Across 138 unique CTIS-authorized European psychiatry Phase 2 & 3 trial records, safety and adverse-event endpoints are the most common recurring endpoint family, appearing in 66 trials (47.8%). Among standardized clinical scales, functioning/quality-of-life endpoints appear in 54 trials (39.1%), Clinical Global Impression (CGI) in 53 (38.4%), and Montgomery-Åsberg Depression Rating Scale (MADRS) in 41 (29.7%). MADRS is the leading primary endpoint family, while CGI, functioning/quality of life, and safety dominate secondary endpoints.
Safety/adverse-event endpoints appear in 66 of 138 trials (47.8%), followed by heterogeneous disease-specific endpoints in 65 (47.1%), functioning/quality of life in 54 (39.1%), CGI in 53 (38.4%), and MADRS in 41 (29.7%).
Psychiatry endpoint strategy is split between universal safety capture and disease-specific symptom measurement. CGI and functioning/quality-of-life endpoints act as cross-disease secondary anchors, while MADRS is the most visible disease-specific standardized scale.
Primary endpoint selection is led by MADRS in 28 trials (20.3%). Secondary endpoints are broader: CGI appears in 51 trials (37.0%), functioning/quality of life in 50 (36.2%), and safety in 49 (35.5%). Exploratory/other endpoints are visible in only 4 trials (2.9%).
| Endpoint family | Primary | Secondary | Exploratory / other |
|---|---|---|---|
| MADRS depression score | 28 | 29 | 2 |
| Safety / adverse events | 15 | 49 | 3 |
| Response / remission / relapse | 11 | 31 | 1 |
| Substance use / abstinence / craving | 10 | 12 | 0 |
| Biomarkers / imaging / EEG | 9 | 24 | 1 |
| PANSS schizophrenia score | 8 | 9 | 0 |
| CGI global impression | 1 | 51 | 2 |
| Functioning / quality of life | 7 | 50 | 1 |
Primary endpoints concentrate around disease-defining symptom scales, especially MADRS in depression and PANSS in schizophrenia. Secondary endpoints carry the broader clinical interpretation layer: CGI, quality of life, safety, response/remission, suicidality, and biomarker signals.
Depression disorders are the largest group with 48 of 138 trials (34.8%), followed by schizophrenia/psychosis with 21 (15.2%), substance use disorders with 13 (9.4%), neurodevelopmental disorders with 10 (7.2%), dementia-related neuropsychiatry with 9 (6.5%), and bipolar disorder with 7 (5.1%).
The European psychiatry Phase 2 & 3 endpoint landscape is primarily shaped by depression and schizophrenia programs. Smaller but analyzable clusters exist for substance use, autism/ADHD, dementia-related symptoms, and bipolar disorder.
Depression is anchored by MADRS in 29 of 48 trials (60.4%). Schizophrenia/psychosis is anchored by CGI in 15 of 21 trials (71.4%) and PANSS in 13 (61.9%). Substance use trials rely on abstinence/craving/use endpoints in 12 of 13 trials (92.3%).
| Disease group | Top endpoint family | Trials |
|---|---|---|
| Depression disorders | MADRS depression score | 29 / 48 · 60.4% |
| Schizophrenia / psychosis | CGI global impression | 15 / 21 · 71.4% |
| Substance use disorders | Use / abstinence / craving | 12 / 13 · 92.3% |
| Neurodevelopmental disorders | Autism / irritability / social scales | 5 / 10 · 50.0% |
| Dementia-related neuropsychiatry | NPI / agitation scales | 7 / 9 · 77.8% |
| Bipolar disorder | CGI global impression | 5 / 7 · 71.4% |
Endpoint standardization is strongest where disease-specific scales are established: MADRS for depression, PANSS/CGI for schizophrenia, NPI/agitation scales for dementia-related symptoms, and TLFB/abstinence/craving endpoints for substance use disorders.
The largest sub-disease clusters are major depressive disorder with 33 trials, schizophrenia with 15, treatment-resistant depression with 9, autism spectrum disorder with 8, alcohol use disorder/dependence with 6, and psychosis with 6.
The most benchmarkable sub-diseases for endpoint planning are major depressive disorder, schizophrenia, treatment-resistant depression, autism spectrum disorder, alcohol use disorder, and psychosis. Smaller sub-diseases are better used for case-level endpoint landscaping rather than percentage-based comparisons.
The phase comparison includes 68 Phase 2 cohort records and 72 Phase 3 cohort records. Phase 2 is more safety/translational: safety appears in 40 of 68 records (58.8%) and biomarkers/imaging/EEG in 18 (26.5%). Phase 3 is more clinical-scale driven: CGI appears in 34 of 72 records (47.2%) and MADRS in 25 (34.7%).
| Endpoint family | Phase 2 | Phase 3 |
|---|---|---|
| Safety / adverse events | 40 / 68 · 58.8% | 27 / 72 · 37.5% |
| Functioning / quality of life | 28 / 68 · 41.2% | 28 / 72 · 38.9% |
| CGI global impression | 20 / 68 · 29.4% | 34 / 72 · 47.2% |
| MADRS depression score | 17 / 68 · 25.0% | 25 / 72 · 34.7% |
| Biomarkers / imaging / EEG | 18 / 68 · 26.5% | 11 / 72 · 15.3% |
| Response / remission / relapse | 19 / 68 · 27.9% | 18 / 72 · 25.0% |
| Suicidality / self-harm | 10 / 68 · 14.7% | 15 / 72 · 20.8% |
Phase 2 psychiatry trials show more exploratory/translational endpoint architecture, with higher safety and biomarker/imaging use. Phase 3 shifts toward regulator-facing clinical rating outcomes, especially CGI and MADRS.
Small molecules dominate the dataset with 111 of 138 trials (80.4%). Peptide/protein/enzyme interventions account for 8 trials (5.8%). Other modalities are individually small and do not support stable percentage comparisons.
| Modality | Most frequent endpoint families |
|---|---|
| Small molecule 111 trials |
Safety 53 / 111 (47.7%); CGI 47 (42.3%); functioning/QoL 45 (40.5%); MADRS 39 (35.1%) |
| Peptide/protein/enzyme 8 trials |
Autism/irritability/social scales 4 / 8 (50.0%); safety 4 (50.0%); biomarkers/imaging/EEG 3 (37.5%) |
Because small molecules account for four out of five psychiatry Phase 2 & 3 records, overall endpoint trends largely reflect small-molecule development. Peptide/protein/enzyme trials appear more concentrated in autism/neurodevelopmental endpoint patterns.
The CTIS-authorized psychiatry Phase 2 & 3 records are distributed across authorization years as follows: 59 trials in 2024 (42.8%), 57 in 2025 (41.3%), and 22 in 2026 (15.9%). This makes endpoint benchmarking most robust for the 2024–2025 CTIS period.
For EU submissions, CTIS endpoint disclosure makes it possible to benchmark whether a proposed psychiatry endpoint package aligns with recent European precedent by disease, phase, and endpoint role before protocol finalization.
The same CTIS endpoint data supports three practical planning questions for psychiatry protocol teams.
MADRS is the leading primary endpoint family with 28 of 138 trials (20.3%), followed by safety/adverse events in 15 (10.9%), response/remission/relapse in 11 (8.0%), and substance-use endpoints in 10 (7.2%).
Substance use disorders show the strongest concentration, with use/abstinence/craving endpoints in 12 of 13 trials (92.3%). Dementia-related neuropsychiatry follows with NPI/agitation scales in 7 of 9 trials (77.8%).
No. Exploratory/other endpoint fields are visible in 4 of 138 trials (2.9%), while primary endpoints appear in 126 trials and secondary endpoints in 107 trials.
MADRS = Montgomery-Åsberg Depression Rating Scale. CGI = Clinical Global Impression. PANSS = Positive and Negative Syndrome Scale. NPI = Neuropsychiatric Inventory. HAM-A = Hamilton Anxiety Rating Scale. HAMD/HDRS = Hamilton Depression Rating Scale. CTIS = Clinical Trials Information System used for EU clinical trial submissions and authorization records.