For postmenopausal women who fear hormone therapy, women 60 years of age with continuous, severe hot flushing or women with a history of breast cancer, we should consider selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) as therapeutic agents. Base on the results from a meta-analysis and clinical trials regarding hot flushing, paroxetine and the conetrolled-release formultation of paroxetine have been shown to effectively reduce hot flushing by 30~40% and 60~70%, respectively, and 13~41% more reductions as compared to placebo. Venlafaxine reduced hot flushes by 30~60% (133% reductions compared to placebo), and desvenlafaxine reduced hot flushes by 30~70%. Fluoxetine and citalopram were shown to be less effective than paroxetine and venlafaxine, by 20% (113% reductions compared to placebo) and 40~50%, respectively. Sertraline reduced hot flushes 3~18% compared to the placebo group, but was considered ineffective. Citalopram (20 mg), paroxetine (10 mg), venlafaxine (37.5~150 mg), and desvenlafaxine (100~200 mg) not only reduced vasomotor symptoms, but demonstrated additional beneficial outcomes with respect to sleep disturbances, mood, the vigor index, and improved quality of life. Citalopram (20 mg), fluoxetine (20 mg), paroxetine (10 mg), venlafaxine (75~150 mg), and desvenlafaxine (150 mg) are recommended at the corresponding doses after weighing the risks and benefits of these medications. SSRIs and SNRIs were shown to interrupt the conversion of tamoxifen into the active metabolite, endoxifen, and thus SSRIs and SNRIs must not be used in breast cancer patients who are taking tamoxifen. Paroxetine suppressed vasomotor symptoms most potently, followed by fluoxetine, sertraline, citalopram, and venlafaxine.
Breast Neoplasms ; Citalopram ; Cyclohexanols ; Female ; Fluoxetine ; Flushing ; Humans ; Menopause ; Norepinephrine ; Paroxetine ; Quality of Life ; Risk Assessment ; Serotonin ; Serotonin Uptake Inhibitors ; Sertraline ; Tamoxifen ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

Venlafaxine is among the most widely prescribed antidepressants. It is extensively metabolized to O-desmethylvenlafaxine via cytochrome P450 (CYP) 2D6. We report a case of acute toxic hepatitis resulting from venlafaxine in a 54-year-old woman with pain disorder. During venlafaxine treatment, laboratory tests revealed elevated liver enzymes with a maximum of 169 IU/L for aspartate transaminase (AST) and 166 IU/L for alanine transaminase (ALT). AST and ALT levels returned to normal after 6 days of discontinuation of venlafaxine. The patient was finally diagnosed with acute toxic hepatitis through liver biopsy. This case indicates the importance that clinicians should be aware of the hepatotoxicity of venlafaxine in practice.
Alanine Transaminase ; Antidepressive Agents ; Aspartate Aminotransferases ; Biopsy ; Cyclohexanols ; Cytochrome P-450 Enzyme System ; Drug Toxicity ; Drug-Induced Liver Injury ; Female ; Humans ; Liver ; Middle Aged ; Somatoform Disorders ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry

Recent studies have indicated that hyponatremia can be associated with antidepressants, and venlafaxine is a widely used serotonin norepinephrine reuptake inhibitor (SNRI) that has been reported to induce this electrolyte abnormality. A 76-year-old female patient was observed to have hyponatremia after an increase in the dosage of venlafaxine from 37.5 mg to 75 mg a day. Her electrolyte level normalized after the venlafaxine therapy was discontinued, but the abnormality recurred after therapy was resumed. A few case reports of hyponatremia associated with venlafaxine can be found in the literature. While the present case is consistent with previous reports, it is still remarkable due to the rapid development of the hyponatremia, which was 2 days in this patient versus several weeks in the other reported cases. Therefore, special attention is required for the use of venlafaxine, especially in elderly psychiatric patients and patients with a previous brain lesion.
Aged ; Antidepressive Agents ; Brain ; Cyclohexanols ; Female ; Humans ; Hyponatremia ; Norepinephrine ; Serotonin ; Venlafaxine Hydrochloride

OBJECTIVE: The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression. METHODS: The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pretreatment. Dexamethasone (10 microM, 6 hours) did not affect the level of HSP70 expression relative to control. RESULTS: Short-term (1 hour) venlafaxine treatment significantly increased the level of HSP 70 expression. Simultaneous long-term (72 hours) venlafaxine and dexamethasone treatment significantly reduced the level of HSP70 expression. Dexamethasone treatment administered following long-term (24 and 72 hours) pretreatment with venlafaxine also significantly reduced the level of HSP70 expression. CONCLUSION: Short-term treatment with venlafaxine increases the expression of HSP70, but prolonged treatment with dexamethasone suppresses the venlafaxine-induced expression of HSP70. These findings suggest that HSP70 and dexamethasone play a significant role in the pathophysiology of depression.
Animals ; Cyclohexanols ; Depression ; Dexamethasone ; Glioma ; Heat-Shock Proteins ; HSP70 Heat-Shock Proteins ; Immunohistochemistry ; Rats ; Venlafaxine Hydrochloride

OBJECTIVETo synthesize venlafaxine with an improved novel method.

METHODSp-methoxypheny lethyl-acid was reacted with SOCl(2) to produce acyl chloride which was reacted with N,N-dimethylamine solution to get amide; then through Ivanov reaction and reduction by KBH(4)/BF(3).Et(2)O to yield venlafaxine.

RESULTVenlafaxine was successfully synthesized by using this method with an yield rate of 50.3%.

CONCLUSIONThe improved method is suitable for industrial production of venlafaxine.

OBJECTIVE: Venlafaxine is an antidepressant with a dual action of blocking reuptake of both serotonin and norepinephrine at therapeutic dose like some tricyclic antidepressants. However it may share the relative safety of SSRIs in overdosage and cardiotoxicity. One common concern for 1st line use of venlafaxine is the risk of hypertension. There have been some controversies about this adverse effect. In present study, we evaluate the effects of venlafaxine on blood pressure in therapeutic dose in acute treatment of major depressive patients. METHODS: The sample consisted of 65 major depressive patients who taken venlafaxine and 65 patients taken paroxetine, respectively. Blood pressure and other variables were evaluated in these subjects at baseline, 1 week, and 4 week of acute phase therapy, and mean blood pressure was compared each other by analysis of covariates. The incidence of sustained elevation of blood pressure during the study period was evaluated and stratified by age, sex, past history of hypertension, obesity, and dose of medication. These data were compared in two groups by chi square test and Fisher's Exact Test. RESULTS: At 1 week point, there were no significant differences between the two groups in mean blood pressure and other variables when controlling the baseline data. But at 4 week point, there was significant difference in mean diastolic pressure change between the two groups (venlafaxine group, -0.20+/- 6.98 mmHg;paroxetine group, 0.82+/-6.75 mmHg, p=0.020). When stratified by obesity (BMI>25), there was also significant difference in mean systolic and diastolic pressure change between the two groups at 4 week point (p=0.002;p=0.026). When comparing the incidence rate of sustained elevation of blood pressure during the study periods, only in venlafaxine group, three subjects developed elevation of blood pressure. When stratified the venlafaxine group with various factors, the incidence rate in the subjects who used high dose of venlafaxine (225 mg/day) was significantly different with those who used lower dose (below 225 mg/day). CONCLUSION: Our findings suggest that the use of venlafaxine can be associated with sustained elevation of blood pressure though used in therapeutic dose, but it can be detected with close monitoring and managed by reducing dose or hold the drug. In the future, to find out the risk factor of sustained elevation of blood pressure associated with venlafaxine use, large scaled and well controlled trials are needed.
Antidepressive Agents, Tricyclic ; Blood Pressure ; Cyclohexanols ; Depressive Disorder, Major ; Humans ; Hypertension ; Incidence ; Norepinephrine ; Obesity ; Paroxetine ; Risk Factors ; Serotonin ; Venlafaxine Hydrochloride

Multiple randomized, double-blind, placebo-controlled trials have explored the efficacy of pregabalin for the treatment of generalized anxiety disorder (GAD) and this novel drug was recently approved in Europe. Short-term efficacy of pregabalin as a treatment modality for GAD is well supported by the positive results of several placebocontrolled studies, and most studies confirmed that pregabalin is superior to placebo and comparable with lorazepam, alprazolam and venlafaxine for the treatment of patients with GAD. Especially, pregabalin has a rapid speed of onset combined with equal efficacy in treating both psychic and somatic symptoms of GAD. Additionally, pregabalin has demonstrated potential for the prevention of relapses of GAD. Efficacy in the elderly patients was also shown in a separate placebo-controlled study. Pregabalin has a favorable safety and tolerability profiles relative to benzodiazepines and has minimal potential for drug-drug interactions, abuse and dependence. In the future, research should target further elucidating the efficacy of pregabalin for GAD in relapse prevention, longterm treatment and special populations. Additional studies are needed to guide clinicians in practical issues of how best to use pregabalin as a newer option for the pharmacotherapy of GAD.
Aged ; Alprazolam ; Anxiety ; Anxiety Disorders ; Benzodiazepines ; Cyclohexanols ; Europe ; gamma-Aminobutyric Acid ; Humans ; Lorazepam ; Recurrence ; Pregabalin ; Venlafaxine Hydrochloride

Multiple randomized, double-blind, placebo-controlled trials have explored the efficacy of pregabalin for the treatment of generalized anxiety disorder (GAD) and this novel drug was recently approved in Europe. Short-term efficacy of pregabalin as a treatment modality for GAD is well supported by the positive results of several placebocontrolled studies, and most studies confirmed that pregabalin is superior to placebo and comparable with lorazepam, alprazolam and venlafaxine for the treatment of patients with GAD. Especially, pregabalin has a rapid speed of onset combined with equal efficacy in treating both psychic and somatic symptoms of GAD. Additionally, pregabalin has demonstrated potential for the prevention of relapses of GAD. Efficacy in the elderly patients was also shown in a separate placebo-controlled study. Pregabalin has a favorable safety and tolerability profiles relative to benzodiazepines and has minimal potential for drug-drug interactions, abuse and dependence. In the future, research should target further elucidating the efficacy of pregabalin for GAD in relapse prevention, longterm treatment and special populations. Additional studies are needed to guide clinicians in practical issues of how best to use pregabalin as a newer option for the pharmacotherapy of GAD.
Aged ; Alprazolam ; Anxiety ; Anxiety Disorders ; Benzodiazepines ; Cyclohexanols ; Europe ; gamma-Aminobutyric Acid ; Humans ; Lorazepam ; Recurrence ; Pregabalin ; Venlafaxine Hydrochloride

Although selective serotonin reuptake inhibitors (SSRIs) have been widely used in both psychiatry and other medicine, few cases have been reported SSRI-related hyperprolactinemia and/or galactorrhea. We experienced one case which showed both galactorrhea and hyperprolactinemia following treatment with paroxetine. In the case, a 37-year-old multiparous woman reported galactorrhea after 8-weeks paroxetine treatment for her depression. After 1 month prescription of bromocriptine, dopamine agonist, as well as switching medication from paroxetine to venlafaxine, serotonin-norepinephrine reuptake inhibitor, both galactorrhea and hyperprolactinemia were disappeared. Both hyperprolactinemia and galactorrhea have not been observed even after the cessation of bromocriptine prescription.
Adult ; Bromocriptine ; Cyclohexanols ; Depression ; Dopamine Agonists ; Female ; Galactorrhea ; Humans ; Hyperprolactinemia ; Paroxetine ; Pregnancy ; Prescriptions ; Serotonin Uptake Inhibitors ; Venlafaxine Hydrochloride