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. 2014 Sep;23(3):157-66.

Combination and switching of stimulants in children and adolescents with attention deficit/hyperactivity disorder in quebec

Leila Ben Amor  1 , Vanja Sikirica  2 , Martin Cloutier  3 , Jean Lachaine  4 , Annie Guerin  2 , Valerie Carter  3 , Paul Hodgkins  5 , Judy van Stralen  6
Affiliations

Combination and switching of stimulants in children and adolescents with attention deficit/hyperactivity disorder in quebec

Leila Ben Amor et al. J Can Acad Child Adolesc Psychiatry. 2014 Sep.

Abstract
in English, French

Objective: To assess the one-year period prevalence of stimulant combination therapy and switching in children/ adolescents with attention deficit/hyperactivity disorder (ADHD) in Quebec, Canada.

Method: Patients aged 6-17 years, with at least two ADHD diagnosis codes documented in different visits and at least 30 days' supply of a stimulant during their most recent one-year observation period were selected from the Regie de l'assurance maladie du Quebec database (03/2007-02/2012). Combination therapy was defined as at least 30 consecutive days of concomitant use of multiple stimulants with different active moieties, or use of a stimulant and another psychotropic medication. Therapy switching was defined as a prescription claim for a new psychotropic medication less than 30 days before or after the end of supply of a stimulant. The one-year period prevalence of therapy combination and switching was calculated.

Results: The one-year period prevalence of combination therapy and switching among 9,431 children and adolescents with ADHD treated with stimulants was 19.8% and 18.7%, respectively. The most frequent combination categories were atypical antipsychotics (AAP: 10.8%), atomoxetine (ATX: 5.5%) and clonidine (5.3%). The most frequent switched-to categories were other stimulants (7.9%), AAP (5.5%) and ATX (4.7%).

Conclusions: Approximately one in five children/adolescents with ADHD on a stimulant experienced combination therapy or therapy switching; however, the majority of the medications used in combination or switching were not label-indicated for the treatment of ADHD in Canada. These results highlight the need for further research to evaluate the risk-benefit of stimulant combination and switching in children and adolescents with ADHD.

Objectif: Évaluer la prévalence sur une période d’un an de la traitement par combinaison et par changement de stimulants chez les enfants et les adolescents souffrant du trouble de déficit de l’attention avec hyperactivité (TDAH) au Québec, Canada.

Méthode: Des patients de 6 à 17 ans, ayant au moins deux codes diagnostiques de TDAH documentés à différentes visites et une provision d’au moins 30 jours d’un stimulant durant leur plus récente période d’observation d’un an, ont été choisis dans la base de données de la Régie de l’assurance maladie du Québec (03/2007–02/2012). La traitement par combinaison a été définie comme étant au moins 30 jours consécutifs d’utilisation concomitante de multiples stimulants ayant différentes parties actives, ou d’utilisation d’un stimulant et d’un autre médicament psychotrope. La traitement par changement a été définie comme étant une demande de prescription d’un nouveau médicament psychotrope moins de 30 jours avant ou après la fin d’une provision d’un stimulant. La prévalence sur une période d’un an de la traitement par combinaison et par changement a été calculée.

Résultats: La prévalence sur une période d’un an de la traitement par combinaison et par changement chez 9 431 enfants et adolescents souffrant de TDAH traités par stimulants était de 19,8% et 18,7%, respectivement. Les catégories de combinaison les plus fréquentes étaient les antipsychotiques atypiques (APA: 10,8%), l’atomoxétine (ATX: 5,5%) et la clonidine (5,3%). Les catégories pour lesquelles les changements se faisaient le plus souvent étaient d’autres stimulants (7,9%), les APA (5,5%) et l’ATX (4,7%).

Conclusions: Environ un enfant/adolescent sur cinq qui souffrent de TDAH et prennent des stimulants ont fait l’expérience d’une thérapie par combinaison ou par changement; toutefois, la majorité des médicaments utilisés en combinaison ou pour le changement n’étaient pas indiqués sur l’étiquette pour le traitement du TDAH au Canada. Ces résultats font ressortir le besoin de plus de recherche pour évaluer les risques-avantages de la combinaison et du changement de stimulants chez les enfants et adolescents souffrant de TDAH.

Keywords: ADHD; RAMQ; combination therapy; stimulants; switching.

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Figures

Figure 1.
Figure 1.
Sample selection 1The following criteria were used for data extraction from the RAMQ data: patients must be continuously enrolled in both medical and drug plans for at least 18 consecutive months, have at least one diagnosis of ADHD during the continuous enrolment period, have at least one prescription of a stimulant during the continuous enrolment period and within 18 months of a diagnosis of ADHD and must be ≥6 and <18 years old as of January 1st of the year meeting all the above criteria. 2The last 19 months of continuous eligibility meeting all selection criteria were classified into baseline period (six months), followed by study period (12 months) and one month of additional evaluation period. The additional evaluation period is required to evaluate whether a therapy addition to a stimulant during the last month of the study period can be qualified as combination therapy. 3The index year is defined as the year of the index date, which is defined as the first day of the study period. 4Patients with at least one psychiatric/neurological comorbidity diagnosis during the baseline or study period were defined as comorbid. See online Appendix B for the detailed list of psychiatric/neurological comorbidity diagnoses. 5Patients with no psychiatric/neurological comorbidity diagnosis during the baseline or study period were defined as non-comorbid. See online Appendix B for the detailed list of psychiatric/neurological comorbidity diagnoses.
Figure 2.
Figure 2.
Period prevalence of combination therapy1 among patients with ADHD (one-year study period)2–4 1Combination therapy was defined as the combination of a stimulant with a psychotropic medication as listed in online Appendix A. This included a combination of two stimulants with different active moieties. Both medications had to be taken concomitantly for at least 30 consecutive days. 2The one-year period prevalence of combination therapy was defined as the number of patients who had at least one combination therapy during the study period divided by the total number of patients in the sample. The definition of prevalence allowed combination therapy to start during the baseline period and continue in the study period or start during the study period. To calculate period prevalence for combination therapy, the numerator is the number of patients who had a combination therapy (consisting of a stimulant and a medication from the evaluated medication category) that either started during the baseline period (i.e. six months pre-index) and continued during the study period (i.e. 12 months post-index) or started during the study period. The denominator is the number of all patients included in the study. 3Patients with at least one psychiatric/neurological comorbidity diagnosis during the baseline or study period were defined as comorbid. All other patients were defined as noncomorbid. See online Appendix B for the detailed list of psychiatric/neurological comorbidity diagnoses. 4To calculate the one-year period prevalence of combination therapy for each of the nine medication categories, the numerator was the number of patients who had at least one medication from that category used in combination with a stimulant during the study period. Patients could be classified into more than one combination medication category if they had combination therapies with medications from multiple medication categories during the study period. Patients were considered as having only one distinct combination therapy if they experienced combinations with multiple medications in the same category.
Figure 3.
Figure 3.
Period prevalence of therapy switching1 among all patients with ADHD (one-year study period)2–4 1Therapy switching was defined as a prescription fill of another psychotropic medication in one of the nine categories (including a stimulant with a different active moiety) less than 30 days before or after the end of the supply of a stimulant. 2The one-year period prevalence of combination therapy was defined as the number of patients who had at least one combination therapy during the study period divided by the total number of patients in the sample. Switching could only occur during the study period. 3Patients with at least one psychiatric/neurological comorbidity diagnosis during the baseline or study period were defined as comorbid. All other patients were defined as noncomorbid. See online Appendix B for the detailed list of psychiatric/neurological comorbidity diagnoses. 4To calculate the one-year period prevalence of therapy switching for each of the nine medication categories, the numerator was the number of patients who had switched to at least one medication from that category from a stimulant during the study period. Patients could be classified into more than one “switched-to” medication category if they had therapy switching with medications from multiple medication categories during the study period. Patients were considered as having only one distinct therapy switching if they experienced switches with multiple medications in the same category.
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