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Mechanism Of Action
The mechanism of action of REMERON® Tablets, as with other drugs effective in the treatment of major depressive disorder, is unknown.
Evidence gathered in preclinical studies suggests that mirtazapine enhances central noradrenergic and serotonergic activity. These studies have shown that mirtazapine acts as an antagonist at central presynaptic α2 adrenergic inhibitory autoreceptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. The clinical relevance of this finding is unknown.
REMERON® acts as an antagonist at central presynaptic α2 adrenergic inhibitory autoreceptors and heteroreceptors, which results in an increase in central noradrenergic and serotonergic activity. The clinical relevance of this finding is unknown, however, this action may explain its anti-depressant activity.
REMERON® is a potent antagonist of 5-HT2 and 5-HT3 receptors. The clinical relevance of this finding is unclear, however, the 5-HT2 and 5-HT3 antagonism by REMERON® may account for its low rate of nausea, insomnia and anxiety as observed in clinical trials. REMERON® has no significant direct effect on 5-HT1A and 5-HT1B receptors.
Both enantiomers of REMERON® appear to contribute to its pharmacological activity. The (+)enantiomer blocks 5-HT2 receptors as well as α2 receptors, and the (-)enantiomer blocks 5-HT3 receptors. The clinical relevance of this finding is unclear, but this may explain its anti-depressant activity and side-effects profile.
REMERON® is a moderate peripheral α1 adrenergic antagonist, a property which may explain the occasional orthostatic hypotension reported in association with its use.
REMERON® is a moderate antagonist at muscarinic receptors, a property that may explain the occasional occurrence of anticholinergic side effects associated with its use as shown in clinical trials.
REMERON® is well absorbed following oral administration and its absolute bioavailability is approximately 50% after either single or multiple doses. Peak plasma concentrations are reached within about 2 hours following an oral dose. The time to peak plasma concentration is independent of dose. The presence of food in the stomach somewhat slows the rate but not the extent of absorption, and thus does not require a dosage adjustment.
Plasma levels are linear over a dose range of 30 to 80 mg. Steady-state plasma levels are attained within about 5 days. The half-life of elimination of REMERON® after oral administration is approximately 20 - 40 hours.
REMERON® is extensively metabolized and quantitatively eliminated via urine (75%) and feces (15%); approximately 90% of this elimination occurs within the first 72 - 96 hours. Major pathways of biotransformation are demethylation and oxidation followed by conjugation. In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas cytochrome 3A is considered to be responsible for the formation of the N-demethyl and N-oxide metabolite. The demethyl metabolite is pharmacologically active and appears to have a similar pharmacokinetic profile as that of the parent compound.
The (-)enantiomer has an elimination half-life that is approximately twice as long, and achieves plasma levels that are three times as high as that of the (+)enantiomer.
REMERON® is approximately 85% bound to plasma proteins over a concentration range of 10 to 1,000 ng/mL. Binding appears to be both non-specific and reversible. The binding affinity of mirtazapine to human liver proteins is 2.8 times greater than to human plasma proteins. As with all drugs that are protein-bound, care should be exercised when co-administering medications that may interact with REMERON® at protein-binding sites (see WARNINGS AND PRECAUTIONS).
TABLE 2: Effect of age and gender on plasma half-life
|Group||T½ (MEAN ± SD)*|
|Single Dose||Multiple Dose|
|Adult male N=9||21.7 ± 4.2||22.1 ± 3.7|
|Adult female N=9||37.7 ± 13.3||35.4 ± 13.7|
|Elderly# male N=8||32.2 ± 15.4||31.1 ± 15.1|
|Elderly# female N=8||40.6 ± 12.8||39.0 ± 10.8|
|* Expressed in hours.
# The “elderly” group consisted of subjects 55 and older (55 - 75; mean age 65)
Special Populations And Conditions
Pediatrics: REMERON® is not indicated for use in patients below the age of 18 years. Two randomised, double-blind, placebo-controlled trials in children aged between 7 and 18 years with major depressive disorder (n=259) failed to demonstrate significant differences between mirtazapine and placebo on the primary and all secondary endpoints. Significant weight gain ( ≥ 7 %) was observed in 48.8 % of the REMERON® treated subjects compared to 5.7 % in the placebo arm. Urticaria (11.8 % vs. 6.8 %) and hypertriglyceridaemia (2.9 % vs. 0 %) were also commonly observed. (see WARNINGS AND PRECAUTIONS, General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm; and DOSAGE AND ADMINISTRATION).
Following administration of REMERON® 20 mg/day for 7 days, oral clearance was reduced in older subjects (mean age 65; range 55 - 75) compared to younger subjects (see Table 2). The difference was greatest in males, with a 40% lower clearance for REMERON® in the older vs. younger group, while clearance is lowest overall in elderly females. Caution is indicated in administering REMERON® Tablets in the elderly (see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Age and Sex: In the same study above females of all ages (range 25 - 74) exhibited significantly longer elimination half-lives than males (mean half-life 37 hours for females vs. 26 hours for males) (see Table 2). Although these differences result on average in higher AUC for females compared to males, there is considerable overlap in individual AUCs between groups. Because of substantial individual variation of AUC and half-life, no specific dosage recommendations based on sex are indicated (see DOSAGE AND ADMINISTRATION).
Liver Disease: In a single-dose study conducted with REMERON® 15 mg, the elimination half-life of REMERON® was increased 40% in mild to moderately hepatically impaired subjects as compared to patients with normal hepatic function; this effect on elimination resulted in a 57% increase in AUC and a 33% decrease in clearance.
Renal Disease: In a single-dose study conducted with REMERON® 15 mg, subjects with moderate and severe renal impairment showed a significant decrease in the clearance of REMERON® and a consequent increase in the AUC (54% and 215% for moderate and severe renal impairment, respectively). Subjects with severe renal impairment had significantly higher peak plasma levels of REMERON® (about double that of subjects without renal impairment). These results suggest that caution must be exercised in administering REMERON® to patients who may have compromised renal function.
Clinical Trials Showing Efficacy
The efficacy of REMERON® Tablets in the treatment of depression was demonstrated in four U.S. placebo-controlled trials (6 week duration) in adult outpatients meeting DSM III criteria for major depression. Patients were titrated with mirtazapine starting at a dose of 5 mg/day up to a dose of 35 mg/day (by the beginning of Week 3). Outcome measures included the Hamilton Depression Rating Scale (21-item), and the Montgomery and Asberg Depression Rating Scale. The mean mirtazapine dose for patients completing the four studies ranged from 21 to 32 mg/day. Additional supportive studies used higher doses up to 50 mg/day. In the U.S. short-term flexible-dose controlled trials (REMERON® Tablets, n=323), 70% and 54% of the patients received final doses ≥ 20 mg and ≥ 25 mg, respectively.
In a longer-term study, patients meeting DSM-IV criteria for major depressive disorder who had responded during an initial 8 to 12 weeks of acute treatment on REMERON® Tablets were randomized to continuation of REMERON® Tablets or placebo for up to 40 weeks of observation for relapse. Response during the open phase was defined as having achieved a HAMD-17 total score of ≤ 8 and a CGI-Improvement score of 1 or 2 at two consecutive visits, beginning with Week 6 of the 8 - 12 weeks in the open-label phase of the study. Relapse during the double-blind phase was determined by the individual investigators. Patients receiving continued REMERON® treatment experienced significantly lower relapse rates over the subsequent 40 weeks compared to those receiving placebo. This pattern was demonstrated in both male and female patients.
REMERON® and its enantiomers have been studied for their pharmacological effects in behavioural models for depression (Table 3) in mice and rats, in EEG-derived rat sleep-waking analysis and in receptor interaction studies [receptors for noradrenaline, serotonin (5-HT), histamine, acetylcholine and dopamine in rats and guinea pigs].
TABLE 3: CNS-Pharmacological profile of and its
|Anti-depressant-like effects - bulbectomized rat: behavioural||+||+|
|- acquired immobility test||-||-||+|
|Anti-anxiety effects - anxiosoif test||±||±||±|
|- sleep (rat)||+||+||±|
|- sleep (human)||+||+||+|
|- enhancement NA release||+||+|
|- rauwolscine displacement||+||+||-|
|- antagonism clonidine mydriasis||+||+||-|
|- affinity 5HT2||+||+||±|
|- affinity 5HT3||+||-||+|
|- H1 -antagonism||+||+||+|
|- QNB binding||-||-||-|
|- guinea pig ileum||-||-||-|
Pharmacological Indices of Side Effects (Table 3)
The commonly observed side-effects of anti-depressants that can be ascribed to receptor interactions are those of anticholinergic (dry mouth, blurred vision, constipation, urinary retention), α1-adrenolytic (orthostatic hypotension) and antihistaminic (sedation) origin.
REMERON® is virtually devoid of anticholinergic activity, as has been shown in in vitro receptor interactions and confirmed in the in vivo tremorine antagonism test. It is therefore predicted that the incidence of anticholinergic side-effects observed with REMERON® in clinical practice should be low. This has been confirmed in clinical trials.
REMERON® is a moderately weak antagonist at central and peripheral α1 adrenoceptors, as observed in vitro in the labelled prazosin binding assay in rat brain cortex homogenates and in the isolated rat vas deferens assay. On the basis of these observations, a low incidence of orthostatic hypotension would be predicted, which is in line with the clinical observations in depressed patients.
Contribution of REMERON® Enantiomers to its Pharmacological Profile (Table 3)
In the acquired immobility test for anti-depressant activity, both REMERON® and the (S)+enantiomer are inactive, whereas the (R)-enantiomer is active.
In the olfactory bulbectomized rat, subchronic treatment with the (S)+enantiomer reverses deficient behaviour, whereas the (R)-enantiomer is inactive. However, the bulbectomy-induced decreases in noradrenaline and MHPG levels are reversed by subchronic treatment with the (R)-enantiomer, but not with the (S)+enantiomer.
Both enantiomers are active in the conflict-punishment test (display anti-anxiety activity) and in the sleep-waking EEG test in rats (suppression of REM sleep, an effect shared by many psychotropic drugs). In human pharmaco-EEG profiling in healthy volunteers (16), both enantiomers show a clear-cut “anti-depressant” profile, at similar dose levels (0.5 and 1 mg per subject).
The enantiomers of REMERON® differ considerably with respect to biochemical activity. The α2-blocking activity of REMERON® is virtually confined to the (S)+enantiomer, which is also the more potent 5HT2 antagonist. However, the (R)-enantiomer is the active principle in mirtazapine with regard to 5HT3 antagonistic activity. Both enantiomers contribute to a similar extent to the antihistaminic and (weak) α1-adrenolytic properties of REMERON®.
Contribution of REMERON® Main Metabolites to its Pharmacological Profile
Demethyl mirtazapine, the only metabolite found in the rat brain after oral administration of REMERON®, has anti-anxiety activity in the conflict-punishment test in rats, but is less active in the rat EEG profile for anti-depressant activity than the parent compound. The demethyl metabolite is also less active than the parent compound in in vivo tests for α2-blocking and 5HT2 antagonistic activity. This may be due to poor bioavailability upon systemic administration, since the in vitro tests show that the compound is approximately equally active to REMERON® as an α2 and 5HT2 antagonist; important indices for therapeutic anti-depressant activity. With respect to antagonism at the histamine H1 receptor, which is probably related to sedation, the demethyl metabolite appears to be less active than the parent compound. 8-hydroxy mirtazapine, 8-hydroxy demethyl mirtazapine and N(2)-oxide of mirtazapine have not been found to penetrate into the rat brain and are inactive in vivo, with the exception of the N(2)-oxide and the 8-hydroxy metabolite, which display some anti-serotonergic activity. In vitro, these metabolites are much less active than the parent compound at important receptors, like the α2, 5HT2 and histamine H1 receptors. They are, therefore, not considered to be relevant for the pharmacodynamic profile of REMERON®, with regard to therapeutic activity or side-effects.
Glucuronide and sulphonate conjugates are not expected to be pharmacologically active and therefore only a limited number of in vivo and in vitro tests have been performed with these metabolites; they did not show any activity.
Cardiovascular Pharmacology Of REMERON®
In conscious rabbits, REMERON®, at doses of 0.1 and 1.0 mg/kg i.v., has no effect on blood pressure, heart rate and the autonomic nervous system; at 10 mg/kg i.v., REMERON® also has no effect on blood pressure and heart rate but slightly reduces the noradrenaline-induced increase in blood pressure and isoprenaline-induced increase in heart rate.
In anesthetized cats, REMERON®, at doses of 0.1 and 1.0 mg/kg i.v., induces no cardiovascular effects and does not affect the autonomic nervous system; at 10 mg/kg i.v., REMERON® induces a decrease in blood pressure and heart rate and reduces the changes in blood pressure induced by vagus stimulation and carotid occlusion.
In anesthetized dogs, REMERON®, at 0.1 mg/kg i.v., does not induce any hemodynamic changes; at 1.0 mg/kg i.v., REMERON® slightly decreases heart rate and myocardial contractility and slightly increases peripheral vascular resistance; at a dose of 10 mg/kg i.v., REMERON® induces a slight decrease in heart rate and stroke index, resulting in a slightly decreased cardiac index, a decrease in myocardial contractility and an increase in peripheral vascular resistance, resulting in decreased femoral and common carotid blood flow.
In artificially ventilated, anesthetized dogs, cardiotoxicity has been investigated by infusing REMERON® intravenously (30 mg/kg/h) until the animal died from cardiac arrest. If the animal was still alive 5 hours after the start of the infusion, the experiment was stopped. Four out of five dogs died at the end of the 5-hour infusion period and one dog survived the infusion period. The mean extrapolated plasma level of REMERON® prior to death in these four dogs was approximately 20 μg/mL; this is approximately 200 times the anticipated clinical peak plasma levels. There was a linear relationship between the severity of the cardiovascular effects (e.g., decrease in blood pressure, decrease in cardiac output and decrease in dP/dt) and the measured plasma level of REMERON®.
The oral LD50 value for REMERON® in male Swiss mice was 830 mg/kg (760 - 940 mg/kg) after 24 hours and 810 mg/kg (720 - 1,010 mg/kg) after 7 days, and in females, 720 mg/kg (620 - 850 mg/kg) after 24 hours and 7 days.
The oral LD50 value for REMERON® after 24 hours and 7 days was 490 mg/kg (427 - 534 mg/kg) and 320 mg/kg (240 - 430 mg/kg) in male and female Wistar rats, respectively. In a separate study in rats, the enantiomers of REMERON® displayed similar acute toxicity, the LD50 being 222 mg/kg and 208 mg/kg for the (R)- and (S)+enantiomers, respectively. Clinical signs observed in both species, mainly at the highest doses, included motor incoordination, reduced activity, ptosis, twitches, abnormally slow respiration and piloerection; these symptoms reached their peak 2 hours after administration and gradually disappeared during the first day. Gross anatomy revealed no drug-related morphological changes.
Repeated Dose Toxicity
Oral 13-week toxicity studies were carried out with REMERON® in rats of both sexes followed by a 4-week recovery period with daily doses of 10, 40 and 120 mg/kg, and in dogs of both sexes followed by a 7-week recovery period at daily doses of 5, 20, and 80 mg/kg. A second study in dogs was performed at a single dose level of 20 mg/kg/day to investigate possible changes in the prostate seen in the initial study in male dogs. One-year toxicity studies, followed by a five-week recovery period, were carried out in rats and dogs with daily doses of 2.5, 20 and 120 mg/kg and 2.5, 15 and 80 mg/kg, respectively.
Oral administration of REMERON® at 10 mg/kg/day to Wistar rats for 13 consecutive weeks induced no untoward effects, whereas REMERON® at 40 and 120 mg/kg/day induced:
- transient clinical signs including mydriasis, lachrymation, ptosis, hypothermia, bradypnea and hypersalivation (only in females receiving 120 mg/kg)
- transient decrease in body weight gain and initial decrease in food consumption followed by an increase in food intake
- increased thyroidal weight (males only) associated with hypertrophy of thyroid follicular cells, a finding known to occur with compounds inducing microsomal hepatic enzymes in this species (see rat carcinogenicity study)
- increased adrenal gland weight (females only) not associated with morphological changes
- mild vacuolation of cortical renal tubules not associated with any other cytoplasmic or nuclear changes suggestive of degenerative/necrotic response, lipid deposition or any disturbances in renal function tests; this is not a nephrotoxic response as confirmed in the subsequent chronic toxicity study (see below)
- mild hepatic cell hypertrophy not indicative of hepatotoxicity and not accompanied by hepatic functional disturbances or degenerative changes
All these findings were reversible after a 4 week post-dosing period.
Oral administration of REMERON® to Beagle dogs for 13 consecutive weeks induced:
- increased liver weights not associated with hepatotoxicity at dose levels of 5, 20 and 80 mg/kg/day
- behavioural changes including incidental vomiting, loose defecation, reduced motor activity and body tremors at 20 and 80 mg/kg/day
- slight body weight loss in male dogs at 80 mg/kg/day
- decreased red blood cell parameters (hemoglobin and packed cell volume) at 80 mg/kg/day
- decreased testicular weight associated with reduced spermatogenesis, decreased epididymal weights and reduced epididymal spermatozoal content in two out of five animals at 80 mg/kg/day
A significant decrease in prostatic weights was seen in all drug-treated animals, as well as in a male in the control group kept for recovery. This effect was evaluated in a supplementary study (20 mg/kg/day for 13 consecutive weeks), after which it was concluded that the prostatic weight changes found in the first study most probably were not due to REMERON® treatment but related to seasonal variations and age differences (younger males appearing to be more sensitive to changes in prostatic weight than the older animals). There is no evidence from the clinical studies to suggest that REMERON® will affect the prostate in man.
Oral administration of REMERON® for one year to Sprague-Dawley rats (2.5, 20 and 120 mg/kg/day) and Beagle dogs (2.5, 15 and 80 mg/kg/day) did not induce any effects additional to those observed in the subchronic toxicity studies.
In the rat study, body weight in low-dose (males and females) and mid-dose (females) groups was generally slightly lower than in control animals; there was a marked decrease in body weight in the high-dose animals.
Microscopic examinations revealed that the only drug-related finding was an increased incidence of intracytoplasmic vacuolation in the renal proximal convoluted tubules in the high-dose group of rats after 6 months, and those of the high- and intermediate-dose groups after 12 months. In addition, there was an increased incidence of finely granular brown pigment in the cytoplasm of the tubular epithelial cells in the high-dose rats. The above-mentioned changes were not accompanied by any cytoplasmic or nuclear degenerative changes or by any disturbance in the renal function tests. From the light microscopy, it was suggested that the vacuolations are the result of an increase in the size and numbers of the vacuoles constituting the endocytotic/lysosomal system in the proximal convoluted tubules. This was verified by electron microscopic examination of the kidneys. Vacuolations are known to occur whenever there is an incompatibility between material that enters the lysosomes and the digestive enzymes stored there. Thus, in the chronic toxicity study with REMERON® in rats, a transient incompatibility may have taken place due to overloading with the high dose of the test material. As in the subchronic 13-week study, tubular vacuolation and brown pigmentation were reversed during the one-month recovery period.
Oral administration of REMERON® at 2.5 and 15 mg/kg/day to Beagle dogs for 12 months induced no untoward effects, whereas at 80 mg/kg/day, induced:
- neurological signs (trembling and convulsions)
- decline in condition and mild gastro-intestinal disturbances
- body weight loss mainly during the first half of the dosing period
- decreases in red blood cell parameters (RBC, Hb, PCV)
- mild increases in alkaline phosphatase and glutamic-pyruvic transaminase during the first half of the dosing period, together with liver enlargement and hepatic cell hypertrophy, possibly indicative of enzyme induction. These changes were not associated with hepatic morphological changes indicative of hepatotoxicity after six or 12 months
- increases in the erythroid/myeloid ratios in the bone marrow in males and, to a lesser extent, in females receiving 15 or 80 mg/kg/day after 52 weeks of dosing due to mildly decreased total myeloid elements in males and females and mildly increased erythroid elements in males
Reversibility of the drug-related effects was seen after the one-month post-dosing period.
1. Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry 2000;61:656-62.
2. Bremner JD, Smith WT. ORG 3770 vs. amitriptyline in the continuation treatment of depression: A placebo-controlled trial. Eur J Psychiat 1996;10(1):5-15.
3. Dahl ML, Voortman G, Alm C, Elwin CE, Delbressine L, Vos R, et al. In vitro and in vivo studies on the disposition of mirtazapine in humans. Clin Drug Invest 1997;13(Suppl 1):37-46.
4. de Boer T, Ruigt GSF. The selective α2-adrenoceptor antagonist mirtazapine (ORG 3770) enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission. CNS Drugs 1995; 4(Suppl 1):29-38.
5. de Montigny C, Haddjeri N, Mongeau R, Blier P. The effects of mirtazapine on the interactions between central noradrenergic and serotonergic systems. CNS Drugs 1995;4(Suppl)1:13-7.
6. Holm KJ, Markham A. Mirtazapine: A review of its use in major depression. Drugs 1999;57:607-31.
7. Leinonen E, Skarstein J, Behnke K, Agren H, Helsdingen JTH. Efficacy and tolerability of mirtazapine versus citalopram: A double-blind randomized study in patients with major depressive disorder. Intl Clin Psychopharmacol 1999;14:329-37.
8. Leonard BE. Mechanisms of action of antidepressants. CNS Drugs 1995;4(Suppl 1):1-12.
9. Loonen AJM, Doorschot CH, Oostelbos MCJM, Sitsen JMA. Lack of drug interactions between mirtazapine and risperdone in psychiatric patients: A pilot study. Eur Neuropsychopharmacol 1999;10:51-7.
10. Montgomery SA. Safety of Mirtazapine: A review. Int Clin Psychopharmacol 1995;10:37-45.
11. Peroutka SJ. Serotonin receptor subtypes: Their evolution and clinical relevance. CNS Drugs 1995;4(Suppl 1):18-28.
12. Radhakishun FS, Bos JvdB, van der Heijden BCJM, Roes KCB, O'Hanlon JF. Mirtazapine Effects on alertness and sleep in patients as recorded by interactive telecommunication during treatment with different dosing regimens. J Clin Psychopharmacol 2000;20:531-7.
13. Ruwe FJL, Smulders RA, Kleijn HJ, Hartmans HLA, Sitsen JMA. Mirtazapine and paroxetine: A drug-drug interaction study in healthy subjects. Hum Psychopharmacol 2001;16:449-59.
14. Sennef C, Timmer CJ, Sitsen JMA. Mirtazapine in combination with amitriptyline: A drug-drug interaction study in healthy subjects. Hum Psychopharmacol 2003;18(2):91-101.
15. Sitsen JMA, Maris FA, Timmer CJ. Concomitant use of mirtazapine and cimetidine: A drug-drug interaction study in healthy male subjects. Eur J Clin Pharmacol 2000;56:389-94.
16. Sitsen JMA, Maris FA, Timmer CJ. Drug-drug interaction studies with mirtazapine and carbamazepine in healthy male subjects. Eur J Drug Metab Pharmacokinet 2001;26(1/2):109-21.
17. Sitsen JMA, Voortman G, Timmer CJ. Pharmacokinetics of mirtazapine and lithium in healthy male subjects. J Psychopharmacol 2000;14:172-6.
18. Sitsen JMA and Zivkov M. Mirtazapine: Clinical profile. CNS Drugs 1995;4(Suppl 1):39-48.
19. Spaans E, van den Heuvel MW, Schnabel PG, Peeters PAM, Ching-kon-Sung UG, Colbers EPH, et al. Concomitant use of mirtazapine and phenytoin: A drug-drug interaction study in healthy male subjects. Eur J Clin Pharmacol 2002;58:423-9.
20. Wheatly DP, van Moffaert M, Timmerman L, Kremer CME. Mirtazapine: Efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. J Clin Psychiatry 1998;59:306-12.
Last reviewed on RxList: 12/22/2015
This monograph has been modified to include the generic and brand name in many instances.
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