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 I2 values
above 50% and fixed effects model was used for analyses with I2 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, I2=62.4%; SMD for random effect -0.375, 95% CI [-1.24; 0.49],
p=0.400; I2=66.6% and SMD for random effect -0.477, 95% CI [-0.97; 0.01],
p=0.059; I2=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, I2=9.1%; and SMD for
fixed effect=-0.186, 95% CI [-0.37; -0.001], p=0.048, I2=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.
Keywords: Depression, filorexant, orexin receptor antagonist,
seltorexant, suvorexant