How do you sequence pharmacologic treatments for primary insomnia?

First, be sure you have already addressed deficiencies in sleep hygiene:

• Room at 65 degrees F
• Wearing earplugs
• Complete darkness (no visible hand in front of face)
• No clock
• Golden hour before bed
• ETOH, nicotine, and caffeine reduction with cessation of 4 hours before bed
• Writing a list of worries
• Breathing and meditative practices
• No napping
• No taking of beta-blockers at night (they inhibit melatonin synthesis)
• Other items are listed here: AASIM, 2021 

Next, determine by history, if possible, the chronotype; many circadian delayed patients are mistaken for insomniacs. Few clinics (excluding mine) can measure DLMO, but it can be helpful. While actigraphy has been shown to predict DLMO, I have doubts about this approach.

Next, broach the topic of CBT-i, which is available for free virtually at SleepEZ.

Then, I will occasionally employ medications in the following order, trying each one for about 4-12 weeks, often in parallel to addressing the above.

• Magnesium: Adults and kids can do quite well with magnesium (any formulation), start with 400 mg HS and increase by 400 mg every 7 days to the max at 1,600 mg. The only side effect can be a loose stool (no evidence). Can also help prevent migraines.
• Melatonin: Adults and kids can also do well with melatonin (any formulation, start short-acting), start with 0.5 mg (caveat, many suppliers are not accurate in their reported dose) 2-3 hours before bedtime. AASM recommends AGAINST melatonin for insomnia, raising concerns (in children, primarily) that it may mediate unwanted hormone signal changes. While the evidence that melatonin works in insomnia is weak, the evidence against it is also weak, IMO. A potent antioxidant and possibly a hormone booster, benefits have been shown in infertility measures and cancer treatments.
• Anti-histamine-like (TCA's, doxepin, trazodone, OTC's): These all have anticholinergic risk but when used and MONITORED appropriately, they can be effective 2-for-1's (headache, mood), but I avoid them in the elderly.
  • Doxepin at low doses (I use generic liquid, starting at 0.5 mg-3 mg HS) can be valuable in the maintenance of insomnia.
  • The goal is often a 1-6 month course while re-addressing relaxation techniques/meditation tools/CBT-i.
• Z-Drugs (eszopiclone or zolpidem): I will often start with these in ACUTE insomnia and/or new CPAP users, with a plan of 1-4 weeks of use. Using these in chronic insomnia often will fail, but it can be a nice crutch while focusing on other approaches with a plan to wean/discontinue always communicated.
• Orexin Antagonist (suvo/lemborexant) or Alpha Blocker (prazosin): I might consider one of these before anti-histamines and Z-drugs in patients with significant anxiety/PTSD/signs of sympathetic overdrive/hyperarousal (in collaboration with their BH provider). This can also include using alpha 2 agonists (clonidine or guanfacine), but they are the last resort. Even Stellate Ganglion Block (SGB) can be helpful in this population.

I very seldom recommend medications. There is both physical dependency and psychological dependency (patients feeling they need to take something to sleep). I use sleep logs and establish sleep restrictions, e.g., 5 hours only in bed with no naps in the day. Dealing with cognitive distortions where patients feel they absolutely cannot function but they holding down a job often performing at a very high level as well as relaxation exercises before bed with deep breathing to release vagal tone. Medications should only be used as a last resort. A good workbook outlying a program is the insomnia workbook.

1. Sleep diary
2. Sleep hygiene reinforcement
3. GAD/Depression Screening 
4. Discuss actigraphy, irregular sleep wake cycles, and sleep state misperception
5. Trial of melatonin
6. Sleep study (HST/Lab)
7. Treat OSAS if present
8. Trial of somnolence agent therapies

Most of the time, I start with 12.5 mg extended-release zolpidem for my patients. If their sleep remains unsatisfactory, I then consider switching to eszopiclone. Ramelteon is rarely used in my practice, if at all. Trazodone and doxepin would be the next step. I generally avoid benzodiazepines like a plague.

I had a good experience with prescribing orexin inhibitors Dayvigo as well as the new upcoming Quviviq as they block wakefulness and do not induce drowsiness. They may also have a good effect on reducing daytime sleepiness.

I would love to hear how others address the trackers such as Oura rings, Apple watches, etc. I've found that they have dramatically increased my patients' anxiety about sleep and hence, their perceived insomnia.

The best way I've found is to suggest that they speak with their partners who provide support for them to take the device off. Of course, this is part of a larger anxiety about "optimization" which is normalized but not helpful for many people.