Associations Between Over-the-Counter Analgesics Usage and Symptoms of Anxiety and Depression in Adolescents: A Network Analysis

doi:10.21203/rs.3.rs-3627720/v1

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Research Article

Associations Between Over-the-Counter Analgesics Usage and Symptoms of Anxiety and Depression in Adolescents: A Network Analysis

https://doi.org/10.21203/rs.3.rs-3627720/v1

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Background

The use of over-the-counter analgesics (OTCA) is common among adolescents, particularly females. Previous research has linked symptoms of anxiety and depression (AD) with OTCA usage, even after controlling for pain. AD encompasses a wide array of both psychological and physiological symptoms, and little is known about which of these symptoms are most strongly connected to OTCA usage. In the current study we assessed differences in associations between specific AD symptoms and OTCA usage in a large sample of adolescents. Furthermore, we examined whether the associations between AD symptoms and OTCA usage differed across genders.

Method

We included 626,581 participants from the Ungdata survey. AD symptoms were measured with an adapted version of Hopkins Symptom Checklist-10 and the Depression Mood Inventory, while a 5-point scale assessed OTCA usage. Non-regularized partial-correlation networks were constructed to explore conditional dependent relations between the use of OTCA and AD symptoms, including a separate network controlling for symptoms of pain. Gender-specific networks containing all symptoms were created. The networks were visualized and described statistically in terms of edge weights and bridge centrality (bridge expected influence).

Results

OTCA usage demonstrated associations with most AD symptoms, with the strongest links to “sleep problems”, “stiff or tense”, “everything is a struggle” and “suddenly scared”. When including pain symptoms as covariates, OTCA-AD edges weakened, but most edges persisted as significant. The strongest links were observed between OTCA usage and pain symptoms. Key bridging nodes between communities included “headache” and “stiff or tense”. OTCA usage demonstrated higher bridge expected influence in the female network than in the male. Further, “sleep problems” and “hopeless” showed stronger links to OTCA usage among females, whereas “stiff or tense” was more strongly related to OTCA usage among males.

Conclusion

Our study assessed the relationship between OTCA usage and specific symptoms of anxiety and depression in adolescents. Our results indicate that somatic expressions of AD, such as sleep disturbances and tension, displayed stronger associations with OTCA usage than more conventional AD symptoms. This pattern might be even more pronounced in males than females.

analgesics

nonprescription drugs

acetaminophen

ibuprofen

anxiety

depression

pain

adolescent

sex characteristics

network analysis

The use of over-the-counter analgesics (OTCA), such as paracetamol (acetaminophen) and ibuprofen, is highly recurrent and increasing among adolescents, particularly among young girls (1, 2). On-label usage of OTCA implies using analgesics to alleviate pain symptoms. Adolescents with high levels of psychiatric symptoms report more frequent occurrences of pain, such as headaches, abdominal pain and chronic pain (3, 4). Remarkably, even after adjusting for pain symptoms, adolescents with elevated psychiatric symptoms still show more frequent analgesic usage (5, 6). One question that emerges is whether adolescents use OTCA off-label to alleviate psychological and emotional distress. While existing research suggests a relationship between OTCA usage and various psychiatric symptoms, little is known about which specific symptoms are most responsible for this association.

Pain is often accompanied by somatic symptoms such as poor sleep, tension or stiffness, fatigue, and changes in appetite (7). These symptoms are also commonly associated with psychiatric conditions such as anxiety and depression (AD). AD are among the most prevalent classes of psychiatric disorders in adolescents (8). They involve a wide array of psychological, physiological and cognitive symptoms, and have long been acknowledged as multisystem disorders affecting, and affected by, both mental and physical health (9, 10). Both conditions result in substantial disability and pose massive and increasing global health challenges (11). The current diagnostic criteria for AD likely encompass a diverse range of diagnoses with partially overlapping causes and underlying mechanisms, leading to high rates of comorbidity (12).

Several neurofunctional, cognitive and psychosocial factors are linked to OTCA usage. High consumers of OTCA report lower self-esteem, reduced sleep, lower educational ambition, binge drinking, higher caffeine consumption and part-time employment compared to non-weekly users (13). OTCA may influence how people experience distress, process cognitive discrepancies and evaluate stimuli in their environment (14). For example, a single dose of paracetamol in young students can reduce affective reactivity to other people’s positive and negative experiences (15, 16). Daily usage of paracetamol also seems to reduce behavioural and neurofunctional responses associated with the pain of social rejection (17), and victimization from bullying seems to be related to medicine usage in adolescents (18).

Although OTCA are generally considered to be relatively safe, high consumption may have negative side effects, such as severe gastrointestinal ulceration and bleeding (19, 20), cardiac complications (21, 22) and serious and irreversible damage to the kidneys and liver (5, 23, 24). Furthermore, the literature shows that the negative side effects of OTCA usage in adolescents are less understood. A recent meta review identified several knowledge gaps and inconsistencies in findings regarding OTCA usage among children up to the age of eighteen (25). Adolescents in particular face an increased risk of unintentional misuse of OTCA (26, 27).

While research suggests that OTCA usage is associated with increased AD symptoms in adolescents, we have little knowledge as to why this is so. Findings indicating that OTCA may relieve distress and social pain could imply that adolescents’ off-label usage is an attempt to alleviate affective and cognitive AD symptoms. Conversely, it is possible that the association between OTCA usage and AD is driven primarily by somatic symptoms shared between pain and AD, such as muscle stiffness and sleep problems. To increase our understanding of this relationship, it is essential to gain more detailed knowledge of the specific AD symptoms involved. Therefore, the primary aim of the present study was to examine which specific AD symptoms OTCA usage is associated with in adolescents.

Further, several studies have shown that the presence and co-occurrence of pain and AD symptoms are more prevalent in females than males (6, 28, 29), and that young women in particular might use OTCA as a tool to downregulate feelings of distress (2, 30). This is further supported by research indicating gender differences in physical pain perception and response to analgesic usage (31, 32) and experiences of social pain (33). However, it remains unclear whether all AD symptoms are more strongly related to OTCA usage in females compared to males, or if they vary across symptoms. Thus, as a secondary aim we examined whether the association between specific AD symptoms and OTCA usage differed across genders.

Sample Collection

We obtained data from an annual nationwide survey of adolescents in Norway (“Ungdata”). The Ungdata surveys are administrated online during school hours across all municipalities, ensuring representation from both urban and rural areas in Norway. The Norwegian Social Welfare Research Institute (NOVA) manages a national database containing all conducted surveys. For this study, we included all junior and senior high school students aged 12–19 years from municipalities that conducted the Ungdata survey between 2014 and 2019 (N = 626,581). Surveys conducted before 2014 did not include items related to OTCA. Pain-related items underwent a substantial revision in 2019, leading us to exclude all data collected after 2019. By doing this, we also excluded data from the time of the COVID-19 pandemic, which could potentially have influenced the observed relationships. In the gender-specific analysis, we excluded all participants with missing gender data, which amounted to 19,010 participants (3%).

Assessments

Over-the-counter analgesics. Participants were asked how often they had used OTCA (paracetamol, ibuprofen, etc.) over the past month. The response options were: 1) Never, 2) Less than once a week, 3) At least weekly, 4) Several times a week and 5) Daily.

Anxiety and depression symptoms. Ungdata’s main module, titled “Mental Health Issues”, which is administered annually, is based on a combination of the Hopkins Symptom Checklist (HSCL-10; 34) and the Depression Mood Inventory (35), encompassing a total of nine items. Additionally, Ungdata has included a question regarding loneliness, resulting in a total of ten items used to measure AD symptoms in our analysis. These items included: 1) Felt that everything is a struggle, 2) Had sleep problems, 3) Felt unhappy, sad or depressed, 4) Felt hopeless about the future, 5) Felt stiff or tense, 6) Worried too much about things, 7) Felt lonely, 8) Suddenly felt scared for no reason, 9) Felt constant fear or anxiety and 10) Been nervous or felt uneasy. Participants were asked to rate these symptoms during the preceding week on a 4-point scale with the following response options: 1) Not been affected at all, 2) Not been affected much, 3) Been affected quite a lot and 4) Been affected a great deal.

Pain symptoms. The assessment of pain symptoms, which consisted of four items, asked about 1) Headache, 2) Neck and shoulder pain, 3) Joint and muscle pain, and 4) Abdominal pain in the past month. The response options were 1) Never, 2) A few times, 3) Many times and 4) Daily.

Statistical Analyses. We used network analysis (36) to examine the associations between AD symptoms and OTCA usage. Results are presented as graphical networks consisting of nodes representing the study variable and edges between nodes representing conditional independence relations (partial correlations) between them. In line with guidelines (37), node variables were nonparanormally transformed using the R package huge (38). Potential node redundancy among the AD symptoms due to topological overlap was ruled out using the Goldbricker function in networktools (39). Networks were then estimated by computing unregularized Gaussian Graphical Models (GGMs) using the ggmModSelect function in qgraph (version 1.5; 40). This procedure has been demonstrated to exhibit strong specificity in large samples (41, 42). We used full information maximum likelihood estimation, which takes into account all observed data, including missing data (17.4% of data points were missing). Specifically, ggmModSelect employs an iterative process to select the optimal GGM based on an extended Bayesian information criterion (42). This procedure eliminates spurious associations (edges) attributable to the influence of other nodes in the network and shrinks trivially small associations to zero, thereby reducing the number of potentially false positive edges from the network and producing a sparse graph comprising only the strongest edges. Nodes which serve as bridges in connecting AD symptoms, OTCA usage and pain (i.e., bridge nodes) were identified by computing the Bridge Expected Influence (BEI) index using the R package networktools (43, 44). Accuracy of the network estimates was assessed using the bootnet R package version 1.5.1 (45) with 1,000 bootstrap samples. The analyses were performed using R version 4.3.2 on October 31, 2023.

The analysis consisted of three stages. In the first stage, we estimated a network consisting of AD symptoms and OTCA usage. This network highlights associations between specific symptoms of AD and analgesic usage. In the second stage, we added the pain nodes, thereby controlling for the effect of pain. Notable edges and bridge nodes were identified at this stage. In the final stage, we computed one network for females and one network for males and examined the differences between them by head-to-head comparisons of AD-OTCA edges (i.e., edge weights) and BEI of the OTCA node, using Holm–Bonferroni correction for multiple comparisons. Differences in edge weights and BEI between the networks were evaluated statistically using the R package network comparison test (NCT) version 2.2.1 (46) with 1,000 iterations.

Sample Characteristics

The total sample consisted of 303,059 (49.9%) females and 304,512 (50.1%) males.

The proportion of weekly OTCA users was 23.4% among females and 11.2% among males. The majority of the sample (62.5%) attended junior high school (ages 12–16), while 37.5% were enrolled in senior high school (ages 16–19).

Associations between OTCA Usage and AD Symptoms

Associations between OTCA usage and AD symptoms are presented in Fig. 1A. Here, nodes represent the study variables, and the edges represent associations between them. Thicker edges represent stronger associations. In line with our objective on OTCA-symptom associations, only edges that were connected to OTCA were visualized.

OTCA usage was most strongly associated with “sleep problems” (edge strength = 0.10), “stiff or tense” (0.09), “everything is a struggle” (0.07) and “suddenly scared” (0.05). When adding pain variables to the model (Fig. 1B), results showed that OTCA usage was most strongly associated with “headache” (0.29) and “abdominal pain” (0.08). There were still associations between OTCA usage and most AD symptoms, but the associations were weaker.

Figure 1A

Non-regularized partial-correlation network of AD symptoms and OTCA usage.

Figure 1B

Non-regularized partial-correlation network with pain symptoms as covariates.

Blue edges represent positive and red edges represent negative partial correlations. The OTCA node is placed in the centre of a circle consisting of the remaining variables. The thickness and brightness of an edge indicate association strength. Legends: OTCA: Paracetamol, ibuprofen or similar, AD1: Felt that everything is a struggle, AD2: Had sleep problems, AD3: Felt unhappy, sad or depressed, AD4: Felt hopeless about the future, AD5: Felt stiff or tense, AD6: Worried too much about things, AD7: Felt lonely, AD8: Suddenlty felt scared for no reason, AD9: Felt constant fear or anxiety, AD10: Been nervous or felt uneasy. Blue edges represent positive and red edges represent negative partial correlations. The OTCA node is placed in the centre of a circle consisting of the remaining variables. The thickness and brightness of an edge indicate association strength, P1: Headache, P2: Neck and shoulder pain, P3: Joint and muscle pain, P4: Abdominal pain.

Bridge centrality indices are presented in Fig. 2 and signify which nodes are most central in explaining associations between OTCA usage, AD symptoms, and pain. Among the AD symptoms, “stiff or tense” was the most important bridge node, while “headache” was the most important bridge node among the pain variables.

Figure 2

Bridge expected influence for Network 2

We defined three communities (i.e. OTCA + AD symptoms + pain symptoms) to check for bridge nodes between communities. Bridge expected influence 1-step refers to the sum of the value (positive or negative) of all edges connecting node A to all nodes not in the same community as node A (47). Legends: OTCA: Paracetamol, ibuprofen or similar, AD1: Felt that everything is a struggle, AD2: Had sleep problems, AD3: Felt unhappy, sad or depressed, AD4: Felt hopeless about the future, AD5: Felt stiff or tense, AD6: Worried too much about things, AD7: Felt lonely, AD8: Suddenlty felt scared for no reason, AD9: Felt constant fear or anxiety, AD10: Been nervous or felt uneasy. Blue edges represent positive and red edges represent negative partial correlations. The OTCA node is placed in the centre of a circle consisting of the remaining variables. The thickness and brightness of an edge indicate association strength, P1: Headache, P2: Neck and shoulder pain, P3: Joint and muscle pain, P4: Abdominal pain.

Gender Differences

Figure 3 shows the networks for female and male participants. Visual inspection revealed that the most prominent edges between OTCA usage and AD symptoms in the female and male networks were the same as those identified in our previous networks. Statistical comparison of edge weights between OTCA and AD symptoms identified three edges that were significantly different between females and males (p <. 001): “sleep problems” and “hopeless” displayed a stronger connection with OTCA in the female network, whereas “stiff or tense” was more closely linked to OTCA in males.

Figure 3 here

Separate networks for female (A) and male (B) participants.

Non-regularized partial correlation networks containing OTCA, AD symptoms and pain symptoms. Blue edges represent positive and red edges represent negative partial correlations. The thickness and brightness of an edge indicate association strength. Legends: OTCA: Paracetamol, ibuprofen or similar, AD1: Felt that everything is a struggle, AD2: Had sleep problems, AD3: Felt unhappy, sad or depressed, AD4: Felt hopeless about the future, AD5: Felt stiff or tense, AD6: Worried too much about things, AD7: Felt lonely, AD8: Suddenlty felt scared for no reason, AD9: Felt constant fear or anxiety, AD10: Been nervous or felt uneasy. Blue edges represent positive and red edges represent negative partial correlations. The OTCA node is placed in the centre of a circle consisting of the remaining variables. The thickness and brightness of an edge indicate association strength, P1: Headache, P2: Neck and shoulder pain, P3: Joint and muscle pain, P4: Abdominal pain.

The bridge expected influence (BEI) measure for the female and male network is presented in Fig. 4. The most central nodes bridging the three communities in both networks were the same as presented earlier. However, OTCA showed a significantly higher degree of BEI in the female (0.58) than the male (0.49) network (p < .05).

We defined three communities in the female and male network (i.e. OTCA + AD symptoms + pain symptoms) to check for bridge nodes between communities. Bridge expected influence 1-step refers to the sum of the value (positive or negative) of all edges connecting node A to all nodes not in the same community as node A (47). Legends: OTCA: Paracetamol, ibuprofen or similar, AD1: Felt that everything is a struggle, AD2: Had sleep problems, AD3: Felt unhappy, sad or depressed, AD4: Felt hopeless about the future, AD5: Felt stiff or tense, AD6: Worried too much about things, AD7: Felt lonely, AD8: Suddenlty felt scared for no reason, AD9: Felt constant fear or anxiety, AD10: Been nervous or felt uneasy. Blue edges represent positive and red edges represent negative partial correlations. The OTCA node is placed in the centre of a circle consisting of the remaining variables. The thickness and brightness of an edge indicate association strength, P1: Headache, P2: Neck and shoulder pain, P3: Joint and muscle pain, P4: Abdominal pain.

Accuracy and Stability Checks

The test of network accuracy and stability is presented in the supplementary materials (Fig. S1-S8). Bootstrap analyses showed that the network estimates were highly accurate and stable.

The current study set out to explore using network analysis the associations between the use of OTCA and distinct symptoms of anxiety and depression in adolescents. Results showed associations between OTCA usage and most AD symptoms. These links remained, albeit with reduced strength, after including pain symptoms in the network. The strongest associations were observed with “sleep problems”, “stiff or tense”, “everything is a struggle” and “suddenly scared”.

A secondary aim was to examine if the OTCA-AD associations differed between genders. Comparing the female and male networks demonstrated a significant difference in three edge weights (i.e. association strength between two nodes). The associations between “sleep problems” and OTCA, as well as “hopeless” and OTCA, appeared stronger among females. Conversely, “stiff or tense” was more strongly related to OTCA among males. Furthermore, we found that OTCA exhibited higher bridge expected influence (BEI) in the female network compared to the male network, indicating stronger connections to other communities (AD and pain) among females.

Psychological Features of Anxiety and Depression Showed Weaker Links to OTCA

Our key finding was that overall symptoms characterized by somatic manifestations of AD, such as sleep problems and stiffness and tension, were most closely associated with OTCA usage. AD symptoms with clearer cognitive and affective aspects, such as “worrying too much” and “hopeless”, showed no associations with OTCA usage when we adjusted for pain symptoms. The absence of a link between these symptoms and OTCA suggests that their relationship was influenced solely by other symptoms in the network, indicating conditional independence. Thus, when controlling for pain symptoms, it appears that the core psychological features of AD are less relevant for the usage of OTCA.

“Everything is a struggle” and “suddenly scared” were also associated with OTCA usage after adjusting for pain symptoms. There is no standardized classification of symptoms into categories such as somatic, cognitive and affective, and several AD symptoms encompass both psychological and physiological aspects. One could assume that “feeling that everything is a struggle” overlaps with somatic symptoms, such as “feeling low on energy” and “fatigue”, as well as with more cognitive and affective symptoms, such as “loss of interest/joy” (34, 48). Similarly, “suddenly feeling scared for no reason” is not a distinctly somatic, cognitive or affective symptom. It can involve both physiological reactions, such as heart pounding, trembling and trouble catching one’s breath, and psychological appraisals of being in danger (48).

On-Label Symptoms were Most Prominently Related to OTCA Usage

On-label symptoms for OTCA usage include headaches, neck and shoulder pain, muscle and joint pain and abdominal pain. These pain symptoms were hypothesized to be strongly related to the use of OTCA, as it would suggest that the majority of participants use OTCA primarily for its intended purpose. Indeed, including pain symptoms in the network revealed substantially stronger associations between OTCA usage and on-label symptoms than between OTCA and AD. This is in line with previous research on OTCA usage among adolescents (26). However, we cannot know for certain what initially triggered the adolescents’ use of OTCA. Frequent OTCA usage could potentially lead to headaches (49, 50) and abdominal issues (19), and we cannot rule out the possibility that part of the observed association is due to OTCA usage having triggered pain symptoms. Our study cannot shed further light on this, as we have not captured the temporal or motivational aspects of this association on an individual level.

While it is reassuring that the associations between OTCA usage and pain symptoms were markedly larger than the associations with AD symptoms, there is a need for a deeper understanding of the factors that influence decision-making regarding OTCA usage. There could be other variables affecting OTCA usage among adolescents that this study did not control for. For example, it has been suggested that variations in autonomy, inclination for critical risk assessment, and independence from parental influence might contribute to differences in OTCA usage (26, 27). Additionally, socio-demographic variables and differences in health literacy are among the aspects that have been suggested as possible factors related to OTCA usage (51). Even though dosage instructions and usage guidelines are readily available on the medicine packages, a sufficient level of basic health literacy is necessary to understand and make use of this information (51, 52). Future studies should consider including a wider range of variables in their analysis to obtain an even more comprehensive overview of the specific factors related to off-label OTCA usage among adolescents.

Social Pain as a Possible Mediating Factor

As the use of OTCA is associated with social rejection and bullying, and could potentially decrease empathy and pro-social behaviour, it has been suggested that analgesics might be used to alleviate social pain, rather than emotional pain in general (15, 16). If the observed associations between OTCA usage and AD symptoms were mediated by social pain, we might anticipate a strong relationship between OTCA usage and the symptom “lonely”, which is closely related to social exclusion and has previously been associated with both acute and chronic pain (53). However, our findings revealed a slight negative relation between the two in all our network analyses. One possible explanation is that individuals who frequently used OTCA experienced reduced feelings of loneliness due to the medication blunting or diminishing such emotions. Social pain, like the unpleasant emotional state of loneliness, shares similarities with the discomfort felt in response to physical pain (54), and research has demonstrated that brain activation patterns in response to social pain overlap significantly with those observed in studies of physical pain (55). Thus, it seems plausible that adolescents might turn to painkillers when feeling lonely, and that these pills may have an analgesic effect on the social pain. Nevertheless, given the weak relation observed in this study, our findings did not indicate that social pain, as measured by feelings of loneliness, played a particularly central role in explaining off-label OTCA usage.

Males Showed Stronger Relations between Somatic Symptoms and OTCA Usage

Several studies point to a stronger relation between AD symptoms and OTCA usage among females compared to males (2, 30). To enhance our understanding of this relationship, we examined potential gender differences in associations between OTCA usage and specific AD symptoms. The analysis of female and male networks revealed significant distinctions in three edge weights. Among females, the edges linking "sleep problems" and OTCA, as well as "hopeless" and OTCA, appeared notably stronger compared to males. Conversely, the association between "stiff or tense" and OTCA was stronger among males. Moreover, our findings indicated that OTCA displayed a higher BEI within the female network, suggesting stronger ties between OTCA and other communities (AD and pain) among females compared to males.

Research on gender differences in physical pain perception tend to show that, compared to males, females have lower pain thresholds, higher pain ratings and reduced tolerance for painful stimuli (31). Considering this, one might expect clearer somatic symptoms such as stiffness and tension to trigger more OTCA usage in females, as women might more easily find these symptoms painful. Nonetheless, our findings yielded the opposite result; “stiff or tense” was more closely related to OTCA usage in males than females. This could be explained by the fact that males seem to obtain a greater analgesic effect from OTCA than females (32), thus making them turn more easily to analgesics for somatic complaints.

That OTCA are less effective in reducing physical pain in females than in males, while females are highly overrepresented among high-frequency OTCA users, makes it even more pivotal to gain more information on potential off-label usage across genders. A study by Vangelisti et al. (56) sought to assess gender differences in social pain experiences in response to ibuprofen. sought to assess gender differences in social pain experiences in response to ibuprofen. Results revealed that female participants in the ibuprofen group reported reduced social pain on several tasks, while males in the same group exhibited the opposite pattern: the ibuprofen group experienced more social pain than the control group. If the ibuprofen’s effect on social pain was mainly physiological, we would expect to see a greater effect in the male group, and not the other way around. The researchers therefore suggested that their results had to have a social cognitive explanation: ibuprofen reduced females’ sensitivity to social pain due to its pain-relieving effects, while it disrupted males’ natural inclination to suppress emotional pain. If, indeed, OTCA make females feel better, and males feel worse, at least when it comes to the social aspects of pain, this could help explain why OTCA usage is much more common among females. However, our results showed that sleep problems and feelings of hopelessness were more closely related to OTCA usage in females than males, while the rest of the AD symptoms, including feelings of loneliness, showed no difference.

Though it is compelling to dwell on the highlighted disparities between the gender-specific networks in our study, it is worth noting that the observed differences were relatively small. A visual inspection of the two networks revealed that the associations’ structure and strength did not differ greatly. Given the highlighted research on gender differences, one might wonder why the observed connections were not even more pronounced in females compared to males. It is plausible that this can be ascribed to females experiencing more pain than males, resulting in increased OTCA usage, while the proportion of off-label usage remains similar between the two groups. More studies like Vangelisti’s, with strict designs and randomization into groups, should be carried out to gain more information on how OTCA directly influence different emotional, social and cognitive factors across genders.

Strengths, Limitations and Implications for Future Research

To our knowledge, the current study is to date the only network analysis assessing OTCA usage and AD symptoms in adolescents. The sample was population-wide and thus representative of adolescents in Norway. Another strength of this study was its focus on the individual symptoms of anxiety and depression, rather than diagnostic categories. This approach allowed for a more detailed examination of specific symptoms that might be particularly central in explaining the association between AD and OTCA usage in adolescents, and across genders. Including even more symptoms in the network, such as all 58 items from the original HSCL (34), could provide us with an even more comprehensive and nuanced understanding of which symptoms, and groups of symptoms, are most central in explaining off-label OTCA usage among adolescents.

In the current study, conducted on Norwegian adolescents, it is reasonable to assume that OTCA usage primarily comprises paracetamol (acetaminophen) and ibuprofen. However, exploring other pain relievers containing different active ingredients, not restricted solely to OTCA, would provide more valuable insights as to how analgesics relate to psychological and physiological pain across genders. For instance, existing research suggests that the gender differences in the effects of morphine are more pronounced than those observed with OTCA (57).

As our research indicates a gender difference in on- and off-label OTCA usage in certain specific domains among adolescents, it should be of high priority to further investigate and gain a deeper understanding of how these differences manifest in their daily lives. This knowledge could potentially contribute to reducing unnecessary and frequent use of OTCA. Moreover, it would be intriguing to compare various subgroups within the population, such as high-frequency versus low-frequency OTCA users and those with many AD symptoms versus those with few. Further, measuring OTCA usage over time and in controlled settings, would provide a more comprehensive understanding of the complex relationship between OTCA usage and AD symptoms.

Our research provides an extensive examination of the complex interplay between OTCA usage and distinct symptoms of anxiety and depression in adolescents. OTCA usage was most strongly associated with on-label symptoms, such as headache, neck and shoulder pain, muscle and joint pain and abdominal pain. However, OTCA usage was also associated with AD symptoms. Most prominent were the associations with sleep problems, stiffness and tension, feeling that everything is a struggle, and feeling suddenly scared for no reason. Symptoms marked by somatic manifestations of AD exhibited more robust associations with OTCA usage compared to conventional AD symptoms. This was even more pronounced in the male network compared to the female, though the disparities were somewhat modest, and the overall pattern remained consistent. Thus, to identify excessive off-label OTCA usage among adolescents, our findings suggest that it could be wise to be more aware of sleep issues and tension as opposed to emotional problems.

OTCA: Over-the-counter analgesics

AD: Anxiety and depression

HSCL: Hopkins Symptom Checklist

GGM: Gaussian Graphical Models

BEI: Bridge Expected Influence

Ethics approval and consent to participate.

The study was approved by the ethical committer of NSD, Norwegian Centre for Research Data (reference number: 821474). The young people were informed that participation was voluntary, and parents were informed at least 2 weeks prior to the study and could contact the school if they wanted to reserve their child from participation. The use of informed consent to participate was waived and approved by the The Norwegian National Committee for Research Ethics in the Social Sciences and the Humanities (NESH) (reference number: 2021/121). Accessing the data for the present analyses did not require additional ethics approval.

Availability of data and materials

The datasets analyzed during the current study are not publicly available due to lack of consent to sharing individual data. Meta data is available from the corresponding Young Data Survey on reasonable request. Data and material are stored at Oslo Metropolitan University P.O. Box 4, St. Olavs plass. N-0130 OSLO, Norway.

Competing interests

ERS, SK, BK, SS, MA and RJ declare that they have no competing interests.

Funding

The Young Data Survey is funded over the national budget in Norway.

Authors' contributions

All authors (ERS, SK, BK, SS, MA and RJ) provided substantial contributions to the conception and design of the work. The data acquisition was done by ERS and SK. Statistical analyses and interpretations of data for the work were done by ERS, SK, BK and RJ. All authors contributed in drafting the work and reviewed it critically for important intellectual content and approved the final version for publication. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgements

We want to thank all the young people that used their time to answer the survey, and Senior Researcher Anders Bakken at the section for Youth Research at Norwegian Social Research (NOVA) for providing access and guidance on the Young data survey.

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No competing interests reported.

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Associations Between Over-the-Counter Analgesics Usage and Symptoms of Anxiety and Depression in Adolescents: A Network Analysis

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Abstract

Background

Method

Results

Conclusion

Figures

Background

Method

Sample Collection

Assessments

Results

Sample Characteristics

Associations between OTCA Usage and AD Symptoms

Bridge expected influence for Network 2

Gender Differences

Accuracy and Stability Checks

Discussion

Psychological Features of Anxiety and Depression Showed Weaker Links to OTCA

On-Label Symptoms were Most Prominently Related to OTCA Usage

Social Pain as a Possible Mediating Factor

Males Showed Stronger Relations between Somatic Symptoms and OTCA Usage

Strengths, Limitations and Implications for Future Research

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

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Version 1