Summary
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. ClinicalTrials.gov lists 1 registered trial linking Norepinephrine to Schizophrenia: 1 has completed. The most advanced is Phase 4 (NCT00488163). It plans or enrolled 20 participants. Registered activity dates to 2005. The literature layer holds 14 publications for this pair: 3 Cochrane reviews, 4 meta-analyses, 2 randomised controlled trial publications and 5 clinical trial publications. Publication years run from 2009 to 2024. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Schizophrenia ranks 499 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Spontaneous full remission rare (<10%); after first episode, ~80% relapse within 5 years without maintenance antipsychotic; functional disability accumulates over time; 20% achieve good long-term outcome.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 54.5 (trials 4.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 1 total: 0 recruiting, 0 active / not yet recruiting, 1 completed, 0 other |
| Linked publications | 14 (5 clinical trial publications, 4 meta-analyses, 3 Cochrane reviews, 2 randomised controlled trial publications) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRA1B |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00488163 | Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia 2005 | completed | Phase 4 | 20 |
Published literature
- Cochrane review The effect of second-generation antipsychotics on anxiety/depression in patients with schizophrenia: A systematic review and meta-analysisAbdolizadeh A, Hosseini Kupaei M, Kambari Y et al. · Schizophrenia research · 2024 · PMID 38843584
- Meta-analysis Meta-analysis on the efficacy of the norepinephrine reuptake inhibitors reboxetine and atomoxetine for the treatment of schizophrenia and attention deficit hyperactivity disorderHu X, Pan L, Li W · Advances in clinical and experimental medicine : official organ Wroclaw Medical University · 2023 · PMID 36449401
- Meta-analysis Application of antidepressants in depression: A systematic review and meta-analysisYuan Z, Chen Z, Xue M et al. · Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2020 · PMID 33099342
- Cochrane review Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic ReviewYuen JWY, Kim DD, Procyshyn RM et al. · Frontiers in neuroscience · 2018 · PMID 29670504
- Meta-analysis Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer's Disease, Parkinson's Disease and Schizophrenia: Evidence Based on Currently Available LociTang S, Yao B, Li N et al. · Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018 · PMID 30453293
- Meta-analysis Genetic Association of the Norepinephrine Transporter Gene G1287A Polymorphism with Risk of Schizophrenia: A Case-Control Study and Meta-AnalysisZhao X, Zhang Y, Li H et al. · Genetic testing and molecular biomarkers · 2018 · PMID 29431473
- Clinical trial publication Heart-rate response to alpha(2)-adrenergic receptor antagonism by antipsychoticsKim DD, Lang DJ, Warburton DER et al. · Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2017 · PMID 28674870
- Clinical trial publication Duloxetine Add-On to Risperidone for Treatment of Negative Symptoms in Patients with Stable Schizophrenia: Randomized Double-Blind Placebo-Controlled StudyNikbakhat MR, Arabzadeh S, Zeinoddini A et al. · Pharmacopsychiatry · 2016 · PMID 26902281
- Clinical trial publication Double-blind, placebo-controlled study of the efficacy of reboxetine and citalopram as adjuncts to atypical antipsychotics for negative symptoms of schizophreniaUsall J, López-Carrilero R, Iniesta R et al. · The Journal of clinical psychiatry · 2014 · PMID 25004184
- Clinical trial publication The effect of reboxetine co-administration with olanzapine on metabolic and endocrine profile in schizophrenia patientsAmrami-Weizman A, Maayan R, Gil-Ad I et al. · Psychopharmacology · 2013 · PMID 23828160
- Clinical trial publication Norepinephrine transporter occupancy in the human brain after oral administration of quetiapine XRNyberg S, Jucaite A, Takano A et al. · The international journal of neuropsychopharmacology · 2013 · PMID 23809226
- Cochrane review Risks and benefits of bupropion treatment in schizophrenia: a systematic review of the current literatureEnglisch S, Morgen K, Meyer-Lindenberg A et al. · Clinical neuropharmacology · 2013 · PMID 24201231
- Randomized controlled trial Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combinationPoyurovsky M, Fuchs C, Pashinian A et al. · Psychopharmacology · 2013 · PMID 23239133
- Randomized controlled trial A randomized double-blind trial of atomoxetine for cognitive impairments in 32 people with schizophreniaKelly DL, Buchanan RW, Boggs DL et al. · The Journal of clinical psychiatry · 2009 · PMID 19358788
Mechanism and notes
Recorded mechanism or class: agonist.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA1B. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Norepinephrine approved for Schizophrenia?
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Norepinephrine in clinical trials for Schizophrenia?
ClinicalTrials.gov lists 1 registered trial linking Norepinephrine to Schizophrenia: 1 has completed. The most advanced is Phase 4 (NCT00488163). It plans or enrolled 20 participants. Registered activity dates to 2005.
What does the evidence show for Norepinephrine in Schizophrenia?
Norepinephrine has both completed registered trials and synthesis-level publications linked to Schizophrenia. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA1B. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.