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 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
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PMID:Safety of mirtazapine: a review. 893 8

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonist of presynaptic alpha 2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5-HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors. The net outcome of these effects is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5-HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects common to both tricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2-4 weeks similar to other antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and weight gain are more common with mirtazapine than with placebo. An elimination half-life of 20-40 hours enables once-daily bedtime dosing. The recommended initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range of 15-45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.
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PMID:Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. 901 62

Mirtazapine is a newer antidepressant that exhibits both noradrenergic and serotonergic activity. It is at least as effective as the older antidepressants for treating mild to severe depression. Sedation is the most common side effect. Although agranulocytosis is the most serious side effect, it is rare (approximately one in 1,000) and usually reversible when the medication is stopped. Mirtazapine is relatively safe in overdose. Many clinicians consider mirtazapine a second-line or even third-line antidepressant to be used when older antidepressants are not tolerated or are ineffective. Physicians who are concerned about the risks of elevated lipid levels and agranulocytosis may choose to reserve mirtazapine as a third-line choice. It is particularly useful in patients who experience sexual side effects from other antidepressants. Mirtazapine is also a good choice in depressed patients with significant anxiety or insomnia. Although mirtazapine has been used successfully in Europe for a number of years, its place in the care of patients with depression in the United States has not yet been established.
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PMID:Mirtazapine: a newer antidepressant. 1050 41

Mirtazapine is a presynaptic alpha-2 antagonist that has dual action by increasing noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors because mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist. In addition, mirtazapine has only a weak affinity for 5-HT1 receptors and has very weak muscarinic anticholinergic and histamine (H1) antagonist properties. As a consequence of its unique pharmacodynamic properties, mirtazapine is an effective, safe and well-tolerated addition to the antidepressant armamentarium. Mirtazapine is well absorbed from the gastrointestinal tract following oral administration, and it is extensively metabolized in the liver to four metabolites via demethylation and hydroxylation, followed by glucuronide conjugation. The unconjugated desmethyl metabolite is pharmacologically less active than the parent compound. Mirtazapine lacks auto-induction of hepatic isoenzymes. Although mirtazapine is a substrate of P450 isoenzymes 1A2, 2D6 and 3A4, in vitro studies show that it is not a potent inhibitor or inducer of any of these enzymes. Mirtazapine has been evaluated in a worldwide clinical development program involving approximately 4500 patients. Controlled clinical trials involving almost 2800 mirtazapine-treated patients have demonstrated the compound to be effective for the treatment of moderate-to-serve major depression. Mirtazapine was consistently superior to placebo, and equivalent in efficacy to the tricyclic antidepressants amitriptyline, doxepin and clomipramine, but with an improved tolerability profile. Mirtazapine has shown a rapid onset of action in patients with predominantly severe depressive illness in a comparative study against fluoxetine. Mirtazapine has a unique tolerability profile, since the specific postsynaptic 5-HT2 and 5-HT3 receptor blockade of mirtazapine provides early antidepressant effects without causing unwanted serotonin-related side-effects. Transient somnolence, hyperphagia and weight gain are the most commonly reported adverse events, which may be attributed to the antihistaminic (H1) activity of mirtazapine at low doses. Somnolence, the most commonly reported side-effect, appears to be less frequent at higher dosages. Mirtazapine also demonstrates important anxiolytic and sleep-improving effects, which may be related to its pharmacodynamic properties. In addition, mirtazapine does not appear to be associated with sexual dysfunction. Mirtazapine has shown no significant cardiovascular adverse effects at multiples of 7 to 22 times the maximum recommended dose. Mirtazapine is a unique addition to the antidepressant armamentarium as first-line therapy in patients with major depression and symptoms of anxiety/agitation or anxiety/somatization or complaints of insomnia and as a useful alternative in depressed patients who do not adequately respond to or are intolerant of tricyclic antidepressants or serotonin-specific reuptake inhibitors.
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PMID:Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. 1033 82

Currently available antidepressants interact with several types of receptors, which may explain both wanted and unwanted effects of these drugs. These effects are different and distinctive, and knowledge about them may help clinicians understand differences between compounds in terms of their tolerability profiles. Given roughly comparable efficacy, tolerability profile is the critical determinant in selecting an antidepressant medication for a particular patient. In addition, tolerability is inseparably linked to patient compliance, both in acute and long-term treatment, and ultimately to overall success of treatment. Refinement in pharmacologic profiles of all newly introduced antidepressants resulted in overall advantages in tolerability in comparison with older tricyclic compounds. However, differences in receptor interactions between antidepressants are directly reflected in tolerability (adverse event) profiles. Among new antidepressants, mirtazapine and the selective serotonin reuptake inhibitors share favorable overall tolerability and safety, especially with respect to low premature termination rates because of adverse events, cardiac safety, and safety in overdose. However, the different pharmacologic profile of mirtazapine is reflected in its different tolerability profile. Because of interactions with the histamine (H1) receptor, mirtazapine may be related to transient initial somnolence and weight gain in some patients. Its serotonin-2 (5-HT2)-blocking properties may account for lack of sexual dysfunction, insomnia, nervousness, and agitation. Mirtazapine's 5-HT3-blocking properties are unique among all currently available antidepressants and may account for lack of gastrointestinal adverse events.
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PMID:Tolerability and patient compliance. 1044 36

Anxiety frequently coexists with depression, either as a comorbid anxiety disorder or as anxiety symptoms accompanying a primary depressive disorder. Effective therapy for the treatment of depressive illness must include a consideration of anxiety symptoms, since anxiety has been estimated to be present in up to 96% of patients with depressive illness. Available data also indicate that depressed patients with significant anxiety may be at greater risk for suicide. Of particular clinical importance are symptoms of somatic anxiety: they are present in up to 86% of depressed patients, and the failure to treat them effectively can diminish the ability of a patient to function. Since the overall prognosis for recovery from a major depressive episode is less than optimal in patients with significant anxiety, treatments that can provide an effective and early relief of both depressive and anxiety symptoms are of paramount importance. Drugs with serotonin reuptake inhibition (such as selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs]) may produce transient increases in anxiety symptomatology presenting as jitteriness, agitation, insomnia, and gastrointestinal symptoms when treatment is initiated. Mirtazapine has intrinsic receptor-blocking properties (in particular, serotonin-2 [5-HT2] receptor blockade) that can be linked to an early relief of anxiety symptoms during the treatment. The available data show that mirtazapine is superior to placebo in depressed patients with high baseline anxiety and/or agitation. Furthermore, mirtazapine was statistically significantly superior to both citalopram and paroxetine in alleviating anxiety symptoms early in treatment as assessed by changes from baseline on the Hamilton Rating Scale for Anxiety or the Hamilton Rating Scale for Depression anxiety/somatization factor, respectively. Mirtazapine provides early and effective relief of both depressive and anxiety symptoms, reducing the need for polypharmacy. These therapeutic actions of mirtazapine persist throughout the course of treatment.
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PMID:Care of depressed patients with anxiety symptoms. 1044 38

Mirtazapine is an antidepressant that has a receptor-binding profile that may suit it for use in controlling the nausea and insomnia of highly emetic cancer chemotherapy. Mirtazapine binds to and is antagonistic at the 5HT3 receptor, as are the group of medicines related to ondansetron. Mirtazapine is anxiolytic by virtue of its antagonism of the 5HT2 receptor, and is strongly sleep inducing. The resulting sleep quality tends to be superior to that induced by benzodiazapines. There has been concern about mirtazapine's potential to suppress bone marrow function, so that further study is required before routine use in chemotherapy can be adopted.
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PMID:Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. 1158 76

The bi-directional nature of the neurovegetative symptoms of depression, as well as the differential response to antidepressant medications, underscore the existence of possible subtypes of this disorder. This study surveyed 56 physicians practicing psychiatry in Hawaii for opinions regarding the most effective antidepressant medication for the following symptoms: hypersomnia vs. insomnia, psychomotor agitation vs. retardation, and gain vs. loss of appetite or weight. Fluoxetine was found to be the drug of choice for weight and appetite gain, hypersomnia, and psychomotor retardation. Mirtazapine was viewed as most effective for weight and appetite loss. Trazodone was found most effective for insomnia and nefazodone for psychomotor agitation. It is concluded that subtyping of depression should be investigated at the symptom level and the generalizability of the effects of each specific compound should be tested.
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PMID:The relationship between type of antidepressant and neurovegetative symptoms in adult unipolar nonpsychotic depression: an opinion survey. 1178 64

BACKGROUND: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is characterized by a unique receptor-specific pharmacologic profile and tolerable side-effect profile in comparison to other antidepressants. It has been reported to have a low incidence of agitation, anxiety, and insomnia, which may be due to blockade of 5-HT(2) and 5-HT(3) receptors. This unique multireceptor-mediated clinical pharmacologic profile may reduce the need for polypharmacy in selected patients. CASE REPORTS: Three cases are presented. In case 1, mirtazapine was able to rapidly treat anxiety and agitation in a 90-year-old woman. This was confirmed with 3 consecutive challenges with mirtazapine. In case 2, both a mood disorder and insomnia were successfully treated with rapid resolution in a patient by using mirtazapine. In case 3, the patient experienced sexual dysfunction while receiving sertraline and developed insomnia with the addition of bupropion. The addition of mirtazapine and the discontinuation of sertraline and bupropion resolved the sexual dysfunction and insomnia. Polypharmacy interventions were decreased in these patients through receptor-specific events from mirtazapine. CONCLUSION: The new antidepressant mirtazapine appears to be an effective strategy for treating anxiety, agitation, and insomnia and for diminishing SSRI-related sexual dysfunction without compromising the patient's therapeutic response to the medication while decreasing the need for additional pharmacotherapies. More than 70% of patients with major depression will have anxiety symptoms. The 5-HT(2) receptor seems to play a major role in the regulation of anxiety. The anxiolytic properties of mirtazapine may be due to its antagonism of 5-HT(2) receptors and can appear as early as the first week of treatment.
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PMID:A Trilogy Case Review Highlighting the Clinical and Pharmacologic Applications of Mirtazapine in Reducing Polypharmacy for Anxiety, Agitation, Insomnia, Depression, and Sexual Dysfunction. 1501 75

Depressive and anxiety disorders appear during the transplant process due to psychological stressors, medications and physiological disturbances. Treatment is necessary to prevent impact on patient compliance, morbidity and mortality. Psychotropic medications provide an effective option, although most are only available as oral formulations. Because of this, they are more susceptible to alterations in pharmacokinetic behaviour arising from organ dysfunction in the pretransplant period. Kinetics are also an issue when considering potential drug-drug interactions before and after transplantation. Prior to transplant, organ dysfunction can change the pharmacokinetic behaviour of some psychotropic agents, requiring adjustment of dosage and schedules. Thoracic or abdominal organ failure may reduce drug absorption through disturbances in intestinal motility, perfusion and function. Cirrhotic patients experience increased drug bioavailability due to portosystemic shunting, and thus dosage is adjusted downward. In contrast, dosage needs to be raised when peripheral oedema expands the drug distribution volume for hydrophilic and protein-bound agents. Drug clearance for most psychotropic medications is dependent upon hepatic metabolism, which is often disrupted by endstage organ disease. Selection of drugs or their dosage may need to be adjusted to lower the risk of drug accumulation. Further adjustments in dosage may be called for when renal failure accompanies thoracic or abdominal organ failure, resulting in further impairment of clearance. Studies regarding the treatment of anxiety and depressive disorders in the medically ill are limited in number, but recommendations are possible by review of clinical and pharmacokinetic data. Selective serotonin reuptake inhibitors are well tolerated and efficacious for depression, panic disorder and post-traumatic stress disorder. Adjustments in dosage are required when renal or hepatic impairment is present. Among them, citalopram and escitalopram appear to have the least risk of drug-drug interactions. Paroxetine has demonstrated evidence supporting its use with generalised anxiety disorder. Venlafaxine is an alternative option, beneficial in depression, post-traumatic stress and generalised anxiety disorders. Nefazodone may also be considered, but there is some risk of hepatotoxicity and interactions with immunosuppressant drugs. Mirtazapine still needs to be studied further in anxiety disorders, but can be helpful for depression accompanied by anorexia and insomnia. Bupropion is effective in the treatment of depression, but data are sparse about its use in anxiety disorders. Psychostimulants are a unique approach if rapid onset of antidepressant action is desired. Acute or short-term anxiolysis is obtained with benzodiazepines, and selection of particular agents entails consideration of distribution rate, half-life and metabolic route.
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PMID:Treatment of anxiety and depression in transplant patients: pharmacokinetic considerations. 1508 75


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