This study set out to review and analyse aspects of antidepressant prescribing in children and adolescents in a section of the private health care sector of South Africa. The research was conducted in two phases, namely a literature review and an empirical investigation. The aim of the literature review was to provide background to the study by conceptualising antidepressants. The empirical review followed a retrospective, descriptive, observational design. The data employed in the study was obtained from the medicine claims database of a South African Pharmaceutical Benefit Management (PBM) company. The study population consisted of 3 611 children and adolescents receiving ≥1 antidepressants from 1 January 2010 to 31 December 2010. Basic descriptive statistics, such as frequency, prevalence, average, weighted average, standard deviation, weighted standard deviation, median, effect sizes, prescribed daily dosages and DU95% methodology were used to characterise the study sample, and were calculated using the Statistical Analysis System SAS® for Windows 9.3® program. The data were used to determine the prescribing patterns of antidepressants with regard to age, gender, geographic area, type of prescriber, the comparison of prescribed daily dosages vs. recommended daily dosages, and the prevalence of potential drug-drug interactions. Potential drug-drug interactions were identified and compiled by using various interaction compendia, whereas recommended daily dosages were identified by cross-referencing various dosage compendia. The study population consisted of 1 850 girls and 1 761 boys. The mean age of girls was 13.7 ± 3.9 years, vs. 12.3 ± 3.8 years for boys (d = 0.4). A total of 11 735 prescriptions containing 12 272 antidepressants were documented in 2010. Results of the study furthermore showed that the average number of prescriptions claimed per patient increased with age, from an average of 1.0 ± 0.28 among those up to the age of 2 years, to an average of 3.4 ± 3.21 among those 16 to 18 years of age. Prescribing with regard to age groups differed, rising gradually from birth and peaking at middle childhood for boys, whereas antidepressant use in girls increased from birth up to 6 years of age, reaching a plateau and increases again from age 13 and onward. Approximately 25% (n = 12 272) of antidepressants prescribed were either not indicated in children, or the dosages were deemed too high. More than 50% (n = 12 272) of antidepressants prescribed were in the Gauteng province. The SSRIs (selective serotonin re-uptake inhibitors) and the TCAs (tricyclic antidepressants) were the most prescribed antidepressants in both gender groups. The male-to-female ratio for the selective serotonin re-uptake inhibitors was 0.9, compared to 1.2 for the tricyclic antidepressants. The top three antidepressants prescribed were imipramine (21.8%), citalopram (15.3%) and escitalopram (14.7%, n = 12 272). Potential DDIs were observed on 284 (2.4%) (n = 11 743) prescriptions. The drug pairs with potential drug-drug interactions prescribed most, were imipramine with methylphenidate [43 cases (15.1%)] and valproic acid [38 cases (13.4%)], and followed by methylphenidate in combination with fluoxetine and sertraline [both documenting 32 cases (11.3%), respectively. The TCAs accounted for 182 (64.1%) cases of possible DDIs (drug-drug interactions), whereas combination therapy of SSRIs and TCAs accounted for 21.4% of potential DDIs. In conclusion, this study determined that there were a number of differences with regard to antidepressant prescribing in children and adolescents. Recommendations for future studies were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

This study set out to review and analyse aspects of antidepressant prescribing in children and adolescents in a section of the private health care sector of South Africa. The research was conducted in two phases, namely a literature review and an empirical investigation. The aim of the literature review was to provide background to the study by conceptualising antidepressants. The empirical review followed a retrospective, descriptive, observational design. The data employed in the study was obtained from the medicine claims database of a South African Pharmaceutical Benefit Management (PBM) company. The study population consisted of 3 611 children and adolescents receiving ≥1 antidepressants from 1 January 2010 to 31 December 2010. Basic descriptive statistics, such as frequency, prevalence, average, weighted average, standard deviation, weighted standard deviation, median, effect sizes, prescribed daily dosages and DU95% methodology were used to characterise the study sample, and were calculated using the Statistical Analysis System SAS® for Windows 9.3® program. The data were used to determine the prescribing patterns of antidepressants with regard to age, gender, geographic area, type of prescriber, the comparison of prescribed daily dosages vs. recommended daily dosages, and the prevalence of potential drug-drug interactions. Potential drug-drug interactions were identified and compiled by using various interaction compendia, whereas recommended daily dosages were identified by cross-referencing various dosage compendia. The study population consisted of 1 850 girls and 1 761 boys. The mean age of girls was 13.7 ± 3.9 years, vs. 12.3 ± 3.8 years for boys (d = 0.4). A total of 11 735 prescriptions containing 12 272 antidepressants were documented in 2010. Results of the study furthermore showed that the average number of prescriptions claimed per patient increased with age, from an average of 1.0 ± 0.28 among those up to the age of 2 years, to an average of 3.4 ± 3.21 among those 16 to 18 years of age. Prescribing with regard to age groups differed, rising gradually from birth and peaking at middle childhood for boys, whereas antidepressant use in girls increased from birth up to 6 years of age, reaching a plateau and increases again from age 13 and onward. Approximately 25% (n = 12 272) of antidepressants prescribed were either not indicated in children, or the dosages were deemed too high. More than 50% (n = 12 272) of antidepressants prescribed were in the Gauteng province. The SSRIs (selective serotonin re-uptake inhibitors) and the TCAs (tricyclic antidepressants) were the most prescribed antidepressants in both gender groups. The male-to-female ratio for the selective serotonin re-uptake inhibitors was 0.9, compared to 1.2 for the tricyclic antidepressants. The top three antidepressants prescribed were imipramine (21.8%), citalopram (15.3%) and escitalopram (14.7%, n = 12 272). Potential DDIs were observed on 284 (2.4%) (n = 11 743) prescriptions. The drug pairs with potential drug-drug interactions prescribed most, were imipramine with methylphenidate [43 cases (15.1%)] and valproic acid [38 cases (13.4%)], and followed by methylphenidate in combination with fluoxetine and sertraline [both documenting 32 cases (11.3%), respectively. The TCAs accounted for 182 (64.1%) cases of possible DDIs (drug-drug interactions), whereas combination therapy of SSRIs and TCAs accounted for 21.4% of potential DDIs. In conclusion, this study determined that there were a number of differences with regard to antidepressant prescribing in children and adolescents. Recommendations for future studies were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014