PREreview del AI Perspectives on the Present and Future of Antidepressant Pharmaceutical Treatment Based on Anti-inflammatory Strategies: A Scoping Review of Randomised Controlled Clinical Trials

This review is the result of a virtual, collaborative live review discussion organized and hosted by PREreview and JMIR Publications on January 23, 2026. The discussion was joined by 24 people: 4 facilitators from the PREreview Team, 1 member of the JMIR Publications team, and 19 live review participants. The authors of this review have dedicated additional asynchronous time over the course of two weeks to help compose this final report using the notes from the Live Review. We thank all participants who contributed to the discussion and made it possible for us to provide feedback on this preprint.

Summary:

The bridge between inflammation and depression remains understudied, despite strong biological evidence linking inflammatory processes to depressive disorders. This scoping review assessed the role of anti-inflammatory pharmacological (and relevant non-pharmacological) interventions in cohorts of patients with depression. Using a structured search of the PubMed database from inception to December 11, 2024, the authors identified 11 eligible RCTs, comprising a total of 907 participants. The evidence was then synthesized narratively to assess the extent, consistency, and clinical relevance of inflammation-based treatment approaches and to identify gaps and future research directions.

Across studies, anti-inflammatory interventions were associated with reductions in inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor–alpha (TNF-α). However, improvements in depressive symptoms were modest, inconsistent, and largely confined to subgroups with elevated baseline inflammation. Importantly, these interventions did not demonstrate clear clinical superiority over existing standard treatments, raising concerns about feasibility, scalability, and overall clinical value. Moreover, this review broaches the potential role of AI-assisted platforms in optimising anti-inflammatory and antidepressant care.

This study is timely, overall interesting, and a novel topic being researched. However, the article needs to be simplified further, as it is full of redundant statements and repetition. The research question could be well defined to answer the question through evidence. The study also lacks the methodological structure and clarity that are necessary for a scoping review. The scoping review exhibits significant deficiencies, including non-adherence to PRISMA-ScR standards, narrow database selection, potential single-screener bias, and an extremely low inclusion rate without transparent justification. To meet publication standards, the author must effectively address the major and minor issues identified, including the involvement of a second reviewer to mitigate potential bias and the expansion of the search strategy. Furthermore, a thorough technical revision is needed to address existing redundancy, presentation, formatting, and citation issues.

List of major concerns:

The following are significant issues that should be addressed before the paper is suitable for publication:

The manuscript addresses a relevant topic and demonstrates a potential contribution to the literature. However, several major methodological, structural, and reporting issues must be addressed by the author before the manuscript can be considered for publication. The comments below are provided to improve clarity, methodological rigor, and alignment with PRISMA-ScR and journal standards.

1. Search Strategy and Database Selection

The scoping review relies on a limited number of databases. The justification provided (lines 416–421) is inadequate and does not align with PRISMA-ScR expectations. Excluding major databases capable of yielding relevant studies is a significant methodological weakness. The author is strongly encouraged to expand the search to include additional databases and grey literature. If this is not feasible, the limitation must be explicitly acknowledged and justified. In addition, the involvement of multiple reviewers, assessment of inter-rater reliability, and inclusion of subject-matter experts would considerably strengthen the methodological robustness. Moreover, the AI perspectives on the present and future, which were presented in the article title, are mandatory to be included in the search strategy.

2. Single-Screener Bias

The use of a single screener for study selection is a serious concern in a PRISMA-guided scoping review. The proposed mitigation strategy, that is, screening the same records multiple times by one reviewer (lines 431–434), does not adequately address potential bias and may introduce further concerns. The author should either engage a second independent reviewer or clearly acknowledge this limitation and provide a stronger justification for why dual screening was not feasible.

3. Study Selection and Inclusion Rate

Out of 1,057 screened records, only 11 studies were included in the final analysis. This low inclusion rate raises concerns regarding overly restrictive inclusion criteria or potential selection bias. The screening and exclusion process should be described in greater detail and justified. The manuscript should be explicitly structured in accordance with PRISMA-ScR to ensure transparency and completeness.

4. Geographical Imbalance of Included Studies

The included studies are disproportionately concentrated in the UK (n = 3) and China (n = 3, including Taiwan), with limited representation from other regions. The author should clarify whether this imbalance reflects the search strategy, eligibility criteria, or availability of studies. If unavoidable, this limitation should be clearly acknowledged and discussed.

5. Abstract Structure

The Abstract includes an “Interpretation” section, which deviates from standard academic structure and may confuse readers. This should be replaced with “Conclusion” to align with conventional journal formatting.

6. Figures and Tables – Methodological Clarity

• Figure 1 refers to panels A and B in the legend, but these labels are not shown on the figure. This inconsistency must be corrected.

• Table 3 is difficult to read due to the small font size, and the accuracy of the table contents in reflecting study findings must be ensured.

• Table 2, while informative, does not fully comply with PRISMA-ScR guidance. Important elements such as study duration, primary outcomes, and key findings should be included.

7. Terminology and Conceptual Accuracy

The term “liver-sparing granules (SGKL)” is not commonly used, is not supported by the cited reference, and is difficult to verify. The author should avoid using this term or provide a clear definition and justification supported by the literature.

8. Limitations Section

The limitations section is underdeveloped. Key issues related to search strategy, reviewer bias, database selection, and study design must be explicitly discussed.

9. Ethical Considerations

Although the study appears to involve secondary data, ethical considerations are not explicitly stated. The Methods section should clearly address ethical compliance, including whether formal approval was required or waived.

10. Title

There is a major disconnect between the title and the content of the paper which could confuse the readers. The title should be revised to accurately reflect the specific scope and findings of the scoping review.

List of minor concerns:

1. Formatting and Readability

• Lines 422–430 are poorly formatted and should be revised in accordance with the journal’s formatting guidelines.

• Section 1 overlaps substantially with the “Introduction” and should be integrated to improve logical flow.

2. Tables and Presentation

• Table 2 includes a “Study type” column, which is redundant, given that all included studies are randomised controlled trials. This column should be removed or replaced with more informative variables.

• Tables should include clear publication or study years to improve interpretability and access

• The use of alternating colours in tables may distract readers; a uniform colour scheme is recommended.

3. Terminology and Consistency

• The correct acronym for damage-associated molecular patterns is DAMPs, not DMAPs.

• “Lipolyaccharide” is a misspelling and should be replaced with lipopolysaccharide (LPS) throughout.

• Generic drug names should not be capitalised, whereas brand names should be.

• Greek symbols and Latin spellings (e.g., TNF-α vs. TNF-alpha) are used inconsistently; one format should be selected and applied consistently.

• Oxford commas are used inconsistently and should follow journal style.

4. Language and Academic Style

• First-person expressions (e.g., “my searches”) are inappropriate for a scholarly review and should be replaced with neutral phrasing.

• British and American spellings (e.g., “randomised” vs. “randomized”) are inconsistently used and should be standardised.

5. Referencing and Citations

• Claims regarding a “substantial body of clinical research” (lines 70–72) require supporting references.

• Reference 16 has an incorrect publication year and should be corrected to 2016.

• Reference 5 is incomplete and requires full bibliographic details.

• Reference 18 lacks sufficient citation information and should be completed.

• In-text citations should include a period after “et al.” and the year of publication.

6. Clarity and Accuracy

• SSRI should be defined as Selective Serotonin Reuptake Inhibitor at first mention.

• Statements such as “most people with depression are middle-aged” should be supported with evidence or rephrased to avoid overgeneralisation.

• The mention of “31 animal studies” should be clearly distinguished from the primary clinical dataset to avoid confusion.

• The phrase “regular drugs and anti-inflammatory drugs” is ambiguous and should be clarified.

• Figure 1 contains a typographical error (“bone narrow” instead of “bone marrow”).

• The manuscript contains duplicated or overlapping text, which could be as a result of copy-paste errors, and requires careful proofreading.

Additional comments:

Between the introduction and the conclusion, there is a disconnect in the research rationale, scope of investigation, findings, and interpretation, which suggests the author should reframe the initial research question. Regardless, there is still some valid content in the paper. Together with the list of major concerns and the minor concerns, we believe the paper needs to be redrafted (need to start with research questions, adding more databases for search, adding more coders and reviewers). A scoping review of this sort requires systematic analysis (as suggested in the method), which implicates a certain level of bias, hence following PRISMA guidelines will help to guide the conduct of this review. Therefore, the data extracted/analyzed requires a second person, who will help to minimise the risk of bias in the research. Providing clear definitions of the search keywords would clarify the intent of the link and support a more accurate evaluation of the findings and methodological flow within the scoping review.

Concluding remarks

We thank the authors of the preprint for posting their work openly for feedback. We also thank all participants of the Live Review call, for their time and for engaging in the lively discussion that generated this review.

Competing interests

The authors declare that they have no competing interests.

Use of Artificial Intelligence (AI)

The authors declare that they did not use generative AI to come up with new ideas for their review.