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Mirtazapine and Depressions

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NeuroPsychopharmacotherapy
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Abstract

Mirtazapine was introduced into the United States in 1996 as a norepinephrine and specific serotonergic antidepressant which would have a broad spectrum of activity and hopefully fewer side effects compared with selective serotonin reuptake inhibitors. Mirtazapine consists of S- and R-enantiomers which are metabolized by cytochromes CYP1A2, CYP2D6, and CYP3A4 which are then glucuronidated. Metabolites account for only 10% of mirtazapine antidepressant activity. Oral bioavailability is approximately 50% and half-life 20–40 h. Mirtazapine inhibits presynaptic alpha-2 adrenergic autoreceptors, presynaptic alpha-2 adrenergic heteroreceptors, and two postsynaptic serotonin receptors, 5 HT-2 and 5 HT-3. Mirtazapine labeled indication for treatment of outpatient major depressive disorder. Mirtazapine responses were noted to occur within 1 week of starting therapy and differ significantly from placebo. Responses are equivalent to amitriptyline and, in some reviews, superior to selective serotonin reuptake inhibitors. Mirtazapine appears to be a very cost-effective antidepressant when weighing, response, tolerance, and drug costs. Major side effects are sedation and weight gain. Mirtazapine transiently impairs driving skills. Hyponatremia, sexual dysfunction, and seizure risks are lower with mirtazapine than seen with SSRIs. There are relatively few drug-drug interactions. Mirtazapine has been combined with SSRIs to augment SSRI antidepressant responses. It is the most frequently used antidepressant by survey used to treat depression in cancer.

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References

  • Abo-Zena RA, Bobek MB, Dweik RA. Hypertensive urgency induced by an interaction of mirtazapine and clonidine. Pharmacotherapy. 2000;20:476–8.

    CAS  PubMed  Google Scholar 

  • Acharya T, Acharya S, Tringali S, Huang J. Association of antidepressant and atypical antipsychotic use with cardiovascular events and mortality in a veteran population. Pharmacotherapy. 2013;33:1053–61.

    CAS  PubMed  Google Scholar 

  • Afshar M, Knapp CM, Sarid-Segal O, Devine E, Colaneri LS, Tozier L, Waters ME, Putnam MA, Ciraulo DA. The efficacy of mirtazapine in the treatment of cocaine dependence with comorbid depression. Am J Drug Alcohol Abuse. 2012;38:181–6.

    PubMed  PubMed Central  Google Scholar 

  • Alderman CP, Condon JT, Gilbert AL. An open-label study of mirtazapine as treatment for combat-related PTSD. Ann Pharmacother. 2009;43:1220–6.

    CAS  PubMed  Google Scholar 

  • Altintoprak AE, Zorlu N, Coskunol H, Akdeniz F, Kitapcioglu G. Effectiveness and tolerability of mirtazapine and amitriptyline in alcoholic patients with co-morbid depressive disorder: a randomized, double-blind study. Hum Psychopharmacol. 2008;23:313–9.

    CAS  PubMed  Google Scholar 

  • Ansermot N, Hodel PF, Eap CB. Serotonin toxicity after addition of mirtazapine to escitalopram. J Clin Psychopharmacol. 2014;34:540–1.

    PubMed  Google Scholar 

  • Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001;7:249–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Anttila AK, Rasanen L, Leinonen EV. Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold. Ann Pharmacother. 2001;35:1221–3.

    CAS  PubMed  Google Scholar 

  • Arora S, Vohora D. Comparative evaluation of partial alpha2 -adrenoceptor agonist and pure alpha2 -adrenoceptor antagonist on the behavioural symptoms of withdrawal after chronic alcohol administration in mice. Basic Clin Pharmacol Toxicol. 2016;119:202–9.

    CAS  PubMed  Google Scholar 

  • Banerjee S, Hellier J, Romeo R, Dewey M, Knapp M, Ballard C, Baldwin R, Bentham P, Fox C, Holmes C, Katona C, Lawton C, Lindesay J, Livingston G, Mccrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O’brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Burns A. Study of the use of antidepressants for depression in dementia: the HTA-SADD trial – a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine. Health Technol Assess. 2013;17:1–166.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barkin RL, Chor PN, Braun BG, Schwer WA. A trilogy case review highlighting the clinical and pharmacologic applications of mirtazapine in reducing polypharmacy for anxiety, agitation, insomnia, depression, and sexual dysfunction. Prim Care Companion J Clin Psychiatry. 1999;1:142–5.

    PubMed  PubMed Central  Google Scholar 

  • Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. Int J Neuropsychopharmacol. 2001;4:337–45.

    CAS  PubMed  Google Scholar 

  • Benazzi F. Mirtazapine withdrawal symptoms. Can J Psychiatr. 1998a;43:525.

    Google Scholar 

  • Benazzi F. Serotonin syndrome with mirtazapine-fluoxetine combination. Int J Geriatr Psychiatry. 1998b;13:495–6.

    CAS  PubMed  Google Scholar 

  • Bomholt SF, Mikkelsen JD, Blackburn-Munro G. Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. Neuropharmacology. 2005;48:252–63.

    CAS  PubMed  Google Scholar 

  • Botts S, Diaz FJ, Santoro V, Spina E, Muscatello MR, Cogollo M, Castro FE, De Leon J. Estimating the effects of co-medications on plasma olanzapine concentrations by using a mixed model. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32:1453–8.

    CAS  Google Scholar 

  • Bremner JD, Wingard P, Walshe TA. Safety of mirtazapine in overdose. J Clin Psychiatry. 1998;59:233–5.

    CAS  PubMed  Google Scholar 

  • Cankurtaran ES, Ozalp E, Soygur H, Akbiyik DI, Turhan L, Alkis N. Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine. Support Care Cancer. 2008;16:1291–8.

    PubMed  Google Scholar 

  • Carpenter LL, Jocic Z, Hall JM, Rasmussen SA, Price LH. Mirtazapine augmentation in the treatment of refractory depression. J Clin Psychiatry. 1999;60:45–9.

    CAS  PubMed  Google Scholar 

  • Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry. 2002;51:183–8.

    CAS  PubMed  Google Scholar 

  • Chang HS, Won ES, Lee HY, Ham BJ, Kim YG, Lee MS. Association of ARRB1 polymorphisms with the risk of major depressive disorder and with treatment response to mirtazapine. J Psychopharmacol. 2015;29:615–22.

    PubMed  Google Scholar 

  • Chew-Graham CA, Shepherd T, Burroughs H, Dixon K, Kessler D. The value of an embedded qualitative study in a trial of a second antidepressant for people who had not responded to one antidepressant: understanding the perspectives of patients and general practitioners. BMC Fam Pract. 2018;19:197.

    PubMed  PubMed Central  Google Scholar 

  • Chung MY, Min KH, Jun YJ, Kim SS, Kim WC, Jun EM. Efficacy and tolerability of mirtazapine and sertraline in Korean veterans with posttraumatic stress disorder: a randomized open label trial. Hum Psychopharmacol. 2004;19:489–94.

    CAS  PubMed  Google Scholar 

  • Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018a;391:1357–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cipriani A, Williams T, Nikolakopoulou A, Salanti G, Chaimani A, Ipser J, Cowen PJ, Geddes JR, Stein DJ. Comparative efficacy and acceptability of pharmacological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Psychol Med. 2018b;48:1975–84.

    PubMed  Google Scholar 

  • Connor KM, Davidson JR, Weisler RH, Ahearn E. A pilot study of mirtazapine in post-traumatic stress disorder. Int Clin Psychopharmacol. 1999;14:29–31.

    CAS  PubMed  Google Scholar 

  • Cornelius JR, Chung TA, Douaihy AB, Kirisci L, Glance J, Kmiec J, Wesesky MA, Fitzgerald D, Salloum I. A review of the literature of mirtazapine in co-occurring depression and an alcohol use disorder. J Addict Behav Ther Rehabil. 2016;5. https://doi.org/10.4172/2324-9005.1000159.

  • Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427–52.

    CAS  PubMed  Google Scholar 

  • Davidson JR, Weisler RH, Butterfield MI, Casat CD, Connor KM, Barnett S, Van Meter S. Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial. Biol Psychiatry. 2003;53:188–91.

    CAS  PubMed  Google Scholar 

  • Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Symptom Manag. 2003;25:288–91.

    Google Scholar 

  • De Boer T. The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. Int Clin Psychopharmacol. 1995;10(Suppl 4):19–23.

    PubMed  Google Scholar 

  • De Boer T. The pharmacologic profile of mirtazapine. J Clin Psychiatry. 1996;57(Suppl 4):19–25.

    PubMed  Google Scholar 

  • De Boer T, Broekkamp CL, Gower A, De Graaf JS, De Vos CJ, Rae D, Van Delft AM. The pharmacological profile of Org 6906, a potential non-sedative antidepressant that combines monoamine uptake inhibition with alpha 2-adrenolytic activity. Neuropharmacology. 1988a;27:251–60.

    PubMed  Google Scholar 

  • De Boer TH, Maura G, Raiteri M, De Vos CJ, Wieringa J, Pinder RM. Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers. Neuropharmacology. 1988b;27:399–408.

    PubMed  Google Scholar 

  • De Boer T, Nefkens F, Van Helvoirt A. The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur J Pharmacol. 1994;253:R5–6.

    PubMed  Google Scholar 

  • De Boer TH, Nefkens F, Van Helvoirt A, Van Delft AM. Differences in modulation of noradrenergic and serotonergic transmission by the alpha-2 adrenoceptor antagonists, mirtazapine, mianserin and idazoxan. J Pharmacol Exp Ther. 1996;277:852–60.

    PubMed  Google Scholar 

  • Decoutere L, De Winter S, Vander Weyden L, Spriet I, Schrooten M, Tournoy J, Fagard K. A venlafaxine and mirtazapine-induced serotonin syndrome confirmed by de- and re-challenge. Int J Clin Pharm. 2012;34:686–8.

    PubMed  Google Scholar 

  • Delbressine LP, Moonen ME, Kaspersen FM, Wagenaars GN, Jacobs PL, Timmer CJ, Paanakker JE, Van Hal HJ, Voortman G. Pharmacokinetics and biotransformation of mirtazapine in human volunteers. Clin Drug Investig. 1998;15:45–55.

    CAS  PubMed  Google Scholar 

  • Demers JC, Malone M. Serotonin syndrome induced by fluvoxamine and mirtazapine. Ann Pharmacother. 2001;35:1217–20.

    CAS  PubMed  Google Scholar 

  • Deuschle M, Gilles M, Scharnholz B, Lederbogen F, Lang UE, Hellweg R. Changes of serum concentrations of brain-derived neurotrophic factor (BDNF) during treatment with venlafaxine and mirtazapine: role of medication and response to treatment. Pharmacopsychiatry. 2013;46:54–8.

    CAS  PubMed  Google Scholar 

  • Dev V, Dixon SN, Fleet JL, Gandhi S, Gomes T, Harel Z, Jain AK, Shariff SZ, Tawadrous D, Weir MA, Garg AX. Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study. BMC Nephrol. 2014;15:79.

    PubMed  PubMed Central  Google Scholar 

  • Dimellis D. Serotonin syndrome produced by a combination of venlafaxine and mirtazapine. World J Biol Psychiatry. 2002;3:167.

    PubMed  Google Scholar 

  • Dodd S, Boulton DW, Burrows GD, De Vane CL, Norman TR. In vitro metabolism of mirtazapine enantiomers by human cytochrome P450 enzymes. Hum Psychopharmacol. 2001;16:541–4.

    CAS  PubMed  Google Scholar 

  • Dolev Z. Case series of perimenopausal women with insomnia treated with mirtazapine followed by prolonged-release melatonin add-on and monotherapy. Arch Womens Ment Health. 2011;14:269–73.

    PubMed  Google Scholar 

  • Dubovsky SL. Beyond the serotonin reuptake inhibitors: rationales for the development of new serotonergic agents. J Clin Psychiatry. 1994;55(Suppl):34–44.

    PubMed  Google Scholar 

  • Eshun-Wilson I, Siegfried N, Akena DH, Stein DJ, Obuku EA, Joska JA. Antidepressants for depression in adults with HIV infection. Cochrane Database Syst Rev. 2018;1:CD008525.

    Google Scholar 

  • Falkai P. Mirtazapine: other indications. J Clin Psychiatry. 1999;60(Suppl 17):36–40; discussion 46–8

    CAS  PubMed  Google Scholar 

  • Farah A. Lack of sexual adverse effects with mirtazapine. Am J Health Syst Pharm. 1998;55:2195–6.

    CAS  PubMed  Google Scholar 

  • Farah A. Relief of SSRI-induced sexual dysfunction with mirtazapine treatment. J Clin Psychiatry. 1999;60:260–1.

    CAS  PubMed  Google Scholar 

  • Farmand S, Lindh JD, Calissendorff J, Skov J, Falhammar H, Nathanson D, Mannheimer B. Differences in associations of antidepressants and hospitalization due to hyponatremia. Am J Med. 2018;131:56–63.

    CAS  PubMed  Google Scholar 

  • Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61(Suppl 11):37–41.

    CAS  PubMed  Google Scholar 

  • Fava M, Dunner DL, Greist JH, Preskorn SH, Trivedi MH, Zajecka J, Cohen M. Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial. J Clin Psychiatry. 2001;62:413–20.

    CAS  PubMed  Google Scholar 

  • Fava M, Rush AJ, Wisniewski SR, Nierenberg AA, Alpert JE, Mcgrath PJ, Thase ME, Warden D, Biggs M, Luther JF, Niederehe G, Ritz L, Trivedi MH. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR∗D report. Am J Psychiatry. 2006;163:1161–72.

    PubMed  Google Scholar 

  • Fawcett J, Barkin RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry. 1998a;59:123–7.

    CAS  PubMed  Google Scholar 

  • Fawcett J, Barkin RL. Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. J Affect Disord. 1998b;51:267–85.

    CAS  PubMed  Google Scholar 

  • Fekete S, Simko J, Mzik M, Karesova I, Zivna H, Pavlikova L, Palicka V. Effect of mirtazapine on rat bone tissue after orchidectomy. Pharmacology. 2015;95:166–72.

    CAS  PubMed  Google Scholar 

  • Frey N, Bodmer M, Bircher A, Jick SS, Meier CR, Spoendlin J. Stevens-Johnson syndrome and toxic epidermal necrolysis in association with commonly prescribed drugs in outpatient care other than anti-epileptic drugs and antibiotics: a population-based case-control study. Drug Saf. 2019;42:55–66.

    PubMed  Google Scholar 

  • Freynhagen R, Muth-Selbach U, Lipfert P, Stevens MF, Zacharowski K, Tolle TR, Von Giesen HJ. The effect of mirtazapine in patients with chronic pain and concomitant depression. Curr Med Res Opin. 2006;22:257–64.

    CAS  PubMed  Google Scholar 

  • Galling B, Calsina Ferrer A, Abi Zeid Daou M, Sangroula D, Hagi K, Correll CU. Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis. Expert Opin Drug Saf. 2015;14:1587–608.

    PubMed  Google Scholar 

  • Gandhi S, Shariff SZ, Al-Jaishi A, Reiss JP, Mamdani MM, Hackam DG, Li L, Mcarthur E, Weir MA, Garg AX. Second-generation antidepressants and hyponatremia risk: a population-based cohort study of older adults. Am J Kidney Dis. 2017;69:87–96.

    CAS  PubMed  Google Scholar 

  • Gandotra K, Chen P, Jaskiw GE, Konicki PE, Strohl KP. Effective treatment of insomnia with mirtazapine attenuates concomitant suicidal ideation. J Clin Sleep Med. 2018;14:901–2.

    PubMed  PubMed Central  Google Scholar 

  • Gelenberg AJ, Mcgahuey C, Laukes C, Okayli G, Moreno F, Zentner L, Delgado P. Mirtazapine substitution in SSRI-induced sexual dysfunction. J Clin Psychiatry. 2000;61:356–60.

    CAS  PubMed  Google Scholar 

  • Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB. Interaction of serotonergic antidepressants and opioid analgesics: is serotonin syndrome going undetected? J Am Med Dir Assoc. 2005;6:265–9.

    PubMed  Google Scholar 

  • Goodnick PJ, Puig A, Devane CL, Freund BV. Mirtazapine in major depression with comorbid generalized anxiety disorder. J Clin Psychiatry. 1999;60:446–8.

    CAS  PubMed  Google Scholar 

  • Guelfi JD, Ansseau M, Timmerman L, Korsgaard S, Mirtazapine-Venlafaxine Study G. Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. J Clin Psychopharmacol. 2001;21:425–31.

    CAS  PubMed  Google Scholar 

  • Gupta R, Gupta K, Tripathi AK, Bhatia MS, Gupta LK. Effect of mirtazapine treatment on serum levels of brain-derived neurotrophic factor and tumor necrosis factor-alpha in patients of major depressive disorder with severe depression. Pharmacology. 2016;97:184–8.

    CAS  PubMed  Google Scholar 

  • Hage B, Britton B, Daniels D, Heilman K, Porges SW, Halaris A. Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression. World J Biol Psychiatry. 2019;20(5):359–367. https://doi.org/10.1080/15622975.2017.1376113. Epub 2017 Oct 5.

  • Harada T, Hirosawa T, Morinaga K, Shimizu T. Metoclopramide-induced Serotonin Syndrome. Intern Med. 2017;56:737–9.

    PubMed  PubMed Central  Google Scholar 

  • Hayashi Y, Watanabe T, Aoki A, Ishiguro S, Ueda M, Akiyama K, Kato K, Inoue Y, Tsuchimine S, Yasui-Furukori N, Shimoda K. Factors affecting steady-state plasma concentrations of enantiomeric mirtazapine and its desmethylated metabolites in Japanese psychiatric patients. Pharmacopsychiatry. 2015;48:279–85.

    CAS  PubMed  Google Scholar 

  • Hoes MJ, Zeijpveld JH. Mirtazapine as treatment for serotonin syndrome. Pharmacopsychiatry. 1996;29:81.

    CAS  PubMed  Google Scholar 

  • Holm KJ, Markham A. Mirtazapine: a review of its use in major depression. Drugs. 1999;57:607–31.

    CAS  PubMed  Google Scholar 

  • Honig A, Kuyper AM, Schene AH, Van Melle JP, De Jonge P, Tulner DM, Schins A, Crijns HJ, Kuijpers PM, Vossen H, Lousberg R, Ormel J, MIND-IT Investigators. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med. 2007;69:606–13.

    CAS  PubMed  Google Scholar 

  • Horstmann S, Dose T, Lucae S, Kloiber S, Menke A, Hennings J, Spieler D, Uhr M, Holsboer F, Ising M. Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action. Psychoneuroendocrinology. 2009;34:238–48.

    CAS  PubMed  Google Scholar 

  • Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Ann Pharmacother. 2004;38:411–3.

    PubMed  Google Scholar 

  • Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol. 2004;50:889–91.

    PubMed  Google Scholar 

  • 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;28:523–8.

    CAS  PubMed  Google Scholar 

  • Jaquenoud Sirot E, Harenberg S, Vandel P, Lima CA, Perrenoud P, Kemmerling K, Zullino DF, Hilleret H, Crettol S, Jonzier-Perey M, Golay KP, Brocard M, Eap CB, Baumann P. Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression. J Clin Psychopharmacol. 2012;32:622–9.

    PubMed  Google Scholar 

  • Jha MK, Malchow AL, Grannemann BD, Rush AJ, Trivedi MH. Do baseline sub-threshold hypomanic symptoms affect acute-phase antidepressant outcome in outpatients with major depressive disorder? Preliminary findings from the randomized CO-MED trial. Neuropsychopharmacology. 2018;43:2197–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang SM, Jia L, Liu J, Shi MM, Xu MZ. Beneficial effects of antidepressant mirtazapine in functional dyspepsia patients with weight loss. World J Gastroenterol. 2016;22:5260–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kamijima K, Yasuda M, Yamamura K, Fukuta Y. Real-world effectiveness and safety of aripiprazole augmentation therapy in patients with major depressive disorder. Curr Med Res Opin. 2018;34:2105–12.

    PubMed  Google Scholar 

  • Kang RH, Choi MJ, Paik JW, Hahn SW, Lee MS. Effect of serotonin receptor 2A gene polymorphism on mirtazapine response in major depression. Int J Psychiatry Med. 2007;37:315–29.

    PubMed  Google Scholar 

  • Karsten J, Hagenauw LA, Kamphuis J, Lancel M. Low doses of mirtazapine or quetiapine for transient insomnia: a randomised, double-blind, cross-over, placebo-controlled trial. J Psychopharmacol. 2017;31:327–37.

    CAS  PubMed  Google Scholar 

  • Kasper S. Clinical efficacy of mirtazapine: a review of meta-analyses of pooled data. Int Clin Psychopharmacol. 1995;10(Suppl 4):25–35.

    PubMed  Google Scholar 

  • Kasper S. Efficacy of antidepressants in the treatment of severe depression: the place of mirtazapine. J Clin Psychopharmacol. 1997;17(Suppl 1):19S–28S.

    CAS  PubMed  Google Scholar 

  • Kato M, Takekita Y, Koshikawa Y, Sakai S, Bandou H, Nishida K, Sunada N, Onohara A, Hatashita Y, Serretti A, Kinoshita T. Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT. J Psychiatr Res. 2017;89:97–104.

    PubMed  Google Scholar 

  • Kato T, Furukawa TA, Mantani A, Kurata K, Kubouchi H, Hirota S, Sato H, Sugishita K, Chino B, Itoh K, Ikeda Y, Shinagawa Y, Kondo M, Okamoto Y, Fujita H, Suga M, Yasumoto S, Tsujino N, Inoue T, Fujise N, Akechi T, Yamada M, Shimodera S, Watanabe N, Inagaki M, Miki K, Ogawa Y, Takeshima N, Hayasaka Y, Tajika A, Shinohara K, Yonemoto N, Tanaka S, Zhou Q, Guyatt GH, SUND Investigators. Optimising first- and second-line treatment strategies for untreated major depressive disorder – the SUND study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial. BMC Med. 2018;16:103.

    PubMed  PubMed Central  Google Scholar 

  • Kessler DS, Macneill SJ, Tallon D, Lewis G, Peters TJ, Hollingworth W, Round J, Burns A, Chew-Graham CA, Anderson IM, Shepherd T, Campbell J, Dickens CM, Carter M, Jenkinson C, Macleod U, Gibson H, Davies S, Wiles NJ. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). BMJ. 2018;363:k4218.

    PubMed  PubMed Central  Google Scholar 

  • Khoo AL, Zhou HJ, Teng M, Lin L, Zhao YJ, Soh LB, Mok YM, Lim BP, Gwee KP. Network meta-analysis and cost-effectiveness analysis of new generation antidepressants. CNS Drugs. 2015;29:695–712.

    CAS  PubMed  Google Scholar 

  • Kilic FS, Dogan AE, Baydemir C, Erol K. The acute effects of mirtazapine on pain related behavior in healthy animals. Neurosciences (Riyadh). 2011;16:217–23.

    PubMed  Google Scholar 

  • Kim SW, Shin IS, Kim JM, Kang HC, Mun JU, Yang SJ, Yoon JS. Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Psychosomatics. 2006;47:440–2.

    PubMed  Google Scholar 

  • Kirchheiner J, Henckel HB, Meineke I, Roots I, Brockmoller J. Impact of the CYP2D6 ultrarapid metabolizer genotype on mirtazapine pharmacokinetics and adverse events in healthy volunteers. J Clin Psychopharmacol. 2004;24:647–52.

    CAS  PubMed  Google Scholar 

  • Kolla BP, Mansukhani MP, Bostwick JM. The influence of antidepressants on restless legs syndrome and periodic limb movements: a systematic review. Sleep Med Rev. 2018;38:131–40.

    PubMed  Google Scholar 

  • Koutouvidis N, Pratikakis M, Fotiadou A. The use of mirtazapine in a group of 11 patients following poor compliance to selective serotonin reuptake inhibitor treatment due to sexual dysfunction. Int Clin Psychopharmacol. 1999;14:253–5.

    CAS  PubMed  Google Scholar 

  • Kouwenhoven TA, Van De Kerkhof PCM, Kamsteeg M. Use of oral antidepressants in patients with chronic pruritus: a systematic review. J Am Acad Dermatol. 2017;77:1068–1073.e7.

    CAS  PubMed  Google Scholar 

  • Kraus T, Haack M, Schuld A, Hinze-Selch D, Koethe D, Pollmacher T. Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine. Pharmacopsychiatry. 2002;35:220–5.

    CAS  PubMed  Google Scholar 

  • Laakmann G, Schule C, Baghai T, Waldvogel E. Effects of mirtazapine on growth hormone, prolactin, and cortisol secretion in healthy male subjects. Psychoneuroendocrinology. 1999;24:769–84.

    CAS  PubMed  Google Scholar 

  • Laakmann G, Schule C, Baghai T, Waldvogel E, Bidlingmaier M, Strasburger C. Mirtazapine: an inhibitor of cortisol secretion that does not influence growth hormone and prolactin secretion. J Clin Psychopharmacol. 2000;20:101–3.

    CAS  PubMed  Google Scholar 

  • Laakmann G, Hennig J, Baghai T, Schule C. Influence of mirtazapine on salivary cortisol in depressed patients. Neuropsychobiology. 2003;47:31–6.

    CAS  PubMed  Google Scholar 

  • Ladino M, Guardiola VD, Paniagua M. Mirtazapine-induced hyponatremia in an elderly hospice patient. J Palliat Med. 2006;9:258–60.

    PubMed  Google Scholar 

  • Laimer M, Kramer-Reinstadler K, Rauchenzauner M, Lechner-Schoner T, Strauss R, Engl J, Deisenhammer EA, Hinterhuber H, Patsch JR, Ebenbichler CF. Effect of mirtazapine treatment on body composition and metabolism. J Clin Psychiatry. 2006;67:421–4.

    CAS  PubMed  Google Scholar 

  • Lee HY, Kang RH, Paik JW, Jeong YJ, Chang HS, Han SW, Lee MS. Association of the adrenergic alpha 2a receptor – 1291C/G polymorphism with weight change and treatment response to mirtazapine in patients with major depressive disorder. Brain Res. 2009;1262:1–6.

    CAS  PubMed  Google Scholar 

  • Lee SH, Paz-Filho G, Mastronardi C, Licinio J, Wong ML. Is increased antidepressant exposure a contributory factor to the obesity pandemic? Transl Psychiatry. 2016;6:e759.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leth-Moller KB, Hansen AH, Torstensson M, Andersen SE, Odum L, Gislasson G, Torp-Pedersen C, Holm EA. Antidepressants and the risk of hyponatremia: a Danish register-based population study. BMJ Open. 2016;6:e011200.

    PubMed  PubMed Central  Google Scholar 

  • Lind AB, Reis M, Bengtsson F, Jonzier-Perey M, Powell Golay K, Ahlner J, Baumann P, Dahl ML. Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour. Clin Pharmacokinet. 2009;48:63–70.

    CAS  PubMed  Google Scholar 

  • Loonen AJ, Doorschot CH, Oostelbos MC, Sitsen JM. Lack of drug interactions between mirtazapine and risperidone in psychiatric patients: a pilot study. Eur Neuropsychopharmacol. 1999;10:51–7.

    CAS  PubMed  Google Scholar 

  • Lovecchio F, Riley B, Pizon A, Brown M. Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. J Emerg Med. 2008;34:77–8.

    PubMed  Google Scholar 

  • Lozupone M, La Montagna M, D’urso F, Piccininni C, Sardone R, Dibello V, Giannelli G, Solfrizzi V, Greco A, Daniele A, Quaranta N, Seripa D, Bellomo A, Logroscino G, Panza F. Pharmacotherapy for the treatment of depression in patients with Alzheimer’s disease: a treatment-resistant depressive disorder. Expert Opin Pharmacother. 2018;19:823–42.

    CAS  PubMed  Google Scholar 

  • Malamood M, Roberts A, Kataria R, Parkman HP, Schey R. Mirtazapine for symptom control in refractory gastroparesis. Drug Des Devel Ther. 2017;11:1035–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mattila M, Mattila MJ, Vrijmoed-De Vries M, Kuitunen T. Actions and interactions of psychotropic drugs on human performance and mood: single doses of ORG 3770, amitriptyline, and diazepam. Pharmacol Toxicol. 1989;65:81–8.

    CAS  PubMed  Google Scholar 

  • Mcgrane IR, Shuman MD. Mirtazapine therapy for posttraumatic stress disorder: implications of alpha-adrenergic pharmacology on the startle response. Harv Rev Psychiatry. 2018;26:36–41.

    PubMed  Google Scholar 

  • Melo G, Dutra KL, Rodrigues Filho R, Ortega AOL, Porporatti AL, Dick B, Flores-Mir C, De Luca Canto G. Association between psychotropic medications and presence of sleep bruxism: a systematic review. J Oral Rehabil. 2018;45:545–54.

    CAS  PubMed  Google Scholar 

  • Menon V, Madhavapuri P. Low-dose mirtazapine-induced nightmares necessitating its discontinuation in a young adult female. J Pharmacol Pharmacother. 2017;8:182–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meyboom RH, Edwards IR, Egberts AC. Mirtazapine and the granulocytes – so far so good. N Z Med J. 1999;112:104.

    CAS  PubMed  Google Scholar 

  • Mirtazapine – a new antidepressant. Med Lett Drugs Ther. 1996;38:113–4.

    Google Scholar 

  • Monden R, Roest AM, Van Ravenzwaaij D, Wagenmakers EJ, Morey R, Wardenaar KJ, De Jonge P. The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: a Bayesian meta-analysis of Food and Drug Administration reviews. J Affect Disord. 2018;235:393–8.

    CAS  PubMed  Google Scholar 

  • Montgomery SA. Safety of mirtazapine: a review. Int Clin Psychopharmacol. 1995;10(Suppl 4):37–45.

    PubMed  Google Scholar 

  • Montgomery SA, Reimitz PE, Zivkov M. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. Int Clin Psychopharmacol. 1998;13:63–73.

    CAS  PubMed  Google Scholar 

  • Na KS, Jung HY, Cho SJ, Cho SE. Can we recommend mirtazapine and bupropion for patients at risk for bleeding?: a systematic review and meta-analysis. J Affect Disord. 2018;225:221–6.

    CAS  PubMed  Google Scholar 

  • Navarro V, Boulahfa I, Obach A, Jerez D, Diaz-Ricart M, Gasto C, Guarch J. Switching to imipramine versus add-on mirtazapine in venlafaxine-resistant major depression: a 10-week randomized open study. J Clin Psychopharmacol. 2019;39:63–6.

    CAS  PubMed  Google Scholar 

  • Nelson JC. Safety and tolerability of the new antidepressants. J Clin Psychiatry. 1997;58(Suppl 6):26–31.

    CAS  PubMed  Google Scholar 

  • Niedermaier N, Bohrer E, Schulte K, Schlattmann P, Heuser I. Prevention and treatment of poststroke depression with mirtazapine in patients with acute stroke. J Clin Psychiatry. 2004;65:1619–23.

    CAS  PubMed  Google Scholar 

  • Nishihara M, Arai YC, Yamamoto Y, Nishida K, Arakawa M, Ushida T, Ikeuchi M. Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases. Pain Physician. 2013;16:E547–52.

    PubMed  Google Scholar 

  • Noma H, Furukawa TA, Maruo K, Imai H, Shinohara K, Tanaka S, Ikeda K, Yamawaki S, Cipriani A. Exploratory analyses of effect modifiers in the antidepressant treatment of major depression: individual-participant data meta-analysis of 2803 participants in seven placebo-controlled randomized trials. J Affect Disord. 2019;250:419–24.

    CAS  PubMed  Google Scholar 

  • Nutt D. Mirtazapine: pharmacology in relation to adverse effects. Acta Psychiatr Scand Suppl. 1997;391:31–7.

    CAS  PubMed  Google Scholar 

  • Nutt DJ. Care of depressed patients with anxiety symptoms. J Clin Psychiatry. 1999;60(Suppl 17):23–7; discussion 46–8

    PubMed  Google Scholar 

  • Okubo M, Murayama N, Miura J, Chiba Y, Yamazaki H. Effects of cytochrome P450 2D6 and 3A5 genotypes and possible coadministered medicines on the metabolic clearance of antidepressant mirtazapine in Japanese patients. Biochem Pharmacol. 2015;93:104–9.

    CAS  PubMed  Google Scholar 

  • Orgeta V, Tabet N, Nilforooshan R, Howard R. Efficacy of antidepressants for depression in Alzheimer’s disease: systematic review and meta-analysis. J Alzheimer’s Dis. 2017;58:725–33.

    CAS  Google Scholar 

  • Ottman AA, Warner CB, Brown JN. The role of mirtazapine in patients with fibromyalgia: a systematic review. Rheumatol Int. 2018;38:2217–24.

    PubMed  Google Scholar 

  • Pallanti S, Quercioli L, Bruscoli M. Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study. J Clin Psychiatry. 2004;65:1394–9.

    CAS  PubMed  Google Scholar 

  • Palleria C, Roberti R, Iannone LF, Tallarico M, Barbieri MA, Vero A, Manti A, De Sarro G, Spina E, Russo E. Clinically relevant drug interactions between statins and antidepressants. J Clin Pharm Ther. 2019; https://doi.org/10.1111/jcpt.13058.

  • Papakostas GI, Homberger CH, Fava M. A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. J Psychopharmacol. 2008;22:843–8.

    CAS  PubMed  Google Scholar 

  • Perry LA, Ramson D, Stricklin S. Mirtazapine adjunct for people with schizophrenia. Cochrane Database Syst Rev. 2018;5:CD011943.

    Google Scholar 

  • Poole M, Quimby JM, Hu T, Labelle D, Buhles W. A double-blind, placebo-controlled, randomized study to evaluate the weight gain drug, mirtazapine transdermal ointment, in cats with unintended weight loss. J Vet Pharmacol Ther. 2019;42:179–88.

    CAS  PubMed  Google Scholar 

  • Ramaekers JG, Conen S, De Kam PJ, Braat S, Peeters P, Theunissen EL, Ivgy-May N. Residual effects of mirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype. Psychopharmacology (Berl). 2011;215:321–32.

    CAS  PubMed  Google Scholar 

  • Rocha FL, Fuzikawa C, Riera R, Hara C. Combination of antidepressants in the treatment of major depressive disorder: a systematic review and meta-analysis. J Clin Psychopharmacol. 2012;32:278–81.

    CAS  PubMed  Google Scholar 

  • Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, Warden D, Morris DW, Luther JF, Husain MM, Cook IA, Shelton RC, Lesser IM, Kornstein SG, Wisniewski SR. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry. 2011;168:689–701.

    PubMed  Google Scholar 

  • Salvi V, Mencacci C, Barone-Adesi F. H1-histamine receptor affinity predicts weight gain with antidepressants. Eur Neuropsychopharmacol. 2016;26:1673–7.

    CAS  PubMed  Google Scholar 

  • Sandker GW, Vos RM, Delbressine LP, Slooff MJ, Meijer DK, Groothuis GM. Metabolism of three pharmacologically active drugs in isolated human and rat hepatocytes: analysis of interspecies variability and comparison with metabolism in vivo. Xenobiotica. 1994;24:143–55.

    CAS  PubMed  Google Scholar 

  • Sanjida S, Mulvogue K, Shaw J, Couper J, Kissane D, Pearson SA, Price MA, Janda M. What type and dose of antidepressants are cancer and non-cancer inpatients being prescribed: a retrospective case-control study at an Australian tertiary hospital. Support Care Cancer. 2018;26:625–34.

    PubMed  Google Scholar 

  • Sasada K, Iwamoto K, Kawano N, Kohmura K, Yamamoto M, Aleksic B, Ebe K, Noda Y, Ozaki N. Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers. Hum Psychopharmacol. 2013;28:281–6.

    CAS  PubMed  Google Scholar 

  • Schneier FR, Campeas R, Carcamo J, Glass A, Lewis-Fernandez R, Neria Y, Sanchez-Lacay A, Vermes D, Wall MM. Combined mirtazapine and SSRI treatment of PTSD: a placebo-controlled trial. Depress Anxiety. 2015;32:570–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schule C, Baghai T, Rackwitz C, Laakmann G. Influence of mirtazapine on urinary free cortisol excretion in depressed patients. Psychiatry Res. 2003;120:257–64.

    CAS  PubMed  Google Scholar 

  • Schule C, Baghai TC, Eser D, Hecht S, Hermisson I, Born C, Hafner S, Nothdurfter C, Rupprecht R. Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study. World J Biol Psychiatry. 2007;8:112–22.

    PubMed  Google Scholar 

  • Schule C, Baghai TC, Eser D, Nothdurfter C, Rupprecht R. Lithium but not carbamazepine augments antidepressant efficacy of mirtazapine in unipolar depression: an open-label study. World J Biol Psychiatry. 2009;10:390–9.

    PubMed  Google Scholar 

  • Scoralick FM, Louzada LL, Quintas JL, Naves JO, Camargos EF, Nobrega OT. Mirtazapine does not improve sleep disorders in Alzheimer’s disease: results from a double-blind, placebo-controlled pilot study. Psychogeriatrics. 2017;17:89–96.

    PubMed  Google Scholar 

  • Sennef C, Timmer CJ, Sitsen JM. Mirtazapine in combination with amitriptyline: a drug-drug interaction study in healthy subjects. Hum Psychopharmacol. 2003;18:91–101.

    CAS  PubMed  Google Scholar 

  • Seo HJ, Jung YE, Woo YS, Jun TY, Chae JH, Bahk WM. Effect of augmented atypical antipsychotics on weight change in patients with major depressive disorder in a naturalistic setting. Hum Psychopharmacol. 2009;24:135–43.

    PubMed  Google Scholar 

  • Sitsen J, Maris F, Timmer C. Drug-drug interaction studies with mirtazapine and carbamazepine in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2001;26:109–21.

    CAS  PubMed  Google Scholar 

  • Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393:768–77.

    CAS  PubMed  Google Scholar 

  • Smit M, Dolman KM, Honig A. Mirtazapine in pregnancy and lactation – a systematic review. Eur Neuropsychopharmacol. 2016;26:126–35.

    CAS  PubMed  Google Scholar 

  • Smit M, Wennink H, Heres M, Dolman KM, Honig A. Mirtazapine in pregnancy and lactation: data from a case series. J Clin Psychopharmacol. 2015;35:163–7.

    CAS  PubMed  Google Scholar 

  • Smith WT, Glaudin V, Panagides J, Gilvary E. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull. 1990;26:191–6.

    CAS  PubMed  Google Scholar 

  • Spaans E, Van Den Heuvel MW, Schnabel PG, Peeters PA, Chin-Kon-Sung UG, Colbers EP, Sitsen JM. Concomitant use of mirtazapine and phenytoin: a drug-drug interaction study in healthy male subjects. Eur J Clin Pharmacol. 2002;58:423–9.

    CAS  PubMed  Google Scholar 

  • Spyridi S, Sokolaki S, Nimatoudis J, Iacovides A, Kaprinis G. Status epilepticus in a patient treated with olanzapine and mirtazapine. Int J Clin Pharmacol Ther. 2009;47:120–3.

    CAS  PubMed  Google Scholar 

  • Stahl S, Zivkov M, Reimitz PE, Panagides J, Hoff W. Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression. Acta Psychiatr Scand Suppl. 1997;391:22–30.

    CAS  PubMed  Google Scholar 

  • Steinert T, Froscher W. Epileptic seizures under antidepressive drug treatment: systematic review. Pharmacopsychiatry. 2018;51:121–35.

    CAS  PubMed  Google Scholar 

  • Stimmel GL, Dopheide JA, Stahl SM. Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. Pharmacotherapy. 1997;17:10–21.

    CAS  PubMed  Google Scholar 

  • Stormer E, Von Moltke LL, Shader RI, Greenblatt DJ. Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos. 2000;28:1168–75.

    CAS  PubMed  Google Scholar 

  • Szegedi A, Rujescu D, Tadic A, Muller MJ, Kohnen R, Stassen HH, Dahmen N. The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. Pharmacogenomics J. 2005;5:49–53.

    CAS  PubMed  Google Scholar 

  • Tack J, Carbone F. Functional dyspepsia and gastroparesis. Curr Opin Gastroenterol. 2017;33:446–54.

    CAS  PubMed  Google Scholar 

  • Tadic A, Muller MJ, Rujescu D, Kohnen R, Stassen HH, Dahmen N, Szegedi A. The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:325–31.

    CAS  PubMed  Google Scholar 

  • Terhardt J, Lederbogen F, Feuerhack A, Hamann-Weber B, Gilles M, Schilling C, Lecei O, Deuschle M. Heart rate variability during antidepressant treatment with venlafaxine and mirtazapine. Clin Neuropharmacol. 2013;36:198–202.

    CAS  PubMed  Google Scholar 

  • Thase ME, Nierenberg AA, Vrijland P, Van Oers HJ, Schutte AJ, Simmons JH. Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int Clin Psychopharmacol. 2010;25:189–98.

    PubMed  Google Scholar 

  • Theobald DE, Kirsh KL, Holtsclaw E, Donaghy K, Passik SD. An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms. J Pain Symptom Manag. 2002;23:442–7.

    CAS  Google Scholar 

  • Timmer CJ, Paanakker JE, Vrijmoed-De Vries M. Mirtazapine pharmacokinetics with two dosage regimens and two pharmaceutical formulations. Pharm Res. 1997;14:98–102.

    CAS  PubMed  Google Scholar 

  • Timmer CJ, Sitsen JM, Delbressine LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet. 2000;38:461–74.

    CAS  PubMed  Google Scholar 

  • Tzeng DS, Chien CC, Lung FW, Yang CY. MAOA gene polymorphisms and response to mirtazapine in major depression. Hum Psychopharmacol. 2009;24:293–300.

    CAS  PubMed  Google Scholar 

  • Varia I, Venkataraman S, Hellegers C, Gersing K, Doraiswamy PM. Effect of mirtazapine orally disintegrating tablets on health-related quality of life in elderly depressed patients with comorbid medical disorders: a pilot study. Psychopharmacol Bull. 2007;40:47–56.

    PubMed  Google Scholar 

  • Verster JC, Van De Loo AJ, Roth T. Mirtazapine as positive control drug in studies examining the effects of antidepressants on driving ability. Eur J Pharmacol. 2015;753:252–6.

    CAS  PubMed  Google Scholar 

  • Vidal C, Reese C, Fischer BA, Chiapelli J, Himelhoch S. Meta-analysis of efficacy of mirtazapine as an adjunctive treatment of negative symptoms in schizophrenia. Clin Schizophr Relat Psychoses. 2015;9:88–95.

    PubMed  Google Scholar 

  • Warden D, Trivedi MH, Carmody T, Toups M, Zisook S, Lesser I, Myers A, Kurian KR, Morris D, Rush AJ. Adherence to antidepressant combinations and monotherapy for major depressive disorder: a CO-MED report of measurement-based care. J Psychiatr Pract. 2014;20:118–32.

    PubMed  Google Scholar 

  • Waring WS, Good AM, Bateman DN. Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. Clin Toxicol (Phila). 2007;45:45–50.

    CAS  PubMed  Google Scholar 

  • Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;CD006528.

    Google Scholar 

  • Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Mcguire H, Churchill R, Furukawa TA, Multiple Meta-Analyses of New Generation Antidepressants Study Group. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis. J Clin Psychiatry. 2008;69:1404–15.

    CAS  PubMed  Google Scholar 

  • Welsch P, Bernardy K, Derry S, Moore RA, Hauser W. Mirtazapine for fibromyalgia in adults. Cochrane Database Syst Rev. 2018;8:CD012708.

    Google Scholar 

  • 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;64:1224–9.

    CAS  PubMed  Google Scholar 

  • Wu CS, Tong SH, Ong CT, Sung SF. Serotonin syndrome induced by combined use of mirtazapine and olanzapine complicated with rhabdomyolysis, acute renal failure, and acute pulmonary edema-a case report. Acta Neurol Taiwanica. 2015;24:117–21.

    Google Scholar 

  • Wu Q, Bencaz AF, Hentz JG, Crowell MD. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int. 2012;23:365–75.

    CAS  PubMed  Google Scholar 

  • Wu Q, Liu B, Tonmoy S. Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies. Osteoporos Int. 2018;29:1303–12.

    CAS  PubMed  Google Scholar 

  • Wu Q, Qu W, Crowell MD, Hentz JG, Frey KA. Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies. J Bone Miner Res. 2013;28:753–63.

    PubMed  Google Scholar 

  • Yin J, Song J, Lei Y, Xu X, Chen JD. Prokinetic effects of mirtazapine on gastrointestinal transit. Am J Physiol Gastrointest Liver Physiol. 2014;306:G796–801.

    CAS  PubMed  Google Scholar 

  • Yosipovitch G, Bernhard JD. Clinical practice. Chronic pruritus. N Engl J Med. 2013;368:1625–34.

    CAS  PubMed  Google Scholar 

  • Zaini S, Guan NGC, Sulaiman AH, Zainal NZ, Huri HZ, Shamsudin SH. The use of antidepressants for physical and psychological symptoms in cancer. Curr Drug Targets. 2018;19:1431.

    CAS  PubMed  Google Scholar 

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Davis, M.P. (2022). Mirtazapine and Depressions. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-030-62059-2_102

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