Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder

The psychostimulants methylphenidate, amphetamine and pemoline are among; t he most common medications used today in child and adolescent psychiatry fo r the treatment of patients with attention-deficit hyperactivity disorder. Frequently, these medications are used in combination with other medication s on a short or long term basis. The present review examines psychostimulan t pharmacology, summarises reported drug-drug interactions and explores und erlying pharmacokinetic and pharmacodynamic considerations for interactions . A computerised search was undertaken using Medline (1966 to 2000) and Cur rent Contents to provide the literature base for reports of drug-drug inter actions involving psychostimulants. These leads were further cross-referenc ed for completeness of the survey. Methylphenidate appears to be more often implicated in pharmacokinetic inte ractions suggestive of possible metabolic inhibition, although the mechanis ms still remain unclear. Amphetamine was more often involved in apparent ph armacodynamic interactions and could potentially be influenced by medicatio ns affecting cytochrome P450 (CYP) 2D6. No published reports of drug intera ctions involving pemoline were found. The alpha (2)-adrenergic agonists clonidine and guanfacine have been implic ated in several interactions. Perhaps best documented is their antagonism b y tricyclic antidepressants and phenothiazines. In additional, concurrent b eta -blocker use, or abrupt dis continuation, can lead to hypertensive resp onse. Although there are few published well-controlled interaction studies with p sychostimulants and alpha (2)-adrenergic agonists, it appears that these ag ents may be safely coadministered. The interactions of monoamine oxidase in hibitors with psychostimulants represent one of the few strict contraindica tions.