This section highlights how continuous revision of grammar, sentence structures, synergy between narrative and data, and overall cohesiveness completes a satisfactory research paper. Moreover, the importance of citing sources correctly was also emphasized in this written piece. In light of pharmacotherapy usage as treatment for Autism Spectrum Disorder (ASD), this research paper aims to compare Aripiprazole or Risperidone to find which of the two is most tolerable and safer in terms of its side effects for both children and adolescents suffering from ASD.
Original:
Introduction
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized through undermined social interaction and communication as well as restricted and repetitive patterns of behaviors. It is a disorder that transcends ethnic, racial, and even economic boundaries across the globe. According to the American Psychiatric Association, ASD affects one (1) in fifty-nine (59) children and is often diagnosed at early developmental stages. A child’s likability of having ASD can be attributed to diverse factors such as environmental, biologic and genetic considerations. Unfortunately, there are no current vaccines or cure for ASD. However, there are available treatment options to control and alleviate symptoms of ASD and its associated medical conditions. Pharmacotherapy or the use of medications is one of the widely known methods used by medical professionals to accommodate ASD behavioral symptoms. The Food and Drug Administration (FDA) have not yet approved psychopharmacologic drugs that specifically target core symptoms of ASD. But atypical antipsychotic drugs such as aripiprazole and risperidone are FDA-approved for the treatment of irritability and aggression in children and adolescents with autistic disorder. Both medications have been proven to be effective and tolerable in minimizing behavioral disturbances and further improving the ability of individuals with ASD to adapt to their surroundings. Nevertheless, the increase in atypical antipsychotic medications usage among children and adolescents with ASD subsequently heightens the concern for the adverse effects that these drug treatments can have on these individuals. Several studies conducted with regards to the efficacy and tolerability of aripiprazole and risperidone denoted little to no significant differences in the treatment of ASD symptoms but demonstrated crucial distinctions in terms of each drug’s side effects. All research papers utilized a variety of methods to create an in-depth analysis of these medications and their side effects which included the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification as well as the Aberrant Behavior Checklist (ABC) and Clinical Global Impression (CGI) scales through which they accurately assess psychiatric symptoms, behavioral problems of individuals with ASD, and the severity of each ASD patient. With these in mind, a detailed inquiry and analysis in which drug, aripiprazole and risperidone, is most tolerable and safer in terms of side effects for children and adolescents with autism was performed.
Methods
A statistical analysis was carried out by Dr. Hesapcioglu involving 309 patients between ages 9 to 15 at the Child and Adolescent Psychiatry Department clinic of Ankara Yildirim Beyazit University, diagnosed with ASD according to DSM-5 classification and having ABC and CGI scale scores in hospital records. Of the 309 patients, 168 of them were treated with antipsychotics such as risperidone, olanzapine and aripiprazole prior to the study. From this subset, 42 risperidone and 40 aripiprazole related patients fulfilled the study’s calculated inclusion criterion of 50-200 mg/day chlorpromazine equivalences of the drugs’ dosage following at least eight (8) weeks of treatment. Therefore, an analysis was conducted using these patients. If scales used to assess ASD reported missing data, then such cases were excluded from the study. Otherwise, all of the selected patients of the study were monitored at the baseline and on the eighth week of treatment.
Data on the side effects of the drugs when compared were evaluated and obtained using the Udvalg für Kliniske Undersogelser (UKU) Side Effect Rating Scale. According to the study, UKU “assesses psychotropic treatment side effects and divides them into the ‘psychic, neurologic, autonomic, and other’ categories. The extent of the side effect is scored between 0 and 3.” (Hesapcioglu et al., 2020). It consisted of 48 individual side effects commonly associated with the drugs. This data was analyzed with the use of SPSS software which compared the drugs via the Chi Square Test, after which, pairwise comparisons were also filtered between groups. The results obtained were then compiled in a table.
By the same token, Dr. Ahmad Ghanizadeh also conducted a statistical analysis in an attempt to have a head to head comparison between aripiprazole and risperidone. The study involved 59 children and adolescents with ASD, who fulfilled the test criterion of not receiving aripiprazole and risperidone two (2) weeks prior to the trial and having no marked changes in concurrent medications. The participants were then randomly assigned to each drug group and given varying amounts of aripiprazole and risperidone for a period of two (2) months to account for clinical efficacy and adverse side effects of each drug. However, the maximum dose possible for children under 40 kg was 2 mg for risperidone and 10 mg for aripiprazole while 3 mg and 40 mg respectively for children above 40 kg. Although the primary outcome of the study was the irritability subscale score from the ABC scale, emphasis was made on the side effects. The side effects were systematically examined and assessed using a checklist fabricated by the researchers which considered weight, height, and blood pressure. (Ghanizadeh, Sahraeizadeh and Berk)
According to the study “The children were assessed three times, including at baseline, 1 month after the onset of intervention, and 2 months after the onset of intervention (Endpoint) using all of the questionnaires and checklists” (Ghanizadeh, Sahraeizadeh and Berk). As with the previous statistical analysis by Dr. Hesapcioglu, side effects in this research were also compared with the SPSS software through the Chi Square Test, whenever applicable.
On the other hand, a meta-analysis carried out by Dr. David Cohen resulted in a search and study selection that produced 128 potentially relevant publications relating to the drug’s side effects. This was eventually narrowed down to 8 important studies among children and adolescents having refined their word choices and key terms from the Medline and EMBASE databases, from which the analysis was conducted. The researchers extracted relevant data independently and were then compared to ensure accuracy. Missing data were left out rather than finding replacement values. In order to assess the quality of the adverse side effect reportings of the drugs, researchers of the study constructed their own following score: “a point when detailed data were given (meaning for continuous variables mean and standard deviation) and 0 when data were incomplete or absent; the adverse effect quality score (AEQS) was the sum. It could range from 1 to 13” (Cohen et al., 2013). Mean changes were examined during each trial for variables that were reported the largest amongst the studies. The data was analyzed using a Bayesian method to keep the maximum amount of information in the meta-analysis. A logistic regression model was used as all data were binary outcome variables. The Bayesian model was implemented using WinBUGS version 1.4 (Cohen et al., 2013).
Results
All tables and figures are included in the original pdf file submitted.
Discussion
According to the results obtained by the head to head study carried out on the efficacy and tolerability of aripiprazole and risperidone by Dr. Ghanizadeh Ahmad as seen in figure two, “no significant difference was observed between the two groups regarding the rate of adverse effects.” (Ghanizadeh, Sahraeizadeh and Berk), since the percentage of the side effects were more or less the same for both drugs and neither shared a stark deviation from one another for a side effect to be uniquely associated with either drug. However, the data from the study suggests that the most common side effects between aripiprazole and risperidone included drooling (31.0% vs 40.0%) increased appetite (34.5% vs 40.0%) and drowsiness (20.7% vs 16.7%) respectively (Ghanizadeh, Sahraeizadeh and Berk). It should be noted that this study did not cover weight gain and extrapyramidal side effects (EPS) such as hypokinesia akinesia and akathisia under side effects.
However, the second statistical analysis carried out by Dr. Helma Hesapcioglu did. The study showed weight gain to be one of the most common side effects between risperidone and aripiprazole, but according to the study “ no statistically significant difference was found in weight gain between risperidone (19.0 %) and aripiprazole (37.5 %) in autistic children”(Hesapcioglu et al., 2020) therefore, the side effect was not as pronounced in one drug as compared to the other. Furthermore, the study also incorporated another study that focused primarily on the body mass index (BMI) gains for both drugs in adolescents and although a significant BMI was noticed between the two drugs, statistically speaking “ there was no significant difference in BMI change when the two treatment groups were compared”(Hesapcioglu et al., 2020). This suggests that anti -psychotic-induced weight gain may result in a high risk of cardiovascular diseases and diabetes as table 3 might suggest.
In addition, drowsiness was also a noticeable side effect between the two drugs, similar to the findings reported by Dr. Ahmad in his statistical analysis. According to table 2, 42.5% patients reported feeling tired when using aripiprazole compared to 9.5% of patients using risperidone (Hesapcioglu et al., 2020). Coincidentally, a near direct proportional relationship followed an increased duration of sleep, with 9.5% of patients reported an increase in sleep having used risperidone while 40.0% of patients reported having an increase in sleep having used aripiprazole. Unrest and lassitude follow the general pattern outlined in table 2. Surprisingly, constipation was a common side effect noticed in patients in the study, 10% in aripiprazole and 7.1% in risperidone, although it is hardly an adverse side effect (Hesapcioglu et al., 2020).
According to the study “ no significant difference was found in the neurological side effects between three antipsychotics” since their p values hardly differed by no more than 0.1 although an overdose of either drug is likely to increase the severity of EPS side effects. (Hesapcioglu et al., 2020). Having said that, the study had many limitations. Sample sizes were quite small and they also lacked a placebo whilst BMI and biochemical data were missing or difficult to obtain with the tools available.
Finally, a meta analysis by Dr. David Cohen provided meaningful insight into the side effects in support of the two statistical analyses and its data having analyzed eight independent studies. According to the study “somnolence/sedation effects were the most frequently reported adverse event in both drugs”, which is illustrated in figure two (Cohen et al., 2013) and given the odds ratio, there were no significant differences between active compounds. This was important to take into consideration as it can affect motor and learning abilities in children. The study also reported a significant increase in the amount of persons with weight gain having used both risperidone and aripiprazole as shown in figure one, although the odd ratios; aripiprazole (OR = 6.28 [1.64–17.12]) and risperidone (7.76 [1.88–25.2]) (Cohen et al., 2013) showed no significant differences between the two.
Moreover, the study also pointed out differences in the the metabolic content of individuals having used aripiprazole and risperidone, however due to a lack of hormonal data for risperidone in some studies a binary linear regression model was not possible, although risperidone has shown to increase the risk of hyperprolactinemia two times in female as compared to mael suffering from ASD (Cohen et al., 2013). With regards to EPS, the study noted that only risperidone increased the risk of EPS when compared to aripiprazole as illustrated in figure three, as the specificity of aripiprazole allows it to exhibit both dopamine receptors having agonist and antagonist properties (Cohen et al., 2013).
Conclusion
Countless research studies have determined the efficacy and tolerability of aripiprazole and risperidone as effective agents in controlling behavioral problems in children and adolescents with autism spectrum disorder. However, the persistent unease in the usage of pharmacotherapies in these individuals has undoubtedly prompted researchers to question its severity. The aim of this research paper was to determine which drug, aripiprazole or risperidone, were most tolerable and safer for children and adolescents battling from autism spectrum disorder. Thus, an in-depth comparison between atypical antipsychotics in terms of their adverse effects was performed. From the percentage perspective, some data suggest that one drug has lesser secondary effects than the other when considering factors such as weight gain, sleep duration, drowsiness, constipation, increased appetite, and so on. However contrary to what we believed in the beginning as well as the recorded data under the results and discussion section, all incorporated studies identified no statistically significant distinctions between the drugs that could suggest one is dominant than the other.
Revised:
Introduction
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized through undermined social interaction and communication as well as restricted and repetitive patterns of behaviors (Centers for Disease Control and Prevention; National Institute of Mental Health; Hesapcioglu et al., 2020). It is a disorder that transcends ethnic, racial, and even economic boundaries across the globe. According to the American Psychiatric Association, ASD affects one (1) in fifty-nine (59) children and is often diagnosed at early developmental stages. A child’s likability of having ASD can be attributed to diverse factors such as environmental, biologic and genetic considerations.
Unfortunately, there are no current vaccines or cure for ASD. However, there are available treatment options to control and alleviate symptoms of ASD and its associated medical conditions. Pharmacotherapy or the use of medications is one of the widely known methods used by medical professionals to accommodate ASD behavioral symptoms (DeFilippis, M. and Wagner, K., 2016). The Food and Drug Administration (FDA) have not yet approved psychopharmacologic drugs that specifically target core symptoms of ASD (Hesapcioglu et al., 2020). But atypical antipsychotic drugs such as aripiprazole and risperidone are FDA-approved for the treatment of irritability and aggression in children and adolescents with autistic disorder (Cohen et al., 2013; Lamberti et al., 2015; Hesapcioglu et al., 2020). Both medications have been proven to be effective and tolerable in minimizing behavioral disturbances and further improving the ability of individuals with ASD to adapt to their surroundings (Hesapcioglu et al., 2020).
Nevertheless, the increase in atypical antipsychotic medications usage among children and adolescents with ASD subsequently heightens the concern for the adverse effects that these drug treatments can have on these individuals. Several studies conducted with regards to the efficacy and tolerability of aripiprazole and risperidone denoted little to no significant differences in the treatment of ASD symptoms but demonstrated crucial distinctions in terms of each drug’s side effects. All research papers utilized a variety of methods to create an in-depth analysis of these medications and their side effects which included the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification as well as the Aberrant Behavior Checklist (ABC), Clinical Global Impression (CGI), Udvalg für Kliniske Undersogelser (UKU) scales through which they accurately assess psychiatric symptoms, behavioral problems of individuals with ASD, the severity of each ASD patient, and side effect rates (Cohen et al., 2013; Ghanizadeh et al., 2014; Hesapcioglu et al., 2020). With these in mind, a detailed inquiry and analysis in which drug, aripiprazole and risperidone, is most tolerable and safer in terms of side effects for children and adolescents with autism was performed.
Discussion
Results from Dr. Ahmad Ghanizadeh’s head-to-head analysis on the efficacy and tolerability of aripiprazole and risperidone indicated that the rate of adverse effects had no significant differences between aripiprazole and risperidone groups (see table 2) (Ghanizadeh et al., 2014). The percentage of side effects were more or less the same for both atypical antipsychotic drugs and neither shared a stark deviation from one another for a side effect to be uniquely associated with either drug. However, data from the study suggested that the most common side effects between aripiprazole and risperidone included drooling (31.0% vs 40.0%), increased appetite (34.5% vs 40.0%), and drowsiness (20.7% vs 16.7%) respectively (Ghanizadeh et al., 2014). In light of the study’s scope, it should be noted that weight gain and extrapyramidal side effects (EPS) such as hypokinesia akinesia and akathisia were not covered.
On the contrary, the statistical analysis of Dr. Selma Hesapcioglu did. Their inquiry determined weight gain as one of the most common side effects between aripiprazole and risperidone. But according to the study, no manifestation of statistically significant difference in weight gain was established between risperidone (19.0 %) and aripiprazole (37.5 %) groups (Hesapcioglu et al., 2020). Thus, disclosed the side effect was not as pronounced in one drug as compared to the other. To further examine other side effects, the study incorporated another research focusing primarily on Body Mass Index (BMI) gains for both medications in children and adolescents. Despite the notable increase in BMI, statistically speaking, there was no significant variation in the BMI change between aripiprazole and risperidone treatment groups (Hesapcioglu et al., 2020). In connection, their results are indicative that antipsychotic-induced weight gain can result in a high risk of cardiovascular diseases and diabetes as table 3 also suggested.
Drowsiness was another noticeable side effect between the two drugs in Dr. Selma Hesapcioglu’s exploration which was similar to the findings reported by Dr. Ahmad Ghanizadeh’s comparison. According to table 1, 42.5% patients reported feeling tired when using aripiprazole compared to 9.5% patients using risperidone (Hesapcioglu et al., 2020). Coincidentally, a near direct proportional relationship followed an increased sleep duration, with 9.5% of patients reported an increase in sleep having used risperidone while 40.0% of patients experienced an increase in sleep having used aripiprazole. Unrest and lassitude follow the general pattern outlined in table 1. Surprisingly, constipation was another common side effect observed in participants of the study, 10% and 7.1% in aripiprazole and risperidone respectively (Hesapcioglu et al., 2020). But it is hardly an adverse side effect.
In like manner, the statistical assessment of Dr. Selma Hesapcioglu and the others further reported that no significant distinction was found in terms of neurological side effects between the antipsychotics since their p values hardly differed by no more than 0.1. Although, an overdose of either drug is likely to increase the severity of EPS side effects (Hesapcioglu et al., 2020). The study had many limitations such as non-randomized and small sample sizes, non-existent placebo groups for comparisons, missing BMI data, and irregularly checked biochemical data.
Meanwhile, data from the meta-analysis of Dr. David Cohen demonstrated that somnolence/sedation were the most frequently reported adverse effects in both drugs (see fig. 2) (Cohen et al., 2013). Given the odd ratios, there were no crucial variations between active compounds. This was important to be taken into consideration as it can affect motor and learning abilities in children. The study further indicated a notable increase in people with weight gain having used both risperidone and aripiprazole (see fig. 1). Although the odd ratios: aripiprazole (OR = 6.28 [1.64–17.12]) and risperidone (7.76 [1.88–25.2]) showed no significant differences between the two (Cohen et al., 2013).
Moreover, the study also pointed out dissimilarities in the metabolic content of individuals having used aripiprazole and risperidone. But due to the lack of hormonal data for risperidone, a binary linear regression model was not possible. On the other hand, risperidone was shown to increase the risk of hyperprolactinemia two times in females as compared to males with ASD (Cohen et al., 2013). With regards to EPS, only risperidone increased the risk of EPS when compared to aripiprazole (see fig. 3) as the specificity of aripiprazole allowed it to exhibit both dopamine receptors having agonist and antagonist properties (Cohen et al., 2013).
