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Pregabalin Effective and Safe for Generalised Anxiety Disorder in Elderly Patients: Presented at ECNP

By Chris Berrie

PARIS, FRANCE -- September 18, 2006 -- Pregabalin is efficacious in relieving the symptoms of generalised anxiety disorder (GAD) in patients aged 65 years or older, according to an 8-week, multicentre, randomised, flexible-dose, placebo-controlled, double-blind, parallel-group, phase 3 trial.

Efficacy and safety data from a study of pregabalin -- a new alpha 2 delta -1 subunit voltage-gated calcium-channel antagonist and analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) -- were presented here on September 17^th at the 19^th Congress of the European College of Neuropsychopharmacology (ECNP).

"Generalised anxiety disorder is a disorder with many concepts and a mean age of 35 years, and in some studies it has been shown to be the most prevalent anxiety disorder in those over the age of 60," said principal investigator Stuart A. Montgomery, MD, PhD, emeritus professor of psychiatry, department of psychiatry, Imperial College School of Medicine, London, United Kingdom.

The reported prevalence of GAD in the elderly is approximately 7%, and these patients tend to have chronic symptoms that can last for years to decades, Dr. Montgomery noted.

Dr. Montgomery and colleagues were interested in pregabalin as a treatment for GAD in older patients because the elderly have more sleep disturbance, and they are more sensitive to drug adverse events, and because previous studies showed that the drug appears to have benefits on both these areas.

The study design consisted of 3 phases: a 1-week screening phase; an 8-week double-blind treatment phase; and a 1-week double-blind taper and follow-up phase. At entry, the 96 patients in the placebo group had a mean age of 72.2 years and were 25.0% male, and the 177 patients on pregabalin had a mean age of 72.4 years and were 30.9% male. Pregabalin dosing was 150 to 600 mg/day twice or three times daily.

Inclusion criteria were for outpatients 65 years of age or greater with a Hamilton Anxiety Rating Scale (HAM-A) total score >/=20 at screening, a Mini-Mental State Examination (MMSE) Folstein total score of 24 or greater and general good health. Patients were exclusion if they had a current or past diagnosis of a range of related disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Revision IV), or alcohol or substance abuse/dependence without at least 6 months of remission.

The primary efficacy assessment was based on a change from baseline to endpoint, as last observation carried forward (LOCF), in the HAM-A total score. Secondary assessments included the same for their Hamilton Depression Rating Scale (HAM-D) total score and their Symptom Checklist 90 Revised (SCR-90-R) subscales.

Baseline and disease characteristics across the placebo and pregabalin treatment groups were not significantly different following randomisation, with a mean time from onset of GAD of 17 years and 16 years, respectively, duration of current GAD episodes of 56 and 63 weeks, and a total number of previous GAD episodes of 4 and 3, respectively.

Of the 202 patients who completed this study, 69 (71.9%) were in the placebo group and 133 (75.1%) were in the pregabalin group.

For the primary efficacy assessment, at 8 weeks as LOCF, pregabalin-treated patients achieved a significantly greater reduction in HAM-A total scores (-12.84, vs -10.65 for placebo; P = .0437). This reduction remained significant from week 4 of treatment (week 4, P = .0043; week 6, P = .0011; week 8, P = .0070).

Dr. Montgomery stressed that patients in the pregabalin group showed significantly greater changes over placebo in both the HAM-A psychic and HAM-A somatic factors scores. In contrast, he noted, the selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors only work on the psychic symptoms.

At week 8 as LOCF, the placebo and pregabalin reductions were: HAM-A psychic, -6.3 versus -7.8; P < .05; HAM-A somatic, -5.4 versus -6.6; P < .05).

Similarly, at 8 weeks as LOCF, the pregabalin-treated patients achieved a significant decrease from baseline over the placebo group for their HAM-D total scores (-5.48, vs -4.02 for placebo; P = .041). For the final secondary assessment, baseline reductions in the SCL-90-R anxiety subscale scores for the pregabalin group were also significantly greater than for placebo (P = .041).

The most common adverse events seen in the study for pregabalin-treated patients versus placebo were dizziness (20.3% vs 11.5%), somnolence (13.0% vs 7.3%), headache (10.2% vs 8.3%) and nausea (9.0% vs 6.3%). The majority of events were mild to moderate in severity.

The main reasons for discontinuation among the pregabalin group were dizziness (4.5%), somnolence (1.1%) and vomiting (1.1%), while for the placebo group this was nausea (3.1%).

These results demonstrate that pregabalin is indeed efficacious for reducing the symptoms of GAD in patients aged 65 years and older, while it remained safe and well tolerated in this elderly population.

"This is the first time that we have had evidence of efficacy in this age group for any of these drugs," he added.

This study was supported by Pfizer Inc.


[Presentation title: Efficacy and Safety of Pregabalin for the Treatment of Generalised Anxiety Disorder in Elderly Patients. Abstract P.4.a.020]

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