Robert J. Bielski

To evaluate the efficacy and tolerability of extended-release gepirone (gepirone-ER), a 5-HT(1A) agonist, versus placebo in the treatment of adult outpatients with major depressive disorder (MDD). A double-blind, randomized, placebo-controlled, parallel-group, 8-week study was conducted from October 2003 to August 2004 in outpatients 18 to 64 years old with moderate-to-severe MDD, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), and a baseline Hamilton Rating Scale for Depression (HAM-D(17)) total score > or = 20. Patients were titrated from 20 to 80 mg/day of gepirone-ER or placebo (most patients received gepirone-ER 60 or 80 mg/day by week 3). The primary outcome measure was baseline-to-endpoint mean change in HAM-D(17) total score. Secondary outcome measures included the 28-item version of the HAM-D, HAM-D depressed mood (item 1), Bech Six-Item Scale, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions scale. Significantly greater reductions in HAM-D(17) total scores occurred in gepirone-ER-treated patients compared with placebo-treated patients by week 4 (p = .004) and continued through weeks 6 (p = .006) and 8 (p = .032). Secondary outcomes also improved significantly at multiple timepoints, including at endpoint. The most frequently reported adverse events in the gepirone-ER versus placebo groups were dizziness (45% vs. 10%), nausea (36% vs. 13%), and headache (24% vs. 16%). Dizziness occurred most frequently during initial dosing and up-titration. Gepirone-ER significantly reduced depression symptoms and illness severity in MDD outpatients through the end of the study and was generally well tolerated, confirming previous findings.

This study compared the efficacy and tolerability of escitalopram, a newer SSRI, with paroxetine in the treatment of generalized anxiety disorder (GAD). Patients with DSM-IV-defined GAD were randomized to receive 24 weeks of double-blind flexible-dose treatment with either escitalopram (10-20 mg/day) or paroxetine (20-50 mg/day), followed by a 2-week, double-blind, down-titration period. Mean change from baseline to endpoint (LOCF) in Hamilton Anxiety Scale (HAMA) scores was the primary efficacy variable. Mean baseline HAMA scores for the escitalopram (N = 60) and paroxetine (N = 61) groups were 23.7 and 23.4, respectively. After 24 weeks of treatment, mean changes in HAMA scores were -15.3 and -13.3 for escitalopram and paroxetine, respectively (p = 0.13). Significantly fewer patients withdrew from escitalopram than paroxetine treatment due to adverse events (6.6% vs. 22.6%; p = 0.02). The frequency of treatment-emergent adverse events was higher with paroxetine vs. escitalopram: overall (88.7% vs. 77.0%), insomnia (25.8% vs. 14.8%), constipation (14.5% vs. 1.6%), ejaculation disorder (30.0% vs. 14.8%), anorgasmia (26.2% vs. 5.9%), and decreased libido (22.6% vs. 4.9%). Conversely, diarrhea and upper respiratory tract infection were reported more with escitalopram than paroxetine (21.3% vs. 8.1%, and 14.8% vs. 4.8%, respectively). These results support the use of escitalopram as a first-line treatment for GAD.

Escitalopram is the most selective serotonin reuptake inhibitor (SRI) antidepressant available. Venlafaxine is a non-selective SRI that also inhibits noradrenergic re-uptake. This study compared escitalopram and venlafaxine extended release (XR) in depressed outpatients at the highest doses recommended in the United States. In this randomized trial, patients (diagnosis of DSM-IV-defined major depressive disorder; baseline Hamilton Rating Scale for Depression score of >/= 20) received 1 week of single-blind placebo treatment, followed by 8 weeks of double-blind, fixed-dose treatment with either escitalopram or venlafaxine XR (rapidly titrated to 20 mg/day and 225 mg/day, respectively, in accordance with prescribing information). The primary efficacy variable was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Data were collected from May to December 2002. Mean baseline MADRS scores for the escitalopram (N = 97) and venlafaxine XR (N = 98) groups were 30.7 and 30.0, respectively. There were no significant differences in measures of efficacy between the 2 antidepressants. Mean changes from baseline to endpoint in MADRS total score for escitalopram and venlafaxine XR were -15.9 and -13.6, respectively. Remission (MADRS score of /= 50% reduction from baseline MADRS score) rates for the escitalopram and venlafaxine XR groups were 58.8% and 48.0%, respectively. Tolerability measures favored escitalopram over venlafaxine XR treatment. The venlafaxine XR group had a higher incidence than the escitalopram group of treatment-emergent adverse events (85.0% vs. 68.4%) and discontinuation due to adverse events (16.0% vs. 4.1%; p <.01). Results of this study indicate that, when titrated rapidly to their maximum recommended doses, escitalopram is at least as effective as venlafaxine XR and significantly better tolerated. These results do not support the hypothesis that nonselective SRIs have greater efficacy than selective SRIs.