The Use of Venlafaxine in the Treatment of Major Depression and Major Depression Associated With Anxiety

Abstract

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.

Evaluating the relationship of high-dose venlafaxine prescribing to treatment-resistant depression

“…The results of this study reflect findings of formal studies of treatment-resistant depression (Nierenberg et al, 1994;Poirier et al, 1999), where higher doses of venlafaxine were found to be effective. The mechanism of venlafaxine's apparent efficacy in treating resistant…”

“…Venlafaxine is an effective antidepressant (Khan et al, 1998;Schweizer et al, 1991) that may have some advantages over other antidepressants. Comparative studies against amitriptyline (Gentil et al, 2000) report no difference in efficacy in treating depressive symptoms, whereas comparisons with imipramine (Shrivastava et al, 1994) and fluoxetine (Clerc et al, 1994) have suggested venlafaxine to be significantly superior in certain populations.…”

“…It should be noted that the doses used in these trials were at the higher end of the dose range. Treatment-resistance in these trials was defined as failure to respond to at least two (Poirier et al, 1999) or three (Nierenberg et al, 1994) antidepressants, given at therapeutic doses for more than 4 weeks.…”

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder

“…A fixed dose-response study with sertraline failed to find a dose-response relationship with doses from 50 mg/day to 200 mg/day [Sheikh et al, 2000], whereas a fixeddose study with paroxetine reported significant separation from placebo at 40 mg/day but not at 20 mg/day [Ballenger et al, 1998b]. Venlafaxine has demonstrated a positive dose-response relationship for the treatment of major depression [Kelsey, 1996;Khan et al, 1998;Rudolph et al, 1998], and it is possible that such a response would also be observed among patients with panic and comorbid major depression treated with venlafaxine ER. However, this issue cannot be addressed in this study, which excluded patients with significant depression.…”

Depression: Diagnosis and Management for the Primary Care Physician

“…Starting therapy at lower dosages and gradually titrating upward can minimize nausea, the most common side effect; nausea also diminishes with time after the maintenance dosage has been reached. 16,23,24 Studies have shown that a response to venlafaxine can occur as early as week 1. 23 As the result of a positive doseresponse curve, increasing the dosage has been shown to increase rates of response and remission.…”