Amitriptyline HCL (Elavil) for Insomnia
Amitriptyline hcl is an old tertiary amine tricyclic antidepressant indicated for the treatment of major depressive disorder. It is a potent antidepressant with strong sedative properties.
Amitriptyline is used to treat depression, mainly melancholic and endogenous, or when anxiety or insomnia coexist. This antidepressant is also used to treat obsessive-compulsive disorders, chronic pain, and bed-wetting in children over 6 years of age (enuresis). Amitriptyline plus perphenazine works well in psychotic depression.
Amitriptyline is widely used in the management of chronic pain syndromes such as migraines, headaches, vulvodynia, fibromyalgia, and irritable bowel syndrom.
Amitriptyline Effectiveness for Insomnia
Insomnia is an insufficient amount of night sleep or a non-restorative, poor-quality sleep. Once the problem has lasted longer than 30 days, the patient is considered to have chronic insomnia. Although sleeping pills may help fall asleep quicker and increase total time asleep, they may not improve the actual quality of sleep.
Amitriptyline is not specifically licensed for insomnia and there is only limited evidence from clinical trials of its effectiveness. However, amitriptyline is widely prescribed by doctors for sleep problems28, particularly when insomnia is associated with anxiety, depression, or other psychiatric disorders. It is also effective for sleep problems related to pain. Amitriptyline is generally considered an effective sleep aid and suitable for long-term use28.
Amitriptyline is as effective as lorazepam (Ativan) for insomnia due to opiate withdrawal29.
The principal advantage of amitriptyline over traditional hypnotics is lack of abuse potential. On the other hand daytime sleepiness and sedation are significant problem with amitriptyline.
Amitriptyline effects on sleep:3
- Increased total sleep time
- Decreased sleep latency (the time period from from "lights out" to sleep onset)
- Increased percentage of Stage 2 sleep
- Decreased percentage of REM sleep
- Increased REM latency (the time it takes for the first onset of REM sleep)
- increase sleep efficiency
Dosage for Insomnia
Amitriptyline is commonly used at doses 10 or 25 mg to promote sleep3. At this dose the drug is probably acting mostly as a histamine H1 receptor antagonist.
Reasons to avoid Amitriptyline as a sleep aid:
- Cardiac arrhythmias, myocardial infarction, and other cardiovascular problems
- Children <12 years of age
- Use of MAOIs
- Elderly with risk of falls
- Persons at high risk of overdose.
- Low-dose amitriptyline is generally safe and suitable for long-term use
- Benefitial for chronic insomnia associated with fibromyalgia 10
- Effective for sleep problems related to pain
- Suitable sleep aid in substance abusers because of low risk of addiction
- Low cost and generic availability
- Not officially approved for the treatment of insomnia.
- Lack of comparative clinical studies with other hypnotics.
- Amitriptyline has a long half-lives, which often leads to daytime sleepiness and sedation 6.
- May exacerbate restless legs syndrome or periodic limb movement disorder, or precipitation of REM sleep behavior disorder 9.
- Dangerous in overdose -- may cause convulsions, cardiac arrhythmias, severe hypotension.
- May increase appetite and cause sweet craving 20
- Potential for weight gain 19, 20
- May cause Impairment of cognitive skills and psychomotor abilities
- Poor tolerability -- the burden of anticholinergic effects like dry mouth, drowsiness, constipation and fatigue. Being the is the most anticholinergic tricyclic antidepressant amitriptyline is most likely to produce delirium.
- Cardiotoxicity: high risk of cardiovascular side effects, including orthostatic hypotension, changes in heart rhythm and conduction 1
- Absorption: appears in plasma within 30 to 60 minutes after oral ingestion and 5 to 10 minutes after intramuscular injection.
- Elimination half-life: varies from 9 to 27 hours (average: 15 hours); nortriptyline, the most important metabolite, has a half-life of 38 hours (18-60 hours) 2
- Metabolism: demethylated in the liver to its primary active metabolite, nortriptyline; Metabolism may be impaired in the elderly.
- Excretion: urine (18% as unchanged drug), feces (small amounts)
Mechanism of action
Amitriptyline increases the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane 22. The medication also produces antimuscarinic and antihistaminic effects by blocking histamine H1 receptors 5.
Amitriptyline's sleep promoting effects are mediated by antagonistic effects on histamineH1, serotonin 5HT2, and alfa-adrenergic receptors. Also, amitriptyline is a strong REM sleep suppressorl7, 8.
Sedative antidepressants, which can substitute for amitriptyline include:
- 1. Jefferson JW. A review of the cardiovascular toxicity of tricyclic antidepressants. Psychosomatic Medicine 1975 Mar-Apr;37(2):160-79.
- 2. Ghose K. Decreased tyramine sensitivity after discontinuation of amitriptyline therapy. An index of pharmacodynamic half-life. Eur J Clin Pharmacol. 1980 Aug;18(2):151-17.
- 3. S. Chokroverty. Sleep Disorders Medicine. (3rd Ed) Philadelphia: W.B. Saunders, 2009, pp. 374-375
- 4. Brenne E, van der Hagen K, Maehlum E, Husebo S. Amitriptyline for chronic pain: a double-blind study with determination of serum levels. Tidsskr Nor Laegeforen. 1997 Oct 10;117(24):3491-4.
- 5. Kachur JF, Allbee WE, Gaginella TS. Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and in vitro. J Pharmacology Experimental Therapeutics 1988 May;245(2):455-9.
- 6. Doerr JP, Spiegelhalder K, Petzold F, Feige B, Hirscher V, Kaufmann R, Riemann D, Voderholzer U. Impact of escitalopram on nocturnal sleep, day-time sleepiness and performance compared to amitriptyline: a randomized, double-blind, placebo-controlled study in healthy male subjects. Pharmacopsychiatry. 2010 Jul;43(5):166-73. PubMed
- 7. Scharf MB, Hirschowitz J, Zemlan FP, Lichstein M, Woods M. Comparative effects of limbitrol and amitriptyline on sleep efficiency and architecture. J Clin Psychiatry. 1986 Dec;47(12):587-91. PubMed
- 8. Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am J Gastroenterol. 1998 Feb;93(2):160-5. PubMed
- 9. Goerke M, Rodenbeck A, Cohrs S, Kunz D. The influence of the tricyclic antidepressant amitriptyline on periodic limb movements during sleep. Pharmacopsychiatry. 2013 May;46(3):108-13. PubMed
- 10. Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010 Feb 1;110(2):604-10. PubMed
- 19. Berilgen MS, Bulut S, Gonen M, Tekatas A, Dag E, Mungen B. Comparison of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels. Cephalalgia. 2005 Nov;25(11):1048-53.
- 20. Berken GH, Weinstein DO, Stern WC. Weight gain. A side-effect of tricyclic antidepressants. J Affect Disord. 1984 Oct;7(2):133-8. PubMed
- 21. Riemann D, Velthaus S, Laubenthal S, Müller WE, Berger M. REM-suppressing effects of amitriptyline and amitriptyline-N-oxide in healthy volunteers: results of two uncontrolled pilot trials. Pharmacopsychiatry. 1990 Nov;23(6):253-8.
- 22. Hyttel J, Christensen AV, Fjalland B. Neuropharmacological properties of amitriptyline, nortriptyline and their metabolites. Acta Pharmacol Toxicol (Copenh). 1980 Jul;47(1):53-7. PubMed
- 23. Amitriptyline Hydrochloride Monograph from American Society of Health-System Pharmacists
- 27. Wilson S, Nutt D. Management of insomnia: treatments and mechanisms. Br J Psychiatry. 2007;191:195–197.
- 28. Everitt H, McDermott L, Leydon G, Yules H, Baldwin D, Little P. GPs’ management strategies for patients with insomnia: a survey and qualitative interview study. Br J Gen Pract. 2014 Feb;64(619):e112-9.
- 29. Srisurapanont M, Jarusuraisin N. Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study. Acta Psychiatr Scand. 1998 Mar;97(3):233-5. PubMed
- Generic name: Amitriptyline Hydrochloride
- Brand names: Amitrol, Elavil, Endep, Levate, Tryptizol, Vanatrip
- Dosages: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets
- Pharmacologic category: Tricyclic antidepressant, Tertiary amine
- Habit forming? No
- Pregnancy risk factor: C
- Many doctors prefer amitriptyline to other TCAs for the treatment of chronic pain. However, many TCAs may be effective for chronic pain.
- They remained the first line of treatment for depression through the 1980s, before newer SSRI antidepressants arrived.
- Amitriptyline is a strong antihistamine.