Philadelphia, May 21 -- In head-to-head studies of Pfizer Inc's pregabalin versus two widely prescribed medicines, pregabalin was shown to be effective in reducing symptoms of anxiety and sustaining this improvement in patients with moderate to severe generalized anxiety disorder (GAD), according to data presented here today at the annual meeting of the American Psychiatric Association.
Data from two separate short-term studies demonstrate that pregabalin was more effective than placebo and as effective as the benzodiazepine Xanax (alprazolam) and the antidepressant Effexor (venlafaxine) at reducing the symptoms of anxiety. Pregabalin, which has a novel mechanism of action for a potential treatment for anxiety disorders, also achieved significantly faster onset of sustained clinical improvement within the first week of treatment than placebo. Similar significant and sustained improvement within the first week was not achieved by either Xanax or Effexor.
GAD, which affects an estimated five percent of people at some point in their lives, is a psychiatric disorder characterized by chronic and excessive worry and tension as well as physical symptoms such as poor sleep, fatigue, difficulty concentrating and restlessness. GAD affects slightly more women than men, and symptoms are often chronic and worsen during times of stress. It is estimated that only one-third of sufferers seek treatment.
Benzodiazepines, the most widely prescribed treatment for GAD, and antidepressants are effective for treating this condition.
"We continue to search for effective and well-tolerated treatments for GAD and other anxiety disorders," said Dr. Mark Pollack, study investigator and Director of the Anxiety Disorders Program, Massachusetts General Hospital and Associate Professor of Psychiatry, Harvard Medical School.
"Pregabalin appears to have a more rapid onset compared to antidepressants," he said. "It also appears to have fewer complications, such as physical dependence and abuse liability, and appears to cause less sedation and cognitive impairment than benzodiazepines."
Highlights from the pregabalin studies follow. Patients in the studies suffered from moderate to severe GAD for an average of eight to 12 years. Symptoms were assessed using the standard Hamilton Rating Scale for Anxiety (HAM-A).
Pregabalin - Xanax - placebo study
In a four-week randomized, double-blind trial, 455 patients with moderate to severe GAD received either pregabalin (300 mg/day, 450 mg/day or 600 mg/day), Xanax (1.5 mg/day) or placebo. Both pregabalin-treated and Xanax-treated patients showed statistically significant improvements in their anxiety symptoms as measured by the HAM-A versus placebo at the end of the study. Treatment with all three doses of pregabalin resulted in significantly greater early (week one) improvement in anxiety than placebo. This improvement was sustained through the end of the study. In an analysis of time to response, patients treated with all three pregabalin doses achieved significantly faster sustained improvement than patients treated with Xanax.
"Pregabalin is at least as efficacious as Xanax - even a little more effective at week one - and showed comparable efficacy throughout the four-week study, even at a dose of 300 milligrams," said Dr. Karl Rickels, lead investigator and Stuart and Emily Mudd Professor of Psychiatry at the University of Pennsylvania. "In addition, patients on pregabalin had fewer discontinuation symptoms compared to benzodiazepines."
Drowsiness and dizziness were the most frequently reported side effects in the pregabalin and Xanax groups. Discontinuation rates due to side effects were 3 percent, 8 percent and 15 percent for the pregabalin groups (300 mg, 450 mg and 600 mg, respectively) compared to 13 percent for patients who took Xanax and 10 percent for placebo.
Pregabalin - Effexor IR - placebo study
A double-blind study of 426 patients with moderate to severe GAD compared pregabalin (400 mg/day or 600 mg/day) to the antidepressant Effexor (75 mg/day) and placebo. Both pregabalin and Effexor were statistically superior to placebo in reducing anxiety symptoms at the end of six weeks of treatment. Pregabalin patients who completed six weeks of treatment showed significant and sustained clinical improvement versus placebo starting at the first week of therapy. Among these patients, 33 percent of those who received 400 mg of pregabalin and 46 percent who received 600 mg of pregabalin compared with 29 percent who took placebo achieved this early and sustained improvement in anxiety symptoms (a difference that is statistically significant). Improvement on Effexor (23 percent) was not statistically different from placebo at week one.
Dizziness and drowsiness were the most frequently reported adverse events by pregabalin-treated patients; nausea was the most frequently reported adverse event in the Effexor group. Adverse events in both groups were generally mild to moderate. Twenty percent of Effexor-treated patients discontinued treatment due to adverse events versus 6 percent in the 400 mg pregabalin group, 14 percent in the 600 mg pregabalin group, and 10 percent in the placebo group.
Developed by Pfizer, pregabalin has been studied in an extensive clinical program involving over 8,000 patients worldwide. The company plans to submit a New Drug Application to the U.S. Food and Drug Administration by the end of the year for pregabalin in the treatment of GAD, neuropathic pain and as an add-on therapy for epilepsy.
Pfizer Neuroscience is committed to pioneering innovative therapies for neurological and psychiatric disorders. Pfizer's experience in the areas of depression, anxiety, schizophrenia, Alzheimer's disease and epilepsy has helped bring leading medicines to market for the treatment of these disorders.
Neurologic and psychiatric disorders represent an important priority in Pfizer's $5.2 billion development effort, with more than 20 percent of the research and development budget allocated to the development of more effective neuroscience medicines for disorders such as mood and anxiety disorders, migraine, neuropathic pain, fibromyalgia, epilepsy and smoking cessation.
Pfizer Inc discovers, develops, manufactures and markets leading prescription medicines for humans and animals and many of the world's best-known consumer brands.
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