Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers.

An antidepressant for use in the patient receiving concomitant drug treatment, over-the-counter medications, or herbal products should lack cytochrome P-450 (CYP) 3A4 inductive or inhibitory activity to provide the least likelihood of a drug-drug interaction. This study addresses the potential of 4 diverse antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit or induce CYP3A4. In a 4-way crossover design, 16 subjects received clinically relevant doses of venlafaxine, nefazodone, or sertraline for 8 days or fluoxetine for 11 days.

Clinical pharmacokinetics of sertraline.

Sertraline is a naphthalenamine derivative with the predominant pharmacological action of inhibiting presynaptic reuptake of serotonin from the synaptic cleft. It was initially marketed for the treatment of major depressive disorder and is now approved for the management of panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Sertraline is slowly absorbed following oral administration and undergoes extensive first-pass oxidation to form N-desmethyl-sertraline, a weakly active metabolite that accumulates to a greater concentration in plasma than the parent drug at steady state.

Charleston Antidepressant Drug Interactions Surveillance Program (CADISP).

A prospective antidepressant drug interaction surveillance program was established and collected data for over 4 years in Charleston, SC (Charleston Antidepressant Drug Interactions Surveillance Program, CADISP). One hundred and seventy patients were enrolled. The plasma concentrations and/or clinical effects of drug combinations were monitored in psychiatric patients who received therapy with a selective serotonin reuptake inhibitor (SSRI) or one of the other newer antidepressants (nefazodone, venlafaxine) when combined with other drugs metabolized by the cytochrome P-450 (CYP) enzyme system.

An explanation of the second-dose effect in pharmacokinetics and its meaning for clinical psychopharmacology.

Most psychopharmacologic agents are administered in multiple dosing regimens. Frequently, the relative intensity and/or duration of action of a second dose of medication appear to differ from the initial dose. A theoretical pharmacokinetic basis exists for this phenomenon.

In vitro P-glycoprotein affinity for atypical and conventional antipsychotics.

The transmembrane transporter P-glycoprotein (P-gp) is an ATP-dependent efflux pump for a wide range of drugs. P-gp potentially limits access to brain tissue of psychoactive substrates, but little is known about its specificity for antipsychotics. The objective of this study was to assess the affinity of some atypical antipsychotic drugs in vitro for P-gp as indicative of their potential as P-gp substrates in vivo.

Differential time course of cytochrome P450 2D6 enzyme inhibition by fluoxetine, sertraline, and paroxetine in healthy volunteers.

The selective serotonin reuptake inhibitors (SSRIs) paroxetine, sertraline, and fluoxetine have varying degrees of potency in inhibiting the hepatic cytochrome P450 (CYP) 2D6 enzyme. However, the time course for maximum inhibition to occur or for inhibition to dissipate when dosing is discontinued, requires clarification. In an open label, parallel group study of 45 healthy volunteers, the time course of CYP2D6 inhibition of the above SSRIs was evaluated.

The effects of probenecid on the disposition of risperidone and olanzapine in healthy volunteers.

Study Design: The metabolic pathways of most xenobiotics and endogenous compounds can be divided into phase 1 (oxidative, reductive, and hydrolytic) and phase 2 (glucuronidation, sulfate conjugation, glycine and glutathione conjugation, and acetylation and methylation) processes. Oxidative metabolism by the cytochrome P450 system has been intensively investigated compared with glucuronidation and other conjugation pathways. The primary aim of this study was to evaluate the disposition of olanzapine or risperidone in healthy volunteers with and without coadministration of the uridine diphosphoglucuronate-glucuronosyltransferase inhibitor probenecid.

Hypotension and bradycardia in a healthy volunteer following a single 5 mg dose of olanzapine.

Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and other manifestations of psychotic illness. Common side effects include somnolence, constipation, weight gain, and postural hypotension. The authors report a case of hypotension accompanied by bradycardia in a normal, healthy volunteer participating in an olanzapine pharmacokinetic study following a single 5 mg dose.

Intranasal sumatriptan in post-ECT headache: results of an open-label trial.

Background: Significant headaches occur in up to 45% of patients receiving electroconvulsive therapy (ECT) as a result of treatment. Headaches may at times be severe and affect patient compliance with this treatment modality. The 5-HT(1B/1D) receptor agonist sumatriptan has been reported to be effective for post-ECT headache in several case reports.

Drug glucuronidation in clinical psychopharmacology.

Glucuronidation is a phase II metabolic process and one of the most common pathways in the formation of hydrophilic drug metabolites. At least 33 families of uridine diphosphate-glucuronosyltransferases have been identified in vitro, and specific nomenclature similar to that used to classify the cytochrome (CYP) P450 system has been established. The UGT1 and UGT2 subfamilies represent the most important of these enzymes in human drug metabolism.

An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram.

The selective serotonin reuptake inhibitors (SSRIs) have recently been associated with a variety of somatic and psychiatric symptoms upon abrupt drug discontinuation. These symptoms have been variously termed SSRI withdrawal, or SSRI discontinuation syndrome. Although all of the available SSRIs have been reported to cause discontinuation symptoms, some appear to have a greater propensity to cause these adverse events than others.

The association of the combination of sumatriptan and methysergide in myocardial infarction in a premenopausal woman.

Acute myocardial infarction occurred in a 43 year-old premenopausal woman with controlled hypertension and no known coronary artery disease following the use of the antimigraine medications sumatriptan succinate injectable form and methysergide maleate. The use of sumatriptan is contraindicated within 24 hours of using ergotamine or ergotamine-type medications such as methysergide. This contraindication is based on the theoretical possibility of prolonged vasospasm with the combined use.