Summary
Amphetamine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. ClinicalTrials.gov lists 8 registered trials linking Amphetamine to Major Depressive Disorder: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT02058693). The largest enrolment is 1197 participants (NCT01435759). Registration activity spans 2001 to 2025. The literature layer holds 4 publications for this pair: 2 systematic reviews and 2 clinical trial publications. Publication years run from 2016 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 Major Depressive Disorder ranks 580 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: Relapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication vs on) falls from 3.69x at 2 months to 1.34x at 5 years.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 60.0 (trials 30.0, literature 10.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 0 active / not yet recruiting, 6 completed, 1 other |
| Linked publications | 4 (2 systematic reviews, 2 clinical trial publications) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT02058693 | Adjunctive Mixed Salts Amphetamine for Depressed Adults With Incomplete Response to Current Antidepressant Therapy 2010 | completed | Phase 4 | 41 |
| NCT01148979 | Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder. 2010 | completed | Phase 4 | 35 |
| NCT00296686 | Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression 2001 | terminated | Phase 4 | 31 |
| NCT01436162 | Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder 2011 | completed | Phase 3 | 1,105 |
| NCT00985725 | SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder 2009 | completed | Phase 2 | 143 |
| NCT01435759 | SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder 2011 | completed | Phase 2 | 1,197 |
| NCT00905424 | Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant 2009 | completed | Phase 2 | 246 |
| NCT06967857 | Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression 2025 | recruiting | Phase 2 | 105 |
Published literature
- 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
- Clinical trial publication Longitudinal study of impact of medication for opioid use disorder on Hamilton Depression Rating ScaleWang K, DiChiacchio T, Fang W et al. · Journal of affective disorders · 2022 · PMID 34670131
- Systematic review Amphetamine Use in the Elderly: A Systematic Review of the LiteratureSassi KLM, Rocha NP, Colpo GD et al. · Current neuropharmacology · 2020 · PMID 31660835
- Clinical trial publication Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studiesRichards C, McIntyre RS, Weisler R et al. · Journal of affective disorders · 2016 · PMID 27474961
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 Major Depressive Disorder?
Amphetamine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Amphetamine in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Amphetamine to Major Depressive Disorder: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT02058693). The largest enrolment is 1197 participants (NCT01435759). Registration activity spans 2001 to 2025.
What does the evidence show for Amphetamine in Major Depressive Disorder?
Amphetamine has both completed registered trials and synthesis-level publications linked to Major Depressive Disorder. 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.