Adequate Psychodrugs Do Not Impair Gait Speed in Older, Relatively Healthy, Independent Patients: A Cross-Sectional Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for the opportunity to review your manuscript entitled “Adequate Psychodrugs Do Not Impair Gait Speed in Older, Relatively Healthy, Independent Patients: A Cross‑Sectional Study.” The topic is clinically relevant and timely, particularly given the increasing use of psychotropic medications in older adults and the importance of gait speed as a functional metric in geriatric assessment. Your study addresses an important gap in the literature, and I commend you for undertaking this work.

After a thorough review, I believe the manuscript would benefit from several clarifications, methodological enhancements, and structural improvements. My detailed comments are as follows:

Major Comments

1. Title and spelling

I am uncertain if the title “adecuate” is appropriately spelt, instead of “adequate”. Additionally, perhaps replace psychodrugs with psychotropic agents?

2. Study Timeline and Ethical Approval

The manuscript would benefit from clearer reporting of the study timeline. Please specify when the study was conducted, as this is essential for assessing contextual relevance and potential temporal biases. Who were the individuals who collected the data? Any information on their professional backgrounds?

Additionally, while ethical approval is mentioned, please include the full name of the ethics committee that granted approval, as per standard reporting guidelines.

3. Sample Size Calculation and Statistical Rationale

A major methodological concern is the absence of a sample size or power calculation. Providing this information is critical for establishing whether the study is adequately powered to detect meaningful differences.

Similarly, before presenting means and standard deviations, please clarify whether normality testing was performed. Reporting the tests used (e.g., Shapiro–Wilk) and their outcomes would strengthen the validity of your statistical approach.

4. Handling of Exclusion Criteria and Their Impact

The study appears to have a notably high exclusion rate. Although the criteria themselves seem reasonable, the implications of excluding such a large proportion of potential participants should be discussed in depth. Consider elaborating on how this may affect external validity, potential selection bias, and the generalizability of the findings.

Who were the individuals who collected the data? Any information on their professional backgrounds?

5. In‑Depth Statistical Analyses and Post Hoc Procedures

Section 3.2, which discusses mean gait speed across subgroups, would be clearer and more accessible if presented in tabular form rather than narrative text.

Furthermore, for the reported ANOVA results, please indicate whether any post hoc analyses were conducted. Similarly, it would be helpful to include any univariate or multivariate analyses performed to further explore associations. These additions would considerably strengthen the rigour of your analysis.

6. Content‑Related and Structural Comments

Background on Key Clinical Indices

The manuscript assumes familiarity with the Barthel Index, Lawton Index, and Charlson Comorbidity Index. To facilitate readability for a broader audience, please provide brief background descriptions and clinical relevance of each instrument.

7. Correction of Grammatical Error

On Page 1, line 70, the phrase “these useful drugs” should be revised to “this useful drug” for grammatical accuracy.

8. Tables, Formatting, and Abbreviations

Several tables require attention to alignment and layout, as the current formatting is inconsistent and difficult to follow.

Additionally, please ensure that each table includes complete legends for all abbreviations used. This will help readers interpret the findings clearly without needing to refer back to the text.

9. Overall, the manuscript appears to lack several critical elements recommended by the STROBE guidelines. Please provide a detailed description of how the STROBE guidelines are reported in this cross-sectional study.

Summary

Overall, your study addresses an important and clinically meaningful question. With improvements in methodological transparency, statistical rigour, structural clarity and linguistic enhancement, the manuscript has the potential to make a valuable contribution to understanding psychotropic medication use and functional outcomes in older adults.

I appreciate your efforts and hope that these comments help strengthen your manuscript. I look forward to reviewing the revised version.

Sincerely,

Comments on the Quality of English Language

The manuscript would benefit from professional English edits before it is ready for publication. 

Author Response

Thank you very much for your kind comments, which have helped us to improve our manuscript.

Comments 1: Title and spelling I am uncertain if the title “adecuate” is appropriately spelt, instead of “adequate”. Additionally, perhaps replace psychodrugs with psychotropic agents?

Response 1: Thank you very much for this helpful comment. We have corrected the spelling in the title from “adecuate” to “adequate” and have replaced the term “psychodrugs” with “psychotropic agents” in the title and consistently throughout the manuscript, as suggested.

Comments 2: Study Timeline and Ethical Approval
The manuscript would benefit from clearer reporting of the study timeline. Please specify when the study was conducted, as this is essential for assessing contextual relevance and potential temporal biases. Who were the individuals who collected the data? Any information on their professional backgrounds?

Response 2: Thank you very much for this helpful comment. We have now clarified the study timeline in the manuscript by specifying the period during which the study was conducted. In addition, we have included details on who collected the data and their professional backgrounds, to improve transparency and facilitate assessment of sources of bias.

Comments 3: Additionally, while ethical approval is mentioned, please include the full name of the ethics committee that granted approval, as per standard reporting guidelines.

Response 3: Thank you very much for your query. The hospital’s ethics committee does not have distinct formal English title; its official name is in Spanish: “Comité de Ética del Hospital General Universitario de Getafe.” In the manuscript, we refer to it as the “Ethics Committee of Hospital General Universitario de Getafe,” as reflected on line 255. We would be happy to adjust the wording to the journal’s preferred style if needed.

Comments 4: Sample Size Calculation and Statistical Rationale. A major methodological concern is the absence of a sample size or power calculation. Providing this information is critical for establishing whether the study is adequately powered to detect meaningful differences

Response 4: We thank the reviewer for this helpful comment. We have now included a detailed description of the sample size calculation and the statistical rationale in the Methods section of the manuscript.

Comments 5: Similarly, before presenting means and standard deviations, please clarify whether normality testing was performed. Reporting the tests used (e.g., Shapiro–Wilk) and their outcomes would strengthen the validity of your statistical approach.

Response 5: Thank you for this helpful comment. We have now detailed our assumption checks. Before conducting inferential analyses, we assessed: normality (Shapiro–Wilk smaller samples and Kolmogorov–Smirnov otherwise), homogeneity of variances (Levene’s test), linearity (scatterplot matrices and residual plots), and independence of errors (Durbin–Watson). These details have been added to the Methods section.

Comments 6: The study appears to have a notably high exclusion rate. Although the criteria themselves seem reasonable, the implications of excluding such a large proportion of potential participants should be discussed in depth. Consider elaborating on how this may affect external validity, potential selection bias, and the generalizability of the findings.

Response 6: We are grateful to the reviewer for this thoughtful comment. We agree that the relatively high exclusion rate warrants explicit consideration in terms of external validity, potential selection bias, and the generalisability of our findings.  

As requested, we have now clarified the flow of participants in the Methods section. Of the 235 individuals who met the inclusion criteria and were informed about the study, 17 declined to participate. Of the 218 individuals who agreed to take part, 91 were excluded according to the pre-specified exclusion criteria (11 due to limiting osteoarthritis, 8 due to parkinsonism or Parkinson’s disease, 9 due to cerebrovascular disease, 24 due to dementia or the MEC-based exclusion criterion, 10 due to major depression or follow-up in Mental Health services, 5 due to peripheral artery disease or peripheral neuropathy, 9 due to ischaemic heart disease, 2 due to severe visual impairment, 9 due to episodes of vertigo in the previous 6 months, and 4 due to active cancer with poor prognosis). Of the remaining 127 individuals, 4 did not attend the examination visit. A total of 123 subjects therefore underwent the baseline assessment. Three were subsequently excluded from the analytical sample (1 because of an episode of vertigo during the assessment and 2 because they had an ankle–brachial index below 0.9). In addition, Fried’s frailty criteria were not available for one participant, who was therefore excluded. The final analysable baseline sample consisted of 119 participants.  

In addition, we have expanded the Discussion to address the implications of this exclusion rate. In the revised manuscript, we now explicitly acknowledge that the stringent exclusion criteria, while improving internal validity by reducing the influence of severe neurological, cardiovascular, sensory, and psychiatric conditions on gait and balance, also limit external validity. The resulting sample is likely to be healthier and less multimorbid than the broader population of older adults attending primary care, and our findings are therefore most directly generalisable to community-dwelling older adults without major disabling comorbidities. We also note that non-participation (individuals who declined or did not attend the examination) may have introduced some selection bias if these individuals differed systematically from participants, and we highlight this as an additional limitation to be considered when interpreting our results.

Comments 7: Who were the individuals who collected the data? Any information on their professional backgrounds?

Response 7:  Thank you for this comment. This point is addressed in our response to Question 2. Following that suggestion, we have now added to the Methods a clear description of who collected the data, including the assessors’ roles and professional backgrounds.

Comments 8: Furthermore, for the reported ANOVA results, please indicate whether any post hoc analyses were conducted. Similarly, it would be helpful to include any univariate or multivariate analyses performed to further explore associations. These additions would considerably strengthen the rigour of your analysis.

Response 8: Thank you for this helpful comment. Post hoc pairwise comparisons were not performed, as the ANOVA was used as an omnibus test to assess overall between-group differences and the study was not designed to evaluate specific pairwise contrasts. We have now included this clarification in the manuscript.  You may find this description in the Statistical Analysis section (2.6).

Comments 9: The manuscript assumes familiarity with the Barthel Index, Lawton Index, and Charlson Comorbidity Index. To facilitate readability for a broader audience, please provide brief background descriptions and clinical relevance of each instrument.

Response 9: Thank you for this helpful comment. We have now included brief descriptions of the Barthel Index, Lawton (IADL) Index, Charlson Comorbidity Index and MMSE in the Methods section to improve clarity and readability for a broader audience.

Comments 10: On Page 1, line 70, the phrase “these useful drugs” should be revised to “this useful drug” for grammatical accuracy.

Response 10: Thank you for noting this. We have corrected the wording on page 1, line 70 from “these useful drugs” to “this useful drug” for grammatical accuracy.

Comments 11: Several tables require attention to alignment and layout, as the current formatting is inconsistent and difficult to follow.

Response 11: Thank you for this observation. We have revised the alignment and layout of all tables to ensure consistent formatting and improve readability throughout the manuscript.

Comments 12: Additionally, please ensure that each table includes complete legends for all abbreviations used. This will help readers interpret the findings clearly without needing to refer back to the text.

Response 12: Thank you for this helpful suggestion. We have now updated the manuscript to ensure that all abbreviations are defined in full (and included in the relevant table legends where applicable), so that the tables and text can be read and interpreted without referring elsewhere.

Comments 13: Overall, the manuscript appears to lack several critical elements recommended by the STROBE guidelines. Please provide a detailed description of how the STROBE guidelines are reported in this cross-sectional study.

Response 13: Thank you for this important comment. We agree that transparent reporting in accordance with STROBE is essential. We have therefore revised the manuscript to ensure alignment with the STROBE statement for cross-sectional studies and we now describe explicitly how each recommended item is addressed.

Specifically, we have:

•Structured the manuscript to cover all STROBE domains, including a clear statement of the study design in the title/abstract, the setting and dates, participant eligibility, recruitment and study flow, variables/outcomes/exposures, data sources and measurement methods, and statistical methods (including handling of confounding and missing data).

•Expanded the Methods to provide fuller detail on participants, measurement instruments, and bias/precision considerations.

•Expanded the Results to report participant numbers at each stage (including exclusions and reasons), descriptive data, and main outcome estimates with appropriate measures of precision.

•Expanded the Discussion to address key STROBE items on limitations (including potential selection bias), interpretation, and generalisability.

 

Thank you for your thoughtful and constructive summary. We appreciate your recognition of the clinical relevance of our study and your helpful recommendations regarding methodological transparency, statistical rigour, structural clarity and language. We have carefully addressed all comments and revised the manuscript accordingly, and we hope that the revised version is clearer and more robust. We are grateful for your time and expertise, and we look forward to your further review.

Reviewer 2 Report

Comments and Suggestions for Authors

The topic is relevant and of clear clinical interest, particularly in the context of psychotropic drug use and fall risk in older adults. The idea of distinguishing between adequate and inadequate prescriptions is interesting and potentially useful.

However, there are several issues that should be addressed before the manuscript can be considered for publication.

First, the main limitation is the study design. This is a cross-sectional study, so it does not allow causal interpretation. In several parts of the manuscript, especially in the abstract and conclusions, the wording is too strong. For example, statements such as “do not impact on gait speed” should be revised. It would be more appropriate to say “were not associated with gait speed” or “no association was observed”. This should be corrected throughout the manuscript.

Second, the definition of “adequate” versus “inadequate” psychotropic use is not fully clear. Although STOPP/START and Beers criteria are mentioned, additional criteria (such as half-life or anticholinergic effects) are also used without a clear framework. It would be important to describe more explicitly how this classification was done, ideally in a way that is reproducible.

Third, there is likely residual confounding. The analysis does not account for the indication of the psychotropic drugs (for example, depression, anxiety or insomnia), which could independently affect gait speed. This should at least be clearly discussed as a limitation, and if possible adjusted for.

Fourth, the sample size is relatively small, especially in the subgroups. This limits statistical power and makes the interpretation of non-significant findings, particularly in the “adequate” group, more uncertain.

Fifth, different types of psychotropic drugs are grouped together, despite having different pharmacological profiles. If possible, it would be useful to provide more detail by drug class or explore this in additional analyses.

Regarding the presentation, Table 2 is difficult to interpret and should be simplified or clarified. Also, the manuscript would benefit from language revision. The term “psycho-drugs” should be replaced by “psychotropic drugs”, and some sentences should be rephrased for clarity.

In summary, this is a relevant study with an interesting approach, but it requires clearer methodology, more cautious interpretation, and improvements in presentation.

 

Comments on the Quality of English Language

The manuscript would benefit from language editing to improve clarity and scientific tone. A general English language revision is recommended.

Author Response

Thank you very much for your kind comments, which have helped us to improve our manuscript.

Comments 1: First, the main limitation is the study design. This is a cross-sectional study, so it does not allow causal interpretation. In several parts of the manuscript, especially in the abstract and conclusions, the wording is too strong. For example, statements such as “do not impact on gait speed” should be revised. It would be more appropriate to say “were not associated with gait speed” or “no association was observed”. This should be corrected throughout the manuscript.

Response 1:  We thank the reviewer for this important and constructive comment. We fully agree that, given the cross‑sectional design of the study, causal interpretations are not supported.

In response, we have carefully revised the wording throughout the manuscript to avoid causal language. Specifically, expressions such as “do not impact on gait speed” or “impair gait speed” have been replaced with non‑causal formulations, including “were not associated with gait speed” or “no association was observed”.

These changes have been applied consistently across the title, abstract, results, discussion, and conclusions to ensure that the interpretation of the findings appropriately reflects the study design.

Comments 2: Second, the definition of “adequate” versus “inadequate” psychotropic use is not fully clear. Although STOPP/START and Beers criteria are mentioned, additional criteria (such as half-life or anticholinergic effects) are also used without a clear framework. It would be important to describe more explicitly how this classification was done, ideally in a way that is reproducible.

Response 2:  We would like to respectfully comment on the reviewer’s suggestion regarding the definition of “appropriate” versus “inappropriate” psychotropic medication use.

We agree that transparency and reproducibility are essential. We would like to note that, in the current version of the manuscript, the criteria used for this classification are already described in detail. Specifically, prescribing appropriateness is defined based on established explicit criteria (STOPP/START and Beers), complemented by clearly specified geriatric pharmacological considerations.

In addition, we believe that reproducibility is further supported by the explicit reporting of the individual psychotropic medications and dosages taken by participants, which allows other researchers to apply the same criteria in comparable populations.

That said, we fully acknowledge the reviewer’s point and are happy to further clarify and structure the description of the classification process if the editorial team considers that this would improve the manuscript’s clarity and reproducibility.

Comments 3: Third, there is likely residual confounding. The analysis does not account for the indication of the psychotropic drugs (for example, depression, anxiety or insomnia), which could independently affect gait speed. This should at least be clearly discussed as a limitation, and if possible adjusted for.

Response 3: 

We thank the reviewer for this important comment regarding potential residual confounding by indication. We agree that conditions such as depression, anxiety, or insomnia may independently influence gait speed and therefore represent a potential source of confounding in observational studies of psychotropic medication use.

In the revised manuscript, we have expanded the Limitations section to explicitly acknowledge this issue and to clarify that the analyses were not adjusted for specific depression, anxiety, or insomnia scales due to time constraints during the assessment. Although individuals with major depression according to DSM‑IV criteria were excluded, and the associations persisted after adjustment for frailty (which includes exhaustion, reduced activity, and weight loss), we now explicitly state that residual confounding by indication cannot be fully ruled out.

We have also clarified that all psychotropic medications had been taken at stable therapeutic doses for at least six months prior to assessment, which reduces the likelihood of acute treatment effects but does not eliminate the possibility that subclinical affective symptoms or differences in indication severity may have influenced gait speed independently of medication use.

We believe that these revisions appropriately contextualise the findings, avoid over‑interpretation, and align their interpretation with the cross‑sectional design of the study.

Comments 4: Fourth, the sample size is relatively small, especially in the subgroups. This limits statistical power and makes the interpretation of non-significant findings, particularly in the “adequate” group, more uncertain.

Response 4: Thank you for this important comment. We agree that the modest overall sample size, and particularly the smaller subgroup sizes, may limit statistical power and the precision of estimates. To address this, we have now added to the Methods section a detailed a priori sample size calculation/power justification undertaken before the study commenced, demonstrating that the planned recruitment target was appropriate to test our primary hypothesis and to support the prespecified multivariable model. We have also retained a cautionary statement in the Discussion noting that non-significant findings—especially within the “adequate” group—should still be interpreted in light of reduced subgroup power.

Comments 5: Fifth, different types of psychotropic drugs are grouped together, despite having different pharmacological profiles. If possible, it would be useful to provide more detail by drug class or explore this in additional analyses.

Response 5: We thank the reviewer for this thoughtful comment. We agree that psychotropic medications encompass heterogeneous drug classes with different pharmacological profiles, and that class‑specific analyses could provide additional insight.

The primary aim of the study was to examine the association between prescribing appropriateness (appropriate versus inappropriate psychotropic medication use) and gait speed, rather than to assess the effects of individual drug classes. Accordingly, psychotropic medications were grouped to address this a priori research question and to preserve statistical power, given the limited sample size and small numbers within specific drug classes.

We have now expanded the Limitations section to explicitly acknowledge this issue and to clarify that stratified analyses by drug class were not feasible and that potential class‑specific associations cannot be excluded. We also emphasise that larger studies are needed to explore differential effects by pharmacological class and dose.

Comments 6: Regarding the presentation, Table 2 is difficult to interpret and should be simplified or clarified. Also, the manuscript would benefit from language revision. The term “psycho-drugs” should be replaced by “psychotropic drugs”, and some sentences should be rephrased for clarity.

Response 6: Thank you for these helpful comments. We agree that the original Table 2 was difficult to interpret. We have therefore revised the presentation and reorganised the information into three clearer tables, with improved formatting and complete legends, to facilitate reading and interpretation. In addition, we have undertaken a thorough language revision throughout the manuscript. We have replaced the term “psycho-drugs” with “psychotropic drugs” consistently and rephrased a number of sentences to improve clarity and precision.

 

Thank you for your thoughtful and constructive comments. We have sought to incorporate all of your recommendations into the revised manuscript to improve its methodological transparency, clarity of presentation and overall readability. We remain at your disposal should you require any further clarification or additional information.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the revision. 

I have no further comments. 

Reviewer 2 Report

Comments and Suggestions for Authors

I would like to thank you for your thorough and constructive revision of the manuscript. You have substantially improved the clarity and robustness of the paper.
In particular, I appreciate that you:
Consistently rephrased the main messages to avoid causal language and to report associations, which is more appropriate for a cross-sectional design.
Clarified in detail how you classified psychotropic medications as “adequate” or “inadequate”, including the role of STOPP/START and Beers criteria, as well as clinical pharmacological considerations and explicit lists of drugs and doses.
Expanded the methodological description (sample size justification, model specification, assumption checks) and strengthened the limitations section, especially regarding residual confounding by indication, small subgroup sizes, and heterogeneity of psychotropic classes.
These changes make the manuscript much clearer and more informative for readers. 
Overall, I believe the revised version is suitable for publication and that your work provides a useful contribution on the relationship between psychotropic prescribing quality and gait speed in community-dwelling older adults.

Comments on the Quality of English Language

The manuscript would benefit from language editing to improve clarity and scientific tone. A general English language revision is recommended.