Revision Summary:
Prevalence of depression,
anxiety, and PTSD symptoms among patients of opioid agonist treatment
programmes in Ukraine during wartime {peer reviewed}
We
appreciate the reviewers’ thoughtful and constructive feedback, which has
significantly strengthened the manuscript. In response, we have carefully
revised the text to address all comments and suggestions. Below, we provide a
detailed summary of the changes made, organised by reviewer and comment. Where
appropriate, we also clarify our rationale and indicate specific locations in
the revised manuscript.
Reviewer:
Kamala Poudel
Also, the benefit of the research for the subjects of research
has not been mentioned either directly or indirectly. It is very important
that the research should aim at comforting the subjects so that they
cooperate happily in the research process. Here, 1/3 of the OAT therapy
patients declined to cooperate fully in the research. "Trauma and PTSD
data were collected in 2/3 of the patients screened for Depression and
Anxiety, and the other 1/3 refused to fill in the LEC-5 and PCL-5 screeners.
Therefore, it is impossible to make reliable conclusions on PTSD
prevalence." Counselling, other psychosocial supports such as breathing
exercises, etc., could have persuaded the 1/3 subjects to fill in the
screeners. Nothing has been mentioned to the effect that efforts were made to
persuade the 1/3 of the patients. Of course, the patients' cooperation had to
be voluntary, but little counselling could have made them understand that the
screener survey was for their benefit, as it would decide the medicines and terminir
dosage for these 1/3 patients. |
In the revised
manuscript, we have added a clarification that all participants were informed
of the study’s purpose, including its potential to inform service
improvements and individualised care. All participants could receive on-site psychological
support after the data collection. However, due to the limited resources at the time of
data collection, structured counselling or relaxation techniques were not
feasible prior to screener administration. |
Also, there are no specific recommendations made in the paper.
The conclusion is very general. Specific recommendations are lacking. |
We appreciate the reviewer’s observation and agree
that actionable recommendations are essential to enhance the utility of our
findings. In response, we have revised the conclusion section to include
specific, context-sensitive recommendations for both clinical practice and
policy development. These include: Integrating routine mental health screening (e.g.,
PHQ-4, LEC-5, PCL-5) into OAT programmes, especially during periods of
heightened stress such as armed conflict. Training OAT staff in trauma-informed care, including
brief psychosocial interventions to improve patient engagement and reduce
screener refusal rates. Establishing referral pathways for patients with
elevated symptoms of depression, anxiety, or PTSD to receive timely
psychological support. Advocating for policy-level support to ensure mental
health resources are embedded within addiction treatment services,
particularly in conflict-affected regions. These recommendations are now reflected in the
revised conclusion, and we hope they will support both immediate service
improvements and longer-term system strengthening. |
Dosage variation due to heightened stress of war is not
recommended when it is categorically mentioned that "A significant
deterioration in the mental health of OAT patients in Ukraine during the
second year of the full-scale Russian invasion" was found. |
We thank the reviewer for raising this important
concern. We agree that dosage adjustments in opioid agonist treatment (OAT)
must be approached with caution, particularly in contexts of psychological
distress and systemic instability. In our manuscript, we do not advocate for dosage
variation as a direct response to mental health deterioration. Rather, we analys
the data on the correclation between the dosage satisfaction and
psychological wellbeing of the patients. |
The absence of any change in suicidal ideation is interesting.
Some additional authorities could be added to explain that generally, suicide
ideation does not increase during wartime, rather it increases in the
post-war phases. |
We thank the reviewer for this thoughtful
observation. We agree that the stability in suicidal ideation rates, despite
elevated symptoms of depression and anxiety, is noteworthy and merits further
contextualization. In response, we have expanded the discussion section
to include references to literature suggesting that suicidal ideation may not
peak during active conflict. |
Reviewer: Kateryna Bikir
There is a
discrepancy in the reported gender distribution. The body of the article
states: “Among study participants (95 males and 889 females),” while Tables
1–3 show the opposite: 95 females and 889 males. This inconsistency should be
corrected to ensure clarity and accuracy. |
We thank the reviewer for
this observation, it is corrected now: 95 females and 889 males. |
While the study
is robust, it would benefit from the inclusion of additional demographic and
clinical characteristics commonly reported in similar research. For example,
age, marital status, employment status, duration in treatment, mean
percentage of opioid-positive drug screens, total number of opioid screens
prior to and during study enrollment. These variables
are routinely included in comparable studies, such as: Rosic et al.
(2025), PLOS ONE, https://doi.org/10.1371/journal.pone.0314296 Yang et al.
(2025), Pain Medicine, https://doi.org/10.1093/pm/pnaf011 Including these
would enhance the study’s comparability and depth. |
The inclusion of additional
demographic and clinical characteristics would definitely benefit the study;
however, the article presented all characteristics that were collected during
the second study. During the first study, the set of collected characteristics
was even lower due to certain organisational limitations in the study
process. |
Reviewer: Mariia
Mezhenska
The central inference hinges
on comparing two independent clinic cohorts. Comparability of the two cohorts
is currently under-reported and needs to be shown. Because the pre-war sample
(Kyiv/Lviv/Sumy) differs in composition from the wartime sample (Vinnytsia/Lviv/Sumy),
readers need to see whether cross-cohort differences reflect true changes or
simply different case-mix. The article would benefit from adding two concise
descriptive tables, one for each cohort, reporting, at a minimum, gender,
age, city, and OAT medication (methadone/buprenorphine/buvidal), with n/N
shown for each stratum. Alongside those tables, acknowledge explicitly that
Kyiv was replaced by Vinnytsia in the wartime wave. If possible, include a
brief sensitivity check restricting pre/post comparisons to the overlapping
sites (Lviv and Sumy); if re-analysis is not feasible, a clear caveat in
Results and Limitations about the site swap and possible influence of
confounders that was not tested is sufficient. |
We thank the reviewer for
this important methodological observation. We agree that the comparability of
the pre-war and wartime cohorts is essential to interpreting observed
differences in mental health outcomes. We have also explicitly
acknowledged that Kyiv was replaced by Vinnytsia in the wartime wave due to
logistical constraints. While a full sensitivity re-analysis restricted to
Lviv and Sumy was not feasible given the original data structure, we have
added a clear caveat in the Limitations sections noting that site composition
may have influenced observed differences. |
The pre/post analyses
themselves are currently unadjusted (Mann–Whitney U for severity; χ² for
prevalence), and therefore they compare the two time periods without
controlling for things that also differed between periods (site mix: Kyiv vs
Vinnytsia; season/month of data collection (pre-war (Oct–Jan) vs war-year-2
(Apr–Oct)) invites seasonal effects on mood/anxiety; gender proportions;
medication mix). If those factors relate to the outcomes, they can confound
the pre-/post-contrast. Reasonable confounders should be mentioned in the
Discussion and the Limitations sections. Reporting effect sizes with 95% CIs
throughout the article and interpreting the results as associations rather
than causal effects is necessary. If the authors can add one lightweight robustness
model (e.g., a site-adjusted logistic regression for the primary prevalence
outcomes (pre vs during + site as a covariate), that would further strengthen
confidence without expanding the paper. |
We thank the reviewer for
this rigorous and constructive feedback. We agree that unadjusted comparisons
may be influenced by contextual and demographic differences between the
pre-war and wartime cohorts. In response, we now explicitly discuss key
potential confounders, including site composition (Kyiv vs Vinnytsia),
season/month of data collection (Oct–Jan vs Apr–Oct), gender proportions, and
medication mix, in Limitations sections. We have revised the language
throughout the manuscript to interpret findings as associations rather than
causal effects, in line with the observational design. |
In the Participants section
(in the Methods section, not the Results), reporting sample sizes for each
cohort and providing a brief description of each sample (sites, gender
distribution, age, and OAT medication mix) is highly desirable. |
The inclusion of additional
demographic and clinical characteristics would definitely benefit the study;
however, the article presented all characteristics that were collected during
the second study. During the first study, the set of collected characteristics
was even lower due to certain organisational limitations in the study
process. |
The manuscript should also
explicitly state that informed consent was obtained. |
The “Informed consent was
obtained from all participants.” was added to the to the “Pariticipants”
section. |
Moreover, because screening
was interviewer-administered by clinic staff, noting in the Limitations the
risks of social desirability and interviewer bias, especially potential
underreporting of suicidal ideation, and briefly describing privacy
safeguards (private setting, standardized script, and whether a
self-administration option was offered) is highly recommended. |
Thank you for this notion,
the relevant part was added to the Limitation section. |
Finally, nonresponse on
trauma/PTSD is substantial and likely informative (376 refused LEC-5; only
608 completed LEC-5, and 549 trauma-exposed completed PCL-5), so PTSD
prevalence is plausibly underestimated (people with the highest trauma may
refuse). |
Thank you for this notion,
the relevant part was added to the Limitation section. |
Furthermore, the manuscript
would benefit from a brief Methods subsection describing each measurement
scale (PHQ-9, GAD-7, PCL-5 with LEC-5 anchoring, and PHQ-9 item 9 for
suicidal ideation; number of items used in the current study) and reporting
summary statistics for each cohort; as well as a succinct Data Analytics
section explaining the rationale for each analysis choice. |
We thank the reviewer for this thoughtful
recommendation. While we agree that detailed descriptions of instruments and
analytic rationale can enhance transparency, we respectfully believe that the
current manuscript structure sufficiently addresses these elements within the
constraints of journal length and scope. Specifically, each instrument is referenced with its
full name and citation, and the number of items used is standard across
validated formats. Summary statistics for each cohort are already reported in
the Results section and accompanying tables. Additionally, the rationale for
analytic choices (e.g., Mann–Whitney U for non-parametric severity
comparisons, χ² for prevalence contrasts) is briefly noted in the
Methods and further contextualized in the Discussion and Limitations
sections. To maintain clarity and conciseness, we have opted
not to expand these sections further. However, we have reviewed the
manuscript to ensure that all analytic decisions and measurement tools are
clearly described and appropriately cited. |
Medication group contrasts
(higher suicidal ideation/PTSD among buprenorphine vs methadone recipients)
are valuable but potentially influenced by confounders. Framing these as
exploratory and presenting minimal adjusted comparisons (medication + age +
gender + site) with adjusted odds ratios and CIs, ideally in a compact
supplement, would temper inference. |
We thank the reviewer for highlighting the potential
influence of confounders in medication group contrasts. We agree that these
findings should be interpreted with caution and have now explicitly framed
them as exploratory in the revised manuscript. While we recognize the value of adjusted comparisons,
we respectfully note that the sample size and data structure do not support
robust multivariable modeling without risking overfitting or unstable
estimates. Given the observational design and limited statistical power for
subgroup analysis, we have opted not to include adjusted odds ratios or a
supplemental model at this stage. |
Clinical relevance warrants
explicit comment where statistically significant differences are small. For
example, the PHQ-9 mean increase from 7.42 to 7.90 is modest; reporting the
standardized mean difference and noting that the absolute change appears below
typical minimal clinically important difference thresholds would help avoid
over-interpretation of p-values. |
Thank you for this notion, the relevant notion was
added to the Results section. |
Several small inconsistencies
are present, which I believe are typos, but should be fixed. Sex counts are
reversed in text (it says “95 males, 889 females”; tables indicate 95
females, 889 males) and the methadone totals (764 in tables vs 746
elsewhere). |
Thank you, corrected |