Mirtazapine Administration Research Articles

Mirtazapine inhibits salivary cortisol concentrations in anorexia nervosa

The antidepressant mirtazapine has been demonstrated to acutely inhibit cortisol concentrations in healthy subjects and depressed patients. Since both depressed and anorectic patients are characterized by hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) system, the clinical usefulness and the endocrinological effects of mirtazapine were investigated in anorexia nervosa (AN). Five female patients suffering from AN restricting subtype (DSM-IV criteria) were admitted to a closed ward and treated with mirtazapine for three weeks receiving 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 up to the end of the study (day 21). Besides weekly determination of clinical parameters (Body Mass Index [BMI], Hamilton Depression Rating Scale [21-HAMD]), salivary cortisol concentrations were measured before treatment (day − 1), at the beginning of treatment (day 0), after 1 week (day 7), and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 0800 up to 1400 h. Repeated-measures ANOVA revealed a significant inhibition of salivary cortisol levels during 3-week treatment with mirtazapine ( p < 0.05) which became obvious already after the first mirtazapine administration (day 0). Moreover, a trend for an increase in BMI was seen ( p = 0.063), whereas no significant changes in 21-HAMD sum scores could be demonstrated. Double-blind, placebo-controlled studies are needed to clarify the question whether the observed changes in BMI are related to the mirtazapine-induced attenuation of HPA axis activity or whether they are due to monitoring of food intake and purgative behaviour on the closed ward.

Stress‐induced sensitization of the limbic system in ovariectomized rats is partly restored by cyclic 17β‐estradiol administration

Chronic stress induces neurobiological alterations which have consequences for subsequent stress handling. In the current experiment, ovariectomized rats were subjected daily to a stressor for 21 days. Thereafter, the rats were treated for 21 days with 17beta-estradiol benzoate (10 microg/250 g, once every 4 days) or mirtazapine (10 mg/kg, daily). In this way, we were able to evaluate the ability of these compounds to reverse chronic stress-induced changes in the activity of the limbic system. After 21 days of recovery and treatment, the rats were re-exposed to the adverse environment of the initial stressor and perfused 2 h later. Ovariectomized rats displayed increased numbers of c-Fos-positive nuclei, after re-exposure to the stressor, in the paraventricular nucleus of the hypothalamus, dentate gyrus, medial prefrontal cortex and central and medial amygdala. Cyclic estradiol treatment attenuated the sensitization of the paraventricular nucleus and central amygdala. Mirtazapine increased the number of c-Fos-positive nuclei in the central amygdala and dentate gyrus. Long-term transcriptional changes induced by chronic stress were determined with DeltaFosB immunoreactivity. The medial prefrontal cortex showed an increased number of DeltaFosB-positive nuclei after chronic stress and this was not affected by estradiol or mirtazapine administration during recovery. In conclusion, cyclic estradiol administration reversed chronic stress-induced sensitization in the limbic system, the paraventricular nucleus and central amygdala of female rats, output regions of the limbic system involved in fear responses. Mirtazapine did not achieve this reversal of stress-induced aberrations in the limbic system after 21 days of treatment.

Polysomnographic and Symptomatological Analyses of Major Depressive Disorder Patients Treated with Mirtazapine

This study aimed to characterize the effects of mirtazapine on polysomnographic sleep, especially slow wave sleep (SWS) and rapid eye movement (REM) sleep, as well as its effects on clinical symptoms in patients with major depressive disorder (MDD). Sixteen MDD patients were treated with mirtazapine 30 mg taken 30 minutes before bedtime. Polysomnographic and subjective sleep, as well as other clinical data, were collected at baseline and on Days or Nights 2, 9, 16, 30, and 58 during treatment. We used repeated measures analysis of variance, including pairwise comparison, to analyze data statistically. Mirtazapine administration increased total SWS and the SWS in the first sleep cycle, but not SWS in the second sleep cycle. The medication increased REM latency and the duration of the first REM episode; it also decreased the number of REM episodes. Simultaneously, mirtazapine significantly reduced wake-after-sleep onset and scores on the Athens Insomnia Scale. After patients took the medication, scores on the Hamilton Depression Rating Scale-17 (HDRS-17) decreased rapidly and continuously. The changes on the Beck Depression Inventory-II were consistent with those on the HDRS-17. The medication has a tendency to increase weight. Mirtazapine significantly improved sleep quality, reversed sleep markers of depression, and reduced depressive symptoms in this group of MDD patients.

Mirtazapine Treatment for Pathological Laughing and Crying After Stroke

Selective serotonin reuptake inhibitors (SSRIs) have been recognized as the treatment of choice for pathological laughing and crying (PLC), which is a common, distressing condition that follows stroke. There have been few reports about other treatment options for PLC. Here, the authors report rapid responses to mirtazapine in two patients with poststroke PLC who failed to respond to SSRIs or bupropion. In the first case, a 63-year-old woman with severe long-standing crying spells that had persisted for 3 months responded well to low-dose mirtazapine within a few days; she could not tolerate citalopram or sertraline. In the second case, both the laughing and crying spells of a 64-year-old woman were improved within a few days of mirtazapine administration, after they had not responded to bupropion. This is one of the first reports to suggest that mirtazapine may be an alternative to SSRIs for treating poststroke PLC.

Study of mirtazapine antidepressant effects in rats

Mirtazapine is a widely used antidepressant and the aim of this study was to further investigate its antidepressant activity in rats. Thus, the efficacy of long-term mirtazapine treatment was assessed in three models of depressive symptoms induced by stress exposure: the acute escape deficit, the chronic escape deficit, and the stress-induced disruption of the acquisition of an appetitive behaviour sustained by a palatable food (vanilla sugar). Administration of mirtazapine for 2 wk prevented the escape deficit development induced by acute exposure to unavoidable stress. This protective effect was antagonized by the administration of a beta-adrenergic or a 5-HT1A receptor antagonist just before stress exposure; that is, mirtazapine effect was dependent on functional beta-adrenergic and 5-HT1A receptor systems. Repeated stress exposure indefinitely prolongs the condition of escape deficit and a 40-d mirtazapine treatment reversed this model of chronic escape deficit. In a Y-maze satiated rats learn to choose the arm baited with vanilla sugar, and exposure to stress during Y-maze training prevents this learning. Repeated mirtazapine administration completely antagonized the disrupting effect of chronic stress on the acquisition of this instrumental behaviour. We consider these effects to be crucial in the definition of antidepressant activity.

P.5.046 Mirtazapine and venlafaxine administration in alcohol detoxification: Impact on anxiety and depression symptoms

P.5.046 Mirtazapine and venlafaxine administration in alcohol detoxification: Impact on anxiety and depression symptoms

Glycoprotein IIb/IIIa complex is the target in mirtazapine-induced immune thrombocytopenia

Mirtazapine (MW 265.36), a tetracyclic antidepressant of the piperazine-azapine group which augments central noradrenergic and serotonergic activity, is currently used as an oral antidepressant. We report a case of severe thrombocytopenia in a 66-year-old patient occurring after mirtazapine administration, suggesting an immune mechanism. This report documents the first case of mirtazapine-induced immune thrombocytopenia. The patient’s serum was screened for drug-induced anti-platelet antibody with the chromium 51 (Cr 51) platelet lysis technique. The drug-dependent antibody was characterized using flow cytometry, the monoclonal antibody immobilization of platelet antigens assay (MAIPA assay), and immunoprecipitation. By the Cr 51 platelet lysis technique, we obtained an equivocal result for the detection of mirtazapine-induced antibody. However, the patient’s serum tested positive for mirtazapine-induced antibody by flow cytometry. The results showed that the binding ratio of 5.7 (mean fluorescence intensity) in the presence of the patient’s serum and mirtazapine in a final concentration of 1.0 mmol/L was strongly positive. The antibody was found to bind the glycoprotein (GP) IIb/IIIa complex by MAIPA assay by using five different monoclonal antibodies against GP complexes Ib/IX, GPIIb/IIIa, or GPIa/IIa. Immunoprecipitation studies showed that the GPIIb/IIIa complex was precipitated by antibody in the presence, but not in the absence, of mirtazapine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidepressant mirtazapine. This is the first well-documented case of mirtazapine-induced immune thrombocytopenia.

Alcohol detoxification and social anxiety symptoms: a preliminary study of the impact of mirtazapine administration

Background: Social anxiety disorder is fairly prevalent among alcohol abusing/dependent subjects. The objective of the present study was to investigate: (a) the incidence of social anxiety symptoms in inpatient alcoholics, (b) the effect of alcohol detoxification on these symptoms, and (c) whether a combined psychotherapeutic/mirtazapine treatment during the post-detoxification phase of alcoholism has a greater impact on the aforementioned symptoms than a non-pharmacological approach. Method: Social anxiety symptoms were assessed through the Liebowitz Social Anxiety Scale (LSAS) following a 4–5-week detoxification period in two groups: group A ( n=21) that followed a detoxification protocol of cognitive–behavioral orientation and group B ( n=33) that was assigned to mirtazapine in addition to the standard protocol. Concomitant psychopathology was monitored through the HARS and HDRS, and level of functioning through the GAS. Results: A marked reduction of social anxiety symptoms was evidenced in both groups. However, patients on mirtazapine improved significantly more compared to controls. Limitations: A single measure of social anxiety, i.e., the LSAS was used. Also, a longer follow-up period is needed to ascertain remission of social anxiety symptoms. Conclusions: The present study found a rather high incidence of social anxiety symptoms in inpatient alcoholics which subsided following alcohol detoxification; moreover, it provides preliminary evidence that a combined psychotherapeutic/mirtazapine treatment (30–60 mg/daily) has a greater impact on the aforementioned symptoms than non-pharmacological treatment alone.