ 55).

Methods Seventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions targeting cognitive biases in loneliness. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait- like loneliness measured at baseline, after the intervention, and again at two follow-up time points (three weeks and three months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D).

Results The psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members.

Conclusion Despite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long- term benefits.

The authors have declared no competing interest.

NCT04137432

S.G.S-T, R.H., and D.S. were supported by a German-Israel Foundation for Scientific Research and Development grant (GIF, I-1428-105.4/2017). R.H. and D.S. were supported by a German Research Foundation (DFG) grant (HU 1302/11-1 and SCHE 1913/5-1).

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