My Author and Lyme Literate (LLMD) Doctor: Some Partial Insomnia Ideas [Part I]

The Three Bs All Can Cause Trouble Sleeping

Evidence Key

• A — Strong: Good clinical evidence/guideline support
• B — Moderate: Meaningful human evidence, but limitations
• C — Limited: Small/inconsistent studies
• D — Insufficient/Experimental: Primarily preliminary evidence

65 Insomnia Treatments — OTC First

#	Treatment	Type / What It Does	Evidence	Reference
1	Melatonin	OTC hormone supplement; influences circadian timing and sleep propensity.	C	Choi K, Lee YJ, Park S, et al. “Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses.” Sleep Medicine Reviews. 2022;66:101692. PMID: 36179487. DOI: 10.1016/j.smrv.2022.101692.
2	Prolonged-Release Melatonin	Sustained melatonin exposure; particularly studied in older adults.	B/C	Lemoine P, Nir T, Laudon M, Zisapel N. “Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older.” International Clinical Psychopharmacology. 2007;22(5):245-251.
3	Diphenhydramine	OTC H1 antihistamine; sedating/anticholinergic.	C / Not preferred	AASM. “Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults.” Journal of Clinical Sleep Medicine. 2017;13(2):307-349. Diphenhydramine was evaluated as an OTC insomnia treatment; current VA/DoD guidance suggests against it for chronic insomnia.
4	Doxylamine	Sedating first-generation antihistamine.	C / Not preferred	VA/DoD. Clinical Practice Guideline for the Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea. 2025. Doxylamine is included in the pharmacologic evidence review.
5	Valerian	Herbal sedative; traditionally used for sleep/anxiety.	C	AASM. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults. 2017. Valerian was included among OTC agents evaluated for insomnia.
6	Valerian + Hops	Herbal combination intended to increase sedative effects.	C	AASM. 2017 pharmacologic insomnia guideline; valerian + hops was specifically evaluated.
7	Magnesium	Mineral supplement; proposed effects through neuronal excitability and GABA-related mechanisms.	C	Abbasi B, et al. “The effect of magnesium supplementation on primary insomnia in elderly: A double-blind randomized clinical trial.” Journal of Research in Medical Sciences. 2012;17(12):1161-1169.
8	Glycine	Amino acid; investigated for thermoregulation and sleep-quality effects.	C	Bannai M, Kawai N, Ono K, et al. “The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers.” Frontiers in Neurology. 2012;3:61.
9	L-Tryptophan	Serotonin/melatonin precursor.	C	AASM. 2017 insomnia pharmacologic guideline; tryptophan was included as an OTC intervention.
10	GABA	OTC gamma-aminobutyric-acid supplement marketed for relaxation/sleep.	D	VA/DoD. 2025 insomnia guideline evidence search includes GABA among herbal/supplement interventions.
11	Chamomile	Herbal preparation/tea; traditionally calming.	C	VA/DoD. 2025 insomnia guideline evidence search includes chamomile among herbal interventions.
12	Lavender	Aromatherapy/oral botanical preparations.	C	VA/DoD. 2025 insomnia guideline evidence search includes oral lavender.
13	Passionflower	Herbal anxiolytic/sedative.	C	Miroddi M, et al. “Passiflora incarnata L.: ethnopharmacology, clinical application, safety and evaluation of clinical trials.” Journal of Ethnopharmacology. 2013;150(3):791-804.
14	Lemon Balm	Melissa officinalis; traditionally used for anxiety and sleep.	C	Cases J, Ibarra A, Feuillère N, et al. “Pilot trial of Melissa officinalis L. leaf extract in volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbance.” Mediterranean Journal of Nutrition and Metabolism. 2011;4:211-218.
15	Hops	Herbal sedative, commonly combined with valerian.	C	AASM. 2017 pharmacologic guideline; valerian/hops preparations were included in the evidence base.
16	Tart Cherry	Juice/concentrate; contains melatonin and polyphenols.	C	Pigeon WR, Carr M, Gorman C, Perlis ML. “Effects of a tart cherry juice beverage on the sleep of older adults with insomnia.” Journal of Medicinal Food. 2010;13(3):579-583.
17	Ashwagandha	Botanical adaptogen; investigated for stress and sleep.	C	Langade D, Kanchi S, Salve J, Debnath K, Ambegaonkar D. “Efficacy and safety of Ashwagandha root extract in insomnia and anxiety.” Cureus. 2019;11(9).
18	Saffron	Botanical supplement investigated for sleep and mood.	C	Moeini M, et al. Randomized clinical research on saffron and sleep outcomes; evidence remains preliminary.
19	CBD	Cannabidiol; marketed for anxiety/sleep.	D	VA/DoD. 2025 insomnia guideline evidence search includes cannabidiol/CBD but does not establish it as a standard insomnia treatment.
20	THC/Cannabis	Cannabinoid products; can alter sleep architecture and subjective sleep.	C/D	VA/DoD. 2025 insomnia guideline evidence search includes cannabis, THC and cannabidiol.

Behavioral and non-drug treatments

#	Treatment	Type / What It Does	Evidence	Reference
21	CBT-I	Cognitive behavioral therapy specifically designed for insomnia.	A+	VA/DoD. Clinical Practice Guideline for Management of Chronic Insomnia Disorder and OSA. 2025. CBT-I is a central recommended treatment.
22	Sleep-Restriction Therapy	Restricts time in bed to consolidate sleep and increase sleep efficiency.	A	Trauer JM, et al. “Cognitive behavioral therapy for chronic insomnia: a systematic review and meta-analysis.” Annals of Internal Medicine. 2015;163(3):191-204.
23	Stimulus-Control Therapy	Reassociates bed/bedroom with sleep rather than wakefulness.	A	Trauer JM, et al. Ann Intern Med. 2015;163:191-204.
24	Cognitive Therapy	Changes catastrophic or dysfunctional beliefs about sleep.	A	Trauer JM, et al. Ann Intern Med. 2015;163:191-204.
25	Relaxation Therapy	Progressive relaxation, breathing and arousal reduction.	B	VA/DoD. 2025 insomnia guideline.
26	Brief Behavioral Treatment for Insomnia (BBT-I)	Condensed behavioral insomnia treatment.	A/B	Manber R, et al. Behavioral treatment of insomnia; incorporated into contemporary insomnia guidelines.
27	Digital CBT-I	Internet/app-delivered CBT-I.	A/B	VA/DoD. 2025 guideline includes digital/remote delivery of behavioral insomnia treatment.
28	Mindfulness Meditation	Reduces cognitive/emotional arousal.	B/C	Rusch HL, et al. Mindfulness meditation and sleep quality systematic review/meta-analysis.
29	Mindfulness-Based Stress Reduction	Structured mindfulness program.	B/C	Gross CR, et al. Mindfulness-based stress reduction for chronic insomnia.
30	Acceptance and Commitment Therapy	Addresses sleep-related struggle and maladaptive control strategies.	C	Hertenstein E, et al. Psychological treatments for insomnia; ACT studied as an emerging behavioral approach.
31	Aerobic Exercise	Regular physical activity can improve sleep quality and insomnia symptoms.	B	Passos GS, et al. “Effects of moderate aerobic exercise training on chronic primary insomnia.” Sleep Medicine. 2011;12(10):1018-1027.
32	Yoga	Physical movement + breathing + relaxation.	B/C	Cramer H, et al. Yoga for improving sleep quality and insomnia symptoms; systematic-review evidence.
33	Tai Chi	Slow movement, breathing and relaxation.	B/C	Irwin MR, et al. “Improving sleep quality in older adults with moderate sleep complaints: a randomized clinical trial of Tai Chi.” Sleep. 2014;37(9):1543-1552.
34	Qigong	Traditional movement/breathing practice.	C	Chan J, et al. Systematic reviews of Tai Chi/Qigong for sleep outcomes.
35	Bright-Light Therapy	Uses timed light exposure to alter circadian phase.	B	van Maanen A, et al. Bright light therapy for insomnia/circadian sleep disturbance; systematic-review evidence.
36	Chronotherapy	Deliberately shifts sleep timing to correct circadian misalignment.	B/C	Auger RR, et al. American Academy of Sleep Medicine circadian rhythm sleep-wake disorder practice parameters.
37	Sleep-Environment Optimization	Darkness, temperature, noise, bedding and environmental control.	B/C	VA/DoD. 2025 insomnia guideline.
38	Biofeedback	Teaches control/reduction of physiological arousal.	C	Morin CM, et al. Nonpharmacologic treatments for chronic insomnia; behavioral evidence review.
39	Hypnotherapy	Hypnosis to reduce arousal and modify sleep-related cognition.	C	Trauer JM, et al. Nonpharmacologic insomnia evidence.
40	Acupuncture	Needle stimulation of traditional acupuncture points.	C	Cheuk DKL, et al. Acupuncture for insomnia; Cochrane/systematic-review evidence.
41	Acupressure	Manual pressure rather than needles.	C	Chen HY, et al. Acupressure for insomnia; systematic-review evidence.
42	Massage Therapy	Physical relaxation and reduction of arousal.	C	Harris PE, et al. Complementary approaches for insomnia; systematic-review literature.
43	Music Therapy	Structured music intended to decrease arousal.	B/C	Jespersen KV, et al. “Music for insomnia in adults.” Cochrane Database of Systematic Reviews. 2021.
44	Slow Breathing	Reduces autonomic arousal before sleep.	C	Jerath R, et al. Physiology of slow breathing and autonomic regulation.
45	Progressive Muscle Relaxation	Sequential muscle contraction/relaxation.	B	Morin CM, et al. Behavioral treatment evidence for chronic insomnia.
46	Guided Imagery	Mental imagery to reduce cognitive arousal.	C	Morin CM, et al. Behavioral treatments for insomnia.
47	Autogenic Training	Self-induced relaxation using physiological sensations.	C	Stetter F, Kupper S. “Autogenic training: a meta-analysis of clinical outcome studies.” Applied Psychophysiology and Biofeedback. 2002;27:45-98.
48	Aromatherapy	Inhaled essential oils, commonly lavender.	C	Lillehei AS, Halcon LL. “A systematic review of the effect of inhaled essential oils on sleep.” Journal of Alternative and Complementary Medicine. 2014;20(6):441-451.
49	Warm Bath/Thermal Bathing	Raises peripheral skin temperature and may facilitate sleep onset.	B/C	Haghayegh S, et al. “Before-bedtime passive body heating by warm shower or bath to improve sleep.” Sleep Medicine Reviews. 2019;46:124-135.
50	Sleep-Hygiene Education	Regular schedule, caffeine/alcohol timing, bedroom environment and behavioral education.	C alone / B as component	VA/DoD. 2025 insomnia guideline emphasizes that sleep hygiene alone is not equivalent to CBT-I.

Prescription medications

#	Treatment	Type / Primary Action	Evidence	Reference
51	Daridorexant	Dual orexin receptor antagonist; reduces wake drive.	A	De Crescenzo F, et al. “Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults.” Lancet. 2022;400(10347):170-184. DOI: 10.1016/S0140-6736(22)00878-9.
52	Lemborexant	Dual orexin receptor antagonist.	A	De Crescenzo F, et al. Lancet. 2022;400:170-184.
53	Suvorexant	Dual orexin receptor antagonist.	A	De Crescenzo F, et al. Lancet. 2022;400:170-184.
54	Eszopiclone	Nonbenzodiazepine hypnotic/Z-drug.	A	De Crescenzo F, et al. Lancet. 2022;400:170-184.
55	Zolpidem	Z-drug; GABA-A receptor modulation.	A	De Crescenzo F, et al. Lancet. 2022;400:170-184.
56	Zaleplon	Very short-acting Z-drug, primarily sleep initiation.	A/B	De Crescenzo F, et al. Lancet. 2022;400:170-184.
57	Low-Dose Doxepin	H1 histamine antagonist at insomnia doses; particularly sleep maintenance.	A/B	De Crescenzo F, et al. Lancet. 2022;400:170-184.
58	Ramelteon	MT1/MT2 melatonin-receptor agonist.	B	De Crescenzo F, et al. Lancet. 2022;400:170-184.

Additional/Off-Label Prescription Treatments

#	Treatment	Type / Primary Action	Evidence	Reference
59	Temazepam	Benzodiazepine hypnotic.	B	AASM. 2017 Clinical Practice Guideline for Pharmacologic Treatment of Chronic Insomnia.
60	Triazolam	Short-acting benzodiazepine hypnotic.	B	AASM. 2017 pharmacologic insomnia guideline.
61	Estazolam	Intermediate-acting benzodiazepine.	B/C	VA/DoD. 2025 insomnia guideline evidence review.
62	Flurazepam	Long-acting benzodiazepine hypnotic.	B/C	VA/DoD. 2025 insomnia guideline evidence review.
63	Trazodone	Sedating antidepressant; widely prescribed off-label.	C / Not preferred	VA/DoD. 2025 guideline includes trazodone in its pharmacologic evidence review; the guideline recommends against its routine use for chronic insomnia.
64	Gabapentin	α2δ calcium-channel ligand; off-label sleep use, especially with pain/RLS.	C	VA/DoD. 2025 insomnia pharmacologic evidence review includes gabapentin.
65	Mirtazapine	Sedating antidepressant, particularly at lower doses; best considered when depression/anxiety is also being treated.	C	VA/DoD. 2025 insomnia pharmacologic evidence review includes mirtazapine.

What Jumps Out From the Evidence

The OTC section is much weaker than the prescription section. This is especially important because “natural” or “OTC” is sometimes interpreted as meaning “well proven.”

For example, the 2022 systematic review of melatonin found no significant improvement in sleep-onset latency, total sleep time or sleep efficiency in adults with non-comorbid chronic insomnia, although there were positive findings in some subgroups.

Likewise, the American Academy of Sleep Medicine’s pharmacologic guideline specifically evaluated OTC diphenhydramine, melatonin, tryptophan and valerian/hops, alongside prescription agents.

By contrast, a large network meta-analysis of pharmacologic treatments involving 69 studies and 17,319 patients found that orexin receptor antagonists ranked particularly well across sleep-onset latency, wake after sleep onset, total sleep time and sleep efficiency.

My Practical Evidence Ranking

Strongest Overall

1. CBT-I
2. Behavioral components of CBT-I
3. DORAs — daridorexant, lemborexant, suvorexant
4. Selected Z-drugs
5. Low-dose doxepin
6. Ramelteon

OTC Options With the Most Reasonable Scientific Rationale

1. Melatonin — especially when circadian timing is the problem
2. Prolonged-release melatonin in appropriate populations
3. Magnesium when deficiency/low intake is relevant
4. Glycine
5. Valerian/valerian-hops
6. Tart cherry
7. Ashwagandha

OTC Options I Would Not Put Near the Top for Chronic Insomnia

• Diphenhydramine
• Doxylamine
• CBD
• THC/cannabis
• GABA supplements

The 2025 VA/DoD guideline is the most useful current anchor for interpreting the entire list; it specifically searched pharmacologic treatments including DORAs, Z-drugs, benzodiazepines, ramelteon, doxepin, antidepressants, antihistamines, melatonin, valerian and supplements, as well as CBT-I.

2025 VA/DoD Insomnia/OSA Clinical Practice Guideline (opens in new tab)