Summary
Amphetamine 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registered trials linking Amphetamine to Schizophrenia: 1 is currently recruiting; 4 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00208143). The largest enrolment is 92 participants (NCT00922272). Registration activity spans 2003 to 2025. The literature layer holds 15 publications for this pair: 2 Cochrane reviews, 5 meta-analyses, 3 systematic reviews and 5 clinical trial publications. Publication years run from 2001 to 2025. 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 | 71.5 (trials 21.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 0 active / not yet recruiting, 4 completed, 3 other |
| Linked publications | 15 (5 meta-analyses, 5 clinical trial publications, 3 systematic reviews, 2 Cochrane reviews) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ADRA1A |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00208143 | Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia 2003 | completed | Phase 4 | 20 |
| NCT01760993 | Long-term Safety of SPD489 When Added to Stable Doses of Antipsychotic Medications in Clinically Stable Adults With Negative Symptoms of Schizophrenia 2013 | terminated | Phase 3 | 2 |
| NCT01760889 | SPD489 Low Dose and High Dose Ranges When Added to Stable Doses of Antipsychotic Medications in Clinically Stable Adults With Negative Symptoms of Schizophrenia 2013 | terminated | Phase 3 | 1 |
| NCT00922272 | Efficacy, Safety, and Tolerability of SPD489 in Adults With Schizophrenia and Predominant Negative Symptoms 2009 | completed | Phase 2 | 92 |
| NCT00166322 | Dopaminergic Neurotransmission in Schizophrenia, Patients at Risk and Healthy Subjects 2004 | completed | Not applicable | 35 |
| NCT02008292 | Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors 2013 | completed | Not applicable | 80 |
| NCT05770375 | Tolerability of MDMA in Schizophrenia 2025 | recruiting | PHASE1, PHASE2 | 20 |
| NCT03999190 | Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia 2019 | withdrawn | Not applicable | — |
Published literature
- Clinical trial publication Pharmacologic Augmentation of Computerized Auditory Training in Chronic Psychosis: Preliminary Findings From a Single-Site, Double-Blind StudySwerdlow NR, Sprock J, Li F et al. · Schizophrenia bulletin · 2025 · PMID 40227151
- Meta-analysis Safety of Stimulants Across Patient Populations: A Meta-AnalysisOliva HNP, Prudente TP, Mayerson TF et al. · JAMA network open · 2025 · PMID 40343695
- Systematic review Navigating the challenges of substance use and psychopathology in depression, bipolar disorder, and schizophreniaChiappini S, Mosca A, Semeraro F et al. · Comprehensive psychiatry · 2025 · PMID 40652744
- Systematic review Psychostimulant Substitution Therapy for the Treatment of Stimulant Use Disorders in Patients with Schizophrenia or Schizoaffective Disorder: A Systematic ReviewRamasubbu C, Poonia S, Brady-Randle E et al. · Journal of dual diagnosis · 2025 · PMID 40085427
- Clinical trial publication The effects of caffeine and d-amphetamine on spatial span task in healthy participantsKassim FM, Lim JHM, Slawik SV et al. · PloS one · 2023 · PMID 37440493
- Clinical trial publication Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised studyAlisauskiene R, Johnsen E, Gjestad R et al. · General hospital psychiatry · 2023 · PMID 37269769
- Clinical trial publication Dexamphetamine influences funneling illusion based on psychometric scoreKassim FM, Mark Lim JH, Albrecht MA et al. · Human psychopharmacology · 2023 · PMID 36799101
- Clinical trial publication Association of Pharmacological Treatments and Hospitalization and Death in Individuals With Amphetamine Use Disorders in a Swedish Nationwide Cohort of 13 965 PatientsHartikainen M, Taipale H, Tanskanen A et al. · JAMA psychiatry · 2023 · PMID 36383348
- Systematic review Long-Acting Injectable Antipsychotic Treatment in Schizophrenia and Co-occurring Substance Use Disorders: A Systematic ReviewColes AS, Knezevic D, George TP et al. · Frontiers in psychiatry · 2021 · PMID 34975600
- Meta-analysis Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysisMurrie B, Lappin J, Large M et al. · Schizophrenia bulletin · 2020 · PMID 31618428
- Cochrane review Antipsychotics for Amphetamine Psychosis. A Systematic ReviewFluyau D, Mitra P, Lorthe K · Frontiers in psychiatry · 2019 · PMID 31681046
- Meta-analysis Prodopaminergic Drugs for Treating the Negative Symptoms of Schizophrenia: Systematic Review and Meta-analysis of Randomized Controlled TrialsSabe M, Kirschner M, Kaiser S · Journal of clinical psychopharmacology · 2019 · PMID 31688399
- Meta-analysis Systematic review and exploratory meta-analysis of the efficacy, safety, and biological effects of psychostimulants and atomoxetine in patients with schizophrenia or schizoaffective disorderSolmi M, Fornaro M, Toyoshima K et al. · CNS spectrums · 2019 · PMID 30460884
- Meta-analysis Stimulant use disorders in people with psychosis: a meta-analysis of rate and factors affecting variationSara GE, Large MM, Matheson SL et al. · The Australian and New Zealand journal of psychiatry · 2015 · PMID 25518844
- Cochrane review Treatment for amphetamine psychosisSrisurapanont M, Kittiratanapaiboon P, Jarusuraisin N · The Cochrane database of systematic reviews · 2001 · PMID 11687172
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Amphetamine approved for Schizophrenia?
Amphetamine 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 Amphetamine in clinical trials for Schizophrenia?
ClinicalTrials.gov lists 8 registered trials linking Amphetamine to Schizophrenia: 1 is currently recruiting; 4 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00208143). The largest enrolment is 92 participants (NCT00922272). Registration activity spans 2003 to 2025.
What does the evidence show for Amphetamine in Schizophrenia?
Amphetamine 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 Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. 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.