Nice, France, June 25 - At the World Congress of Biological Psychiatry yesterday, a group of international experts discussed the up to 40 per cent failure rate of the most commonly prescribed single mechanism of action antidepressants, called selective serotonin reuptake inhibitors or SSRIs. According to these experts, an antidepressant with a dual mechanism of action, such as venlafaxine, could potentially improve these response rates and provide a greater likelihood of treatment success.
While SSRIs have been widely used in depression therapy for years, it has been estimated that up to 40 per cent of depressed patients using SSRIs for initial therapy experience treatment failure. SSRI antidepressant therapies available on the market include fluvoxamine, fluoxetine, citalopram, paroxetine, and sertraline. Prescribing venlafaxine has been found to be effective in patients with severe, treatment-resistant depression who had failed to respond to multiple vigorous antidepressant treatments.
Venlafaxine is the first antidepressant in the class known as serotonin noradrenaline reuptake inhibitors (SNRIs). With its dual mechanism of action, venlafaxine selectively targets both serotonin and noradrenaline. These two neurotransmitters found in the brain have been implicated in the regulation of mood and emotion. In contrast, SSRIs predominantly target only one of the brain's neurotransmitters involved in depression, serotonin, and are therefore described as having a single mechanism of action.
Marketed as EFEXOR by Wyeth-Ayerst, venlafaxine has demonstrated a faster onset of action when administered according to a specific dosage regimen to severely depressed hospitalised patients. This unique feature may provide more immediate relief than other antidepressants for a greater number of patients and, in theory, may provide savings associated with a reduction in hospitalisation and other related health care costs.
Clinical studies have indicated that between 50 and 70 per cent of patients may be successfully treated with the recommended venlafaxine dose of 37.5 milligrams twice daily. However, unlike SSRIs, the daily dose may be increased according to label recommendations to provide a greater response. This positive dose response relationship is one of the unique clinical benefits thought to be due to venlafaxine's dual-mechanism of action.
In addition, patients taking venlafaxine generally experience fewer and less severe side effects than those associated with tricyclic antidepressants (TCAs). Venlafaxine also has a low risk of toxicity. Side effects of venlafaxine as well as other antidepressants include nausea, somnolence, headaches, dry mouth, dizziness, and insomnia.
Improving Patient Outcomes
"Depression does not discriminate and can affect anyone, anywhere, at anytime," said Mr. Richard Hornsby, of London, United Kingdom, who has suffered from major depression for nearly half of his 48 years. "More than 110 million people worldwide suffer from some form of depression, ranking the disease among other leading public health concerns including coronary heart disease, cancer, and AIDS.
"This statistic, coupled with depression's personal impact, makes it imperative for all those involved in the diagnosis and treatment of the disease to find the most effective medication as early in therapy as possible," concluded Mr. Hornsby.
Francesc Artigas, Ph.D., Director of the Department of Neurochemistry at the Barcelona Institute of Biomedical Research, Spanish Research Council, in Barcelona, Spain, noted, "The classical antidepressants, the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), are very effective. However, their use may be limited by potentially severe side effects. And, while the SSRIs are effective and better tolerated than earlier antidepressants, they may still be less effective than combined serotonin and noradrenaline reuptake inhibitors in increasing the active concentration of serotonin in the synapses of the brain. Also, in certain clinical studies, dual inhibitors of serotonin and noradrenaline reuptake have proven more effective than SSRIs."
After reviewing the advances made in antidepressant pharmacotherapy over the past decade, Sheldon H. Preskorn, M.D., Professor of Psychiatry at the University of Kansas School of Medicine, Wichita, Kansas (U.S.), and Director of the Psychiatric Research Institute, discussed the problem facing physicians: how to choose among the available antidepressant treatments for first time patients, as well as for patients who have not benefited from a previous trial of antidepressant therapy.
"Drugs that inhibit serotonin uptake inhibition, including both SSRIs and SNRIs, have become popular medications of first choice for many physicians because of their efficacy, safety and good tolerability," said Preskorn. "However, rigorous clinical trials have indicated that up to 50 per cent of patients with clinical depression do not achieve a full remission on antidepressants which act through serotonin uptake inhibition alone. Thus, an important issue becomes 'how do we help these patients?"'
Dr. Preskorn reviewed a recent study examining clinical practice situations, whereby 300 primary care and psychiatric physicians completed a questionnaire on the treatment of 3,000 patients. The study found that more than 50 per cent of patients who did not benefit from initial treatment with one SSRI were treated with a second SSRI antidepressant. Further, 40 per cent of those patients who did not benefit from this second trial of a different SSRI were treated with a third drug from the SSRI class.
"There have been no rigorous data to date to prove whether this strategy of switching antidepressants among the SSRI class makes sense or is an exercise in futility for the patient," said Preskorn. "The pharmacological similarities between the various SSRIs raise questions about the appropriateness of what seems to be a common practice."
To further evaluate and compare the efficacy of SSRIs and SNRIs, as well as the appropriateness of switching antidepressant therapies, a multinational, double-blind comparative study, funded by Wyeth-Ayerst, is being conducted.
The goal of the study is to compare the efficacy of citalopram, a SSRI, against venlafaxine, a SNRI, in patients who have not benefited from prior treatment with a SSRI other than citalopram. It has been hypothesised that the study's response rates will be higher with the use of venlafaxine because of the drug's impact on both serotonin and noradrenaline, in comparison to citalopram, which like other SSRIs appears to act predominantly on serotonin.
Approximately 450 patients will be treated in this study, which will be conducted in numerous countries throughout the world, including Australia, Belgium, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom.
"Rigorous research of this type is critical to the physician and to the patient. These findings will provide physicians with a scientifically based rationale which can aid in treatment selection for both first time patients and the patient who has not benefited from a prior trial of antidepressant therapy," concluded Dr. Preskorn.
The research protocol is one of dozens of studies that have been conducted by Wyeth-Ayerst as part of its commitment to advancing depression therapy.
The discussion among experts was held during a media roundtable sponsored by Wyeth-Ayerst.
Wyeth-Ayerst is a major research-oriented pharmaceutical company with leading products in the areas of women's health care, cardiovascular and metabolic disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines, and infant nutritionals. American Home Products Corporation is one of the world's largest research-based pharmaceutical and health care products companies and is a leading developer, manufacturer and marketer of prescription drugs and over-the-counter medications. It also is a leader in vaccines, biotechnology, agricultural products, animal health care and medical devices.
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