Venlafaxine chemical structureAn Effexor XR 75mg Capsule
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Venlafaxine

Venlafaxine hydrochloride is a synthetic derivative of phenethylamine and a prescription antidepressant first introduced by Wyeth in 1993, and marketed under the trade names Effexor® for tablets and Effexor XR® for extended-release capsules. Efexor® / Efectin® and Efexor XR® / Efexor® Depot / Efectin ER® are alternate trade name spellings used in some countries. Since venlafaxine is under patent, under current United States law, a generic will not be available to U.S. citizens until 2008. The European patent on the drug will hold until 2017. more...

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Uses

Venlafaxine is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. It is known as one of the most activating of the newer antidepressants. While this can be helpful to some, as many depressed patients report feeling exhausted and unmotivated, to others it poses the risk of increased anxiety and agitation.

Venlafaxine is an effective antidepressant for many persons; however, it seems to be especially effective for those with treatment-resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. It has also been found to reduce the severity of 'hot-flashes' in menopausal women. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. (However, this should not be considered a definitive finding, and responses to psychiatric medications vary significantly from individual to individual.)

Off-label / Investigational Uses

Substantial weight loss in patients with major depression, generalized anxiety disorder, and social phobia has been noted, but the manufacturer does not recommend the use as anorectical drug either alone or in combination with phentermine or other amphetamine-like drugs.

Description of Compound

The chemical structure of venlafaxine is designated (R/S)-1- cyclohexanol hydrochloride or (±)-1- cyclohexanol hydrochloride and it has the empirical formula of C17H27NO2 · HCl. It is a white to off-white crystalline solid, distributed in pentagon-shaped peach-colored tablets of 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg. There is also an extended-release version distributed in capsules of 37.5 mg (gray/peach), 75 mg (peach), and 150 mg (brownish red).

Mechanism of Action

Venlafaxine is a bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor, but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active in the synapse. At low dosages, venlafaxine blocks serotonin reuptake alone, similarly to a selective serotonin reuptake inhibitor (SSRI). At medium dosages (about 225mg/day), venlafaxine blocks the reuptake of norepinephrine as well as serotonin. At dosages above 300mg/day, it blocks dopamine reuptake in addition to serotonin and norepinephrine.

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Venlafaxine relieves menopausal hot flashes
From American Family Physician, 11/1/05 by Anne D. Walling

Hot flashes are the most common and troublesome symptoms reported by women during and after perimenopause. For more than 80 percent of these women, hot f lashes persist for more than a year; 9 percent of women older than 70 years report experiencing hot f lashes. For some women, f lashes are inconvenient but not troublesome; however, about 25 percent of these women report severe symptoms that interfere with sleep and daily function. Use of the most effective therapy for hot f lashes, estrogen, has dramatically decreased since publication of the Women's Health Initiative study, which linked hormone use to increased risk of breast cancer and thromboembolic events. Many suggested alternative therapies are based on modulation of the serotonergic and noradrenergic pathways. Venlafaxine (Effexor) inhibits both pathways and has been used to treat hot flashes in women who have a history of or are at high risk of breast cancer. Evans and colleagues studied a long-acting form of venlafaxine in a general population of women experiencing hot f lashes.

The 80 participants were recruited through media advertising and information distributed by clinics. All participants were postmenopausal and reported that they experienced more than 14 hot flashes per week. Women were excluded if they were taking reproductive hormones or antidepressant medications, or if they had any contraindications to antidepressant medications. All participants completed an interview and questionnaire that included mood symptoms. The women also scored the impact of hot flashes on daily activities using a rating scale. During the 12-week study, participants completed a daily diary of hot flashes (occurrence and severity) plus any perceived adverse effects of treatment. The study participants were randomly assigned to receive placebo or extended-release venlafaxine. Participants were asked to take one tablet (placebo or 37.5 mg venlafaxine) daily for one week, then two tablets daily for 11 weeks.

The two groups were comparable in all major variables, but the treatment group reported more frequent and more severe hot flashes, as well as more frequent alcohol use. Eleven women in the treatment group withdrew from the study because of problems with sleeping, anxiety, nausea, or decreased libido. Eight women withdrew from the placebo group because of lack of impact on symptoms. By the end of the first month of the study, patient scores of the effect of hot flashes on daily activities had declined substantially in both groups. In the venlafaxine group, these scores continued to decline until week 12; the scores of the women in the placebo group reverted to baseline. The mean treatment group score fell from 72.4 to 35.3, whereas that of the placebo group returned to around 62. The reduction of 51 percent in the venlafaxine group was significantly greater than the 15 percent recorded in the placebo group. Data from patient diaries showed a reduction in hot flash severity in both groups with a greater, but not significant, improvement in the treatment group. Dry mouth, decreased appetite, and sleeplessness were more common in the venlafaxine group; however, dizziness, tremors, anxiety, diarrhea, and rash were more common in the placebo group. Almost all (93 percent) of the patients treated with venlafaxine chose to continue this medication after the study had ended.

The authors conclude that in this study extended-release venlafaxine significantly modulated the impact of hot flashes on daily activities, but it did not dramatically reduce the apparent frequency or severity of hot flash episodes. They suggest that these results indicate mood elevation or increased coping ability in women with menopause.

ANNE D. WALLING, M.D.

Evans ML, et al. Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial. Obstet Gynecol January 2005;105:161-6.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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