Intranasal Oxytocin for Negative Symptoms of Schizophrenia: Systematic Review, Meta-Analysis, and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Sabe M, Zhao N, Crippa A, Strauss GP, Kaiser S

The international journal of neuropsychopharmacology1 Aug 2021Cited by 31 (Europe PMC)

PMID33890987PMCIDPMC8378078DOI10.1093/ijnp/pyab020PepBankPUB-33890987

Summary

BackgroundNegative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear.MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.ResultsIn an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40-80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses.ConclusionsThe present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with schizophrenia, intranasal oxytocin showed no significant effect on negative symptoms across all 9 randomized trials.
In plain wordsIn people with schizophrenia, nasal oxytocin showed no significant effect on negative symptoms compared with placebo across all 9 trials.
Peptide
Oxytocin
Outcome
No significant changeNegative symptoms of schizophrenia, all trials
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms.
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect.
Show in the study text Report a problemFND-3389098701
02HumanSystematic reviewEfficacy outcome
At higher doses (>40-80 IU), intranasal oxytocin had a moderate beneficial effect on negative symptoms, which disappeared after exclusion of one outlier study.
In plain wordsIn people with schizophrenia, higher nasal oxytocin doses seemed to help negative symptoms, but the effect vanished when one outlier study was removed.
Peptide
Oxytocin
Outcome
MixedNegative symptoms of schizophrenia, higher doses
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
>40-80 IU · intranasalAs given in this study (human).
Source sentences
Summary
For higher doses (>40-80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study.
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect.
Show in the study text Report a problemFND-3389098702
03HumanSystematic reviewEfficacy outcome
The dose-response meta-analysis predicted that higher doses of intranasal oxytocin may be more efficacious for negative symptoms.
In plain wordsA dose-response analysis predicted that higher doses of nasal oxytocin may work better for negative symptoms in schizophrenia, but this is not firm.
Peptide
Oxytocin
Outcome
DecreaseNegative symptoms, dose-response prediction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms.
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect.
Show in the study text Report a problemFND-3389098703
04HumanSystematic reviewEfficacy outcome
In the main meta-analysis, intranasal oxytocin had no beneficial effect on positive symptoms of schizophrenia.
In plain wordsIn people with schizophrenia, nasal oxytocin showed no benefit for positive symptoms compared with placebo in the main analysis.
Peptide
Oxytocin
Outcome
No significant changePositive symptoms of schizophrenia, main analysis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect.
Show in the study text Report a problemFND-3389098704
05HumanSystematic reviewEfficacy outcome
The dose-response meta-analysis suggested a potential advantage of higher doses of intranasal oxytocin for positive symptoms.
In plain wordsA dose-response analysis suggested that higher nasal oxytocin doses might help positive symptoms in schizophrenia, but this is not firm.
Peptide
Oxytocin
Outcome
DecreasePositive symptoms, dose-response
Study
n: not reported in source
Comparator
Placebo
Outcome group
Psychiatric symptoms · Mental health and mood
Studied dose
Dose not stated · intranasalAs given in this study (human).
Source sentences
Summary
the dose-response meta-analysis suggested a potential advantage of higher doses.
1 context sentence(design, population, supporting numbers)
Summary · context
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect.
Show in the study text Report a problemFND-3389098705

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:48 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

Keywords

PepBank is a research reference. Talk to a doctor before you use any peptide.