A randomized trial of combined citalopram and naltrexone for nonabstinent outpatients with co-occurring alcohol dependence and major depression.

Despite the high rate of co-occurrence of major depression and alcohol dependence, the role of pharmacotherapy in their treatment remains unclear. In the new era of naltrexone for alcohol dependence, it is notable that only 1 study to date has examined the efficacy of antidepressant medication prescribed concurrently with naltrexone. We aimed to determine whether combining naltrexone with citalopram produced better treatment outcomes than naltrexone alone in patients with co-occurring alcohol dependence and depression, and to investigate whether either sex or depression type (independent or substance-induced depression) moderated treatment response. Participants were 138 depressed alcohol-dependent adults who were not required to be abstinent at the commencement of the trial. They were randomized to 12 weeks of citalopram or placebo, plus naltrexone and clinical case management. Treatment was well attended, and medications were reasonably well tolerated with high adherence rates. Substantial improvements in both mood and drinking occurred in both groups, with no significant differences between groups on any of the mood or drinking outcome measures, whether or not other variables were controlled for. No interaction effect was found for independent/substance-induced depression status, whereas there was a marginal effect found by sex, with greater improvement in 1 drinking outcome measure (percent days abstinent) in women taking citalopram. These findings suggest that citalopram is not a clinically useful addition to naltrexone and clinical case management in this treatment population. Independent/substance-induced depression status did not predict treatment response. Findings for sex were equivocal.

Selective inhibition of soluble TNF using XPro1595 improves hippocampal pathology to promote improved neurological recovery following traumatic brain injury in mice.

AIMS: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). BACKGROUND: Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. OBJECTIVES: Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity, and associated functional impairments. METHODS: Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. RESULTS: We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology's within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. CONCLUSION: Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.