Study type

Study topic

Human medicinal product
Disease /health condition

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness
Effectiveness study (incl. comparative)

Data collection methods

Secondary data collection
Non-interventional study

Non-interventional study design

Cohort
Other

Non-interventional study design, other

Retrospective, observational study
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(N06AB) Selective serotonin reuptake inhibitors
(N06AB10) escitalopram
(N06AB03) fluoxetine
(N06AB06) sertraline
(N06AB05) paroxetine
(N06BA04) methylphenidate
(N06BA09) atomoxetine

Medical condition to be studied

Attention deficit hyperactivity disorder
Population studied

Short description of the study population

Adult patients aged 18 years or older who had prescribed with methylphenidate (MPH) for attention deficit hyperactivity disorder (ADHD) and selective serotonin reuptake inhibitor (SSRI) for depressive disorder identified from national claims database from the Health Insurance Review and Assessment Service of South Korea.
Inclusion criteria:
● Adolescents who prescribed MPH for ADHD and have depressive disorder
- ≥18 years old adults
- ADHD diagnosis for the first time in the patient’s history on or before the index date
- Depressive disorder diagnosis for the first time in the patient’s history on or before the index date
- At least 365 days of observation time prior to the index date
- No other ADHD medications such as atomoxetine, clonidine, or bupropion

● Adults who prescribed MPH for ADHD and prescribed any SSRI for depressive disorder.
- ≥18 years old adults
- ADHD diagnosis for the first time in the patient’s history on or before the index date
- Depressive disorder diagnosis for the first time in the patient’s history on or before the index date
- At least 365 days of observation time prior to the index date
- No other ADHD medications such as atomoxetine, clonidine, and bupropion
- No other antidepressant drugs except the target ingredient before the index date

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Other

Special population of interest, other

Patients with attention deficit hyperactivity disorder

Estimated number of subjects

8000
Study design details

Main study objective

We aimed to conduct comparative effectiveness research to establish real-world evidence for the safety of MPH and SSRIs in patients with ADHD.

Outcomes

The primary outcomes are neuropsychiatric events that include anxiety, extrapyramidal symptoms, mania, hospitalization related to ADHD or schizophrenia. The secondary outcomes are safety events including cardiovascular, gastrointestinal, and other events.

Data analysis plan

• Primary analyses: As-treated risk window • Sensitivity analyses: Intention-to-treat risk window Risk window starts from 1 day to last observation after the index date. • Preventing bias from left censoring of data In order to prevent bias in the first visit and first prescription due to left censoring, the patients diagnosed and prescribed for the first year of the data period will not be used. • Preventing bias from time-related settings In order to reduce time-related bias, sensitivity analysis will be additionally performed in addition to the main analysis. Sensitivity analyses according to time-at-risk setting (As-treated or Intention-to-treat) and different gap durations between the concomitant drugs will be performed (e.g. between MPH and SSRI: 30 days, 0 days). • Preventing bias from reverse causality To avoid reverse causality due to outcome variables, additional sensitivity analysis will be conducted in which symptomatic patients are removed.
Documents
Study publications
Kim C, Lee DY, Park J, Yang SJ, Tan EH, Prieto-Alhambra D, Lee YH, Lee S, Kim S…