Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation

Abstract

Blockade of the inflammatory cytokine tumor necrosis factor (TNF) in depressed patients with increased inflammation has been associated with decreased depressive symptoms. Nevertheless, the impact of TNF blockade on sleep in depressed patients has not been examined. Accordingly, sleep parameters were measured using polysomnography in 36 patients with treatment resistant major depression at baseline and 2 weeks after 3 infusions (week 8) of either the TNF antagonist infliximab (n=19) or placebo (n=17). Markers of inflammation including c-reactive protein (CRP) and TNF and its soluble receptors were assessed along with depression measured by the 17-item Hamilton Depression Rating Scale. No differences in sleep parameters were found as a function of infliximab treatment over time. Nevertheless, Wake After Sleep Onset (WASO), the spontaneous arousal index and sleep period time significantly decreased, and sleep efficiency significantly increased, from baseline to week 8 in infliximab-treated patients with high (CRP>5mg/L)(n=9) versus low inflammation (CRP≤5mg/L)(n=10), controlling for changes in scores of depression. Stage 2 sleep also significantly decreased in infliximab-treated patients with high versus low inflammation. Decreases in soluble TNF receptor 1 significantly correlated with decreases in WASO and increases in sleep efficiency in infliximab-treated subjects with high inflammation. Placebo-treated subjects exhibited no sleep changes as a function of inflammation, and no correlations between inflammatory markers and sleep parameters in placebo-treated patients were found. These data suggest that inhibition of inflammation may be a viable strategy to improve sleep alterations in patients with depression and other disorders associated with increased inflammation.

Examining the role of neuroinflammation in major depression

“…Weinberger et al (2014) sought out to determine whether TNF blockade might improve sleep in TRD patients with high levels of inflammation (CRP 45 mg/L). Patients were randomized to receive infliximab (n ¼19) or placebo (n ¼17) biweekly for 6 weeks, in which polysomnography was conducted at baseline and 2 weeks following the last injection, in addition to measurements of CRP and TNF.…”

Inflammation and the Silent Sequelae of Stroke

“…And in experimental models, SSRIs attenuate lipopolysaccharide-induced inflammation [91]. A variety of more traditional antiinflammatory therapies has also been used for the treatment of depression, including aspirin and other nonsteroidal antiinflammatory drugs, statins, and cytokine inhibitors like etanercept (which blocks TNF) [92][93][94][95]. Agomelatine is a a b c d member of a novel class of new antidepressants which are melatonin agonists; it has been approved by the European Union, after being shown to have similar efficacy to SSRIs for the treatment of depression [96,97].…”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Interestingly, although IFN-α-treated patients exhibited marked fatigue, mean sleep latency tests during daytime hours revealed that IFN-α-treated patients took significantly longer to fall asleep during the day than control subjects. Of note, inhibition of TNF by infliximab was associated with decreased wake after sleep onset and spontaneous arousals and increased sleep efficiency in infliximab-treated depressed patients with high (CRP 45 mg/l) versus low inflammation (CRP ⩽ 5 mg/l), controlling for changes in scores of depression (Weinberger et al, 2015).…”