Remeron
Mirtazapine for treatment-resistant depression: a preliminary report.

Wan DD, Kundhur D, Solomons K, Yatham LN, Lam RW.

Division of Mood Disorders, Department of Psychiatry, University of British Columbia and UBC Hospital, Vancouver, BC.

OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12587851&dopt=Abstract mirtazapine Remeron



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The pharmacovigilance of mirtazapine: results of a prescription event monitoring study on 13554 patients in England.

Biswas PN, Wilton LV, Shakir SA.

Drug Safety Research Unit, Bursledon Hall, Southampton, London, UK. pipasha.biswas dsru.org

Mirtazpine is the first noradrenaline and serotonin specific antidepressant. We monitored the safety of mirtazapine as reported in primary practice in England.The exposure data were provided by monitoring the dispensed prescriptions issued between September 1997 and February 1999. Questionnaires sent to GPs provided outcome data. Drowsiness/sedation and malaise/lassitude were the most frequent ADRs (116, 71 respectively) and had the highest incidence density (per 1000 patient-months) in the first month of treatment (58.1, 27.8 respectively). Agitation (73), aggression (70), rash (20), hallucinations (13) and abnormal dreams (31 were unlabelled AES while abnormal liver function tests (12), syncope (8), abnormal behaviour (4) and visual disturbance (3) were labelled AES possibly due to mirtazapine use. Serious suspected ADRs reported were facial oedema (5), allergy (3), bone marrow toxicity (2) and myelodysplasia (1).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12680749&dopt=Abstract mirtazapine Remeron



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Mirtazapine in L-dopa-induced dyskinesias.

Meco G, Fabrizio E, Di Rezze S, Alessandri A, Pratesi L.

Department of Neurosciences, La Sapienza University, Viale Dell'Universita 30, 00185 Rome, Italy. giuseppe.meco uniroma1.it

Mirtazapine is a novel antidepressant with a pharmacologic profile (alpha-2 antagonist, 5HT-(1A) agonist, and 5HT-(2) antagonist) that renders it potentially useful for l-dopa-induced dyskinesias. Drugs with 5HT-(1A) agonistic activity, such as buspirone and tandospirone, have been reported to be effective in reducing l-dopa-induced dyskinesias. Furthermore, 5HT-(2) antagonism may, by reducing substantia nigra pars reticulata hyperactivity, play a role in the improvement of Parkinsonian symptoms and l-dopa-induced dyskinesias, as has been observed with ritanserin, a 5HT-(2) antagonist. Alpha-2 antagonists, such as idazoxan, have recently also been reported to improve l-dopa-induced dyskinesias. The authors investigated the antidyskinetic properties of mirtazapine by designing an open-label study of 20 Parkinsonian patients with l-dopa-induced dyskinesias. Mirtazapine proved to be moderately effective in reducing l-dopa-induced dyskinesias, either alone or in association with amantadine. Mirtazapine may be of use in patients who do not respond or are intolerant to amantadine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12897636&dopt=Abstract mirtazapine Remeron



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Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia.

Zoccali R, Muscatello MR, Torre DL, Malara G, Canale A, Crucitti D, D'Arrigo C, Spina E.

Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Messina, Italy.

The effect of mirtazapine on steady-state plasma concentrations of the newer atypical antipsychotics clozapine, risperidone and olanzapine was investigated in 24 patients with chronic schizophrenia. In order to treat residual negative symptoms, additional mirtazapine (30 mg per day) was administered for six consecutive weeks to nine patients stabilized on clozapine therapy (200-650 mg per day), eight on risperidone (3-8 mg per day) and seven on olanzapine (10-20mg per day). There were only minimal and statistically insignificant changes in mean plasma concentrations of clozapine and its metabolite norclozapine, risperidone and its metabolite 9-hydroxyrisperidone, and olanzapine during the study period. Mirtazapine co-administration with either clozapine, risperidone or olanzapine was well tolerated. In the overall sample, a slight improvement in negative symptomatology, as assessed by the Scale for Assessment of Negative Symptoms, was observed at final evaluation (P<0.01) and six patients (two in each treatment group) were classified as responders. While double-blind, controlled studies are needed to evaluate the potential clinical benefits of mirtazapine in chronic schizophrenia, our findings indicate that mirtazapine has a negligible effect on the metabolism of clozapine, risperidone and olanzapine and can be added safely to an existing treatment with these antipsychotics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12902213&dopt=Abstract mirtazapine Remeron



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Taurine concentration in human blood peripheral lymphocytes: major depression and treatment with the antidepressant mirtazapine.

Lima L, Obregon F, Urbina M, Carreira I, Baccichet E, Pena S.

Laboratorio de Neuroquimica, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Apdo. 21827, Caracas 1020-A, Venezuela. llima cbb.ivic.ve

Major depression is a serious disease with various systemic effects, including dysfunction of the immune response. Taurine has been known to be related to certain modifications of the immune system. The aim of this study was to determine the taurine concentration in lymphocytes of patients with major depression and to evaluate the influence of the antidepressant treatment with mirtazapine for six weeks on the levels of taurine. Gamma-aminobutyric acid, aspartate, glutamate and glutamine were also determined. Taurine, aspartate and glutamine levels were increased in the lymphocytes of depressed patients before mirtazapine treatment compared to the control group, and were normalized after treatment. Gamma-aminobutyric acid and glutamate did not differ between patients and controls. There was a significant and positive correlation between the severity of the disorder, measured by the Hamilton Rating Scale, and the concentration of taurine in the lymphocytes of depressed patients before treatment. This correlation was not observed after treatment and neither was there a correlation observed for the other amino acids. The present observations could be an indication of the relevance of taurine as a protective agent in the lymphocytes of patients with severe depression, and could be the result of modifications of taurine transport or efflux processes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12908614&dopt=Abstract mirtazapine Remeron



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High-performance liquid chromatographic method with diode array detection for identification and quantification of the eight new antidepressants and five of their active metabolites in plasma after overdose.

Titier K, Castaing N, Scotto-Gomez E, Pehourcq F, Moore N, Molimard M.

Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, Bordeaux, France. karine.titier pharmaco.u-bordeaux2.fr

A high-performance liquid chromatographic method is described for the determination of selective serotonin reuptake inhibitors (fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine), serotonin norepinephrine reuptake inhibitors (milnacipram, venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine), and five pharmacologically active metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethylvenlafaxine, desmethylmirtazapine). After a double-step liquid-liquid extraction, compounds are separated on a Symmetry C8 column eluted with a gradient of acetonitrile-phosphate buffer 10 mM pH 3.8 and detected at 230 nm and 290 nm. Calibration curves were linear in the range 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite). The limit of quantification was 25 ng/mL (100 ng/mL for venlafaxine and its metabolite). For all quality controls good accuracy was achieved (93% to 99.5%) with intraday and interday variation coefficients less than 12%. This method allows simple and rapid (run time 18 min) identification and quantification of the eight new antidepressants and five of their active metabolites. This method can be used for toxicologic purpose.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14508381&dopt=Abstract mirtazapine Remeron