Insights Into Adherence and Attitudes toward Medication In Child And Adolescent Psychiatry: The Influence Of Patient And Medication-Related Factors

doi:10.21203/rs.3.rs-4339327/v1

This study aimed to investigate the impact of perception on adherence and determine the influence of patient- and medication-related factors on both adherence and attitudes toward medication in adolescents with psychiatric disorders receiving medication. The Pediatric Medication Adherence Scale (PMAS)- 9 questions and the Pediatric Attitude toward Medication Scale (PAMS)- 18 questions, two reliable self-report scales designed for this population, were used to assess negative adherence behaviors and patients' perceptions of medication. Data were collected from a sample of adolescents (12-18 years) undergoing psychotropics for 2 months. Statistical analysis was conducted to examine correlations between adherence, attitudes, and patient characteristics. The scales were administered to 288 patients (67% female) and significant correlations were found between anxiety scores and attitudes toward medication (p<0.05). Patients receiving monotherapy showed lower anxiety scores and more positive attitudes (p<0.05). Side effects were associated with reduced adherence and negative attitudes. Patients diagnosed with an eating disorder had more negative attitudes, while those using antidepressant-antipsychotic combinations had more negative attitudes compared to stimulants. This study highlights the importance of considering influential factors in medication adherence and attitudes in clinical practice for adolescents with psychiatric disorders. Addressing anxiety perception, managing side effects, and evaluating polypharmacy were found important for pharmacotherapy optimization.

Adherence is defined as the extent to which an individual complies with prescriptions, such as taking the medication regularly, following a diet plan or implementing other lifestyle changes (1). Non-adherence to medication may lead to a prolonged duration of illness, more frequent clinic visits, uncontrolled clinical symptoms, unnecessary hospitalizations, and increased costs (2). Effective treatments for psychiatric disorders are described as those with the most appropriate use of medication; however, there is a significant difference between intended and actual treatment and this is a major worldwide problem (3). Children with chronic disease experience more difficulties in treatment adherence, such as lifestyle changes and disease acceptance, compared to adults. Poor medication adherence may prevent patients from accessing optimal treatment, especially in the treatment of psychiatric disorders. Beliefs about the disease being treated and the effects of medications can influence decisions about medication use (4).

Non-adherence to treatment can occur intentionally or unintentionally and can be influenced by various factors categorized as medical, individual, and social. Negative factors may lead to concerns about long-term consequences, such as drug addiction and reduced life expectancy. A lack of knowledge about treatment and medication, as well as concerns about the future, have also been associated with medication non-adherence. Other factors that can affect patient adherence include their level of knowledge, the complexity of drug use in relation to their daily routines, their approaches and perspectives towards treatment, their mental health status, the possibility of taking multiple medications, the frequency of medication usage, and the occurrence of side effects (5-7).

Despite the significant attention required by individuals with psychiatric disorders who take psychotropics, the current literature on medication use in this population remains limited. Nevertheless, enhancing medication adherence and improving medication attitudes are crucial goals to address their unique needs and challenges. While some studies indicate that medication attitudes may not be associated with adherence (8, 9), others suggest that attitudes play a crucial role in determining adherence (10).

Two reliable and valid self-report scales, namely the Pediatric Medication Adherence Scale (PMAS) and the Pediatric Attitudes toward Medication Scale (PAMS), were specifically designed for adolescents with psychiatric disorders who are undergoing medication treatment. The PMAS aimed to evaluate negative adherence behaviors, while the PAMS focused on capturing patients' perceptions of medication(11). Comprehensive data regarding medication adherence and attitudes among the patients were gathered by administering these scales. The main purpose of this study is to evaluate the effect of medication attitudes on treatment adherence in adolescents with psychiatric disorders and receiving medication treatment and to determine the effect of patient and medication-related factors on both adherence and attitudes towards medication use.

The study was conducted as a cross-sectional survey at a university hospital's child and adolescent psychiatry outpatient clinic, with approval from the local Ethics Committee. The study's inclusion criteria were explained to patients, and informed consent was obtained from both patients and parents. Both PMAS and PAMS, 5-point Likert self-report scales, were applied to patients by a clinical pharmacist independent from their families.

Patients between the ages of 12 and 18, who were diagnosed with a psychiatric disorder, had been taking medication for at least two months, and had the ability to read and write were eligible for participation during the study period (December 2021 to April 2022). Individuals with physical or mental disabilities, including autism spectrum disorder and mental retardation, were excluded from the study.

Data on the patients' demographics, including gender, age, primary diagnoses (coded according to the International Classification of Diseases- ICD-10), time of diagnosis and treatment onset, current medication were gathered from the hospital information management system.

The validity and reliability of both the PMAS (9 questions) and PAMS (18 questions consist of necessity and concern factors) were well established in the pediatric population. The validity of the scales was assessed using content validity index and exploratory factor analysis. To determine the reliability of the scales, Cronbach's alpha and test-retest (scales were applied again in 2-4 weeks) methods were used. Cronbach’s alpha values and intraclass correlation coefficients for test-retest exceeding 0.7 for each scale. Thus, the PMAS and PAMS have found with high reliability and validity values according to the literature (11).

This study examined the correlations between the PMAS and PAMS and demographic variables using parametric and non-parametric analyses. Specifically, Pearson's correlation test was utilized to investigate the relationship between PMAS and PAMS scores and the patient's age, duration of diagnosis, duration of medication use, number of medications. The Kruskal-Wallis test was applied to determine the association between PMAS and PAMS scores with primary disease diagnoses and medication groups due to the variable and small sample sizes (n<30). Bonferroni-corrected Mann-Whitney U tests were then conducted for pairwise comparisons. Additionally, Student's t-test was used to compare scale scores across gender, side effects (present/absent), adolescent age groups (early vs. middle-late adolescents), and number of medications [monotherapy vs. polypharmacy (≥2 drugs)]. All statistical analyses were performed using IBM SPSS Statistics 23.0, and a significance level of p<0.05 was established for all tests.

In the study period, 288 patients completed the scales. Most patients were female (67%) with a mean age of 15.25 years. The median time since diagnosis was 12 months and median duration of drug usage was 27.42 months. Additionally, 55.56% of the patients used a single medication and 1.46 drugs were prescribed per patient (Table 1). Moreover, 28.13% of the patients were experienced side effects. A total of 107 side effects were reported, with an average of 1.32 side effects per patient. Among them, the most commonly observed side effect was drowsiness (25.24%).

Table 1. Descriptive parameters of patients (n=288)

Age (years), mean (standart deviation)		15.25 (1.59)
Duration of diagnoses (months), median (range)		12 (2-120)
Duration of medication use (months), median (range)		27.42 (2-120)
Stages of adolescents, n (%)	Early adolescence (12-14 years)	110 (38.19)
	Mid-late adolescence (15-18 years)	178 (61.81)
Sex, n (%)	Male	95 (33.0)
	Female	193 (67.0)
Number of medications, n (%)	1	160 (55.56)
	≥2	128 (44.44)
Presence of side effect, n (%)	Yes	81 (28.13)
	No	185 (64.24)
	Unknown	22 (7.64)

Among the patients included in the study, the majority of them were diagnosed with hyperkinetic disorders (adhd?) (n=119; 30.13%), anxiety disorders (n=100; 25.32%), depressive episodes (n=87; 22.03%), eating disorder (n=33; 8.35%) followed by obsessive-compulsive disorder (n=23; 5.82%) as their primary psychiatric diagnoses. Upon analyzing the groups of medications used by the patients, it was determined that the patient mostly use antidepressants (34.72%) followed by antidepressant - antipsychotic combinations (21.53%), stimulants (20.14%), and stimulants-antipsychotic combinations (8.68%). Regarding the specific medications utilized, the most commonly prescribed antidepressant was sertraline (n=112; 26.60%), antipsychotic was risperidone (n=46; 10.93%), and psychostimulant was methylphenidate (n=105; 24.94%) (Table 2).

Table 2. Drug Groups and Medications Used by Patients (n=288).

Classes of Medications	Medications	n (%)
Antidepressant	Sertraline	112 (26.60)
	Fluoxetine	68 (16.15)
	Escitalopram	8 (1.90)
	Venlafaxine	7 (1.66)
Antipsychotic	Risperidone	46 (10.93)
	Aripiprazole	38 (9.03)
	Quetiapine	12 (2.85)
	Olanzapine	8 (1.90)
	Haloperidol	3 (0.71)
Psychostimulant	Methylphenidate	105 (24.94)
Psychostimulant	Atomoxetine	9 (2.14)
Anxiolytic	Alprazolam	3 (0.71)
	Medazepam	1 (0.24)
	Hydroxyzine	1 (0.24)
TOTAL		421 (100.00)

PMAS and PAMS Scores Associations Between Descriptive Parameters

Despite the observed significant correlation between the scores of PMAS and PAMS, it is important to note that the Pearson correlation coefficient indicates a weak relation between the two variables. However, the total score of the PAMS exhibits a noteworthy correlation with both the necessity and concern scores (Table 3). The patients were categorized into two groups based on their age either early or mid-late adolescence. The PMAS and PAMS scores did not indicate any significant difference between the two groups (p>0.05). However, the PMAS score tended to increase with increasing anxiety scores and negative approaches to drug treatment as age increased. Although this association was statistically significant, the correlation was found weak. When comparing scale scores based on gender, there was a significant difference observed in the total PAMS score and anxiety dimension scores (p<0.01). Women had higher mean (standard deviation, SD) total PAMS scores [2.51 (0.69)] and anxiety scores [2.77 (0.92)] than men [2.25 (0.60) and 2.31 (0.80), respectively] (p<0.05).

Table 3. Correlation coefficients of Pediatric Medication Adherence Scale and Pediatric Attitudes toward Medication Scale scores

Scales (n=288)	PMAS	PAMS-N	PAMS-C	PAMS-T
PMAS	1	0,332**	-0,206**	-0,326**
PAMS-N	0,332**	1	-0,124*	-0,571**
PAMS-C	-0,206**	-0,124*	1	0,886**
PAMS-T	-0,326**	-0,571**	0,886**	1

* Correlation is significant at the 0.05 level. ** Correlation is significant at the 0.01 level, PAMS-C: Pediatric Attitudes toward Medication Scale-Concern, PAMS-N: Pediatric Attitudes toward Medication Scale-Necessity, PAMS-T: Pediatric Attitudes toward Medication Scale-Total, PMAS: Pediatric Medication Adherence Scale.

Patients' observation of side effects was significantly negatively correlated with the PMAS scores (p<0.05). Furthermore, presence of side effects was significantly and positively correlated with anxiety and PAMS total scores (p<0.05). Although no significant correlation was found with the number of medications, the PAMS total scores [monotherapy vs. polypharmacy; 2.33 (0.66) and 2.54 (0.67), respectively] and concern scores [monotherapy vs. polypharmacy; 2.46 (0.88) and 2.82 (0.90), respectively] of patients who received monotherapy were significantly lower than those who received more than one medication (p<0.01). However, there was no significant correlation with adherence and necessity scores (p=0.067).

Significant differences were observed among the PAMS scores of patients with different primary psychiatric diagnoses, indicating that there were variations between the groups (p<0.05). Specifically, significant differences were found between hyperkinetic disorders-eating disorders and eating disorders-obsessive-compulsive disorder and PAMS scores. This indicates that patients diagnosed with eating disorders showed a more negative attitude towards drug treatment compared to patients diagnosed with hyperkinetic disorder and obsessive-compulsive disorder. Moreover, patients with eating disorders revealed greater anxiety in approaching medication compared to those with hyperkinetic disorders (p=0.028). However, no significant difference was detected between the adherence scores of patients with different primary diagnoses (p>0.05).

This study analyzed the association between drug combination types of patients and their PMAS, PAMS, and relevant factors. The results revealed that patients taking an antidepressant-antipsychotic combination (n=62) showed significantly higher PMAS scale scores than those solely taking stimulants (n=58) (p<0.005). Furthermore, the group receiving the drug combination also demonstrated higher anxiety scores (p<0.001) (Figure 1).

This study with a large sample size investigated the association between the descriptive characteristics of adolescents with psychiatric diagnoses with the use of psychotropics, and the examination of the relationship with the scales of adherence and attitudes toward medication specifically developed for this vulnerable population. Thus, the findings of this study have important implications for improving our understanding of the factors that contribute to adherence to medication regimens and attitudes towards treatment.

Psychotropic drugs have side effects that may affect many patients, but considering that the pediatric population is more susceptible to side effects (12, 13). In our study, the researchers examined how side effects impact medication adherence in pediatric patients and found that patients who experienced side effects (28.13%) had lower adherence to medication (p<0.05) and were more likely to have concerns about their medication and negative attitudes towards treatment (p<0.05). These results suggest that the presence of side effects was found to have a negative impact on medication adherence, increase the level of concern. Other studies have also reported that side effects can be a potential barrier to medication use and adherence (6, 14). Rapid weight gain was related with non-adherence, and adolescents who reported side effects were three times more likely to be non-adherent compared to those who did not report side effects. However, these studies are not specific to a particular drug group (15).

Different disease groups and medications can affect the behavior of adherence and attitudes towards medication. For example, in a validation study of Medication Adherence Report Scale (MARS) conducted in different chronic disease groups among adults, a significant positive correlation was found between Beliefs about Medicines Questionnaire (BMQ) Necessity scores and MARS scores in asthmatic patients. This indicates that patients who perceive medication as necessary have higher adherence scores, but this correlation was not significant for the diabetes group in the same study. Higher anxiety scores were found to be related with lower adherence in both patients with asthma and diabetes (16). Psychiatric disorders were evaluated, and patients with an eating disorder had more negative attitudes compared to patients diagnosed with attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (p<0.05). Patients with an eating disorder also had higher anxiety scores than those diagnosed with ADHD (p<0.05). However, no significant difference was found in PAMS scale scores among patients with different primary diagnoses. Ferrin et al. did not note the specific relationship between negative attitudes towards treatment and different comorbidities or clinical conditions related to ADHD (17). Hodgkins et al. reported that patients with comorbid diagnoses of ADHD are more likely to change treatment, which could increase the risk of non-adherence (18).

In our study, the most commonly used drug groups were noted to be combination of antidepressants and antipsychotics. Patients using a combination of antidepressant and antipsychotic drugs had significantly higher PAMS and anxiety scores than those using only stimulants (p<0.001). However, no significant difference was observed in PMAS scores. Although the relationship between type of medication and attitude towards medication could not be observed in previous studies, some studies stressed the effect of adherence and prescribed medication. A study evaluated the continuity of treatment in patients using selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors reported a significantly higher likelihood of continuing treatment compared to patients treated with tricyclic antidepressants and older antidepressant drugs. Additionally, the significant effects of antidepressant selection on medication discontinuation was detected not in the first month but in the second month of the treatment (19). In another study, starting treatment with quetiapine was found to be associated with early treatment discontinuation (12). The analysis revealed that there was no significant relationship between psychotropic drug groups and adherence. However, in a study involving patients with ADHD who were receiving medication, it was found that only the use of long-acting methylphenidate was related with adherence (15). Another study reported that patients with comorbid ADHD and major depressive disorder who were prescribed psychostimulants were less likely to have adherence problems. (20).

In our study, it was expected that the concern and necessity scores would show a strong correlation with adherence scores. However, the correlations were found to be weak even though they were statistically significant. Townsend et al. also assessed similar results, wherein positive attitudes among youths displayed a statistically significant, in spite of weak, positive correlation with adherence (9).

Within the context of this vulnerable population during the developmental stage, the identification and assessment of attitudes towards treatment play a crucial role in enhancing the prediction of adherence while reducing instances of non-adherence and negative attitudes towards the treatment. Such evaluations are extremely important for optimizing the effectiveness of pharmacotherapy, minimizing potential side effects, and preventing disease recurrence. As a result, various recommendations and interventions have been proposed by different studies. For example, Floersch et al. identified that adolescents aged 12-17 years who take psychotropic drugs want to know the reasons for taking medication, its effects and side effects, as well as how to administer it (21). Charch et al. suggested that involving adolescents in the treatment process and taking into account the information obtained from them when making clinical decisions could potentially improve the continuity of ADHD treatment (22). Due to changes in adolescents' awareness of mental and social development, clinicians have recommended that necessary information about medications and the treatment process should be provided to these patients and that they should be included in the treatment process (23). It has demonstrated the effectiveness of motivational interviews in improving adherence rates (8). Additionally, the utilization of telehealth programs, which have become more prevalent with the advancement of technology, has also been shown to be favorable in enhancing adherence (24). Therefore, technological applications or electronic journals, and reminders can be useful for both parents and pediatric patients to track treatment progress.

Limitations

Although all patients in the study had a psychiatric diagnosis, a specific primary diagnosis was not established. The distribution of patients across primary disease groups or drug classes was not equally balanced, with some groups having fewer patients than others. Therefore, when comparing the scores of scales according to these classifications, a larger sample size with an equal number of patients in each disease group would have led to a more accurate interpretation.

Considering the obtained results, clinicians should prioritize parameters that can impact adherence and attitudes toward medication, specifically anxiety perception, the presence of side effects, and polypharmacy. Providing comprehensive education to both patients and parents regarding psychiatric diagnosis and psychotropics, as well as encouraging active participation in the treatment process, may improve their attitudes toward medication and increase adherence.

Attitudes, and adherence can be influenced by many factors and can change over the time. It is necessary to identify patient and medication related factors and conduct larger, multicenter, long-term studies with adolescents and their parents’ follow-up to determine which interventions may be beneficial.

Competing interests

The authors declare no competing interests.

Ethical declarations

This study was approved by the local Ethics Committee. Informed consent was obtained from both patients and parents for this study.

Funding

Not applicable.

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No competing interests reported.

Insights Into Adherence and Attitudes toward Medication In Child And Adolescent Psychiatry: The Influence Of Patient And Medication-Related Factors

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Abstract

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Discussion

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