Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials.

OBJECTIVES: Concerns about the safety of benzodiazepines in older adults may have led investigators and clinicians to underestimate the importance of adequately treating generalized anxiety disorder (GAD) in later life. To evaluate the safety and efficacy profile of an alternative treatment in older patients, we conducted a secondary analysis of five randomized, placebo-controlled clinical trials of extended release venlafaxine (venlafaxine ER, Effexor XR) for adult patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of GAD.

DESIGN: The five multicenter, parallel-group, double-blind, prospectively randomized, placebo-controlled clinical trials used similar designs to evaluate short-term efficacy after 8 weeks. In addition, two studies evaluated efficacy and safety over 24 weeks under double-blind conditions.

SETTING: Outpatients from both primary care and specialty mental healthcare settings were included. Three studies were conducted in the United States and two in Europe.

PARTICIPANTS: Intention-to-treat analyses included 1,839 adult outpatients with a DSM-IV diagnosis of GAD and total scores of > or =18 on the Hamilton Rating Scale for Anxiety (HAMA). Ten percent of the patients were aged 60 and older and 5.0% were aged 65 and older.

INTERVENTION: Fixed or flexible doses of venlafaxine ER in the dose range of 37.5 to 225 mg/day or matched placebo were used for 8 weeks in all studies and for 24 weeks in two studies.

MEASUREMENTS: Primary efficacy variables included the HAMA total score and psychic anxiety factor, the anxiety subscale of the Hospital Anxiety and Depression (HAD) Scale, and the Clinical Global Impression of Improvement (CGI-I). Secondary efficacy variables included the HAMA somatic anxiety factor, the depression subscale of the HAD, CGI-3 severity, the Covi Scale for Anxiety, and the Raskin Scale for Depression.

RESULTS: On the CGI, 66% of older patients (> or =60 years) responded to venlafaxine ER, compared with 41% for placebo (P <.01 by logistic regression). For younger patients (<60 years), comparable figures were 67% and 44%, respectively (P <.001). Analysis of variance showed no main effects for age and no age-by-treatment interactions for any of the primary or secondary efficacy outcome measures for either the 8- or 24-week analyses. Within the older adults subgroup, increasing age did not influence responses. In this cohort of GAD patients, higher levels of depression were associated with decreased responses of anxiety symptoms. In older adults, 23% of venlafaxine ER patients discontinued treatment prematurely versus 31% of those who received placebo; comparable figures for younger adult patients were 27% and 28%, respectively. Discontinuations due to adverse events were 15% versus 14% for venlafaxine ER and placebo, respectively, in older adults compared with 15% versus 8%, respectively, for younger adults.

CONCLUSION: Venlafaxine ER is equally safe and well tolerated by and shows similar efficacy in younger and older patients in the treatment of GAD.