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

Recent clinical trials and meta-analyses have indicated that high-intensive statin treatment lowers low-density lipoprotein cholesterol (LDL-C) levels and reduces the risk of nonfatal cardiovascular (CV) events compared with moderate-intensity statin treatment. However, there are residual risks of CV events and safety concerns associated with high-intensity statin treatment. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe plus moderate-intensity statin therapy after acute coronary syndromes incrementally lowers LDL-C levels and improved CV outcomes compared with moderate-intensity statin therapy. However, despite the LDL-C-lowering effects, a substantial residual CV risk still remains, which includes other lipid abnormalities such as low high-density lipoprotein cholesterol (HDL-C). The most representative agents that primarily increase HDL-C are cholesteryl ester transfer protein (CETP) inhibitors. Until now, 4 CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, and anacetrapib, have been introduced and all have significantly raised the HDL-C from 30% to 133%. However, the results for CV outcomes in clinical trials differed, based on the 4 agents. Torcetrapib increased the risk of CV events and total mortality in patients at high CV risk (ILLUMINATE trial). Dalcetrapib and evacetrapib did not result in lower rate of CV events in patients with recent acute coronary syndrome and high risk vascular disease, respectively (dal-OUTCOMES and ACCELERATE trials). However, anacetrapib significantly decreased the incidence of major coronary events in patients with atherosclerotic vascular disease (REVEAL trial). This topic summarizes the major results of recent statin and CETP inhibitor trials and provides framework to interpret and implement the trial results in real clinical practice.
Acute Coronary Syndrome ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Dyslipidemias ; Ezetimibe ; Ezetimibe, Simvastatin Drug Combination ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Incidence ; Lipoproteins ; Mortality ; Vascular Diseases

BACKGROUNDStatins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.

METHODSForty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography.

RESULTSAfter treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P < 0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P < 0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P < 0.05) compared with levels measured during the 4th week.

CONCLUSIONSCoronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Adult ; Aged ; Azetidines ; administration & dosage ; Cholesterol ; metabolism ; Cholesterol, LDL ; blood ; Coronary Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; administration & dosage

No abstract available.
Aminosalicylic Acid* ; Cycloserine* ; Prothionamide* ; Retreatment* ; Tuberculosis, Pulmonary*

PURPOSE: Nocturia has been one of the most bothersome symptoms in benign prostatic hyperplasia (BPH) patients. Therefore, the authors evaluated the effect of tolterodine and oxybutyninin on nocturia in BPH patients. MATERIALS AND METHODS: From September 2006 to March 2007, 82 patients who presented over than 2 in nocturnal bladder capacity index (NCBI) in spite of having alpha blockers for 6 months were enrolled. Group I (n=38) took alpha blocker with tolterodine, group II (n=44) took alpha blocker with oxybutynin. The number of their nocturia episodes was separately evaluated by the time before and after the medication. The complications were assessed using a questionnaire. RESULTS: The number of nocturia episodes decreased by at least 1 in 68.4% (26/38), 84.1% (37/44) of patients in group I, II, respectively, and decreased by 2 or more, 1 and were unchanged or increased were 36.8, 31.6, 31.6% in group I patients and 45.5, 38.6, 15.9% in group II patients, respectively. In baseline nocturia > or =6 group, the nocturia decreased by 1 or more in 66.7%, 77.8% in group I, II, respectively. Adverse events, including dry mouth, dizziness, headache, etc, occurred in 21.1% (8/38) in group I and 27.3% (12/44) in group II patients. The complications between two groups showed no significant differences. CONCLUSIONS: Alpha blockers with tolterodine or oxybutynin can be effectively combined as a treatment option for patients with BPH complaining of unresolved nocturia.
Dizziness ; Headache ; Humans ; Mouth ; Nocturia* ; Prostatic Hyperplasia* ; Surveys and Questionnaires ; Urinary Bladder ; Tolterodine Tartrate

Overactive bladder is a chronic condition defined by bothersome urgency with or without urgency incontinence, usually associated with daytime frequency and nocturia. The treatment of this condition is to control bothersome urinary symptoms and is therefore to improve quality of life. The Korean Continence Society published the overactive bladder guideline in 2007, which suggested the mainstay of management is behavioral therapy and antimuscarinic pharmacotherapy. With growing awareness toward overactive bladder and quality of life, clinical information regarding antimuscarinic agents should be updated. There are several agents with good level of evidence and good grade of recommendation. Newer antimuscarinic agents are available or will be available in near future. The pharmacological properties, efficacy and tolerability of oxybutynin, trospium, propiverine, tolterodine, darifenacin, solifenacin, fesoterodine and imidafenacin are reviewed and discussed here. The results of major clinical studies are summarized.
Cholinergic Antagonists* ; Drug Therapy ; Muscarinic Antagonists ; Nocturia ; Quality of Life ; Urinary Bladder, Overactive* ; Solifenacin Succinate ; Tolterodine Tartrate

PURPOSE: The aim of this study was to investigate the efficacy and adverse effects of oral tolterodine compared to oxybutynin in children with a neurogenic bladder. MATERIALS AND METHODS: 16 patients, with persistent daytime or nighttime wetting after oxybutynin medication for the treatment of a neurogenic bladder, were enrolled. All 16 patients had been crossed-over from oxybutynin to tolterodine due to serious side effects or lack of improvement. The mean age was 6.4 years (range 3 to 11), and the mean body weight was 22kg (range 16 to 33). All patients were initially treated with oral tolterodine, 2mg, twice daily. The efficacy of tolterodine was assessed in comparison to oxybutynin, and considered as improved with a greater than 50% reduction in wetting episodes, as stationary with a less than 50% reduction or as increased or aggravated with a greater than 50% increase. The tolerability was also assessed using a questionnaire for adverse events. RESULTS: The mean duration of tolterodine treatment was 193 days (range 14 to 940). After treatment with an initial tolterodine dose of 2mg bid, 5 patients (31%) were improved, 8 (50%) were stationary and 3 (19%) were aggravated. Overall, the initial tolterodine dose showed equal efficacy to that of oxybutynin (p=0.483). Of the 16 patients, side effects developed in 12 (75%) during the oxybutynin treatment, whereas only 2 (13%) developed side effects during the tolterodine treatment (p=0.001). CONCLUSIONS: Compared to oxybutynin, tolterodine was well tolerated in children, allowing greater compliance and offering an equally effective treatment for neurogenic incontinence in children with a neurogenic bladder. Therefore, it seems that tolterodine can be safely and effectively used to replace oxybutynin in children with a neurogenic bladder.
Body Weight ; Child* ; Compliance ; Humans ; Muscarinic Antagonists ; Surveys and Questionnaires ; Urinary Bladder ; Urinary Bladder, Neurogenic* ; Tolterodine Tartrate

PURPOSE: The incidence of overactive bladder (OAB) and the efficacy of alpha blocker and tolterodine combination therapy were examined in patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Between March 2001 and December 2001, 144 BPH patients were subdivided into those with BPH, or BPH with OAB, based on urodynamic studies. All patients were treated with alpha blockers for 3 months. Patients with no symptomatic improvement were treated with alpha blockers and tolterodine for 2 months. An increase in the International prostate symptom scores (IPSS) of more than 3 points after medication was considered an improvement, but if not, as a failure. RESULTS: Of the 144 patients, 76 (53%) had BPH and 68 (47%) had BPH with OAB. The patients with BPH and OAB were older (p<0.05), but no differences were observed in the serum creatinine, IPSS, prostate volume, maximum flow rate or post-void residual urine (PVR) between the 2 groups. After 3 months treatment with alpha blockers, 79% (60/76) of the BPH and 35% (24/68) of the BPH with OAB patients had improved (p<0.05). Of the patients showing no improvement, 38% (6/16) with BPH and 73% (32/44) with BPH and OAB showed improvement after the addition of tolterodine. CONCLUSIONS: The combination therapy was more effective than alpha blockers alone in the treatment of patients with coexisting BPH and OAB. We recommend identifying these patients with an initial urodynamic study, which allows for the appropriate management and identification of those patients that may benefit from a more invasive treatment.
Creatinine ; Humans ; Incidence* ; Prostate ; Prostatic Hyperplasia* ; Urinary Bladder ; Urinary Bladder, Overactive* ; Urodynamics ; Tolterodine Tartrate

PURPOSE: There are few reports concerning the first-line treatment of choice for an overactive bladder. The aim of this study was to compare the effects of bladder training, tolterodine, and bladder training with tolterodine, as first-line treatments in patients with an overactive bladder. MATERIALS AND METHODS: A prospective randomized study was conducted on 99 female patients with overactive bladders. The patients were treated with bladder training, tolterodine (2mg twice daily), and bladder training with tolterodine, as first-line treatments, for 12 weeks. Of the 99 patients, 74 (bladder training: 24, tolterodine: 24, combined: 26) were followed up for 12 weeks. The treatment efficacy was measured by a micturition diary, subjective urgency scores and subjective perception of bladder condition at the end of the treatment. The safety and tolerability were assessed from adverse events and treatment withdrawals. RESULTS: After 12 weeks of treatment, the mean frequency of micturition and nocturia decreased by 27.1 and 55.8% in the bladder training group, 30.3 and 61.9% in the tolterodine group and 32.6 and 63.2% in the combined therapy group. The subjective mean urgency score decreased by 48.4, 62.5 and 63.2% in the three respective groups. The subjective perception of bladder symptom scores at the end of the treatments were 1.5, 1.42 and 1.31, with significant improvement rates of 50.0, 58.3 and 69.3% in the bladder training, tolterodine and combined therapy groups, respectively. Adverse events, and withdrawals due to adverse events, were 23.1 and 7.7% in the tolterodine and 28.6 and 7.1% in the combined therapy groups, but there were none in the bladder training group. CONCLUSIONS: Bladder training, tolterodine and combined therapy are all effective first-line treatments in female patients with overactive bladders. There are some enhanced effects with the combined therapy than with the bladder training and tolterodine monotherapies. Because of its high success rate, relatively low cost and absence of adverse events, bladder training should be included as a first-line treatment.
Female* ; Humans ; Nocturia ; Prospective Studies* ; Treatment Outcome ; Urinary Bladder* ; Urinary Bladder, Overactive* ; Urination ; Tolterodine Tartrate