Psychiatric Diagnoses and Prescribing Patterns of Psychotropic Polypharmacy among Children and Adolescents in the Jazan Region, Saudi Arabia
Abdulkarim M. Merayaa,b
aDepartment of Clinical Pharmacy, College of Pharmacy, Jazan University, Saudi Arabia.
bPharmacy Practice Research Unit, College of Pharmacy, Jazan University, Saudi Arabia.
Background: Mental disorders are common among children and adolescents, worldwide. However, little is known about the patterns of psychiatric diagnoses in Saudi Arabia in general. Moreover, it is crucial to examine the prescribing patterns of psychotropic medications and polypharmacy among children and adolescents as the benefits versus risks are not clear in this population. This study aimed to evaluate the patterns of psychiatric diagnoses as well as prescribing patterns of psychotropic medications and polypharmacy among children and adolescents in the Jazan region of Saudi Arabia.
Methods: A retrospective cross-sectional study design was conducted with a sample of children and adolescents (N=647) who attended the outpatient clinics in the psychiatric hospital in the Jazan region, Southwest of Saudi Arabia. Age, gender and clinical outcomes were retrieved from the electronic health records of the sample. Outcome Measures included patterns of psychiatric diagnoses and prescribing patterns of psychotropic medications and polypharmacy (>=2 psychotropic medications). Logistic regression models were conducted to examine the relationships between the explanatory variables and the following: polypharmacy, antidepressants, antipsychotics and stimulants prescriptions.
Results: The most prevalent psychiatric diagnosis was attention-deficit hyperactivity disorder (31.5%) followed by autism and pervasive developmental disorders (27.6%) and mental retardation (24%). The most prescribed psychotropic classes were antipsychotics and stimulants. Approximately, a quarter of the children and adolescents were given psychotropic polypharmacy. A higher percentage of adolescents were given polypharmacy than children (31.5% vs 18.2%). In the adjusted analyses, adolescents were more likely to receive psychotropic polypharmacy, antidepressants and stimulants than children. Nevertheless, adolescents were less likely than children to be given antipsychotics.
Conclusions: Psychotropic polypharmacy rates in the Jazan region are concerning, especially among adolescents. Healthcare professionals should closely monitor children and adolescents with psychotropic polypharmacy to minimize the risk of drug-drug and/or drug-disease interactions.
Keywords: psychotropic polypharmacy, drug utilization, psychiatric diagnoses, children, adolescents.
Mental disorders are common among children and adolescents . In fact, 10-20% of them experience mental disorders, worldwide . Previous reports found that attention-deficit-hyperactivity disorder (ADHD), anxiety, and depression are the most common mental disorders among children and adolescents [1, 2]. Additionally, among children and adolescents who seek mental health care, ADHD, autism, depression and anxiety were the most common mental disorders . Unfortunately, national estimates of mental disorders among children and adolescents are scarce in Saudi Arabia. AlBuhairan et al. who used a nationally representative sample of Saudi adolescents to assess their physical and mental health found that 14.3% of the adolescents in Saudi Arabia have depression and 6.7% of them have anxiety . Furthermore, another study indicated that 36.3% of children and adolescents in a selected community in Riyadh city had at least one psychiatric disorder in 2015 . Psychotropic medication prescriptions among children and adolescents have increased dramatically in the last decade due to the increase in the prevalence of mental disorders [6, 7]. However, the benefit versus risk of psychotropic medications among children is not clear as high quality randomized clinical trials in this population are lacking .
The safety of psychotropic medications among children and adolescents is not well studied [8, 9]. Psychotropic medications can induce serious adverse effects such as hormonal imbalances, weight gain, involuntary movements, metabolic disturbances and cardiovascular risks . Furthermore, previous studies indicated that 2.9-45% of children and adolescents use two or more psychotropic medications concomitantly, worldwide [3, 10, 11, 12]. However, the consequences of the use of these medications in combination in children have not been clearly elucidated . Due to the safety concerns, studies on the prescribing patterns of psychotropic medications in children and adolescents in different regions of Saudi Arabia are warranted.
Jazan is the smallest region in Saudi Arabia, with 40% of its population living in rural areas . In the Jazan region, all psychiatric outpatient clinics are within governmental hospitals . Unfortunately, only one hospital within the Jazan region can provide mental healthcare services for children and adolescents. Children and adolescents exposed to psychotropic medications are at a greater risk of adverse drug reactions which can negatively impact their quality of life . Therefore, it is crucial to examine the prescribing patterns of psychotropic medications and polypharmacy among children and adolescents in Saudi Arabia in general and in the Jazan region. Therefore, the first aim of this study is to explore the patterns of psychiatric diagnoses among children and adolescents in the Jazan region, Saudi Arabia. The second aim is to examine the prescribing patterns of psychotropic medications and polypharmacy among children and adolescents.
MATERIALS AND METHODS
This study used a retrospective cross-sectional study design. The Electronic Health Records (EHRs) of children and adolescents aged below 18 years who attended the outpatient clinics in the psychiatric hospital in Jazan between 1 January 2018 and 31 December 2018 were obtained and reviewed. The EHRs in this study are the data that are collected during the routine delivery of care. Previously conducted studies indicated that EHRs are widely used, and they are an accepted data source to conduct clinical research and epidemiology studies including drug utilization research. The Institutional Research Review and Ethics Committee reviewed and approved this study and all its procedures (IRB No. 6401/1708/1440).
(i) Psychiatric Diagnoses were identified by the International Classification of Diseases, tenth edition, Clinical Modification (ICD-10-CM) codes reported by the physicians. Appendix A displays the diagnoses codes used to identify mental disorders. Psychiatric diagnoses were categorized as follows: ADHD, mental retardation, autism spectrum disorders and pervasive developmental disorders, other disorders of psychological development, Conduct and other emotional disorders with onset in childhood, and other psychological disorders.
(ii) Psychotropic medications: To evaluate the prescribing patterns of psychotropic medications, information on psychotropic medications was collected. Medications were classified into the following classes: (a) Antidepressants (selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and others); (b) Antipsychotics: (first-generation, second-generation and atypical); (c) Mood stabilizers; (d) Anxiolytics (short-acting and long-acting benzodiazepines); (e) Anticholinergics; and (f) Stimulants.
(iii) Psychotropic polypharmacy: Following previously conducted studies [6, 16, 17], polypharmacy was defined as prescribing two or more psychotropic medications. Appendix B displays all dispensed psychotropic medications.
Other explanatory variables included are age groups in years (0-9 and 10-17) and gender (male, female).
Descriptive analyses, including frequencies and percentages, were calculated for categorical variables for the sample and by gender and age. Multivariable logistic regressions were also conducted to examine the relationships between the explanatory variables and the following outcomes: polypharmacy, antidepressants, antipsychotics and stimulants prescriptions. All adjusted multivariable regression models included gender, age, and psychiatric diagnoses. The analyses were performed using Stata 15.1 software (Stata Corp LP, College Station, USA). A p-value <0.05 was considered significant in all tests.
Description of the study sample
Six hundred and forty-seven patients between 1-17 years of age attended the outpatient services at the only psychiatric hospital in the Jazan region during 2018. Of those patients, 28.5% were females and 71.5% were males and 51.9% of them were less than 10 years old.
Among the children and adolescents in the sample, 31.5% had ADHD, 27.6% had autism and pervasive developmental disorders, 24% had mental retardation, 6.4% had Conduct and other emotional disorders with onset in childhood, 6.4% had other psychological disorders, and 4.1% had other developmental disorders.
The most prescribed psychotropic medications class was antipsychotic (62.5%) and Risperidone was the most prescribed medication of this class (55.5%). The second most prescribed psychotropic medications class was stimulants (38%) followed by antidepressants (15.4%), mood stabilizers (4.6%), anticholinergics (2%) and sedatives (0.5%). Among children and adolescents, 13% had a combination of antipsychotics and stimulants. Of the study sample, 24.6% were prescribed more than two psychotropic medications concurrently. Table 1 displays the characteristics of the study sample.
Description of the study sample by gender and age
Table 1 shows the sample characteristics by gender and age groups. Bivariate analyses revealed a significant association between gender and the following factors: age, psychiatric diagnoses, antidepressants and mood stabilizers. ADHD was more prevalent among males than females (33.3% vs 27.2%). On the other hand, other psychological disorders -including depression and anxiety- were more prevalent among females than males (12.2% vs 4.2%). Furthermore, a higher percentage of males children andboy and adolescents had antipsychotics than females (64.7% vs 56.5%). Nevertheless, a higher proportion of females had antidepressants than males (22.3% vs 12.8%).
Furthermore, age was significantly associated with gender, psychiatric diagnoses, antipsychotics, antidepressants, stimulants, anticholinergics, mood stabilizers and psychotropic polypharmacy. ADHD was more prevalent among children than adolescents (35.7% vs 26.9%). Additionally, a higher percentage of children had autism and pervasive developmental disorders than adolescents (33.3% vs 21.3%). Also, children had a higher percentage of antipsychotics (73.8% vs 50.2%). However, adolescents had a higher percentage of stimulants (42.2% vs 33.9%), antidepressants (24.4% vs 7.1%) and psychotropic polypharmacy (31.5% vs 18.2%) than children.
Factors associated with psychotropic medications and polypharmacy
Table 2 displays the adjusted odds ratios (AORs) and their 95% Confidence Intervals (95%CI) for clinical and demographic factors from separate logistic regressions on polypharmacy, antidepressants, antipsychotics and stimulants. Adolescents were more likely to be given polypharmacy (OR:1.85; 95%CI: 1.25-2.74) than children. Likewise, adolescents were more likely than children to have antidepressants and stimulants. However, adolescents were less likely than children to be given antipsychotics (OR:0.34; 95%CI: 0.24-0.49). With respect to gender, there were no statistical differences between males and females in polypharmacy, antidepressants, antipsychotics or stimulants prescribing patterns.
Children and adolescents with other psychological development disorders (OR:4.40; 95%CI: 1.20-16.20), mental retardation (OR:4.44; 95%CI: 1.95-10.09), Conduct and other emotional disorders with onset in childhood (OR:10.53; 95%CI: 3.99-27.76), and other psychological disorders (OR:20.55; 95%CI: 7.72-54.65) were more likely than those with autism and pervasive disorders to have antidepressants. Children and adolescents with ADHD were also more likely to have stimulants than those with autism and pervasive disorders (OR:2.14; 95%CI: 1.48-3.09). However, children and adolescents with ADHD, other psychological development disorders, mental retardation, Conduct and other emotional disorders with onset in childhood, and other psychological disorders were less likely than those with autism and pervasive developmental disorders to have antipsychotics.
The current study describes the patterns of psychiatric diagnoses and the prescribing patterns of psychotropic medications and polypharmacy among children and adolescents in the Jazan region of Saudi Arabia. This study has multiple strengths. To the best of the author’s knowledge, this is the first study to determine the prescribing patterns of psychotropic medications in this population in Saudi Arabia in general and in the Jazan region. In Saudi Arabia, more than 80% of healthcare services are provided by governmental hospitals and agencies . In the Jazan region, most of the outpatient mental healthcare is provided by the psychiatric hospital in the region. Therefore, the results of the current study show the current practice of mental healthcare in the region in children and adolescents. The results of this study can be used as a baseline for future studies, and to compare the mental healthcare practice in the Jazan region with other regions in Saudi Arabia. Approximately, 7.0% of the prescriptions during 2018 in the Jazan region were for children and adolescents in this study. As a result, pediatricpaediatric psychiatrists and other healthcare professionals who are trained to identify and manage psychological problems among children and adolescents are needed in the Jazan region.
This study does not provide estimates on the prevalence of mental disorders among children and adolescents in the Jazan region as it included only those who seek mental healthcare. In the United States, 9.4% of children and adolescents received an ADHD Diagnosis, while 7.1% and 3.2% of them have diagnosed with anxiety and depression, respectively. Polanczyk et al. conducted a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents and found that 13.4% of them have anxiety, 6.5% have depression and 3.4% have ADHD. Furthermore, Al Buhairan et al. who used a nationally representative sample of Saudi adolescents to assess their physical and mental health found that 14.3% of the adolescents in Saudi Arabia have depression and 6.7% of them have anxiety . Also, in a selected community in Riyadh city, 8.4% of children and adolescents had ADHD, 7.8% had depression and a similar percentage had anxiety . However, among children and adolescents in this study, 31.5% had ADHD, 27.6% had autism and only 6.4% had any mood disorders including depression and anxiety. These findings suggest that mental disorders especially depression and anxiety among children and adolescents are often remain undiagnosed and hence are untreated. Therefore, it is crucial to screen for depression and other mental health problems among children and adolescents in Saudi Arabia to decrease the burden of mental illnesses in this subpopulation. Furthermore, health programs and initiatives are needed to increase parental awareness about mental disorders and their consequences among children and adolescents. Additionally, more than a quarter of the children and adolescents in this study had autism and other pervasive developmental disorders. Further research is required to measure the quality of mental healthcare for all children and adolescents with a mental disorder and especially those with autism as satisfaction with medical services for children with autism was found to be low in Saudi Arabia .
Approximately, a quarter of the children and the adolescents in the study sample were prescribed two or more psychotropic medications. Furthermore, more than 30% of the adolescents were given two psychotropic medications or more. Prior research found that the range of psychotropic polypharmacy among children and adolescents was between 2.9-45% [3, 10, 11, 12]. Previous studies indicated that there are some benefits to the use of psychotropic polypharmacy among children and adolescents especially for treating ADHD and other diseases . Nevertheless, a review by Jureidini and others suggested that the published evidence for efficacy and safety of psychotropic polypharmacy use among children and adolescents is insufficient . Randomized clinical trials (RCTs) demonstrated statistically significant benefits for combinations of central sympatholytics and stimulants for treating ADHD. However, these RCTs have a small sample size and methodologically weak . With regard to safety, previous reports showed that psychotropic polypharmacy among children and adolescents is associated with multiple adverse drug reactions. For example, one study found that the combination of methylphenidate and atomoxetine was associated with a significant increase in the rates of insomnia, fatigue and anorexia . Additionally, combinations of psychotropic medications were also associated with weight loss, high blood pressure, agitation , metabolic disorders and type 2 diabetes mellitus . Further research is required to assess the efficacy and safety of psychotropic polypharmacy use among children and adolescents using high-quality RCTs. In the Jazan region, psychiatrists, pharmacists and other health care professionals should closely monitor children and adolescents with psychotropic polypharmacy to prevent any unwanted adverse drug reactions, drug-drug interactions and/or drug-disease interactions. Also, interventions including medications reviews by qualified pharmacists are needed to decrease inappropriate psychotropic polypharmacy among children and adolescents.
Despite the multiple strengths, the findings of this study should be interpreted in the context of some limitations. This study did not measure other contextual and socioeconomic factors that can affect the use of psychotropic polypharmacy among children and adolescents. Also, only the primary diagnosis was measured in this study. Finally, not all psychotropic polypharmacy is harmful and future studies need to assess the appropriateness of psychotropic polypharmacy among children and adolescents. Nevertheless, the results of this study shed light on the practice of psychotropic polypharmacy in the Jazan region. Furthermore, the results of this study can be used to assess the mental health care needs of children and adolescents in the Jazan region to better assign healthcare resources.
More than 50% of children and adolescents who seek mental healthcare have either attention-deficit-hyperactivity disorder or autism and pervasive developmental disorders. Further studies are required to assess the community prevalence of mental disorders among children and adolescents in Saudi Arabia. Furthermore, psychotropic polypharmacy was prevalent among almost a quarter of children and adolescents who seek mental healthcare in the Jazan region of Saudi Arabia. Psychotropic polypharmacy rates are concerning, especially among adolescents. Further research is required to explore the factors associated with psychotropic polypharmacy among children and adolescents in the Jazan region and Saudi Arabia in general.
Acknowledgements This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Disclosure statement: The author reports no conflict of interest.
Availability of Data and Materials: The data used in the study cannot be publicly shared, because of restrictions imposed by the IRB at Jazan University. De-identifiable data are available upon reasonable request.
1. Kieling C, Baker-Henningham H, Belfer M, Conti G, Ertem I, Omigbodun O et al. Child and adolescent mental health worldwide: evidence for action. Lancet 2011;378(9801):1515-25.
2. Polanczyk GV, Salum GA, Sugaya LS, Caye A, Rohde LA. Annual Research Review: A meta‐analysis of the worldwide prevalence of mental disorders in children and adolescents. J Child Psychol Psychiatry. 2015;56(3):345-65.
3. Medhekar R, Aparasu R, Bhatara V, Johnson M, Alonzo J, Schwarzwald H et al. Risk factors of psychotropic polypharmacy in the treatment of children and adolescents with psychiatric disorders. Res Social Adm Pharm. 2019;15(4):395-403.
4. AlBuhairan FS, Tamim H, Al Dubayee M, AlDhukair S, Al Shehri S, Tamimi W et al. Time for an adolescent health surveillance system in Saudi Arabia: findings from “Jeeluna”. J Adolesc Health. 2015;57(3):263-9.
5. Al-Modayfer O, Alatiq Y. A Pilot Study on the Prevalence of Psychiatric Disorders among Saudi Children and Adolescents: A Sample from a Selected Community in Riyadh City. The Arab Journal of Psychiatry. 2015;44(2151):1-10.
6. Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry. 2010;67(1):26-36.
7. Karanges EA, Stephenson CP, McGregor IS. Longitudinal trends in the dispensing of psychotropic medications in Australia from 2009–2012: Focus on children, adolescents and prescriber specialty. Aust N Z J Psychiatry. 2014;48(10):917-31.
8. Jureidini J, Tonkin A, Jureidini E. Combination pharmacotherapy for psychiatric disorders in children and adolescents: prevalence, efficacy, risks and research needs. Paediatric Drugs. 2013;15(5):377-91.
9. Rey JM, Omigbodun OO. International dissemination of evidence-based practice, open access and the IACAPAP textbook of child and adolescent mental health. Child Adolesc Psychiatry Ment Health. 2015 Dec;9(1):51.
10. Lohr WD, Creel L, Feygin Y, Stevenson M, Smith MJ, Myers J et al. Psychotropic Polypharmacy Among Children and Youth Receiving Medicaid, 2012-2015. J Manag Care Spec Pharm. 2018;24(8):736-44.
11. Olashore AA, Rukewe A. Polypharmacy among children and adolescents with psychiatric disorders in a mental referral hospital in Botswana. BMC Psychiatry. 2017;17(1):174.
12. Soria Saucedo R, Liu X, Hincapie-Castillo JM, Zambrano D, Bussing R, Winterstein AG. Prevalence, Time Trends, and Utilization Patterns of Psychotropic Polypharmacy Among Pediatric Medicaid Beneficiaries, 1999–2010. Psychiatr Serv. 2018;69(8):919-26.
13. Mahfouz MS, Rahim B-eE, Solan YM, Makeen AM, Alsanosy RM. Khat chewing habits in the population of the Jazan Region, Saudi Arabia: Prevalence and associated factors. PloS One. 2015;10(8):e0134545.
14. Ministry of Health. Annual Statistical Yearbook. Saudi Arabia, 2017. Available from: https://www.moh.gov.sa/en/Ministry/Statistics/book/Pages/default.aspx
15. Cowie MR, Blomster JI, Curtis LH, Duclaux S, Ford I, Fritz F et al. Electronic health records to facilitate clinical research. Clin Res Cardiol. 2017;106(1):1-9.
16. Tapp A, Wood AE, Secrest L, Erdmann J, Cubberley L, Kilzieh N. Combination antipsychotic therapy in clinical practice. Psychiatr Serv. 2003;54(1):55-9.
17. Costa JdO, Ceccato MdGB, Melo APS, Acurcio FdA, Guimarães MDC. Gender differences and psychotropic polypharmacy in psychiatric patients in Brazil: a cross-sectional analysis of the PESSOAS Project. Cad Saude Publica. 2017;33:e00168915.
18. Albejaidi FM. Healthcare system in Saudi Arabia: An analysis of structure, total quality management and future challenges. Journal of Alternative Perspectives in the Social Sciences 2010;2(2):794-818.
19. Alnemary FM, Aldhalaan HM, Simon-Cereijido G, Alnemary FM. Services for children with autism in the Kingdom of Saudi Arabia. Autism. 2017;21(5):592-602.
20. Hammerness P, Georgiopoulos A, Doyle RL, Utzinger L, Schillinger M, Martelon M et al. An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol. 2009;19(5):493-9.
21. Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H et al. Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry. 2005;44(9):915-24.
22. Mamakou V, Hackinger S, Zengini E, Tsompanaki E, Marouli E, Serafetinidis I et al. Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study. BMC Psychiatry 2018;18(1):249.