Eight pivotal trials across major depressive disorder, schizophrenia, and bipolar disorder —
covering stepwise antidepressant strategies, antipsychotic comparisons, mood stabiliser
maintenance, and the role of psychotherapy. Tap any trial to expand.
Major Depressive Disorder3 trials
01
STAR*D
Sequenced Treatment Alternatives to Relieve Depression
📛 Why It's Named So
Acronym for Sequenced Treatment Alternatives to Relieve Depression — a large NIMH-funded pragmatic trial emphasising stepwise switching and augmentation strategies after initial SSRI failure.
💊 Drugs & Doses
Level 1: Citalopram 20 mg/day, titrated up to 40–60 mg/day. Subsequent levels involved switching to or augmenting with other antidepressants (sertraline, bupropion, venlafaxine, nortriptyline, mirtazapine, lithium, thyroid hormone, etc.).
🏁 Key Result
Sequential switching/augmentation yields additional remitters at each step, but cumulative remission falls sharply — only ~33% remit at Level 1, and rates decline with each subsequent step, highlighting the challenge of treatment-resistant depression.
02
TADS
Treatment for Adolescents with Depression Study — fluoxetine ± CBT
📛 Why It's Named So
Treatment for Adolescents with Depression Study — a 4-arm RCT focused specifically on youth depression, comparing pharmacotherapy, psychotherapy, their combination, and placebo.
💊 Drugs & Doses
Fluoxetine 10–40 mg/day alone; CBT (15 sessions over 12 weeks) alone; fluoxetine + CBT combined; or placebo.
🏁 Key Result
Fluoxetine + CBT gave the best symptom improvement; fluoxetine alone outperformed CBT alone but with more adverse-event concerns. Combination therapy produced the largest reduction in suicidal thinking.
⚠️ Suicidality Signal (Stage 1)
Widely cited for its suicidality finding: suicidal thinking fell in all arms, with the largest reduction in the fluoxetine + CBT group — informing the FDA black-box warning and prescribing guidance for antidepressants in youth.
Schizophrenia2 trials
03
CATIE
Clinical Antipsychotic Trials of Intervention Effectiveness
📛 Why It's Named So
Clinical Antipsychotic Trials of Intervention Effectiveness — a large NIMH-funded pragmatic trial comparing first- and second-generation antipsychotics in real-world schizophrenia.
💊 Drugs & Doses
Flexible-dose olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone, adjusted within typical clinical dose ranges over 18 months.
🏁 Key Result
No single antipsychotic was clearly superior for efficacy; olanzapine had slightly better treatment continuation but a worse metabolic profile. Perphenazine (FGA) performed as well as most SGAs — challenging the assumed superiority of newer agents.
04
CUtLASS-1
Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study
📛 Why It's Named So
Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study — a UK pragmatic RCT comparing FGAs versus non-clozapine SGAs, with quality-of-life as the primary outcome.
💊 Drugs & Doses
Clinician-chosen FGA versus clinician-chosen non-clozapine SGA, at standard doses, in patients already requiring a medication change.
🏁 Key Result
SGAs were not superior to FGAs for quality of life or symptom control at 1 year; FGAs trended slightly better on several measures — reinforcing CATIE's conclusion that FGAs remain a valid, cost-effective option.
Bipolar Disorder3 trials
05
STEP-BD
Systematic Treatment Enhancement Program for Bipolar Disorder
📛 Why It's Named So
Systematic Treatment Enhancement Program for Bipolar Disorder — a large NIMH effectiveness programme testing mood stabilisers ± antidepressants and structured psychotherapies in real-world BD care.
💊 Drugs & Doses
Mood stabilisers (lithium, valproate, others) ± antidepressants (paroxetine or bupropion) and structured psychotherapies such as CBT, family-focused therapy (FFT), and IPSRT.
🏁 Key Result
Optimised mood stabilisers plus intensive psychosocial treatments helped recovery; adding antidepressants did not improve bipolar depression outcomes over placebo, discouraging routine antidepressant use in BD.
06
STEP-BD — Acute Depression Sub-Study
Adjunctive antidepressants for bipolar depression on a mood stabiliser background
📛 Why It's Named So
A sub-study within the STEP-BD programme specifically testing whether adjunctive antidepressants offer benefit in bipolar depression when a therapeutic mood stabiliser is already on board.
💊 Drugs & Doses
Mood stabiliser optimised, then randomised to adjunct paroxetine or bupropion versus placebo.
🏁 Key Result
Adjunctive antidepressants were no better than placebo for durable recovery and did not significantly increase manic switch risk when mood stabilisers were at therapeutic levels.
07
BALANCE
Lithium vs valproate vs combination for bipolar maintenance
📛 Why It's Named So
Acronym from Bipolar Affective disorder: Lithium/ANti-Convulsant Evaluation — comparing the two most-used mood stabilisers head-to-head and in combination for relapse prevention in BD.
💊 Drugs & Doses
Lithium (serum level typically 0.4–1.0 mmol/L) versus valproate semisodium (target clinical doses) versus lithium + valproate combination.
🏁 Key Result
Lithium alone and lithium + valproate combination both prevented relapse better than valproate alone; combination was not clearly superior to lithium monotherapy — reaffirming lithium as the gold-standard maintenance mood stabiliser.