Venlafaxine Extended-Release for Depression Following Spinal Cord Injury

Abstract

IMPORTANCE Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury (SCI). Antidepressants are used routinely to treat depression, yet no placebo-controlled trials have been published in this population to our knowledge. OBJECTIVE To determine the efficacy and tolerability of venlafaxine hydrochloride extended-release (XR) for major depressive disorder (MDD) or dysthymic disorder in persons with chronic SCI. DESIGN, SETTING, AND PARTICIPANTS Multisite, randomized (1:1), double-blind, placebo-controlled Project to Improve Symptoms and Mood After SCI (PRISMS) trial. All research staff conducting screening, intervention, and outcome procedures were blinded to randomization status. We screened 2536 patients from outpatient clinics at 6 SCI treatment centers in the United States and randomized 133 participants into the trial. Participants were 18 to 64 years old and at least 1 month after SCI, with MDD or dysthymic disorder. Seventy-four percent of participants were male, and participants were on average 40 years old and 11 years after SCI. Forty-seven percent had cervical injuries, 53.4% had American Spinal Injury Association injury severity A (complete injury) SCI, 24.1% had at least 2 prior MDD episodes, and 99.2% had current MDD. Common comorbidities included chronic pain (93.9%), significant anxiety (57.1%), and history of substance dependence (44.4%). INTERVENTIONS Twelve-week trial of venlafaxine XR vs placebo using a flexible-dose algorithm. MAIN OUTCOMES AND MEASURES The Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks. RESULTS Mixed-effects models revealed a significant difference between the venlafaxine XR and placebo groups in improvement on the Maier subscale from baseline to 12 weeks (treatment effect, 1.6; 95% CI, 0.3-2.9; P = .02) but not on the HAM-D 17-item version (treatment effect, 1.0; 95% CI, −1.4 to 3.4; P = .42). Participants receiving venlafaxine XR reported significantly less SCI-related disability on the Sheehan Disability Scale at 12 weeks compared with placebo (treatment effect, 4.7; 95% CI, 1.5-7.8; P = .005). Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine XR group compared with the placebo group over 12 weeks. CONCLUSIONS AND RELEVANCE Venlafaxine XR was well tolerated by most patients and an effective antidepressant for decreasing core symptoms of depression and improving SCI-related disability. Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic SCI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00592384

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder

“…The SDS is a validated measure of functional impairment that has demonstrated sensitivity to impairment and the effects of treatment across a wide range of disorders, including MDD (Sheehan & Sheehan, 2008). The SDS has been used to assess functional improvement in association with improvements in depressive symptoms for duloxetine (Mancini et al., 2012; Oakes et al., 2012; Sheehan et al., 2011; Wise et al., 2008), desvenlafaxine (Dunlop et al., 2011; Guico‐Pabia et al., 2012; Soares et al., 2009), paroxetine (Wise et al., 2008), bupropion (Hewett et al., 2010; Soczynska et al., 2014), escitalopram (Romera et al., 2012; Soczynska et al., 2014), venlafaxine (Fann et al., 2015; Hewett et al., 2010), levomilnacipran (Asnis et al., 2013; Sambunaris, Bose, et al., 2014), and agomelatine (Montgomery, Nielsen, et al., 2014; Zajecka et al., 2010) with results that have been variable with respect to clinical significance; however, many of these antidepressants showed significant differences versus placebo in the change from baseline versus placebo in the SDS total score when patients were stratified by baseline depressive symptom severity. A recent pooled analysis showed that treatment with duloxetine ( n  = 1,029) and SSRIs ( n  = 835) resulted in significantly greater improvements in the SDS total score (∆ −1.9, p  <   .001; ∆ −1.7, p  <   .01, respectively) compared to placebo ( n  = 329).…”

Changes in pain and quality of life in depressed individuals with spinal cord injury: does type of pain matter?

“…The methodology and primary results can be found elsewhere. 25,28 The study was approved by each of the respective site's internal review board.…”

“…In the parent trial, 25 a total of 2536 subjects with traumatic SCI were screened and 133 were eligible for and consented to the trial. Sixty-four individuals were randomized to receive placebo and 69 individuals were randomized to the venlafaxine condition.…”

“…25 In that trial, a reduction in depression severity was associated with improved QoL 26 and in a separate analysis, treatment with venlafaxine XR improved nociceptive pain, but not neuropathic pain. 27 However, the relationship between pain and QoL was not examined.…”

Studying depression following spinal cord injury: Evidence, policy and practice

“…[14][15][16] Importantly, the first multisite randomized clinical trial of an antidepressant therapy (Venlafaxine XR) for depression among patients with SCI provides critical insights into the potential benefits and possible limitations of this approach. 17 The success of any intervention for depression post-SCI is contingent upon the information obtained in comprehensive, valid and empirically-supported assessments of the correlates, comorbidities, and modifiable risk factors that appear in the Kraft and Dorstyn study and others that do not (e.g. specific type of pain experienced, self-management skills).…”