# “Naloxone? Not for me!” First cross-assessment by patients and healthcare professionals of the risk of opioid overdose

Aurélie Aquizerate, Morgane Rousselet, Axel Cochard, Marylène Guerlais, Marie Gerardin, Emilie Lefebvre, Mélanie Duval, Edouard-Jules Laforgue, Caroline Victorri-Vigneau

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Aurélie Aquizerate, Morgane Rousselet, Axel Cochard, Marylène Guerlais, Marie Gerardin, et al. "Naloxone? Not for me!" First cross-assessment by patients and healthcare professionals of the risk of opioid overdose. Harm Reduction Journal, 2024, 21 (1), pp.20. 10.1186/s12954-024-00941-y. hal-04765025

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# "Naloxone? Not for me!" First cross-assessment by patients and healthcare professionals of the risk of opioid overdose

Aurélie Aquizerate¹, Morgane Rousselet¹,², Axel Cochard¹, Marylène Guerlais¹, Marie Gerardin¹, Emilie Lefebvre¹, Mélanie Duval¹, Edouard-Jules Laforgue¹,² and Caroline Victorri-Vigneau¹,²*

**Abstract**

**Background** Opioid-related mortality is a rising public health concern in France, where opioids were in 2021 implied in 75% of overdose deaths. Opioid substitution treatment (OST) was implicated in almost half of deaths related to substance and drug abuse. Although naloxone could prevent 80% of these deaths, there are a number of barriers to the distribution of take-home naloxone (THN) among opioid users in France. This study is the first one which compares patients' self-assessment of the risk of future opioid overdose with the hetero-assessment provided by health-care professionals in a population of individuals eligible for naloxone.

**Methods** This was a multicenter descriptive observational study carried out in pharmacies across the Pays de la Loire region (France) during April and May 2022. All adult patients who visited a participating pharmacy for a prescription of OST and provided oral informed consent were enrolled in the study. Retrospective data were collected through cross-sectional interviews conducted by the pharmacist with the patient, utilizing an ad hoc questionnaire. The patient's self-assessment of overdose risk was evaluated using a Likert scale from 0 to 10. The pharmacist relied on the presence or absence of overdose risk situations defined by the French Health Authority (HAS). The need to hold THN was assessed using a composite criterion.

**Results** A total of 34 patients were interviewed; near one third were aware of the existence of THN and a minority had THN in their possession. Out of the 34 participants, 29 assessed their own risk of future opioid overdose: 65.5% reported having zero risk, while 6.9% believed they had a high risk. Nevertheless, at least one risk situation of opioid overdose was identified according to HAS criteria in 73.5% of the participants (n = 25). Consequently, 55% of the participants underestimated their risk of experiencing a future opioid overdose. Yet, dispensing THN has been judged necessary for 88.2% of the participants.

**Conclusion** This study underscored the imperative need to inform not only healthcare professionals but also the patients and users themselves on the availability of THN and the risk situations of opioid overdose.

**Keywords** Naloxone, Opioid overdose, Cross-assessment, Opioid substitution treatment

<footnote>*Correspondence:
Caroline Victorri-Vigneau
caroline.vigneau@chu-nantes.fr
Full list of author information is available at the end of the article</footnote>
**Introduction**

Opioid-related mortality represents a significant global public health concern. In France, the number of opioid overdose deaths rose by 146% between 2000 and 2015, from 1.3 to 3.2 deaths per million inhabitants [1], and opioids were implicated in 75% of overdose deaths documented by the French national survey DRAMES (Deaths Related to Drug and Substance Abuse, in French) in 2021. While we are far from the figures of the American epidemic, France was identified in a recent disproportionality analysis conducted using the World Health Organization's pharmacovigilance database as one of the six countries exhibiting the highest indicators of opioid drug abuse and dependence. Notably, the USA was also part of this group [2]. For several consecutive years, methadone has been the primary substance involved in France, surpassing both heroin and buprenorphine. In the year 2020, opioid substitution treatment (OST) was associated with 49% of deaths related to substance and drug abuse [3, 4]. In France, buprenorphine and methadone have been approved as OST since 1995. Buprenorphine is recognized as the primary OST, while methadone is more commonly prescribed for refractory cases and/or complex situations, but the initial choice of an OST is also made in consultation with the patient, taking into consideration their preferences, comorbidities, medical history, potential drug interactions with concurrent treatments, safety considerations, including the risk of diversion via alternative routes of administration (intranasal or injectable) [5]. Both methadone and buprenorphine can be obtained at community pharmacies upon presentation of a medical prescription. By calculating the ratio of individuals receiving OST to the estimated number of people with problematic opioid use, France's OST coverage rate is estimated at 87%. This places France in the third position within Europe [6].

Early administration of naloxone, a competitive opioid receptor antagonist, could prevent 4 out of every 5 deaths from opioid overdose [7]. In France, naloxone is available in 3 different forms: (i) an IV form, for hospital use only [8], and 2 "ready-to-use" forms ("take-home naloxone," THN), intended for outpatient use and usable by all: (ii) a form for intranasal administration, available in pharmacies on prescription and reimbursable [9], and (iii) a form for intramuscular administration, available in pharmacies without prescription and reimbursable upon presentation of a prescription [10]. In France, obtaining THN free of charge in pharmacies currently requires presenting a prescription. This stands in contrast with the noteworthy example of emergency contraception, which has been accessible in pharmacies without a medical prescription or upfront payment for any woman since January 1, 2023 [11]. However, intranasal and intramuscular forms can

also be given free of charge to users in specialized addiction treatment facilities.

Although the usefulness of THN and its safety in use are unanimously recognized [12, 13], there are a number of barriers to its distribution among opioid users in France and many other countries. The literature is replete with studies that evaluate these barriers, primarily focusing on healthcare professionals and healthcare systems, with fewer studies delving into the patient perspective. Some of these barriers include time constraints, follow-up challenges, and financial burdens for patients. However, the most frequently cited obstacles are a lack of knowledge about naloxone and difficulties in identifying the appropriate target patients [14–17]. To the best of our knowledge, all these studies have examined these challenges solely from the perspectives of either healthcare professionals or patients, with none offering a comparative analysis of the two viewpoints. The objective of this article was to compare patients’ self-assessment of the risk of future opioid overdose with the hetero-assessment provided by healthcare professionals in a population of individuals eligible for naloxone.

**Methods**

**General design of the study**

This was a multicenter descriptive observational study carried out in pharmacies across the Pays de la Loire region (PDL, France) during April and May 2022. The data for this study were collected by 6 pharmacists, situated in various settings, including rural, urban, and seaside areas across three departments, who had been employed in the clinical pharmacology department of Nantes University Hospital for the preceding 5 years and were currently working in pharmacies, and thus had specific expertise in addiction surveillance. In France, in 2022, the High Health Authority (HAS) issued recommendations concerning the appropriate use of opioid medications, aiming to enhance their safety, increase the awareness of healthcare professionals in identifying and offering early intervention for problematic drug use, and encourage the widespread distribution of THN. Specifically, the HAS recommended that any healthcare professional caring for patients on opioids systematically assesses the appropriateness of prescribing and dispensing naloxone for all opioid users. The HAS identified specific situations as posing a higher risk of overdose, including patients receiving an OST [18]. We have therefore chosen to focus on this population of patients. All adult patients who visited a participating pharmacy for a prescription of buprenorphine or methadone as part of OST and provided oral informed consent were enrolled in the study. Retrospective data were collected through cross-sectional interviews conducted by the pharmacist
with the patient, utilizing an ad hoc questionnaire. In accordance with current French law, the study was approved by a local ethics committee on March 2022.

## Number of subjects

It is challenging to determine the required number of subjects for this study, as it is exploratory, and there is a lack of existing literature on subjects' self-assessment of overdose risk or pharmacist assessment based on the HAS criteria published in 2022. Consequently, we opted to include pharmacists trained across the region over a specified collection period, rather than attempting to estimate a specific number of subjects.

## Data collection

The following data were collected:

- General characteristics: socio-demographic data of the participants (age and sex), data relating to OSTs (prescribed molecule and history of use; substances at the origin of the initiation of the OST; identification of the OST prescriber) and to THN (patient's knowledge about THN, wish to own THN, knowledge of where THN are available, personal previous use of THN).

- Assessment of the patient's risk of future opioid overdose:

- Patient self-perceived risk of future opioid overdose. Patients were asked to rate their risk using a Likert scale ranging from 0 to 10, where 0 was no risk of future opioid overdose and 10 was extremely high risk of future opioid overdose.

- Pharmacist assessment of the same patient's risk of future opioid overdose. Overdose risk was assessed using situations identified as being at greater risk of overdose by the HAS: history of OST interruption and/or transition period (criterion 1) (the periods of interruption must correspond to real breaks, such as a minimum stoppage of more than 3 to 5 days, taking into account the half-lives of various OSTs), OST overconsumption (criterion 2), diversion of the OST route of administration (criterion 3), concomitant consumption of a substance having a depressant effect on the central nervous system (criterion 4), patient who had previously used naloxone (criterion 5).

- THN acceptance among patients prescribed OST: history of offering or requesting THN, actual acquisition, and information given to family/friends (if applicable).

## Outcomes

- Primary outcome: cross-assessment: comparison of the assessment of the risk of opioid overdose between the patient and the pharmacist.

- Secondary outcome: assessment of the need to dispense THN: dispensing THN has been judged necessary when at least one of the following criteria was validated:

- detection of at least one risk situation by the pharmacist

- patient self-assessment of the risk of future overdose > 5 on the Likert scale

- patient wishing to hold THN.

## Data analysis

We carried out a descriptive analysis of all the variables in the analysis: median and interquartile for quantitative variables, numbers, and percentages by modality for qualitative variables.

## Results

### General characteristics

A total of 34 patients were interviewed in the 6 participating pharmacies: Loire Atlantique (65%, n=22), Vendée (29%, n=10) and Sarthe (6%, n=2). Table 1 shows characteristics of the sample.

Participants were mostly men around 40 years old with a long-standing prescription. Methadone was the most prescribed OST, reported in 61.7% of cases. Heroin was the substance at the origin of the initiation of the OST in nearly ¾ of cases. In the majority of cases, the OST was prescribed by a general practitioner (73.5%, n=25).

Of the 34 participants, only 32.4% (n=11) were aware of the existence of THN: 3 through healthcare professionals or professionals working in a specialized addiction treatment facility and 4 through other channels (media, n=3, another user, n=1). The sources for 4 patients were not disclosed. One-third of the participants were aware of the locations to obtain THN, with the majority mentioning pharmacies as the primary source. At the end of the interview, 52.9% (n=18) of participants said they would like to have THN available. Over half of the participants (55.5%, n=10) who expressed a desire for THN were initially unaware of its existence at the beginning of the interview. None of the patients surveyed had prior experience using THN, either for themselves or for assisting someone else.

### Patient self-perceived risk of future opioid overdose

Out of the 34 participants, 29 assessed their own risk of future opioid overdose using a scale from 0 (indicating no risk) to 10 (maximum risk). These participants generally rated themselves as having a low risk of future opioid
<table><caption>**Table 1** Characteristics of the sample</caption><thead><tr><th></th><th>n (%)</th></tr></thead><tbody><tr><td>Socio-demographic data</td><td></td></tr><tr><td>Median age (in years) [interquartile]</td><td>39 [35–47]</td></tr><tr><td>Sex: male</td><td>23 (67.6)</td></tr><tr><td>Prescribed OST</td><td></td></tr><tr><td>Methadone</td><td>21 (61.7)</td></tr><tr><td>Buprenorphine</td><td>13 (38.3)</td></tr><tr><td>Median history of prescription (in years) [interquartile]</td><td>8 [5–10]</td></tr><tr><td>Substances at the origin of the initiation of the OST</td><td></td></tr><tr><td>Heroin</td><td>24 (70.6)</td></tr><tr><td>Buprenorphine (non-prescribed)</td><td>4 (11.8)</td></tr><tr><td>Codeine</td><td>1 (2.9)</td></tr><tr><td>Morphine</td><td>1 (2.9)</td></tr><tr><td>Other/unknown</td><td>4 (11.8)</td></tr><tr><td>OST prescriber</td><td></td></tr><tr><td>General practitioner</td><td>25 (73.5)</td></tr><tr><td>Hospital practitioner</td><td>4 (11.8)</td></tr><tr><td>Treatment Center</td><td>5 (14.7)</td></tr><tr><td>THN</td><td></td></tr><tr><td>Patient's knowledge about THN (Yes)</td><td>11 (32.4)</td></tr><tr><td>Desire to own THN (Yes)</td><td>18 (52.9)</td></tr><tr><td>Knowledge of where THN are available (Yes)</td><td>13 (38.2)</td></tr><tr><td>Personal previous use of THN (Yes)</td><td>0</td></tr></tbody></table>

overdose, with a median rating of 0 out of 10 and an average rating of 1. Approximately 65.5% of patients (n=19) reported having zero risk of experiencing a future opioid overdose. Among those who assigned a non-zero score, 27.6% (n=8) indicated a risk level of less than 5, while 6.9% (n=2) believed they had a high risk, scoring above 5 on the scale.

## Pharmacist assessment of the same patient's risk of future opioid overdose

Pharmacists identified at least one of the five criteria for assessing the risk of opioid overdose in 73.5% of the participants (n=25). Among the 34 participants, 23.5% (n=8) had one risk factor, 32.3% (n=11) had two risk factors, and 17.7% (n=6) had three risk factors. The most frequently identified risk situations, in order of frequency, were as follows:

(i) Criterion 1, which was present in over half of the patients (58.8%, n=20), involved the following situations: 16 patients reported experiencing interruptions in their OST, while 14 patients reported transitioning periods associated with life changes, such as hospitalization. Notably, 10 patients reported experiencing both periods of interruption and transition.

(ii) Criterion 4, which involves the consumption of substances with a depressant effect on the central nervous system, was reported by 44.1% of patients (n=15). The substances reported in this category were benzodiazepines (n=8), alcohol (n=5), and opioid analgesics (such as codeine, tramadol, and morphine; n=4). Notably, 26.5% of patients (n=9) reported using at least two central nervous system depressants in addition to their OST. Occasional use of heroin was reported in two patients, but not in conjunction with OST—both cases involved methadone. Additionally, three patients reported using cannabis.

(iii) Criterion 2, which was observed in approximately one-third of the patients (35.3%, n=12). These patients reported experiencing episodes of overuse of their OST, with such behavior often occurring during the initial stages of treatment and sometimes driven by a desire for anxiolytic-like psychoactive effects.

(iv) Criterion 3, which pertains to the diversion of the route of administration, was rarely observed, with only one patient reporting that he or she had occasionally taken its OST via nasal administration.

None of the participants reported any prior use of naloxone (criterion 5).

## Cross-assessment

Figure 1 displays the agreement in the assessment of the risk of future opioid overdose between the patients and the pharmacists among the 29 participants who self-assessed their risk.

The left scale shows the patient self-assessment as rated in the Likert scale, divided in 3 categories. The right scale indicates the number of risk situation detected by the pharmacist among the same patient.

Out of the 29 patients, only 45% (n=13) had assessments that aligned with the pharmacist's hetero-assessment. This subgroup consisted of: 6 patients in whom the pharmacists did not identify any overdose risk situations, and these patients self-assessed their risk at 0; 5 patients who perceived a low risk, and the pharmacist found 0 to 1 risk factor; 2 patients who self-assessed a high risk and indeed had at least 2 risk factors detected by the pharmacists.

Conversely, 55% (n=16) of participants underestimated their risk of future opioid overdose. Notably, among the 19 patients who self-assessed a zero risk, 68% of them (n=16) had at least one risk factor for overdose
<figure><img src="image_3.png" /><figcaption>**Fig. 1** Cross-assessment of the patient's risk of future opioid overdose by the patient and by the pharmacist</figcaption></figure>

<table><caption>**Table 2** Need to dispense THN among the participants and corresponding wish to possess THN</caption><thead><tr><td>Number of risk situation detected by the pharmacist</td><td>Number of participants concerned (n = 34)</td><td>Number of participants wishing THN n (% of participants concerned)</td></tr></thead><tbody><tr><td>0</td><td>9</td><td>5 (55.5)</td></tr><tr><td>1</td><td>8</td><td>2 (25.0)</td></tr><tr><td>2</td><td>11</td><td>6 (54.5)</td></tr><tr><td>3</td><td>6</td><td>5 (83.3)</td></tr></tbody></table>

as identified by the pharmacist and up to 3 risk factors for 3 of them (15.8%).

## Assessment of the need to dispense THN and THN acceptance among the participants

Among the 34 participants in this study, the need to dispense THN has been judged necessary for 30 patients (88.2%). These patients validated at least one of the following criteria:

- Detection of at least one risk situation by the pharmacist: **25 patients** were identified.

- Patient self-assessment of the risk of future overdose > 5 on the Likert scale: 2 patients were identified. For each of them, the pharmacist detected at least one risk situation of overdose.

- Patient wishing to hold THN: 18 patients were identified. Table 2 displays the distribution of participants by the number of risk situations detected by the pharmacist and their respective desire to possess THN. The wish to hold THN, which was expressed without knowing the results of the cross-evaluation, was the highest (64.7%, n = 11) among the 17 patients

who presented at least two criteria for assessing the risk of opioid overdose; three of them were already in possession of THN at the time of the interview. Notably, there were **5 patients** who expressed a desire for THN, despite the pharmacist not detecting any risk situation of overdose in their assessment.

Among the 34 participants, five patients had either been offered THN or had requested it from a healthcare professional prior to their participation in this study. All of them actually owned THN, and four of them had informed their family and friends about it. Therefore, the acceptance of THN among these patients was notably high, standing at 80%.

## Discussion

### THN: low distribution in a high-risk population...

Out of the 34 patients receiving OST in our study, only 14.7% (n=5) had access to THN. This proportion is in line with national estimates. In 2019, it was estimated that 177,000 individuals were prescribed OST in France. During the same year, 7667 THN kits were ordered in France by pharmacies, hospitals, and specialized facilities, and these kits were not exclusively provided to patients on OST [6]. Based on these figures, it appears that less than 23% of patients on OST were likely to have access to THN. However, the HAS identifies patients on OSTs, especially those on methadone, as one of the populations at highest risk of overdose, especially during the initiation and discontinuation of treatment [18]. This risk factor is found in several international studies and official recommendations [19–21]. Indeed, there are two primary periods of elevated risk of mortality for patients on OSTs: the initiation of treatment and the month following treatment cessation. These increased risks are largely attributed to the decreased tolerance to opioids during
these transitional periods [22, 23]. According to the Col-
lege of Psychiatrists in Ireland, the risk of a fatal overdose
within 15 days of initiating methadone treatment is esti-
mated to be 6–7 times higher than in heroin users who
are not receiving OST and a striking 98 times higher than
in patients who are well stabilized on OST [24]. Accord-
ing to Webster et al., death occurs within 7 days of the
start of methadone treatment in 70% of methadone-
prescribed overdose victims [22]. Finally, according to a
systematic review of the literature, the first 4 weeks fol-
lowing initiation of methadone treatment and following
cessation of treatment are the periods most at risk of
overdose: 11.4 deaths/1000 users and 32.1 deaths/1000
users, respectively [23]. In our study, although 100% of
the patients had this risk factor since it was an inclusion
criterion, 65.5% of the patients claimed that they had no
risk of experiencing a future opioid overdose.

... despite being in favor of its detention

In our study, all participants who had been offered THN or had requested it from a healthcare professional before their participation actually possessed THN, and 80% of them had informed their family and friends about it. While we acknowledge that our sample size is relatively small and might have some recruitment bias, it does align with a broader trend observed in the literature. For instance, in the French SINFONI study, none of the 355 healthcare professionals mentioned patient refusal as a reason for not prescribing or dispensing THN. Similarly, among the barriers to dispensing naloxone, patient refusal was reported in only 11.6% of cases by opioid treatment program staff [17]. This suggests that patient acceptance of THN may be higher than expected, and the main challenges in expanding its availability might be related to other factors. In our study, the alignment between the need to hold THN and the actual possession of THN was found to be inadequate. Out of the 30 patients for whom the dispensing of THN was considered necessary, only 13.3% (n=4) had THN in their possession. This indicates that a significant portion of patients who are eligible to have THN do not currently possess it. Why is this?"

The main patient-related barriers: a lack of knowledge
about the existence of THN...

Out of the 34 participants, only 32.4% (n=11) were aware
of the existence of THN. The rate of awareness about
naloxone varies in the international literature and may be
influenced by selection bias related to the specific pop-
ulation under study. For instance, in a study conducted
at a residential substance use treatment center, a nota-
bly high 95% of the sample was able to correctly identify
naloxone as the "overdose drug"[25]. However, this lack

of consumer awareness of the existence and usefulness
of THN is widely reported in the literature as one of the
main difficulties in distributing THN [17, 26–28]. It is
also worth highlighting in our study that, by the end of
the interview, more than half of the 18 participants who
expressed a desire for THN were initially unaware of its
existence. This suggests that enhancing communication
about the existence and significance of THN to all opioid
users is a primary strategy to promote the wider dissemi-
nation and adoption of THN.

... and an underestimation of the risk of overdose

In addition to the inherent risks associated with the use
of OST, our study reveals that patients are largely una-
ware of the risk of overdose situations. As much as 55%
of the participants underestimated their risk of experi-
encing a future opioid overdose. This challenge has been
recognized in several studies involving patients on OST,
which have also identified that a lack of communication
on the part of the prescriber and pharmacist contributes
to reinforcing self-perceptions of a low risk of overdose
[25, 28]. The underestimation of the risk of overdose has
also been observed in a study involving incarcerated opi-
oid users: participants demonstrated a strong awareness
of the increased risk of overdose following their release
from prison. However, they displayed little inclination to
purchase THN from pharmacies after their release, pri-
marily due to a perception of having a low personal risk
of overdose [29]. Finally, one of the obstacles identified in
a study of illicit drug users was a feeling of "product con-
trol" on the part of users [30].

The most commonly reported risk criterion among par-
ticipants in our study was a history of OST interruption
and/or transition periods, which was present in 58.8%
(n=20) of the patients. A loss of tolerance to opioids can
occur in as little as 3 days without use. Many publications
have identified loss-of-tolerance situations as particularly
high-risk of opioid overdose [20, 20, 31–37]. For instance,
in Ireland, official recommendations specify that OSTs
should not be provided to patients who have experienced
a treatment interruption of 3 days or more, unless the
prescriber confirms the appropriate dose to be dispensed
[24]. Among these situations, the periods of incarcera-
tion and release from incarceration are the best described
[38]. A similar phenomenon exists for patients leaving a
care center [19, 24, 33, 36, 39].

The second most frequently reported risk situation,
found in 44.1% (n=15) of participants, was the consump-
tion of a substance having a depressant effect on the cen-
tral nervous system (CNS): benzodiazepines (n=8) and
alcohol (n=5) in the forefront. The summary of product
characteristics for methadone and buprenorphine men-
tion an increased risk of sedation, respiratory depression,
coma, and death in the event of concomitant use of seda-
tive substances. A large number of publications warn
that the concomitant use of CNS depressants increases
the risk of opioid overdose [20, 32, 36, 37, 40]. Alcohol
is the substance most commonly found with opiates in
overdose victims [22]; its use significantly increases the
risk of overdose [41]. Concomitant use of benzodiz-
epines is found in 30% of cases of fatal overdose [42, 43],
and, according to Sun et al., opiate users taking benzo-
diazepines are 2.14 times more likely to be admitted to
hospital for opiate overdose than opiate users not tak-
ing benzodiazepines [44]. However, the way in which the
benzodiazepine is obtained and its dose consumed seem
to be factors to be taken into account when assessing the
risk [21]. Finally, it should be noted that in a study car-
ried out in patients on OSTs, methadone taken in combi-
nation with alcohol or benzodiazepines was perceived at
low risk by 55% of patients [45].

Enabling patients to have a more accurate assessment
of their individual risk of overdose could indeed be a sec-
ond effective strategy. It is worth noting that in our study,
among the patients at the highest risk of overdose (com-
prising 50.0% of all participants), two-thirds expressed
a desire to possess THN by the end of their interview.
These high-risk situations can be identified by prescrib-
ing doctors and/or pharmacists during the dispensing of
OST. A systematic evaluation of these factors by health-
care professionals could empower both professionals and
users to more effectively assess the risk of overdose and
the importance of having THN on hand.

Need for shared medical decision-making

Some risks associated with overdose, particularly peri-
ods of tolerance loss, are well documented, as mentioned
earlier. However, we demonstrate that very few patients
receive naloxone despite their willingness to have it when
questioned, even though they often underestimate their
risk of overdose. Why does this occur? The first hypoth-
esis is the insufficient awareness of opioid overdose
prevention methods, both among healthcare profes-
sionals and patients. This lack of awareness may result
in the prescription and guidance for THN not being an
automatic consideration for healthcare professionals.
The limited awareness regarding naloxone may explain
the low risk assessment by healthcare professionals and
patients, particularly given that official recommendations
outlining at-risk situations were only clearly defined in
France as recently as 2022. The pharmacists participating
in this study were selected because they were trained in
these recent recommendations, given their experience in
pharmacology. The second explanation could be the dif-
ference in the dispensing modalities (over-the-counter
or prescription) in France, which may create a sense of

ambiguity and potentially associate certain forms with
risks, even though it is not the case. Finally, the need for
a prescription to receive reimbursement in an economi-
cally disadvantaged population may also explain why
pharmacists are hesitant to assess overdose risks and
dispense without a medical prescription. It seems urgent
to implement training actions for healthcare profession-
als, as well as information campaigns for users to raise
awareness about the importance of having naloxone to
reduce the risks of death in case of overdoses. In the era
of shared medical decision-making, it is also crucial to
encourage shared risk assessments between users and
healthcare professionals to improve the availability and
acceptability of naloxone.

Strengths and limitations

This study marked a pioneering endeavor in objectively
assessing the risk of overdose, as perceived by healthcare
professionals and patients alike. Moreover, it afforded us
the opportunity to delineate the predominant obstacles
on the patient side hindering the distribution of THN
to an eligible population, a significant portion of whom
exhibited multiple risk factors for opioid overdose. Fur-
thermore, it facilitated the evaluation of the imperative
need to dispense THN to patients undergoing OST at
pharmacies, as well as the acceptance of THN among
these individuals. It is worth noting that the participant
count in this study is relatively modest, due to the small
number of pharmacies that met the criteria for taking
part. It is therefore not necessarily in alignment with
the prevailing landscape of OST utilization in France.
In 2021, nearly 162,000 individuals acquired OSTs from
French pharmacies, with the majority of these prescrip-
tions originating from general practitioners.

We cannot be sure that our sample is representative of
patients receiving OST, either in terms of socio-demo-
graphic characteristics or treatments received.

Moreover, buprenorphine emerged as the most fre-
quently prescribed OST, accounting for 55% of patients.
Nevertheless, the proportion of beneficiaries receiving
methadone prescriptions continues to exhibit an upward
trajectory (38% in 2017 vs. 44% in 2021) [6]. In our study,
it is notable that the percentage of participants using
methadone (61.7%) appears to surpass the proportion
observed among all OST users in France. This could be
related to geographical characteristics but also to the fact
that the participating pharmacists could have considered
methadone patients to be at a higher risk of overdose,
leading to a higher likelihood of their inclusion in the
study. This perception aligns with the fact that metha-
done is the substance most frequently implicated in over-
dose deaths, significantly exceeding the involvement of
buprenorphine.
Nevertheless, our study is exploratory in nature and focuses on analyzing predominantly qualitative data. Our goal is not to achieve representativeness but rather to underscore the divergence in assessments between users and healthcare professionals. For healthcare professionals, a thorough evaluation of the necessity for prescribing naloxone and its acceptability to the patient should be conducted systematically. This evaluation should lead to a collaborative medical decision, acknowledging potential disparities between the two perspectives.

It is noteworthy to mention that within the scope of our study, none of the participants had prior experience with THN, either for their own use or for assisting others. Numerous research endeavors have demonstrated a substantial correlation between a prior overdose event, whether experienced personally or observed as a bystander, and an elevated perception of heightened overdose risk [46] and a facilitator for holding THN [47], whereas no prior traumatic experience of overdose in patients on OST is a barrier [25, 28]. Nonetheless, several studies have documented a hesitancy to utilize THN among patients who have previously endured withdrawal symptoms after its administration in the context of a prior overdose [48–50]. Furthermore, the methodology employed in our study may have obscured an additional barrier that has been highlighted in the existing literature: the apprehension of stigma among individuals grappling with addiction, which could lead them to be hesitant in disclosing their addiction issues to pharmacy personnel. Moreover, there exists a concern regarding the potential negative response from patients toward healthcare professionals (48). In our study, the incorporation of both healthcare professionals and patients necessitated their consent, which inherently assumed an absence of hesitancy in discussing the topic. Each patient was appraised in advance that their responses to the questionnaire, as well as their decision to participate or decline, would have no bearing on their customary medical care.

## Conclusion

This study underscored the imperative to broaden the scope of training and information dissemination pertaining to the availability of THN and the risk situations of opioid overdose, reaching not only healthcare professionals but also the patients and users themselves. A substantial segment of patients and users remains unaware that opioid overdoses result from a complex interplay of various factors, necessitating comprehensive consideration when prescribing and dispensing opioids. This holistic evaluation is essential for accurately assessing an individual's risk of opioid overdose and the suitability of providing them with THN.

## Acknowledgements

The authors would like to thank all the pharmacists who included subjects in this study.

## Author contributions

Study concept and design were performed by AA, CVV; acquisition of data by AC, analysis and interpretation of data by AA, MR, AC, MD; drafting of the manuscript by AA; critical revision of the manuscript by CVV, MR, MGu, MGe, EL, EJL. All authors read and approved the final manuscript.

## Funding

None.

## Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

## Declarations

### Ethics approval and consent to participate

The study was approved by the Nantes Health Ethics Group (approval number: 22-3-110). In accordance with current French law, an information note on the study was provided to participants and their oral consent was received.

### Consent for publication

All participants gave oral consent for publication.

### Competing interests

The authors declare that they have no competing interests.

### Author details

¹Nantes Université, CHU Nantes, Centre d'Evaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CÉIP-A), Service de Pharmacologie Clinique, 44000 Nantes, France. ²Nantes Université, Univ Tours, CHU Nantes, CHU Tours, INSERM, MethodS in Patients-Centered Outcomes and Health Research, SPHERE, 44000 Nantes, France.

Received: 4 December 2023 Accepted: 17 January 2024

Published online: 23 January 2024

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