Mirtazapine is an antidepressant used for the treatment of mild to severe depression. Mirtazapine is effective in all levels of severity of depressive illness, as well as is in a broad range of symptoms associated with depression.
Although mirtazapine has a tetracyclic chemical structure it is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). This medication may be used in preference to an SSRI due to the fact that it causes fewer sexual difficulties, that are a relatively common side effects of SSRIs. Due to its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic, adrenolytic, and serotonin-related side effects, and is relatively safe if it is overdosed.
Efficacy for insomnia
Mirtazapine is well-known to produce sedation and so potentially may be helpful in the treatment of insomnia. Although not formally approved by FDA as a sleep aid, mirtazapine is commonly used to improve night-time sleep.
Current research indicates that mirtazapine has definite sleep enhancing effects in patients with major depressive disorder 10-11. But evidence of mirtazapine efficacy for insomnia in relatively healthy people is scanty.
Mirtazapine as a sedating antidepressant may be a good choice for depression accompanied by sleep problems.
There is some evidence, that mirtazapine may be a more effective sleep-promoting medication than SSRIs6. However, the lack of clinical studies directly comparing mirtazapine with other sleeping pills hampers any definitive conclusions regarding its relative efficacy.
Mechanism of sleep promotion
Mirtazapine's sedative action has its roots in an antihistaminergic activity -- via histamine-1 receptor antagonism. Antagonism of serotonin 5-HT2 receptors also contributes to sleep-promoting properties.
Mirtazapine effects on sleep 6:
- Increased total sleep time
- Improved sleep latency (time to fall asleep)
- Decreased wake time after sleep onset
- Increased slow-wave sleep (restorative sleep) 11
- Prolonged REM latency11
- Decreased the number of REM episodes11
Dosage
Mirtazapine dosage for insomnia ranges from 7.5 mg to 30 mg at bedtime. Lower doses of mirtazapine are generally more sedating than higher doses. Sedating effects of mirtazapine diminish in doses higher than 30 mg due to adrenergic effects.
Benefits
- Helps fall asleep and stay asleep throughout the night. Mirtazapine also improves sleep quality and promotes more restful and restorative sleep.
- Decreases the concomitant use of sleep medications 10
- Works at low dosage, resulting in fewer side effects and an easier withdrawal.
- Low toxicity and safety in overdose 2
- Unique pharmacology enables to use mirtazapine in combination with other antidepressants.
- Does not cause sexual dysfunction.
- Antiemetic benefits 4.
Drawbacks
Risks associated with using mirtazapine as a sleep aid:
- Not FDA licensed for insomnia treatment. There are better, proven treatments.
- Lack of strong evidence. There are no data demonstrating the usefulness of mirtazapine for chronic insomnia.
- Daytime sedation because mirtazapine's half-life is greater than the usual sleep period. Approximately half of the patients who take mirtazapine develop noticeable sleepiness, sedation, and exhaustion. Mirtazapine-induced sleepiness can be aggravated by alcohol, benzodiazepines, and other CNS depressants.
- Weight gain. Mirtazapine increases appetite, causes voracious cravings for sweets and carbohydrates 9. In fact, increased appetite and weight gain is the predominant reason why people stop taking mirtazapine (Remeron®).
- Withdrawal. Taking low doses of the drug for the purpose of treating insomnia can still result in discontinuation effects.
Pharmacological characteristics
- Elimination half-life: 20 to 40 h
- Metabolism: extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. CYP2D6 and CYP1A2 are involved in formation of an 8-hydroxy metabolite. CYP3A is responsible for formation of N-desmethyl and N-oxide metabolites.
- Excretion: Primary route of elimination is urine (75%) and feces (15%).
Mechanism of action
Although the precise mirtazapine mechanism of action is not known, it increases the amount of norepinephrine and serotonin in the brain. Norepinephrine and serotonin are neurotransmitters, chemicals that nerves use to communicate with each other.
Mirtazapine blocks histamine-1 receptor, so it acts as an antihistamine similar to diphenhydramine (Benadryl). Mirtazapine also blocks the alpha-2 adrenergic receptor (like yohimbine).
Mirtazapine has been shown to inhibit cortisol secretion by the adrenal glands 7.
Alternative sedative antidepressants
References
- 1. Yeephu S, Suthisisang C, Suttiruksa S, Prateepavanich P, Limampai P, Russell IJ. Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study. Ann Pharmacother. 2013 Jul-Aug;47(7-8):921-32.
- 2. Berling I, Isbister GK. Mirtazapine overdose is unlikely to cause major toxicity. Clin Toxicol (Phila). 2013 Nov 14.
- 3. Iwamoto K, Kawano N, Sasada K, Kohmura K, Yamamoto M, Ebe K, Noda Y, Ozaki N. Effects of low-dose mirtazapine on driving performance in healthy volunteers. Hum Psychopharmacol. 2013 Sep;28(5):523-8. PubMed
- 4. Alam A, Voronovich Z, Carley JA. A review of therapeutic uses of mirtazapine in psychiatric and medical conditions. Prim Care Companion CNS Disord. 2013;15(5). pii: PCC.13r01525. PubMed
- 5. Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: a 12-week open-label pilot study. Neuropsychiatr Dis Treat. 2008;4(5):963–966.
- 6. Winokur A, DeMartinis NA 3rd, McNally DP, Gary EM, Cormier JL, Gary KA. Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. J Clin Psychiatry. 2003 Oct;64(10):1224-9. PubMed
- 7. Schüle C, Baghai TC, Eser D, Schwarz M, Bondy B, Rupprecht R. Effects of mirtazapine on dehydroepiandrosterone-sulfate and cortisol plasma concentrations in depressed patients. J Psychiatr Res. 2009 Feb;43(5):538-45. PubMed
- 8. Fox CB, Treadway AK, Blaszczyk AT, Sleeper RB. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009 Apr;29(4):383-97. PubMed
- 9. Laimer M, Kramer-Reinstadler K, Rauchenzauner M, et al. Effect of mirtazapine treatment on body composition and metabolism. J Clin Psychiatry. 2006;67:421-424. PubMed
- 10. Wang D, Li Z, Li L, Hao W. Real-world, open-label study to evaluate the effectiveness of mirtazapine on sleep quality in outpatients with major depressive disorder. Asia Pac Psychiatry. 2014 Jun;6(2):152-60. PubMed
- 11. Shen J, Chung SA, Kayumov L, Moller H, et al. Polysomnographic and symptomatological analyses of major depressive disorder patients treated with mirtazapine. Can J Psychiatry. 2006 Jan;51(1):27-34. PubMed
By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018
