KT is a 44-year-old female who presents to the sleep medicine clinic with sleep complaints. KT explains that she has had difficulty falling asleep and staying asleep for the past four months. Additionally, she admits that her lack of sleep has negatively impacted her job performance and overall satisfaction. After her visit with the provider, she is diagnosed with insomnia disorder. The third-year medical resident rotating in the clinic has a few questions regarding some of the medications used in the treatment of insomnia and consults the pharmacist.  

Which of the following statements is/are correct regarding the medications used in the management of insomnia? Select all that apply. 

A. Intermezzo is available as an extended-release tablet

B. Dayvigo promotes sleep by blocking the orexin neuropeptide signaling system

C. Ambien should be taken on an empty stomach

D. Unpleasant taste has been reported in patients being treated with Lunesta

E. Silenor and Zelapar may be used in combination to treat insomnia when monotherapy has been shown to be ineffective

F. Rozerem promotes sleep by acting as a melatonin receptor agonist

Brand/Generics covered: Intermezzo (zolpidem), Dayvigo (lemborexant) (Lunesta (eszopiclone), Ambien (zolpidem), Silenor (doxepin), Zelapar (selegiline) and Rozerem (ramelteon) 

Answers with rationale:

The correct answers are B, C, D, and F. 

Insomnia disorder is a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis assigned in individuals who experience the following: dissatisfaction with sleep quantity or quality, sleep disturbances leading to daytime distress or dysfunction, difficulty sleep occurring at least 3 times per week and persisting for 3 months and sleeping disturbance not secondary to other substances or illnesses. According to the American Academy of Sleep Medicine (AASM) guidelines, the treatment strategies for the management of chronic insomnia include psychologic therapy (cognitive behavioral therapy) and pharmacologic therapy (benzodiazepines, non-benzodiazepine hypnotics, orexin receptor antagonists, melatonin receptor agonists and sedating antidepressants).  

Answer choice A is incorrect. Intermezzo (zolpidem) is available as a sublingual tablet. Other formulations of zolpidem include IR and CR tablets (Ambien and Ambien CR) and an oral spray (Zolpimist). All of these formulations are controlled substances (C IV) and are subject to laws regarding dispensing of these medications. 

Answer choice B is correct. Dayvigo (lemborexant) and Belsomra (suvorexant) are both orexin-receptor antagonists. Orexin A and B are hypothalamic neuropeptides which may play a role in promoting wakefulness and regulating sleep-wake cycle. Therefore, antagonizing these neuropeptides may promote sleep. 

Answer choice C is correct. Food decreases the time to absorption of zolpidem and therefore should be taken on an empty stomach to maximize duration of sleep.  

Answer choice D is correct. Patients being treated with Lunesta (eszopiclone) have reported an unpleasant, metallic taste on the tongue. Common drugs that may cause a metallic taste are clarithromycin, metformin, and metronidazole. Other common side effects of Lunesta include headache, somnolence, respiratory infection, dizziness and dry mouth.  

Answer choice E is incorrect. While Silenor (doxepin) is FDA approved for insomnia associated with sleep maintenance difficulties, its use with Zelapar (selegiline) is contraindicated. Zelapar, a monoamine oxidase inhibitor (MAOI) used as an adjunct to carbidopa/levodopa in management of Parkinson's Disease, may enhance the serotonergic effect of tricyclic antidepressants (TCAs) such as doxepin which could result in serotonin syndrome. At least 14 days should elapse between discontinuation of a MAOI and initiation of a TCA. 

Answer choice F is correct. Rozerem (ramelteon) promotes sleep by selectively activating melatonin MT1 and MT2 which are receptors that may be involved in regulation of circadian rhythm and sleep onset. Additionally, Rozerem is not a controlled substance and is typically considered in patients with a history of substance abuse. 

Pray everyone had a great Thanksgiving holiday and got some well needed rest. Believe it or not next week's question will be in December! Keep up the hard work!

Dr. B 

NAPLEX Competencies Covered: Area 1 (Obtain, Interpret, or Assess Data, Medical or Patient Information) 1.5 signs and symptoms of medical conditions, health physiology, etiology of diseases or pathophysiology; Area 2 (Identify Drug Characteristics), 2.1 pharmacology, mechanism of action, or therapeutic class; 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied; Area 3 (Develop or Manage Treatment Plans), drug dosing or dosing adjustments; duration of therapy; 3.5 drug route of administration, dosage forms, or delivery systems; 3.6 drug contraindications, allergies, or precautions; 3.7 adverse drug effects, toxicology or overdose, 3.8 drug interactions 

References:

AASM Insomnia Guidelines