Summary
Epinephrine 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ClinicalTrials.gov lists 8 registered trials linking Epinephrine to Schizophrenia: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00847600). The largest enrolment is 120 participants (NCT00894842). Registration activity spans 2005 to 2011. The literature layer holds 7 publications for this pair: 1 Cochrane review, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 1990 to 2018. 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 | 60.0 (trials 22.0, literature 18.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 6 completed, 2 other |
| Linked publications | 7 (5 clinical trial publications, 1 Cochrane review, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist; 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00847600 | Pregnenolone Augmentation in the Treatment of Patients With Recent-Onset Schizophrenia 2009 | completed | Phase 4 | 60 |
| NCT00867360 | Treatment of Psychotic Major Depression With Mifepristone 2005 | terminated | Phase 3 | 10 |
| NCT00615511 | Efficacy of Pregnenolone in Patients With Schizophrenia 2007 | completed | Phase 2 | 100 |
| NCT00174889 | Pregnenolone in the Management of Schizophrenia Patients 2005 | completed | Phase 1 | 60 |
| NCT00560937 | Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia 2005 | completed | Not applicable | 28 |
| NCT00894842 | Study of a Neurocognition Enhancing Agent in Patients With Schizophrenia 2009 | completed | PHASE2, PHASE3 | 120 |
| NCT00576095 | Clinical and Biological Characteristics of Psychotic Depression 2005 | completed | Not applicable | 73 |
| NCT01831986 | Pregnenolone and L-theanine Augmentation in the Treatment for Schizophrenia and Schizoaffective Disorders 2011 | status unknown | Not applicable | 60 |
Published literature
- 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
- Clinical trial publication Acute Effects of Lysergic Acid Diethylamide in Healthy SubjectsSchmid Y, Enzler F, Gasser P et al. · Biological psychiatry · 2015 · PMID 25575620
- Clinical trial publication Blood biogenic amines during clozapine treatment of early-onset schizophreniaSchulz E, Fleischhaker C, Clement HW et al. · Journal of neural transmission (Vienna, Austria : 1996) · 1997 · PMID 9503259
- Clinical trial publication Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophreniaSchulz E, Fleischhaker C, Remschmidt HE · Journal of child and adolescent psychopharmacology · 1996 · PMID 9231304
- Clinical trial publication Suspension therapy in acute schizophrenia. Clinical and neuroendocrine/biochemical effects of abrupt discontinuation of neuroleptic medicationKuhs H, Folkerts H · Neuropsychobiology · 1995 · PMID 7609862
- Clinical trial publication A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analysesIssa F, Gerhardt GA, Bartko JJ et al. · Psychiatry research · 1994 · PMID 7991718
- Randomized controlled trial Stress, depression, and mania: relationship between perceived role of stressful events and clinical and biochemical characteristicsSwann AC, Secunda SK, Stokes PE et al. · Acta psychiatrica Scandinavica · 1990 · PMID 1693033
Mechanism and notes
Recorded mechanism or class: agonist; 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 Epinephrine approved for Schizophrenia?
Epinephrine 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 Epinephrine in clinical trials for Schizophrenia?
ClinicalTrials.gov lists 8 registered trials linking Epinephrine to Schizophrenia: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00847600). The largest enrolment is 120 participants (NCT00894842). Registration activity spans 2005 to 2011.
What does the evidence show for Epinephrine in Schizophrenia?
Epinephrine 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.