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Many psychotropic drugs may affect plasma lipids profile and their metabolism, with carbamazepine being the best known among them. Methylphenidate is a piperidine derivative structurally related to amphetamines and acts as a central nervous system stimulant. Its effect on lipid metabolism has not been investigated. The authors evaluated how methylphenidate affects the lipid profile in the plasma of patients diagnosed as having attention-deficit hyperactivity disorder (ADHD). All consecutive patients undergoing treatment for ADHD at the Adolescent Psychiatric Clinic (2003-2007) were enrolled. Blood samples for total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein (a) (Lp(a)) were collected before starting treatment and after 3 months of continuous treatment. Forty-two patients (22 men), median age 16, participated. The median total cholesterol count decreased by 9 mg/dL (P < .0002), LDL-C decreased by 5.0 mg/dL (P < .016), and triglycerides decreased by 8.0 mg/dL (P < .016). Changes in the levels of HDL-C, apolipoprotein A, and apolipoprotein B were nonsignificant, and Lp(a) levels decreased by 2.0 mg/dL (P < .0007). Methylphenidate improves the lipid profile by decreasing total cholesterol, triglycerides, LDL-C, and Lp(a).