Venlafaxine XR as an effective treatment of depression in patients that fail to respond or are intolerant to other antidepressants

In the August, 2005 edition of the journal Depression & Anxiety, Baldemero et al published a report "Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure" [abstract]. This was selected for inclusion on LeadDiscovery's November 9th edition of DailyUpdates-Psychiatric, Sleep & Addictive Disorders as our editors considered this study important both with regard to the treatment of depression and the dynamics of the antidepressant market

Major depressive disorder affects an estimated 340 million people worldwide making it the fourth greatest public health problem. In addition to the personal costs of depression, the disorder also results in more than $40 billion in annual costs in the US alone, due to premature death, lost productivity and absenteeism.

The serotonergic class dominates the market, accounting for 58% of market share in 2002. This class includes the serotonin reuptake inhibitors (SSRIs) however only 40–50% of patients achieve response or remission when treated with SSRIs. The serotonergic class also includes dual reuptake inhibitors, often referred to as SNRI which simultaneously block serotonin and norepinephrine uptake. The dual reuptake inhibitors are led by Wyeth’s Effexor which, according to its manufacturer helps significantly more patients achieve remission and resolution of both emotional and physical symptoms than SSRIs. Lilly’s launch of the dual reuptake inhibitor Cymbalta in 2004 represents the first major challenge to Effexor.

An estimated 25-30% of patients fail to respond to antidepressant treatment while a further 10–20% fail to tolerate it, and patients that fall into either of these categories are often switched to a different antidepressant. At present the preferred choice of second line antidepressant is unclear however given the high rate of switching the identification of such a second line treatment would carry a significant market advantage to that therapeutic.

In the August, 2005 edition of the journal Depression & Anxiety, Baldemero and colleagues report the findings of a randomized, open-label, multicenter study comparing effectiveness of venlafaxine XR with that of conventional antidepressants in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a conventional antidepressant in a primary care setting.

Patients who had failed to tolerate or respond to conventional antidepressant treatment in a primary care setting were randomly assigned to treatment with an alternate conventional antidepressants or venlafaxine XR. The antidepressants prescribed most frequently in the conventional antidepressants group were paroxetine, citalopram, sertraline, fluoxetine and mirtazapine. After 24 weeks of treatment, the venlafaxine XR group demonstrated a significantly higher remission rate (59.3%) than did the conventional antidepressants group (51.5%), paralleling this improvement venlafaxine XR produced a greater response. Furthermore both patients and clinicians both reported a very much improved level of depression more frequently when treated with venlafaxine XR as compared to other antidepressants. When compared to conventional antidepressants individually, venlafaxine XR was superior to each of these compounds. On the basis of the current study venlafaxine XR appears to be a antidepressant of choice in patients unresponsive to or intolerant of conventional SSRIs. This will need to be born out by double-blind trials however if this is indeed the case the sales of venlafaxine XR stand to be boosted still further.

The antidepressant market is set to undergo a period of rapid change as seven out of the eight leading brands suffer US patent expiries by 2008 (see Antidepressants - Sliding SSRI Revenues Inevitable). With only a handful of new products anticipated to replace these blockbuster products, Datamonitor conclude in this report that the market will decrease by 21.5% to $13.5 billion by 2011, as physicians are encouraged to utilize cheaper generics. Datamonitor also conclude that brand players should be looking towards maximizing revenues through product differentiation and innovative lifecycle strategies. The present study by Baldemero et al goes part of the way to this goal differentiating further, venlafaxine XR from conventional SSRIs with respect to its second-line potential. This coupled with improved efficacy in a first-line setting should maximize its revenue generating potential.