Comparison of the real-world safety of two different long-acting methylphenidate formulations (Medikinet^® MR and Concerta^®) – a Danish nationwide register-based cohort study

Number of cases and odds ratios with 95% confidence intervals for all outcomes (sensitivity analysis – statistical testing conducted on cases and matched controls)_

Outcome	Patients exposed to Medikinet® MR (N=1249), n (%)	Patients exposed to Concerta® (N=1528), n (%)	p value*	Adjusted p value*	OR (95% CI)
Essential hypertension	<5	<5	0.66	1	1.625 (0.262–10.096)
Sudden death (cause unknown), cardiac arrest	0	<5	-	-	-
Mental and behavioral disorders due to psychoactive substance use	11 (0.88)	29 (2.16)	0.28	1	0.646 (0.305–1.369)
Cerebral arteritis	0	0	-	-	-
Priapism	0	0	-	-	-
Psychiatric disorders	41 (3.28)	33 (2.16)	0.02	0.1386	1.864 (1.125–3.087)
Conduct disorder	5 (0.40)	10 (0.65)	0.10	0.6972	0.372 (0.116–1.195)
Suicidal tendency, intentional self-harm	<5	11 (0.72)	0.44	1	0.299 (0.035–2.521)
Tics	23 (1.84)	16 (1.05)	0.73	1	1.158 (0.576–2.327)
Episodic and seizure disorders	13 (1.04)	8 (0.52)	0.15	1	2.192 (0.835–5.753)
Anorexia	0	<5	-	-	-
Non-organic sleep disorders	0	0	-	-	-

Outcomes with ICD-10 codes

Outcome	ICD-10 codes
Essential hypertension	I10
Sudden death (cause unknown), cardiac arrest	R96, R99, I46
Mental and behavioral disorders due to psychoactive substance use	F10-F19
Cerebral arteritis	I67.7
Priapism	N48.3
Psychiatric disorders
Schizophrenia, schizotypal and delusional disorders	F20-F29
Mood (affective) disorders	F30-F39
Neurotic, stress-related and somatoform disorders	F40-F48
Behavioral syndromes associated with physiological disturbances and physical factors	F50-F59
Conduct disorder	F91
Suicidal tendency, intentional self-harm	X60-X84, EUW
Tics	F95
Episodic and seizure disorders	G40-G47
Anorexia	R63.0
Non-organic sleep disorders	F51

Number of cases and odds ratios with 95% confidence intervals for all outcomes (main analysis – statistical testing conducted on cases and matched controls)_

Outcome	Patients exposed to Medikinet® MR (N=1249), n (%)	Patients exposed to Concerta® (N=2455), n (%)	p value*	Adjusted p value*	OR (95% CI)
Essential hypertension	<5	<5	0.68	1	1.5 (0.28–8.036)
Sudden death (cause unknown), cardiac arrest	0	<5	-	-	-
Mental and behavioral disorders due to psychoactive substance use	11 (0.88)	53 (2.16)	0.33	1	0.69 (0.343–1.389)
Cerebral arteritis	0	0	-	-	-
Priapism	0	0	-	-	-
Psychiatric disorders
All patients	41 (3.28)	77 (3.14)	0.59	1	1.134 (0.747–1.72)
6–11 years	14 (1.98)	12 (1.91)	-	-	-
12–17 years	17 (4.87)	33 (3.27)	-	-	-
≥18 years	10 (5.18)	32 (3.93)	-	-	-
Conduct disorder	5 (0.40)	14 (0.57)	0.30	1	0.491 (0.164–1.474)
Suicidal tendency, intentional self-harm	<5	11 (0.45)	0.16	1	0.196 (0.024–1.631)
Tics	23 (1.84)	24 (0.98)	0.87	1	1.071 (0.572–2.003)
Episodic and seizure disorders	13 (1.04)	15 (0.61)	0.29	1	1.61 (0.709–3.654)
Anorexia	0	<5	-	-	-
Non-organic sleep disorders	0	0	-	-	-

Demographic characteristics of the study population_

	Patients exposed to Medikinet® MR (N=1249)	Patients exposed to Concerta® (N=2455)
Sex, n (%)
Female	347 (27.8)	671 (27.3)
Male	902 (72.2)	1784 (72.7)
Age at index date, n (%)
6–11 years	707 (56.6)	630 (25.7)
12–17 years	349 (27.9)	1010 (41.1)
≥18 years	193 (15.5)	815 (33.2)