Psychiatric Drug Interactions

Dr. Preskorn is Professor, Chair, Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, CEO, Clinical Research Institute

Dr. Flockhart is Professor of Medicine, Genetics, and Pharmacology; Chief, Division of Clinical Pharmacology, Indiana University School of Medicine

Among the most notable pharmacodynamic DDIs involving dopamine, norepinephrine, and serotonin are the following:

Catechol-O-methyltransferase Inhibition

• Potentiate the effects of other drugs increasing the synaptic concentration of dopamine, norepinephrine, and serotonin syndrome.
• Antagonize the effects of drugs that block specific dopamine, norepinephrine, and serotonin receptors.

Monoamine Oxidase Inhibition

• Potentiate the effects of other drugs increasing the synaptic concentration of dopamine, norepinephrine, and serotonin syndrome.
• Augment and prolong the efficacy of dopamine agonists for the treatment of Parkinson’s disease
• Can increase the likelihood and severity of dyskinesia, hyperactivity, and hyperkinesias, and psychosis and hyperactivity induced by dopamine agonists.
• Antagonize the effects of drugs that block specific dopamine, norepinephrine, and serotonin receptors.

Release

• Can amplify the effects of other drugs increasing the synaptic concentration of dopamine, norepinephrine, and serotonin syn-drome.
• Augment and prolong the efficacy of dopamine agonists for the treatment of Parkinson’s disease.
• Can increase the likelihood and severity of dyskinesia, hyperactivity, hyperkinesia, and psychosis induced by dopamine agonists.
• Antagonize the effects of drugs that block specific dopamine, norepinephrine, and serotonin receptors.

Dopamine

Dopamine agonism (General)

• Can ameliorate Parkinson’s disease.
• Can cause dyskinesia, hyperactivity, hyperkinesia, and psychosis.
• Dopamine agonist effects can be augmented by other dopamine agonists and blocked by dopamine antagonists.

Dopamine Uptake Inhibition

• Can ameliorate Parkinson’s disease and cause dyskinesia, hyperactivity, hyperkinesia, and psychosis.

Dopa Decarboxylase Inhibition

• Decrease the peripheral conversion of L-dopa to dopamine and thus increase its availability to the brain.

Selective D₂ Receptor Antagonism

• Can cause EPS, including Parkinsonism
• Can aggravate Parkinson’s disease.
• Can reduce dyskinesias in conditions such as Huntington’s disease and reduce psychosis seen in a number of other illnesses.
• Can reverse hyperactivity and hyperkinesias caused by dopamine agonists.

D2  Receptor Partial Agonism

• Reduced risk of EPS, including Parkinsonism
• Reduced risk of aggravating Parkinson’s disease and bradykinesia seen in other dementing illnesses such as AD.
• Could have variable effects on dyskinesias in conditions such as Huntington’s disease.
• Can reduce psychosis seen in a number of illnesses.
• Should reduce the hyperactivity and hyperkinesias caused by dopamine agonists.

Disclosure: Dr. Preskorn is a consultant to Bristol-Myers Squibb, Cyberonics, Eli Lilly, Johnson&Johnson, Memory, Otsuka, Pfizer, Shire, Somerset, and Wyeth; is on the speaker’s bureaus of Bristol-Myers Squibb, Cyberonics, Forest, Otsuka, and Pfizer; and receives grant support from Brtistol-Myers Squibb, Cyberonics, Johnson&Johnson, Memory, Merck, The National Institute of Mental Health, Novartis, Organon, Otsuka, Pfizer, Predix, Sepracor, and Somerset.

Disclosure: Dr. Flockhart is a consultant to Hoffman-La-Roche.