Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

Figures & data

Table 1 Baseline demographics (safety population)a

Characteristic	LDX (n=111)	Placebo (n=110)	OROS-MPH (n=111)
Age, years, mean (SD)	10.9 (2.9)	11.0 (2.8)	10.9 (2.6)
Sex, male, n (%)	87 (78.4)	91 (82.7)	90 (81.1)
Race, white, n (%)	107 (96.4)	108 (98.2)	107 (96.4)
BMI, kg/m^2, mean (SD)	19.3 (3.7)	19.0 (3.3)	19.1 (3.2)
Baseline ADHD-RS-IV total score, mean (SD)b	41.0 (7.3)	41.2 (7.2)	40.4 (6.8)
Baseline CGI-S rating, mean (SD)b	5.0 (0.8)	4.9 (0.8)	5.0 (0.8)
ADHD subtype, n (%)c
Predominantly inattentive	23 (20.7)	16 (14.5)	14 (12.7)
Predominantly hyperactive-impulsive	2 (1.8)	7 (6.4)	1 (0.9)
Combined	86 (77.5)	87 (79.1)	95 (86.4)
Time since ADHD diagnosis, yearsc
Mean (SD)	2.4 (2.9)	2.2 (2.6)	2.2 (2.5)
Median (range)	1.3 (0.0–10.9)	0.90 (0.0–10.2)	0.8 (0.0–9.0)

Notes: Adapted from Coghill D, Banaschewski T, Lecendreux M, et al. European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol. 2013;23(10):1208–1218.¹⁰

a Demographic and baseline characteristics have previously been reported in detail;

b five patients had no baseline ADHD-RS-IV total score or CGI-S rating;

c one patient in the OROS-MPH group was not evaluated for ADHD subtype or time since ADHD diagnosis; percentages are based on the number of patients in each treatment group.

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; ADHD-RS-IV, ADHD Rating Scale IV; BMI, body mass index; CGI-S, Clinical Global Impressions-Severity; LDX, lisdexamfetamine dimesylate; OROS-MPH, osmotic-release oral system methylphenidate; SD, standard deviation.

Table 2 Summary of lifetime ADHD medications (safety population)

	LDX (n=111) n (%)	Placebo (n=110) n (%)	OROS-MPH (n=111) n (%)	Total (n=332) n (%)
Any selected ADHD medication	64 (57.7)	58 (52.7)	60 (54.1)	182 (54.8)
Methylphenidate or methylphenidate hydrochloride	56 (50.5)	49 (44.5)	53 (47.7)	158 (47.6)
Atomoxetine or atomoxetine hydrochloride	17 (15.3)	15 (13.6)	10 (9.0)	42 (12.7)
Risperidone	7 (6.3)	3 (2.7)	6 (5.4)	16 (4.8)
Amphetamine sulfate	3 (2.7)	7 (6.4)	5 (4.5)	15 (4.5)
Carbamazepine	1 (0.9)	1 (0.9)	2 (1.8)	4 (1.2)
Imipramine or imipramine hydrochloride	1 (0.9)	1 (0.9)	1 (0.9)	3 (0.9)
Tiapride hydrochloride	2 (1.8)	1 (0.9)	0 (0.0)	3 (0.9)
Chloroprothixene or chloroprothixene hydrochloride	1 (0.9)	0 (0.0)	1 (0.9)	2 (0.6)
Piracetam	1 (0.9)	0 (0.0)	1 (0.9)	2 (0.6)
Valproate sodium or valproic acid	1 (0.9)	0 (0.0)	1 (0.9)	2 (0.6)
Amitriptyline	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Clomipramine	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Cyroheptadine	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Desipramine	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Ergenyl chrono	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Fluvoxamine	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Haloperidol	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Lamotrigine	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Omega-3 fatty acids	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Perazine	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Sedariston	0 (0.0)	1 (0.9)	0 (0.0)	1 (0.3)
Sertraline hydrochloride	0 (0.0)	1 (0.9)	0 (0.0)	1 (0.3)
Thioridazine	0 (0.0)	0 (0.0)	1 (0.9)	1 (0.3)
Topiramate	1 (0.9)	0 (0.0)	0 (0.0)	1 (0.3)
Zappelin	0 (0.0)	1 (0.9)	0 (0.0)	1 (0.3)

Notes: Patients may have been previously treated with more than one ADHD medication during their lifetime but were only counted once in each drug category. All medication names are based on the terminology provided by the individual study investigators.

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; LDX, lisdexamfetamine dimesylate; OROS-MPH, osmotic-release oral system methylphenidate.

Figure 1 Change in ADHD-RS-IV total scores from baseline to endpoint in treatment-naïve and previously treated patients (full analysis set).

Notes: ADHD-RS-IV total scores are shown as mean values ±95% CIs. In the left hand panel, open symbols indicate mean baseline scores and closed symbols indicate mean endpoint scores (LDX, circles; placebo, triangles; OROS-MPH, squares). The difference (active drug minus placebo) in LS mean change (±95% CI) from baseline to endpoint is also shown (LDX, circles; OROS-MPH, squares). Gray shading on the left hand panel indicates the 95% CI for the mean ADHD-RS-IV total score at endpoint in the LDX group in the overall study population. On the right hand panel, gray shading indicates the 95% CI for the difference (LDX minus placebo) in LS mean change from baseline to endpoint in the overall study population. Endpoint is the last on-therapy assessment visit with a valid ADHD-RS-IV total score. Immediately prior to randomization is defined as up to 30 days prior to randomization.
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; ADHD-RS-IV, ADHD rating scale IV; CI, confidence interval; LDX, lisdexamfetamine dimesylate; LS, least-squares; MPH, methylphenidate; OROS-MPH, osmotic-release oral system MPH.

Table 3 Proportions of improved patients (CGI-I score of 1 or 2) at endpoint (full analysis set)

Patient subgroups	Percentage of improved patients (CGI-I 1 or 2) at endpoint (95% CI)	Difference in percentage of improved patients relative to placebo (95% CI)
Overall study population (n=317)
LDX (n=104)	78.0 (69.9, 86.1)	63.6 (53.0, 74.1)
Placebo (n=106)	14.4 (7.7, 21.2)
OROS-MPH (n=107)	60.6 (51.2, 70.0)	46.2 (34.6, 57.7)
Patient subgroups based on medication history
Treatment-naïve (n=147)
LDX (n=47)	80.4 (69.0, 91.9)	60.8 (45.0, 76.6)
Placebo (n=51)	19.6 (8.7, 30.5)
OROS-MPH (n=49)	63.8 (50.1, 77.6)	44.2 (26.7, 61.8)
Previously treated with any ADHD medication (n=170)
LDX (n=57)	75.9 (64.5, 87.3)	66.5 (52.6, 80.3)
Placebo (n=55)	9.4 (1.6, 17.3)
OROS-MPH (n=58)	57.9 (45.1, 70.7)	48.5 (33.4, 63.5)

Note: Endpoint was defined as the last on-therapy treatment visit with a valid assessment score.

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; CGI-I, Clinical Global Impressions-Improvement; CI, confidence interval; LDX, lisdexamfetamine dimesylate; OROS-MPH, osmotic-release oral system methylphenidate.

CoghillDBanaschewskiTLecendreuxMEuropean, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorderEur Neuropsychopharmacol201323101208121823332456

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