Evidence map›Paper›PMID 40808264›Full record

SynthesisBipolar disorders2025

The Efficacy of Pharmacological Interventions in the Treatment of Major Depressive Disorder and Bipolar Depression With Mixed Features: A Systematic Review.

Naomi Xiao, Liyang Yin, Serene Lee, Kayla M Teopiz, Sabrina Wong, Gia Han Le, Sebastian Badulescu, Heidi Ka Ying Lo, Maj Vinberg, Bing Cao and 3 more

Abstract readSystematic Review
In one paragraph

Synthesis in Bipolar disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Naomi XiaoBrain and Cognition Discovery Foundation, Toronto, Canada.
Liyang YinBrain and Cognition Discovery Foundation, Toronto, Canada.
Serene LeeBrain and Cognition Discovery Foundation, Toronto, Canada.
Kayla M TeopizBrain and Cognition Discovery Foundation, Toronto, Canada.
Sabrina WongBrain and Cognition Discovery Foundation, Toronto, Canada.ORCID 0009-0002-0928-3433
Gia Han LeBrain and Cognition Discovery Foundation, Toronto, Canada.
Sebastian BadulescuBrain and Cognition Discovery Foundation, Toronto, Canada.
Heidi Ka Ying LoDepartment of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong.
Maj VinbergThe Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Mental Health Centre, Northern Zealand, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark.ORCID 0000-0002-5982-1335
Bing CaoKey Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, P. R. China.
Iria GrandeDepartament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.
Joshua D RosenblatDepartment of Pharmacology and Toxicology, University of Toronto, Canada.
Roger S McIntyreDepartment of Pharmacology and Toxicology, University of Toronto, Canada.ORCID 0000-0003-4733-2523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThere is a need to provide up-to-date, clinically translatable data as it relates to the treatment of a major depressive episode (MDE) with mixed features.

methodsPubMed and OVID were searched from inception to July 22, 2024. Randomized controlled trials (RCTs) investigating the efficacy of pharmacological agents for adults with bipolar disorder (BD) or major depressive disorder (MDD) in an MDE with mixed features were included. Risk of bias was assessed using the Cochrane Risk of Bias Tool for Randomized Studies (RoB2).

resultsA total of seven studies were included in this systematic review. The studies identified were all short-term acute studies ranging from 6 to 8 weeks. Treatment with lurasidone, olanzapine, cariprazine, lumateperone, quetiapine, and ziprasidone was associated with statistically significant reduction of depressive symptoms in MDEs with mixed features. Only lumateperone is studied in both BD subtypes [bipolar I disorder (BD-I), bipolar II disorder (BD-II)] and MDD, wherein efficacy in mixed features was the prespecified primary outcome. Lurasidone has a single study in MDD, while ziprasidone has data in a mixed sample of BD-II and MDD. Data for the other agents in mixed features is post hoc. Co-occurring hypomanic symptoms generally improved, and there was no significant difference between the above treatments and placebo with respect to hypomanic symptom severity intensification or treatment-emergent affective switching.

conclusionSelect atypical antipsychotics are effective in alleviating depressive symptoms in persons with mixed features; albeit, much of the data is obtained from post hoc analysis. Minimal evidence exists for the efficacy of lithium or valproate in the treatment of depressive episodes with mixed features. Antidepressant monotherapy has not been adequately evaluated in depressive episodes with mixed features. In addition, there is a pressing need for a consistent definition of mixed presentations to guide future interventional studies.

Indexed as

Antidepressive AgentsAntipsychotic AgentsBipolar DisorderMajor Depressive DisorderHumansRandomized Controlled Trials as TopicAntidepressive AgentsAntipsychotic Agentsatypical antipsychoticsbipolar disorderdepressionmajor depressive disordermixed featuresmixed features specifiersuicidality

Identifiers

PMID40808264
PMCPMC12397445

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.