Prescription patterns and medication adherence in preadolescent children with attention deficit hyperactivity disorder.

BACKGROUND: Nonadherence in attention deficit hyperactivity disorder (ADHD) can be as high as 80%, yet studies on adherence to medications in preadolescent children are few. Recent Indian trends in prescription patterns are lacking. AIM: The present study assesses prescription patterns and adherence to medications in preadolescent children with ADHD.
MATERIALS AND METHODS: Fifty children aged 5-12 years with ADHD, who were on medications for at least 6 months, were enrolled. Their sociodemographic factors and prescription details were noted. Vanderbilt ADHD Diagnostic Parents Rating Scale and Compliance Rating Scale were administered.
RESULTS: Sixty-two percent of the children had good compliance, whereas 38% showed reluctance. Adherence was better in children with shorter duration of illness, lesser severity, absence of side effects, and stimulant prescription. Non-stimulant-based combination (40%) was more common compared to stimulants (28%), with atomoxetine and risperidone being the most commonly prescribed medications.
CONCLUSIONS: Adherence to medications in preadolescent children with ADHD is good. Associated factors and implications are discussed. Copyright:

INTRODUCTION

Management of attention deficit hyperactivity disorder (ADHD) is often challenging and includes pharmacotherapy, behavioral therapy, or a combination of these.[12] Pharmacotherapy has been shown to be successful in most patients and a variety of drugs are available for use.[3] Stimulants form the mainstay of pharmacotherapy for ADHD and have been shown to be the most commonly prescribed medications in children and adolescents overall.[45] Several non– stimulant medications are also available for ADHD such as atomoxetine, tricyclic antidepressants, antipsychotics, alpha-2 agonists, and anticonvulsants.[6] While stimulant monotherapy is preferred, a combination of medications may be warranted in severe cases or cases with comorbid conduct disorder (CD)/depression/anxiety.[3] Western literature has a volume of research on trends in prescription patterns of ADHD.[4] Indian data, however, in this aspect are characteristically lacking.

Despite such a variety of pharmacotherapy being available for ADHD, compliance to medications is a concerning issue.[1] Adherence being a multifaceted construct is difficult to define, especially in aspect of ADHD as often the responsibility of the medication is handled by the parent(s).[3] Indian data have generally reported adherence rates of 11.3%–16.7%, much lower than world literature (45%–80%).[789] Factors such as being lost to follow-up, cost of medications, fear of dependence, and stigma surrounding medications, all contribute to lower adherence rates in Indian data.[78] A recent single medical record study from the west has put adherence rates between 40% and 50% in children availing psychiatric services.[10] One of the main reasons for such a large variation in nonadherence rates has been due to variations in assessment of adherence, as no standard criteria are available for ADHD.[11] Studies on adherence have assessed compliance to their respective institute's protocols, number and duration to follow-up, pill refill time, and caregiver surveys, among others.[12]

Several factors such as age, gender, dosing, clinical profile, and parental beliefs have been shown to affect adherence.[113] Social factors overall have proven to have a major impact on adherence to ADHD medications.[8] Certain studies have found no impactful factor associated with adherence in ADHD.[14] It should be noted that majority of the literature available is on stimulant medications alone and other pharmacotherapeutic agents have been assessed sparingly.[1] In addition, majority of the data available are on adolescents with ADHD and research on preadolescent children is limited.[1] The present study was thus formulated to study the prescription patterns and adherence in preadolescent children with ADHD.

MATERIALS AND METHODS

The following cross-sectional observational study was conducted in the child guidance clinic of a tertiary care center in Mumbai over a period of 6 months. Ethical clearance was taken from the Institutional Ethics Committee. Fifty consecutive preadolescent children, diagnosed with ADHD as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, between the ages of 5 and 12 years and having been on at least 6 months pharmacotherapy, were enrolled. Children having comorbid medical illnesses such as seizure disorder, etc., and those with intellectual disability and learning disability were excluded. The nature of the study and procedure were explained to the parent and the child and a written informed consent was obtained from the parent and a written assent from the child. A semi-structured pro forma was designed and administered to evaluate sociodemographic factors, clinical profile, and prescription patterns. Clinical variables were extracted from the follow-up records of the patients. Vanderbilt ADHD Diagnostic Parents Rating Scale (VADPRS) was used to assess the severity of ADHD.[15] It contains 47 questions and gives inattention scores, hyperactivity scores, and a total severity score. In addition, it also assesses for comorbidities such as oppositional defiant disorder (ODD), CD, and emotional issues (EI).

Medications which the patient was currently on were noted and not the ones prescribed in the past. For the present study, adherence only to pharmacotherapy was included and the children who were taking medications for at least 80% of the duration of 6 months were defined as being adherent. This was determined after interviewing both parent and child. The level of adherence/nonadherence was subsequently scored using the Compliance Rating Scale (CRS), developed by Kemp et al.[16] It quantifies the clinician's assessment of the level of adherence shown by the patient on a seven point Likert scale. The scoring is as follows: 1 – complete refusal; 2 – partial refusal or accepts only minimum dose; 3 – accepts only because compulsory, or very reluctant/requires persuasion, or questions need often; 4 – occasional reluctance; 5 – passive acceptance; 6 – moderate participation, some knowledge and interest in medication and no prompting required; 7 – active participation, readily accepts, and shows some responsibility for regimen. Thus, higher scores would imply better adherence.

Statistical analysis

Statistical analysis was done using the Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corporation., New York, USA). Data were expressed as mean (standard deviation) for continuous variables and frequency (percentage) for categorical variables. Both univariate and multivariate analyses were undertaken to establish the association of variables with adherence. Pearson's correlation test and point biserial correlation test were performed for univariate correlation for continuous and dichotomous categorical variables, respectively. Linear regression was used for multivariate analysis to derive a statistically significant model. Correlation coefficient (r) and standardized coefficient (β) were used for effect size. P < 0.05 was considered statistically significant.

RESULTS

Mean age of the sample was 9.24 (2.24) years. Forty-three out of fifty subjects were male (86%), whereas the rest were females (14%), which yielded a male: female ratio of 6:1. Ninety-four percent of the samples (47 out of 50) belonged to Hindu families, 4% belonged to Muslim families, and one (2%) to a Christian family. Twenty six out of 50 (52%) belonged to an upper middle class family and the rest were from a lower middle class family. The mean age at onset of ADHD was 5.98 (1.81) years and the mean duration of illness in the sample was 3.22 (1.69) years. Overall severity score on the VADPRS was 64.52 (16.38), with scores on the inattention and hyperactivity domains to be 18.00 (4.07) and 18.58 (5.24), respectively. The most common comorbidity in the sample was ODD seen in 80% of the subjects (40 out of 50), followed by CD, which was seen in 56% of the subjects (28 out of 50). EIs such as depression and anxiety were seen in 24% of the sample (12 out of 50).

Majority of the subjects (52%) received combination therapy, whereas 48% were on monotherapy [Table 1]. The most common combination pattern in the sample was nonstimulant combination (40%). Out of the children receiving monotherapy, the stimulant prescription was more common as compared to nonstimulant (28% vs. 20%). Out of nonstimulants, atomoxetine and risperidone were the most commonly prescribed medications in the sample (50%), while methylphenidate was the only prescribed stimulant. Other drugs infrequently prescribed were aripiprazole (8%), imipramine (4%), and valproate (4%), mainly for their comorbidities. Seventeen out of 50 (34%) reported side effects such as insomnia, headache, excessive salivation, abdominal discomfort, and loss of appetite. Cyproheptadine was required in 5 out of 50 participants (10%) of our sample and trihexyphenidyl was prescribed to 12 participants (24%) for extrapyramidal side effects of antipsychotics.

Table 1

Prescription pattern and adherence in the sample

Factor	Distribution in the sample, n (%)
Prescription pattern
Monotherapy	24 (48)
Stimulant	14 (28)
Nonstimulant	10 (20)
Combination therapy	26 (52)
Stimulant-based combination	6 (12)
Nonstimulant-based combination	20 (40)
Adherence to medications
Complete refusal	0
Partial refusal	3 (6)
Reluctance	16 (32)
Passive acceptance	21 (42)
Moderate participation	8 (16)
Active participation	2 (4)
Medications prescribed
T. aripiprazole (2.5-5 mg)	4 (8)
T. atomoxetine (5-18 mg)	25 (50)
T. imipramine (5-25 mg)	2 (4)
T. methylphenidate (12.5-50 mg)	20 (40)
Syp. risperidone (0.25-1.5 mg)	20 (40)
T. risperidone (1-2 mg)	5 (10)
T. trihexyphenidyl (1-2 mg)	12 (24)
T. valproate (200-300 mg)	2 (4)

T – Tablet; Syp – Syrup

Sixty-two percent of children (31 out of 50) showed good compliance to medications and only 38% had reluctance to take medications. The mean score on CRS in the sample was 4.54 (1.27), which falls in the range of occasional reluctance to passive acceptance. According to the response generated on the CRS [Table 1], 42% of the sample had passive acceptance of the psychotropic medication being prescribed, followed by 20% who had very reluctant or requires persuasion type of adherence. About 4% showed active participation and none had complete refusal. As per univariate analysis [Table 2], duration of illness (r = −0.40, P = 0.004), history of side effects (r = −0.38, P = 0.007), and severity of illness (r = −0.24, P = 0.039) were significant factors. All three had a negative correlation with adherence, implying better adherence in children with a shorter illness, less severe and those who experienced lesser side effects. In the multivariate analysis, factors which were significant were stimulant prescription (β =0.34, P = 0.04) and presence of side effects (β = −0.44, P = 0.003). Stimulant-based prescriptions were associated with better adherence, whereas lesser side effects were associated with better adherence. The overall regression model was statistically significant (F = 3.99, P < 0.001) with adjusted R2 of 0.44. This implies that present factors being studied could contribute to 44% of variance in medication adherence. As per the effect sizes, duration of illness was the most significant factor, followed by side effects. Side effects had the largest effect size in the multivariate analysis, making it the most important predictor in the present analysis.

Table 2

Correlation of various factors and medication adherence

Variable	Distribution in the sample, mean (SD)/, n (%)	Univariate statistics		Multivariate statistics
		Coefficient of correlation (r)	Significance (P)	Standardized coefficient (β)	Significance (P)
Age	9.24 (2.23)	−0.11	0.44	3.61	0.11
Sex
Male	43 (86)	−0.13	0.38	−0.09	0.55
Female	7 (14)
Age of onset	5.98 (1.81)	0.25	0.09	−2.89	0.11
Duration of illness	3.22 (1.69)	−0.40	0.004*	−3.39	0.059
Presence of ODD
Present	40 (80)	−0.06	0.66	0.22	0.39
Absent	10 (20)
Presence of CD
Present	28 (56)	−0.20	0.17	−0.14	0.43
Absent	22 (44)
Presence of EI
Present	12 (24)	−0.21	0.15	−0.36	0.12
Absent	38 (76)
Severity of ADHD	64.52 (16.38)	−0.24	0.039*	0.33	0.54
Inattention scores	18.00 (4.07)	−0.26	0.06	−0.25	0.40
Hyperactivity scores	18.58 (5.24)	−0.13	0.39	−0.39	0.21
Stimulant prescription
Present	20 (40)	0.17	0.24	0.34	0.04*
Absent	30 (60)
Combination/monotherapy
Monotherapy	24 (48)	0.03	0.83	0.15	0.29
Combination therapy	26 (52)
History of side-effects
Present	17 (34)	−0.38	0.007*	−0.44	0.003*
Absent	33 (66)

*Indicates statistically significant. ODD – Oppositional defiant disorder; CD – Conduct disorder; EI – Emotional issues; ADHD – Attention deficit hyperactivity disorder

DISCUSSION

Adherence rate in the present analysis was 62%, out of which 20% had moderate-to-full active participation, while majority of the children had passive acceptance (42%). This is higher than most reported rates in Indian literature[78] and comparable to the ones reported in the world literature (40%–60%).[1017] Preadolescent children with ADHD have shown to have better adherence than adolescents, which has been attributed to the change seen in adolescents regarding their belief systems, questioning every decision and transitioning to take control over their lives.[3] Majority of the children (42%) had passive acceptance to their prescribed medications. Children are often passive recipients of treatments being planned for them by the clinician–parent dyad; though this practice is being reformed to allocate a more active role to the child in his/her treatment.[18] Experiencing adverse effects following medication was the most important factor associated with poor adherence as it is was significant in both the univariate and multivariate analyses. Experiencing physical and psychological side effects of medications has been shown to be associated with poor adherence and our findings support the same.[1920] Risk-benefit analysis of drugs such as methylphenidate and atomoxetine have highlighted that benefits outweigh the risks and caution needs to be ensured in high-risk groups, especially as our analysis highlights that this may be associated with nonadherence.[19]

Stimulant prescription in ADHD has been unanimously associated with better adherence and our findings show the same.[21] This is despite the fact that stimulants were prescribed lesser than atomoxetine and risperidone in our sample. This is in contrast to most Western literature, wherein up to 90% of patients with ADHD receive stimulants.[22] It has been however highlighted that, despite a comparable prevalence of ADHD across the globe, prescription patterns show considerable variations.[23] Augmentation of first-line drugs in ADHD has been shown to be on a rise,[24] and our analysis shows similar trends, with risperidone being used in 50% of the patients for augmentation. Atomoxetine is known to be more cost effective than methylphenidate, though equally effective.[25] As our sample constituted only upper and lower middle class, it would explain its relatively higher prescription rate. Other important factors for adherence in our study were children with shorter duration of illness and lesser severity. Contrarily, greater symptom severity predicts a more robust response and is shown to motivate patients to stay in treatment.[3] The duration of follow-up was less for our study, and hence to comment on its relation with adherence is difficult.

Limitations and strengths

The present study had certain limitations. Our sample size was relatively small which affected many associations in our study. Factors such as comorbidities, age, and inattention/hyperactivity scores, which have been shown to correlate with adherence, did not come significant in our analysis. Many of the social factors were not assessed in the present analysis, which could explain the weak associations in our findings. A few strengths of our study include the use of a novel method of adherence assessment in children, focus on preadolescent children, and highlighting prescription trends missing from recent Indian literature.

CONCLUSIONS AND FUTURE DIRECTIONS

Our findings conclude that overall adherence to medication is good in preadolescent ADHD children (62%), with majority having passive acceptance. A significant number of children (20%) actively participate in treatment process, which calls for measures to involve the children in their treatment decisions and compliance. Development of adverse effects to medications is the most important factor associated with nonadherence, and hence they must be actively screened on follow-up. The use of stimulants should be encouraged, even in preadolescent age group, as it is associated with better adherence. Clinicians should encourage the involvement of the child in making decisions regarding their treatment and discuss possible adverse effects and long-term consequences.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.