Doxepin
In 2016 the American College of Physicians advised that insomnia be treated first by treating comorbid conditions, then with cognitive behavioral therapy and behavioral changes, and then with drugs; doxepin was among those recommended for short-term help maintaining sleep, on the basis of weak evidence. The 2017 American Academy of Sleep Medicine recommendations focused on treatment with drugs were similar. A 2015 AHRQ review of treatments for insomnia had similar findings.
Ventrolateral preoptic nucleus
Lesions in the VLPO in rats results in 50-60% decrease in NREM sleep time and prolonged insomnia. It is hypothesised that disruption of the VLPO results in reduced and irregular inhibition of the arousal system by VLPO meaning patients with insomnia wake up several times during the night. More recent research suggests insomnia could be due to an imbalance of input to arousal system and VLPO neurons, including orexin neuron signalling. Orexin-receptor antagonists are currently being developed for the treatment of insomnia.