Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders

Figures & data

Table 1 Double-blind, placebo-controlled, clinical trials of clonidine in children and adolescents with ADHD

Authors	Subjects enrolled (completed)	Design	CLO daily dose	Efficacy measures	Safety measures	Efficacy	Side effects
Jain et al^Citation15	236 (143)	8-week, two dosage CLO ER groups versus placebo	0.2 mg, 0.4 mg	Multiple ADHD RS and psychological tests by researchers and parents	Clinical report, ECG, VS, laboratory tests	Significantly greater improvement in both CLO ER dosage groups versus placebo	Somnolence Fatigue
Kollins et al^Citation16	198 (165)	8-week, CLO ER add-on versus placebo	Escalating doses, max 0.4 mg	Multiple ADHD RS and psychological tests by researchers and parents	Clinical report, ECG, VS	CLO ER efficacious as an add-on in children with partial response to stimulants	Somnolence Headache Fatigue
Palumbo et al^Citation17	122 (78)	16-week, CLO, MLP, CLO + MLP, placebo	Mean 0.24 ± 0.11 mg Max 0.6 mg	ADHD RS by teachers and parents	Clinical report, ECG, VS	CLO better than placebo by parents reports, but not by teachers’ reports	Sedation
Daviss et al^Citation18	122	16-week, CLO, MLP, CLO + MLP, placebo	Titration max 0.6 mg	N/A	Clinical report, Pittsburgh side effect RS, ECG, VS	N/A	Somnolence Nervousness Bradycardia
Cannon et al^Citation19	122 (84–99)	16-week, CLO, MLP, CLO + MLP, placebo	Mean 0.24 ± 0.11 mg Max 0.6 mg	Questionnaires by parents and ADHD RS by researchers	N/A	CLO + MLP better than placebo	N/A

Abbreviations: ADHD, attention deficit and hyperactivity disorders; CLO, clonidine; ECG, electrocardiogram; ER, extended-release; max, maximum; MLP, methylphenidate; N/A, not available; RS, rating scales; ECG, electrocardiogram; VS, vital sign.

Table 2 Clinical trials of clonidine in children and adolescents with ADHD and comorbidities

Authors	Subjects enrolled (completed)	ADHD comorbid disordersa	Design	CLO daily dose	Efficacy measures	Safety measures	Efficacy	Side effects
Kurlan et al^Citation20	136 (117)	Chronic tic disorder	16-week DB, CLO, MLP, CLO + MLP, placebo	CLO 0.25 mg CLO + MLP 0.28 mg Max 0.6 mg	Multiple ADHD RS and psychological tests completed by researchers, teachers, self, and/or parents	Clinical reports, ECG, VS	CLO better than placebo for hyperactivity and impulsivity, MLP + CLO superior	Sedation, no significant ECG changes
Connor et al^Citation22	24	ODD or CD	3-month SB, CLO, MLP, CLO + MLP, no placebo	Max 0.3 mg	Psychological tests, performance tests, and RS completed by parents and teachers	Clinical reports, side effects RS, ECG, VS	Significant improvement in ADHD, ODD, and CD symptoms for all three groups	CLO + MLP: increase in PR interval and bradycardia (clinically insignificant)
Nair et al^Citation24	50	ODD, CD, or seizures	2-year DB crossover CLO vs CBZ, no placebo	0.008 mg/kg	RS completed by researchers every 4 weeks	Clinical reports, echocardiogram, laboratory tests, chest x-ray, EEG	CLO effective for hyperactivity and impulsivity, but not for inattention	Side effects not stated
Hazell et al^Citation23	67 (60)	ODD or CD	6-week DB, CLO vs placebo as add-on	Min 0.10 mg Max 0.20 mg	ADHD RS by parents and teachers	Clinical reports, side effects RS, VS	Greater reduction in hyperactivity and conduct in CLO group, not statistically significant	Drowsiness Dizziness
Meere et al^Citation21	53	ODD, CD, or depressive/anxiety disorder	7-week, CLO, MLP, placebo	0.004 mg/kg	GO-NO GO Behavioral test	Clinical reports	CLO not effective	N/A

a Note: Subjects in all of the clinical trials had a diagnosis of ADHD and the comorbidities listed.

Abbreviations: ADHD, attention deficit and hyperactivity disorders; ODD, oppositional defiant disorder; CD, conduct disorder; DB, double-blind; ECG, electrocardiogram; EEG, electroencephalogram; SB, single-blind; CLO, clonidine; CBZ, carbamazepine; max, maximum; min, minimum; MLP, methylphenidate; N/A, not available; RS, rating scales; ECG, electrocardiogram; VS, vital signs.

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