BACKGROUND Vasomotor symptoms (VMS), characterized by hot flashes and night sweats, are the most commonly reported symptoms associated with estrogen deficiency during menopause and occur in up to 70% of women. The goal of treatment is to reduce the frequency and severity of symptoms. Although hormone therapy (HT) is generally recommended as first-line treatment, it is not appropriate for all pa...

Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h af...

Paroxetine, a selective serotonin reuptake inhibitor, is metabolized in the liver and excreted into bile and urine as metabolites, but species differences have been observed in hepatic disposition between rats and humans. A major metabolite in rats is M1-glucuronide, whereas M1-glucuronide and M1-sulfate are found in humans. The primary excretion route of paroxetine-derived radioactivity in rat...

We have conducted a phenotypic screening in endothelial cells exposed to elevated extracellular glucose (an in vitro model of hyperglycemia) to identify compounds that prevent hyperglycemia-induced reactive oxygen species (ROS) formation without adversely affecting cell viability. From a focused library of >6,000 clinically used drug-like and pharmacologically active compounds, several classes ...

This study investigated the possible association of the interleukin-1 beta (IL-1beta) C-511T promoter polymorphism and the interleukin-1 receptor antagonist (IL-1Ra) (86bp)(n) variable number of tandem repeats (VNTR) polymorphism with antidepressant response to paroxetine and mirtazapine treatment. The study group consisted of 101 patients suffering from DSM-IV major depression participating in...

PURPOSE This study investigated population pharmacokinetics of paroxetine, and then performed an integrated analysis of exposure and clinical outcome using population pharmacokinetic parameter estimates in depressed patients treated with paroxetine. PATIENTS AND METHODS A total of 271 therapeutic drug monitoring (TDM) data were retrospectively collected from 127 psychiatric outpatients. A pop...

In light of the article ”Understanding CYP2D6 and Its Role in Tamoxifen Metabolism” (Smith, 2013), we feel it imperative to comment on the recent, unexpected approval by the U.S. Food and Drug Administration (2013) of the selective serotonin reuptake inhibitor paroxetine as a nonhormonal treatment for menopausal hot flashes. Paroxetine is a strong inhibitor of CYP2D6, the same enzyme system tha...

BACKGROUND Evidence indicates that venlafaxine hydrochloride extended release (ER) effectively ameliorates anxiety symptoms. OBJECTIVES To evaluate the efficacy, safety, and tolerability of flexible-dose venlafaxine ER compared with placebo in the short-term treatment of generalized social anxiety disorder and, secondarily, to compare paroxetine with venlafaxine ER and paroxetine with placebo...

CONTEXT Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia. OBJECTIVE To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia. DESIGN Randomized, placebo-controlled trial (November 1995-August 1998). SETT...

Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4-phase crossover study assessed the potential differential e...