Orexin Receptor Antagonists as an Adjunct for the Treatment of Depression: A mini meta-analysis

İngilizce (OpenAlex)

Orexin is involved in the functioning of many behavioural processes as a mediator of a system that sends out extensive projections from the lateral hypothalamus to the brain.These processes include wakefulness, emotional behaviour, feeding and foraging, locomotion, metabolism, reward and addiction systems, sexual behaviour, vigilance and alertness (1-4).These are observable similarities between the behavioural and autonomic functions of orexin and the symptoms of major depressive disorder (MDD).In animal studies, orexin has been shown to increase psychological resilience by stimulating Gamma-Aminobutyric Acid (GABA) activity in the pallidum, decreasing the response to foot shock in orexin knockout mice, increasing fear in open spaces, and increasing the fear response to an unpleasant odour (5,6).Acute stress increases orexinergic activity, whereas chronic stress suppresses it (7,8).It has been suggested that the main effect of antidepressants is to increase hippocampal Brain-Derived Neurotrophic Factor (BDNF) messenger ribonucleic acid (mRNA) (9).This leads to an increase in longterm potentiation (LTP) and synaptic connections in this region.Studies Introduction: There is growing interest in the efficacy of orexin receptor antagonists (ORA), one of the new psychopharmacological agents used in the treatment of insomnia, in other psychiatric disorders such as depression.Methods: This meta-analysis was conducted in accordance with PRISMA requirements.Literature searches were conducted using PubMed, Scopus and EBSCO ( Medline)databases.Search words were (depression OR mood disorder OR affective disorder) AND (orexin OR orx OR hypocretin OR orx1 OR orx2 OR orexin receptor antagonist OR almorexant OR suvorexant OR lemborexant OR daridorexant OR seltorexant OR vornorexant OR filorexant).No date restrictions were used.The random effects model was used for analyses with I 2 values above 50% and fixed effects model was used for analyses with I 2 values below 50%.Results: In the acute phase, ORAs had no significant effect on core, sleepadjusted and total symptoms of depression respectively; Standardized Mean Difference (SMD) for random effect -0.422, 95% CI [-0.90; 0.06], p=0.089,I 2 =62.4%;SMD for random effect -0.375, 95% CI [-1.24; 0.49], p=0.400;I 2 =66.6% and SMD for random effect -0.477, 95% CI [-0.97; 0.01], p=0.059;I 2 =83.1%).However, they had a significant effect on core and total symptoms of depression in the early period respectively; SMD for fixed effect=-0.228,95% CI [-0.44; -0.01], p=0.036,I 2 =9.1%; and SMD for fixed effect=-0.186,95% CI [-0.37; -0.001], p=0.048,I 2 =0.0%, respectively).Conclusion: The results of this meta-analysis suggest that ORAs may provide direct antidepressant efficacy when added to existing antidepressant treatment and may also have indirect antidepressant effects through improvement in sleep symptoms.Considering the physiological effects of orexin on behaviors, ORAs may be promising new treatment modalities in the treatment of many psychiatric disorders other than insomnia.However, these results are preliminary and further studies with different ORAs at different doses and with different samples are needed.