Current Phase II investigational therapies for insomnia

Abstract

Introduction: Insomnia is typified by a difficulty in sleep initiation, maintenance and/or quality (non-restorative sleep) resulting in significant daytime distress.

Areas covered: This review summarizes the available efficacy and safety data for drugs currently in the pipeline for treating insomnia. Specifically, the authors performed MEDLINE and internet searches using the keywords ‘Phase II’ and ‘insomnia’. The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT_2A (ITI-007), melatonin/serotonin5-HT_1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.

Expert opinion: Low-priced generic environments and high development costs limit the further development of drugs that treat insomnia. However, the bidirectional link between sleep and certain comorbidities may encourage development of specific drugs for comorbid insomnia. New insomnia therapies will most likely move away from GABA_AR receptors’ modulation to more subtle neurological pathways that regulate the sleep–wake cycle.

Keywords:

• drugs
• GABA
• histamine
• insomnia
• melatonin
• orexin
• receptors
• serotonin

Declaration of interest

N Zisapel is the founder and chief scientific officer of Neurim Pharmaceuticals, the company that developed Circadin and is developing piromelatine for insomnia. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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