Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) which has predominantly been evaluated in the treatment of major depression. The drug had equivalent efficacy to tricyclic antidepressants and it was at least as effective as trazodone in the majority of available short term trials in patients with moderate or severe depression, including those with baseline anxiety symptoms or sleep disturbance and the elderly. A continuation study also showed that sustained remission rates were higher with mirtazapine than with amitriptyline and that the drugs had similar efficacy for the prevention of relapse. There is some evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Mirtazapine was more effective than the SSRI fluoxetine at weeks 3 and 4 of therapy and it was also more effective than paroxetine and citalopram at weeks 1 and 2, respectively, in short term assessments (6 or 8 weeks). Preliminary data suggest that the drug may be effective as an augmentation or combination therapy in patients with refractory depression.
Anticholinergic events and other events including tremor and dyspepsia are less common with mirtazapine than with tricyclic antidepressants. There was a greater tendency for SSRI-related adverse events with fluoxetine than with mirtazapine, but, overall, mirtazapine had a similar tolerability profile to the SSRIs. Increased appetite and bodyweight gain appear to be the only events that are reported more often with mirtazapine than with comparator antidepressants. In vitro and in vivo data have suggested that mirtazapine is unlikely to affect the metabolism of drugs metabolised by cytochrome P450 (CYP)2D6, although few formal drug interaction data are available.
Conclusions: Mirtazapine is effective and well tolerated for the treatment of patients with moderate to severe major depression. Further research is required to define the comparative efficacy of mirtazapine in specific patient groups, including the elderly and those with severe depression. Clarification of its efficacy as an augmentation therapy and in patients with refractory depression and its role in improving the efficacy and reducing the extrapyramidal effects of antipsychotic drugs would also help to establish its clinical value. The low potential for interaction with drugs that are metabolised by CYP2D6, including antipsychotics, tricyclic antidepressants and some SSRIs, may also make mirtazapine an important option for the treatment of major depression in patients who require polytherapy. Mirtazapine also appears to be useful in patients with depression who present with anxiety symptoms and sleep disturbance.
Mirtazapine enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission via antagonism of central (α2-adrenergic autoreceptors and heteroreceptors and postsynaptic blockade of 5-HT2 and 5-HT3 receptors. The drug does not inhibit noradrenaline (norepinephrine) or serotonin reuptake. Mirtazapine has low in vitro affinity for central and peripheral dopaminergic, cholinergic and muscarinic receptors, but has high affinity for central and peripheral histamine H1 receptors. However, it appears that the antihistaminergic effects of the drug are counteracted by noradrenergic transmission when the drug is commenced at dosages ≥15 mg/day, i.e. within the recommended dosage range.
Single doses of mirtazapine 15 or 30mg had beneficial effects on symptoms of sleep disturbance commonly seen with depression, including increased nighttime wakenings, a reduction in the amount of slow wave sleep and a reduction in REM latency, according to electrophysiological studies in patients and volunteers. Night-time administration of mirtazapine 15 to 30 mg/day for 15 days produced slight, but statistically significant, impairment in tracking and actual driving performance in healthy volunteers; however, this was not thought to be sufficient to reduce the safety of motor vehicle operation.
There have been no detailed reports of the cardiovascular effects of mirtazapine in humans.
Overview of Pharmacokinetic Properties
Mirtazapine has linear pharmacokinetics over the recommended dose range (15 to 45mg). It has a mean elimination half-life of 20 to 40 hours following oral administration and is therefore suitable for once daily administration. Up to 85% of an oral dose is excreted in the urine and the remainder is excreted in the faeces. In patients with hepatic and renal impairment, the clearance of mirtazapine is reduced and dosage increases should be performed with caution. Steady-state plasma concentrations are reached after approximately 5 days’ therapy. Age, gender and the intake of a high-fat meal do not affect the pharmacokinetic parameters of mirtazapine. In vitro and in vivo studies indicate that mirtazapine is unlikely to affect the metabolism of drugs metabolised by cytochrome P450 (CYP)1A2, CYP3A4 and CYP2D6 isoenzymes (including tricyclic antidepressants, antipsychotics and some SSRIs); however, few formal drug interaction studies are available.
In well designed clinical studies with an antidepressant comparator, the proportion of responders according to the Hamilton Depression Rating Scale (HDRS) generally ranged from 51 to 80% with mirtazapine. In short term studies (4 to 7 weeks), the drug was as effective as amitriptyline, clomipramine and doxepin, and it was at least as effective as trazodone, in patients with moderate or severe depression, including those with baseline anxiety symptoms or sleep disturbance or the elderly. Mirtazapine was less effective than imipramine in a single study performed in a heterogeneous population including previous nonresponders to antidepressants. Single comparisons between mirtazapine and selective serotonin reuptake inhibitors (SSRIs) demonstrated superior efficacy for mirtazapine versus fluoxetine at weeks 3 and 4, versus paroxetine at week 1 and versus citalopram at week 2, suggesting an earlier onset of efficacy with mirtazapine than with the SSRIs (total assessment times were 6 or 8 weeks). Mirtazapine had equivalent efficacy to the SSRIs at study end-point. In trials where additional scales were used to assess antidepressant efficacy, quality of life, general psychopathology, global functioning and global clinical impression, changes in scores correlated with HDRS results.
In a continuation trial, mirtazapine was associated with higher sustained remission rates than amitriptyline and the drugs had similar efficacy for the prevention of relapse. Initial evidence suggests that mirtazapine may also be effective as an augmentation or combination therapy with a number of other classes of antidepressant in patients with refractory depression.
Mirtazapine was more cost effective than fluoxetine or amitriptyline for the treatment of major depression from the perspectives of the national health funder in France and Austria, despite high acquisition costs for the drug in these countries.
Data from meta-analyses of placebo-controlled trials indicate that dry mouth, drowsiness/sedation, increase in appetite and bodyweight gain are the most common adverse experiences with short term (5 to 6 weeks) mirtazapine therapy. A reduction in the incidence of sedation-related symptoms over time with higher mirtazapine dosages was seen in some studies and is thought to have a pharmacological basis.
Anticholinergic symptoms and events such as drowsiness, tremor and dyspepsia tend to occur less frequently with mirtazapine than with tricyclic antidepressants or trazodone. Typical SSRI adverse events were less common with mirtazapine than with fluoxetine and placebo, although overall mirtazapine appears to have a similar tolerability profile to those of the SSRIs fluoxetine, citalopram and paroxetine. Increased appetite and bodyweight are the only events that have been reported to be more common with mirtazapine than with antidepressant comparators. The drug appears to be well tolerated in elderly patients.
Mirtazapine has not been associated with clinically significant changes in vital signs in clinical trials. Changes in laboratory parameters with mirtazapine are rare. The available data indicate that mirtazapine does not increase the incidence of suicide attempts in patients with depression compared with active comparators, although this parameter was not specifically assessed in clinical trials of any antidepressant. Patients have recovered without adverse sequelae from mirtazapine overdose at doses of up to 30 times the recommended daily amount.
Dosage and Administration
The recommended oral dosage of mirtazapine in adults and elderly patients with depression is 15 to 45 mg/day. Elderly patients and those with hepatic or renal insufficiency should be closely supervised when dosages are increased. Mirtazapine should be taken as a single evening dose. The drug should not be given to patients who are taking monoamine oxidase inhibitors or during pregnancy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Sitsen JMA, Zivkov M. Mirtazapine: clinical profile. CNS Drags 1995; 4 Suppl. 1: 39–48
de Boer TH, Nefkens F, van Helvoirt A, et al. Differences in modulation of noradrenergic and serotonergic transmission by the alpha-2 adrenoceptor antagonists, mirtazapine, mianserin and idazoxan. J Pharmacol Exp Ther 1996 May; 277: 852–60
de Boer T, Maura G, Raiteri M, et al. Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers. Neuropharmacology 1988; 27(4): 399–408
Davis R, Wilde MI. Mirtazapine: a review of its pharmacology and therapeutic potential in the management of major depression. CNS Drags 1996 May; 5: 389–402
Connor KM, Davidson JRT, Weisler RH. A pilot study of mirtazapine in posttraumatic stress disorder [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Stimmel GL, Dopheide JA, Stahl SM. Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. Pharmacotherapy 1997 Jan–Feb; 17: 10–21
Ulbricht D, Hund M, von Cramon DY. Introduction of mirtazapine in the treatment of central post-stroke pain [abstract]. Eur J Neurol 1998 Sep; 5 Suppl. 3: 103
Dunner DL, Hendrickson HE, Budech C, et al. Mirtazapine: treatment of dysthymic disorder [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow
Stamenkovic M, Pezawas L, da Zwaan M. Mirtazapine in recurrent brief depression. Int Clin Psychopharmacol 1998 Jan; 13: 39–40
Hesselmann B, Habeler A, Praschak-Rieder N, et al. Mirtazapine in seasonal affective disorder (SAD): a preliminary report. Hum Psychopharm 1999 Jan; 14: 59–62
Bergeron R, Zivkov M, Muller L. Symptomatic improvement of premenstrual dysphoric disorder with mirtazapine [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Isaac MT, Tome MB. Mirtazapine in peri-menopausal depression: an open label study [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Dahl M-L, Voortman G, Alm C, et al. In. vitro and in vivo studies on the disposition of mirtazapine in humans. Clin Drag Invest 1997 Jan; 13: 37–46
Kasper S, Praschak-Rieder N, Tauscher J, et al. A risk-benefit assessment of mirtazapine in the treatment of depression. Drug Saf 1997 Oct; 17: 251–64
Delbressine LPC, Moonen MEG, Kaspersen FM, et al. Pharmacokinetics and biotransformation of mirtazapine in human volunteers. Clin Drag Invest 1998 Jan; 15: 45–55
Leonard BE. The role of noradrenaline in depression: Areview. J Psychopharmacol 1997; 11(4) Suppl.: S39–47
Delgado PL, Moreno FA, Gelenberg AT, et al. Sequential catecholamine and 5-HT depletion in mirtazapine-treated depressives [abstract no. 346]. Biol Psychiatry 1998 Apr 15; 43 Suppl.: 104S
Pinder RM. The Pharmacologic rationale for the clinical use of antidepressants. J Clin Psychiatry 1997 Nov; 58: 501–8
Benkert O, Szegedi A, Kohnen R. Rapid onset of therapeutic action in major depression: a comparative trial of mirtazapine and paroxetine [poster]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Agren H, Leinonen E, Skarstein J, et al. Efficacy and tolerability of mirtazapine vs citalopram: a double-blind, randomized study in patients with major depressive disorder [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico: 320
Wheatley DP, van Moffaert M, Timmerman L, et al. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. J Clin Psychiatry 1998 Jun; 59: 306–12
Schwaninger M, Weisbrod M, Knepel W. Progress in defining the mechanism of action of antidepressants: across receptors and into gene transcription. CNS Drugs 1997 Sep; 8: 237–43
McGrath C, Burrows GD, Norman TR. Neurochemical effects of the enantiomers of mirtazapine in normal rats. Eur J Pharmacol 1998 Sep 4; 356: 121–6
Peroutka SJ. Serotonin receptor subtypes: their evolution and clinical relevance. CNS Drugs 1995; 4 Suppl. 1: 18–28
Haddjeri N, Blier P, de Montigny C. Effects of long-term treatment with the alpha-2-adrenoceptor antagonist mirtazapine on 5-HT neurotransmission. Naunyn Schmiedebergs Arch Pharmacol 1997 Jan; 355: 20–9
Winokur A, Sateia MJ, Hayes JB, et al. Effects of mirtazapine on sleep architecture in patients with major depression: a pilot study [abstract no. 354]. Biol Psychiatry 1998 Apr 15; 43 Suppl.: 106S–7S
Ruigt GSF, Kemp B, Groenhout CM, et al. Effect of the antidepressant Org 3770 on human sleep. Eur J Clin Pharmacol 1990; 38: 551–4
Sennef C, Heukels A, van Proosdij J, et al. Effects of mirtazapine, amitriptyline and their combination on sleep in healthy volunteers measured by an ambulatory digital recording system (VITAPORTII®) [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow
Ramaekers JG, Muntjewerff ND, Van Veggel LMA, et al. Effects of nocturnal doses of mirtazapine and mianserin on sleep and on daytime psychomotor and driving performance in young, healthy volunteers. Hum Psychopharm 1998 Nov; 13 Suppl. 2: S87–97
Mattila M, Mattila MJ, Vrijmoed-de Vries M, et al. Actions and interactions of psychotropic drugs on human performance and mood: single doses of ORG 3770, amitriptyline, and diazepam. Pharmacol Toxicol 1989 Aug; 65: 81–8
Berendsen HHG, Broekkamp CLE, Pinder RM. Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats. Psychopharmacology 1998 Feb; 135: 284–9
Pinder R, Martorana M, Dickson M, et al. Enhancement of antipsychotic efficacy of typical and atypical antipsychotics by mirtazapine [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Organon Remeron is first alpha-2 receptor antagonist antidepressant recommended by advisory committee; labeling should note neutropenia risk. FDC Rep Pink Sheet 1995 Oct 23: 16–7
Nicholas LM, Ford A, Esposito S, et al. The effects of mirtazapine on plasma lipids in healthy volunteers [abstract]. 37th Annual Meeting of the American College of Neuropsychopharmacology; 1998 Dec 14–18; Las Croabas, Puerto Rico
Tulen JHM, Bruijn JA, de Man KJ, et al. Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770). J Clin Psychopharmacol 1996 Apr; 16: 135–45
Caccia S. Metabolism of the newer antidepressants: an overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 1998 Apr; 34: 281–302
Timmer CJ, Lohmann AAM, Mink CPA. Pharmacokinetic dose-proportionality study at steady state of mirtazapine from Remeron® tablets. Hum Psychopharm 1995; 10 Suppl. 2: S97–106
Voortman G, Paanakker JE. Bioavailability of mirtazapine from Remeron® tablets after single and multiple oral dosing. Hum Psychopharm 1995; 10 Suppl. 2: S83–96
Murdoch DL, Ashgar J, Ankier SI, et al. Influence of hepatic impairment on the pharmacokinetics of single doses of mirtazapine in elderly subjects [abstract]. Br J Clin Pharmacol 1993 Jan; 35: 76P
Bengtsson F, Höglund P, Timmer C, et al. Mirtazapine oral single dose kinetics in patients with different degrees of renal failure. Hum Psychopharm 1998 Jul; 13: 357–65
Timmer CJ, Paanakker JE, van Hal HJM. Pharmacokinetics of mirtazapine from orally administered tablets: influence of gender, age and treatment regimen. Hum Psychopharm 1996 Nov–Dec; 11: 497–509
Cohen M, Panagides J, Timmer CJ, et al. Pharmacokinetics of mirtazapine from orally administered tablets: influence of a high-fat meal. Eur J Drug Metab Pharmacokinet 1997 Apr–Jun; 22: 103–10
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association, 1980
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd rev. ed. Washington, DC: American Psychiatric Association, 1987
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
Halikas JA. Org 3770 (mirtazapine) versus trazodone: a placebo controlled trial in depressed elderly patients. Hum Psychopharm 1995 Jul; 10 Suppl. 2: S125–133
Høyberg OJ, Maragakis B, Mullin J, et al. A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients. Acta Psychiatr Scand 1996 Mar; 93: 184–90
Wittgens W, Trenckman U, Donath O. Mirtazapine in elderly inpatients with somatic or neurological comorbidity [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow, Scotland
Kat MG, Helsdingen JTH, Boumans AAJ. Efficacy and tolerability of mirtazapine used by elderly depressed patients in The Netherlands [abstract]. Eur Neuropsychopharmacol 1998 Nov; 8 Suppl. 2: S147
Bruijn JA, Moleman P, Mulder PGH, et al. A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients. Psychopharmacology 1996 Oct; 127: 231–7
Kreutzenbeck H-J, Zivkov M. The use of mirtazapine in primary care [poster]. 21st Collegium Internationale NeuroPsychopharmacologicum Congress; 1998 Jul 12–16; Glasgow, Scotland
May F, Pattenier J. A naturalistic study of mirtazapine in the German psychiatric practice [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow, Scotland
Renfurm R, Vester E, Helsdingen JTH. Anxiolytic and sleep improving effects of mirtazapine in everyday clinical practice [abstract]. Biol Psychiatry 1997 Jul 1; 42 Suppl.: 248S
Thase ME, Howland RH, Friedman ES. Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry 1998; 59 Suppl. 5: 5–12
Carpenter LL, Jocic Z, Hall JM, et al. Mirtazapine augmentation in the treatment of refractory depression. J Clin Psychiatry 1999 Jan; 60: 45–9
Lennkh C, Fischer P, Kasper S. Combined treatment with mirtazapine and maprotiline in refractory severe depression [abstract]. Eur Neuropsychopharmacol 1997 Sep; 7 Suppl. 2: S183–184
Hesselmann B, Küfferle B, Praschak-Rieder N, et al. Combined antidepressant therapy using mirtazapine and citalopram in therapy resistent depression [abstract]. Eur Neuropsychopharmacol 1997 Sep; 7 Suppl. 2: S152
Stahl S, Zivkov M, Reimitz PE, et al. Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression. Acta Psychiatr Scand 1997; 96 Suppl. 391: 22–30
Kasper S. Clinical efficacy of mirtazapine: a review of metaanalyses of pooled data. Int Clin Psychopharmacol 1995; 10 Suppl. 4: 25–35
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 1998 Mar; 59: 123–7
Montgomery SA, Reimitz P-E, Zivkov M. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. Int Clin Psychopharmacol 1998 Mar; 13: 63–73
Bremner JD. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. J Clin Psychiatry 1995; 56: 519–25
Smith WT, Glaudin V, Panagides J, et al. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull 1990; 26(2): 191–6
Claghorn JL, Lesem MD. A double-blind placebo-controlled study of Org 3770 in depressed outpatients. J Affect Disord 1995 Jun 8; 34: 165–71
Mullin J, Lodge A, Bennie E, et al. A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression. J Psychopharmacol 1996; 10(3): 235–40
Zivkov M, De Jongh GD. Org 3770 versus amitriptyline: a 6-week randomized double-blind multicentre trial in hospitalized depressed patients. Hum Psychopharm 1995 May–Jun; 10: 173–80
Richou H, Ruimy P, Charbaut J, et al. A multicentre, double-blind, clomipramine-controlled efficacy and safety study of Org 3770. Hum Psychopharm 1995 Jul–Aug; 10: 263–71
Marttila M, Jääskeläinen J, Järvi R, et al. A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression. Eur Neuropsychopharmacol 1995; 5(4): 441–6
Kasper S, Zivkov M, Roes KCB, et al. Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline. Eur Neuropsychopharmacol 1997 May; 7: 115–24
Pinder RM, Zivkov M. Imipramine and mirtazapine are less effective than expected. Psychopharmacology 1997 Feb; 129: 297–8
Bruijn JA, Moleman P, Mulder PGH, et al. Comparison of 2 treatment strategies for depressed inpatients: imipramine and lithium addition or mirtazapine and lithium addition. J Clin Psychiatry 1998 Dec; 59 (657-663)
Peyron E. Efficacy of mirtazapine vs clomipramine in severely depressed, hospitalized patients [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6 Suppl. 3: 46–7
van Moffaert M, de Wilde J, Vereecken A, et al. Mirtazapine is more effective than trazadone: a double-blind controlled study in hospitalized patients with major depression. Int Clin Psychopharmacol 1995 Mar; 10: 3–9
Brown MCJ, Nimmerrichter A, Guest JF. Economic impact of using mirtazapine in the management of moderate and severe depression in Austria [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow
Brown MCJ, Guest JF, van Loon J. Economic impact of using mirtazapine in the management of moderate and severe depression in France [abstract]. Eur Neuropsychopharmacol 1998 Nov; 8 Suppl. 2: S150
Montgomery SA. Safety of mirtazapine: a review. Int Clin Psychopharmacol 1995; 10 Suppl. 4: 37–45
Stahl SM, Kremer CME, Pinder RM. Tolerability of mirtazapine used in high or low initial dose [abstract]. Eur Neuropsychopharmacol 1997 Sep; 7 Suppl. 2: S157–158
Farah A. Lack of sexual adverse effects with mirtazapine [letter]. Am J Health System Pharm 1998 Oct 15; 55: 2195–6
Koutouvidis N, Pratikakis M, Fotiadou A, et al. ArticleThe use of mirtazapine in a group of 11 patients following poor compliance to SSRI treatment due to sexual dysfunction [abstract]. Eur Neuropsychopharmacol 1997 Sep; 7 Suppl. 2: S156
Gelenberg AT, Laukes C, McGahuey C, et al. Mirtazapine substitution in SSRI-induced sexual dysfunction. Biol Psychiatry 1998 Apr 15; 43 Suppl.: 104S
Mir S, Taylor D. The adverse effects of antidepressants. Curr Opin Psychiatry 1997; 10(2): 88–94
Klint T, Helsdingen JT, Kremer CME, et al. Lack of typical SSRI-related adverse effects and sexual dysfunction with mirtazapine is related to specific blockade of 5-HT2 and 5-HT3 receptors [abstract]. Eur Neuropsychopharmacol 1996 Sep; 6 Suppl. 4: S61–62
Bremner JD, Smith WT. Org 3770 VS amitriptyline in the continuation treatment of depression: a placebo controlled trial. Eur J Psychiatry 1996; 10(1): 5–15
Henry JA. Epidemiology and relative toxicity of antidepressant drugs in overdose. Drug Saf 1997 Jun; 16(6): 374–90
Bremner JD, Wingard P, Walshe TA. Safety of mirtazapine in overdose. J Clin Psychiatry 1998 May; 59: 233–5
Holzbach R, Jahn H, Pajonk F-G, et al. Suicide attempts with mirtazapine overdose without complications. Biol Psychiatry 1998; 44: 925–6
Hoes MJAJM, Zeijpveld JHB. First report of mirtazapine overdose. Int Clin Psychopharmacol 1996 Jun; 11: 147
Gerritsen AW. Safety in overdose of mirtazapine: a case report. J Clin Psychiatry 1997 Jun; 58: 271
Retz W, Maier S, Maris F, et al. Non-fatal mirtazapine overdose. Int Clin Psychopharmacol 1998; 13: 277–9
Nelson JC. Safety and tolerability of the new antidepressants. J Clin Psychiatry 1997; 58 Suppl. 6: 26–31
Organon Laboratories Limited. Zispin™. ABPI Compendium of Data Sheets and Summaries of Product Characteristics 1998–99. Datapharm Publications Limited. London, 916
Mirtazapine. In: McEvoy GK, editor. AHFS Drug Information® 98. Bethesda (MD): American Society of Health-System Pharmacists Inc., 1998: 1834
Sitsen AJM, Heisdingen JTH. Tolerability of mirtazapine in 15 mg vs 30 mg initial dose: a randomized, double-blind study [poster]. 21st Collegium Internationale Neuro-Psychopharmacologicum Congress; 1998 Jul 12–16; Glasgow, Scotland
Simhandl C, Zhoglami A, Pinder R. Pregnancy during use of mirtazapine [poster]. 21st Collegium Internationale NeuroPsychopharmacologicum Congress; 1998 Jul 12–16; Glasgow
Sitsen AJM, Kremer CME. Lack of pharmacokinetic interactions between mirtazapine and lithium [abstract]. Eur Neuropsychopharmacol 1997 Sep; 7 Suppl. 2: S158
Mink L, Heftink N, Jonkman JGH, et al. Pharmacokinetics of mirtazapine in combination with amitriptyline [abstract no. 357]. Biol Psychiatry 1998 Apr 15; 43 Suppl: 107S–8S
Soutullo CA, McElroy SL, Keck PE Jr. Hypomania associated with mirtazapine augmentation of sertraline. J Clin Psychiatry 1998 Jun; 59: 320
Normann C, Hesslinger B, Frauenknecht S, et al. Psychosis during chronic levodopa therapy triggered by the new anti-depressive drug mirtazapine. Pharmacopsychiatry 1997 Nov; 30: 263–5
Zedkova L, Coupland NJ. Hypertension during coprescription of mirtazapine and low-dose amitriptyline. Can J Psychiatry 1998 Oct; 43(8): 858–9
Henry JA, Rivas CA. Constraints on antidepressant prescribing and principles of cost-effective antidepressant use. Part 1: depression and its treatment. Pharmacoeconomics 1997 May; 11: 419–43
Hirschfeld RMA, Keller MB, Panico S, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997 Jan 22–29; 277: 333–40
Frazer A. Pharmacology of antidepressants. J Clin Psychopharmacol 1997 Apr; 17 Suppl. 1: 2–18
Möller H-J, Volz H-P. Drug treatment of depression in the 1990s: an overview of achievements and future possibilities. Drugs 1996 Nov; 52: 625–38
Leonard BE. New approaches to the treatment of depression. J Clin Psychiatry 1996; 57 Suppl. 4: 26–33
DeVane CL. Differential pharmacology of newer antidepressants. J Clin Psychiatry 1998; 59 Suppl. 20: 85–93
Stahl SM. Are two antidepressant mechanisms better than one? J Clin Psychiatry 1997 Aug; 58: 339–240
Montgomery SA. Efficacy in long-term treatment of depression. J Clin Psychiatry 1996; 57 Suppl. 2: 24–30
Various sections of the manuscript reviewed by: H. Ågren, Karolinska Institute, Division of Psychiatry, Huddinge University Hospital, Huddinge, Sweden; S. Agyropoulos, Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, England; J.D. Bremner, Bremner Research Institute, Olympia, Washington, USA; N. Haddjeri, Department of Psychiatry, McGill University, Montréal, Québec, Canada; R.M.A. Hirschfeld, Department of Psychiatry, University of Texas Medical Branch, Galveston, Texas, USA; S. Hood, Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, England; O.J. Høyberg, Department of Psychiatry, Fylkes Hospital I Molde, Molde, Norway; S. Kasper, Department of General Psychiatry, University of Vienna, Vienna, Austria; B.E. Leonard, Department of Pharmacology, National University of Ireland, Galway, Ireland; G. Stimmel, School of Pharmacy, University of Southern California, Los Angeles, California, USA; M. Van Moffaert, Department of Psychology, University Hospital, Gent, Belgium; W. Wittgens, Department of Geriatric Psychiatry, Hans-Prinzhorn Hospital, University of Witten-Hedecke, Hemer, Germany.
Sources: Medical literature published in any language since 1966 on mirtazapine, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: AdisBase search terms were ‘mirtazapine’, ‘6-azamianserin’, ‘azamianserin’, ‘mepirzapin’, ‘Org-3770’ and ‘depression’. Medline and EMBASE search terms were ‘mirtazapine’ and ‘depression’. Searches were last updated 11 March 1999.
Selection: Studies in patients with major depression who received mirtazapine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic and pharmacoeconomic data are also included.
Index terms: mirtazapine, depression, pharmacodynamics, pharmacokinetics, therapeutic use, dosage and administration, pharmacoeconomics.
About this article
Cite this article
Holm, K.J., Markham, A. Mirtazapine. Drugs 57, 607–631 (1999). https://doi.org/10.2165/00003495-199957040-00010
- Adis International Limited