Four cases of adverse reactions to clonidine, administered alone or with methylphenidate MPH), in children aged 8 to 10 years, are reported from the University of California, LA. Patient 1 taking clonidine 0.1 mg t.i.d. and MPH 20 mg A.M. and 20 mg at noon was sedated and fatigued, blood pressure and pulse rate were 16 - 30% below baseline, ECG showed sinus bradycardia, arrhythmia, and ST elevation, and the Holter monitor revealed junctional escape rhythm, with ventricular rate of 40 while asleep. Patient 2, while on clonidine 0.1 mg P.M. and Dexedrine 12.5 mg daily, forgot to take one clonidine dose; after rollerblading for 10 min she became tremulous, had breathing and swallowing difficulty, she looked terrified, her respiration was >100 min, pulse >170 min, she became combative, had hallucinations and was disorientated and febrile. The next morning she had recovered and had amnesia for the event. Patient 3, on clonidine 0.15 mg P.M., MPH 50 mg/day, and lithium, showed atrioventricular block on ECG, with PR interval lengthened from 148 to 200 msec, and bradycardia. Patient 4 had recurrent episodes of syncope related to exercise during treatment with clonidine patch, 0.2 mg every 5 days. He complained of faintness, passed out, had convulsive movements, and died of cardiac arrest after 45 min swimming exercise. Autopsy revealed a congenital cardiac malformation with stenosis of the left coronary artery. Clonidine blood levels were “normal.” 
COMMENT. The authors recommend guidelines for clonidine in treatment of ADHD that include: 1) screening for prior history of cardiac or vascular disease, a contraindication to clonidine in ADHD; 2) baseline resting pulse and blood pressure measurements, and cardiac consultation for abnormal readings, murmurs, or exercise-related syncopal symptoms; 3) dose changes should not exceed 0.05 mg every 3 days. Until more controlled studies are completed regarding the safety of combined clonidine and stimulant therapy, polypharmacy should probably be avoided when prescibing clonidine for ADHD.