Notably, esmirtazapine has a shorter half life of around 10 hours, compared to R-mirtazapine and racemic mixture, which has a half-life of 18–40 hours.[1] Merck has run several studies on low dose (3–4.5 mg) esmirtazapine for the treatment of insomnia. It is attractive for treating insomnia since it is a potent H1-inhibitor and a 5-HT2A antagonist.[8][1] Unlike low-dose mirtazapine, the half life (10 hours) is short enough that next-day sedation may be manageable, however, for people with CYP2D6 polymorphisms, which constitute a sizable fraction of the population, the half-life is expected to be quite a bit longer. Merck researchers claimed that the incidence of next-day sedation was not a problem in one of their studies, but this claim has been challenged (15% of patients complained of daytime sleepiness vs 3.5% in the placebo group).[9]
In March 2010, Merck terminated its internal clinical development program for esmirtazapine for hot flashes and insomnia, "for strategic reasons".[10]
^Clinical trial number NCT00561574 for "A Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)" at
ClinicalTrials.gov
^Teegarden BR, Al Shamma H, Xiong Y (2008). "5-HT(2A) inverse-agonists for the treatment of insomnia". Current Topics in Medicinal Chemistry. 8 (11): 969–976.
doi:
10.2174/156802608784936700.
PMID18673166.
^Lewis V (November 2009). "Undertreatment of menopausal symptoms and novel options for comprehensive management". Current Medical Research and Opinion. 25 (11): 2689–2698.
doi:
10.1185/03007990903240519.
PMID19775194.
S2CID206964530.
^Stahl SM (2008).
"Antidepresents". Depression and bipolar disorder: Stahl's essential psychopharmacology (3rd ed.). Cambridge, UK: Cambridge University Press.
ISBN978-0-521-88663-5.
^Ivgy-May N, Ruwe F, Krystal A, Roth T (July 2015). "Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial". Sleep Medicine. 16 (7): 838–844.
doi:
10.1016/j.sleep.2015.04.001.
PMID26047892.
Notably, esmirtazapine has a shorter half life of around 10 hours, compared to R-mirtazapine and racemic mixture, which has a half-life of 18–40 hours.[1] Merck has run several studies on low dose (3–4.5 mg) esmirtazapine for the treatment of insomnia. It is attractive for treating insomnia since it is a potent H1-inhibitor and a 5-HT2A antagonist.[8][1] Unlike low-dose mirtazapine, the half life (10 hours) is short enough that next-day sedation may be manageable, however, for people with CYP2D6 polymorphisms, which constitute a sizable fraction of the population, the half-life is expected to be quite a bit longer. Merck researchers claimed that the incidence of next-day sedation was not a problem in one of their studies, but this claim has been challenged (15% of patients complained of daytime sleepiness vs 3.5% in the placebo group).[9]
In March 2010, Merck terminated its internal clinical development program for esmirtazapine for hot flashes and insomnia, "for strategic reasons".[10]
^Clinical trial number NCT00561574 for "A Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)" at
ClinicalTrials.gov
^Teegarden BR, Al Shamma H, Xiong Y (2008). "5-HT(2A) inverse-agonists for the treatment of insomnia". Current Topics in Medicinal Chemistry. 8 (11): 969–976.
doi:
10.2174/156802608784936700.
PMID18673166.
^Lewis V (November 2009). "Undertreatment of menopausal symptoms and novel options for comprehensive management". Current Medical Research and Opinion. 25 (11): 2689–2698.
doi:
10.1185/03007990903240519.
PMID19775194.
S2CID206964530.
^Stahl SM (2008).
"Antidepresents". Depression and bipolar disorder: Stahl's essential psychopharmacology (3rd ed.). Cambridge, UK: Cambridge University Press.
ISBN978-0-521-88663-5.
^Ivgy-May N, Ruwe F, Krystal A, Roth T (July 2015). "Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial". Sleep Medicine. 16 (7): 838–844.
doi:
10.1016/j.sleep.2015.04.001.
PMID26047892.