Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, studies of pharmacotherapy for post-traumatic stress disorder (PTSD) have been focused on serotonin-selective reuptake inhibitors (SSRI), despite a number of treatment-limiting side-effects. Mirtazapine, a novel drug with both noradrenergic and serotonergic properties, may be effective in individuals who demonstrate intolerance to side-effects of and a limited response to SSRIs. Six outpatients with severe, chronic PTSD were treated with mirtazapine, up to 45 mg/day for 8 weeks. Efficacy assessments and side-effect monitoring were performed at baseline and weeks 2, 4, 6 and 8. Fifty percent of the sample demonstrated improvement of 50% or more from baseline using a global rating. In addition, improvements were noted on both interviewer-administered and self-rated scales of PTSD and of depression. The drug was well tolerated with few significant side-effects. Mirtazapine was associated with clinical improvement in 50% of subjects with severe, chronic PTSD, suggesting a need for further investigation in double-blind, placebo-controlled trials.
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PMID:A pilot study of mirtazapine in post-traumatic stress disorder. 1022 39

There is currently available evidence that suggests that drugs combining 2 synergistic mechanisms of action (e.g., enhancement of both noradrenergic and serotonergic neurotransmission) may yield superior therapeutic efficacy compared with a single therapeutic mechanism of highly selective agents such as selective serotonin reuptake inhibitors (SSRIs). The differences in antidepressant efficacy favoring dual-acting drugs may exist in particular for 3 difficult-to-treat groups of patients: those with endogenous depression, those with severe depression, or hospitalized depressed patients. Mirtazapine differs from other new dual-acting antidepressants by not being a reuptake inhibitor. Its antidepressant activity may be related to a direct enhancement of noradrenergic neurotransmission by blockade of alpha2-autoreceptors. The rapid increase in serotonin (5-HT) synaptic levels by blockade of alpha2-heteroreceptors indirectly enhances 5-HT1A-mediated neurotransmission since 5-HT2 and 5-HT3 are blocked by mirtazapine. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. Currently available evidence suggests that mirtazapine is effective in all levels of severity of depressive illness, as well as is in a broad range of symptoms associated with depression.
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PMID:Mirtazapine: clinical overview. 1044 35

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

During the last decade, it became evident that antidepressants may represent a useful treatment option for a variety of primary psychiatric disorders other than depression. Improved understanding of both underlying etiology of these disorders and pharmacologic modes of action of available treatments has led to an improvement in conditions such as panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and premenstrual dysphoric disorder. In addition, evidence is accumulating that some new antidepressants may be of therapeutic value in treatment of some subtypes of depressive disorder previously unresponsive to treatment or difficult to treat, such as seasonal affective disorder, depression with atypical features, and recurrent brief depression. Mirtazapine is an antidepressant with mode of action different from other currently available antidepressants. A review of currently available data of mirtazapine's use in indications other than depression and in some types of depressive disorder is presented.
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PMID:Mirtazapine: other indications. 1044 41

Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine compared to imipramine, we report here an analysis of different symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine, the latter being in excess of the 15-45 mg/day range currently advised. Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients (79%) who were not receiving any co-medication. Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "melancholia", respectively. Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks. Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication. These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.
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PMID:Depressed in-patients respond differently to imipramine and mirtazapine. 1046 74

Mirtazapine, a noradrenergic and specific serotonergic antidepressant, displays strong serotonin (5-HT)2 blocking properties, which may be related to lack of sexual dysfunction. In our open-label study, after a wash-out period of 4-14 days, mirtazapine (30-45 mg/day) was administered for 6 weeks to six male and five female patients who discontinued treatment with selective serotonin reuptake inhibitors (SSRIs) because of sexual dysfunction. The patients were moderately depressed, with baseline Hamilton Depression Rating Scale (17-item HAMD) scores between 19 and 24, and none of them experienced any sexual dysfunction prior to SSRI treatment. Efficacy was assessed weekly by 17-item HAMD, and adverse events were registered at the same time points. All patients completed the study. After 6 weeks of treatment, the individual 17-item HAMD scores were between 5 and 9, indicating significant improvement in depressive symptoms. None of the patients reported any sexual dysfunction symptoms. Other adverse events, mild and transient in nature, were reported only by three patients (somnolence in two, and weight gain in one patient). In conclusion, treatment with mirtazapine was effective in patients who are unable to tolerate SSRIs because of sexual dysfunction and demonstrated no effect on sexual function.
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PMID:The use of mirtazapine in a group of 11 patients following poor compliance to selective serotonin reuptake inhibitor treatment due to sexual dysfunction. 1046 19

We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomized, double-blind, multicentre, 8-week study. Patients with a Major Depressive Episode (DSM-IV) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopram (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton Anxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group mean MADRS scores was large in both groups, reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of responders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM-A and CGI-Severity of illness and Quality of life scores. A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinically relevant superiority between two proven antidepressants. Mirtazapine treatment was also related to faster improvement of sleep, quality of sleep and improved alertness following awakening, as shown by statistically significant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Both drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group. There were no clinically relevant changes in laboratory parameters and vital sign variables with either treatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI Severity of illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of efficacy of mirtazapine over citalopram.
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PMID:Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. 1056 99

Dysthymic disorder is a form of chronic depression which often has its onset in childhood or adolescence and is generally persistent throughout life. Although originally hypothesized to be preferentially treated with psychotherapy, recent pharmacological studies support the use of antidepressants to treat patients with dysthymic disorder. Mirtazapine is an antidepressant which has been recently released on the U.S. market. We studied the effects of 15 to 45 mg of mirtazapine in 15 patients with dysthymic disorder on an open label basis over a 10-week period. Four patients discontinued treatment because of sedation. Mirtazapine was effective and well tolerated in the remaining patients.
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PMID:Dysthymic disorder: treatment with mirtazapine. 1056 29

This double-blind study compared mirtazapine's effects on alertness and sleep between parallel groups treated for 2 weeks according to a fixed regimen of 30 mg at bedtime (N = 69) and one that increased in dose from 15 to 30 mg at bedtime after the first week (N = 71). These patients with depression used an interactive telephone/computer system for daily alertness and sleep recordings on self-rating scales before and during treatment. Efficacy (17-item Hamilton Rating Scale for Depression [HAM-D], Clinical Global Impression Scale [CGI]) and safety assessments were made by participating psychiatrists. Both groups' alertness ratings were subnormal at baseline and even lower after the first dose. The ratings recovered after the second dose and increased progressively to levels 18% higher than those at baseline by the end of treatment. Patients receiving the fixed dose reported earlier sleep onset and longer duration. Similar mean changes in HAM-D scores (approximately -40%) and frequencies of CGI responders (>50%) occurred in both groups. The regimens were equally well tolerated. Somnolence, the most frequent side effect, was reported by only 10% of each group during the first week and by fewer patients during the second. Mirtazapine in fixed and ascending nocturnal dosing regimens was found to facilitate sleep, but it does not generally reduce daytime alertness. The fixed regimen seems preferable because of its greater effects on sleep.
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PMID:Mirtazapine effects on alertness and sleep in patients as recorded by interactive telecommunication during treatment with different dosing regimens. 1100 Dec 37

A method is described for the determination of the two enantiomers of mirtazapine in human blood plasma by high-performance liquid chromatography. Measurements were performed on drug free plasma spiked with mirtazapine and used to prepare and validate standard curves. Levels of enantiomers of mirtazapine were also measured in patients being treated for depression with racemic mirtazapine. Mirtazapine was separated from plasma by solid-phase extraction using CERTIFY columns. Chromatographic separation was achieved using a Chiralpak AD column and pre-column and compounds were detected by their absorption at 290 nm. Imipramine was used as an internal standard. The assay was validated for each analyte in the concentration range 10-100 ng/ml. The coefficient of variance was 16% and 5.5% for(+)-mirtazapine for 10 and 100 ng/ml control specimens respectively and 15% and 7.3% for mirtazapine for 10 and 100 ng/ml control specimens respectively. This assay is appropriate for use in the clinical range. The range of plasma mirtazapine concentrations from eleven patients taking daily doses of 30-45 mg of racemate was <5 to 69 ng/ml for (+)-mirtazapine and 13-88 ng/ml for (-)-mirtazapine for blood specimens collected 10-17.5 h after taking the dose.
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PMID:Chiral determination of mirtazapine in human blood plasma by high-performance liquid chromatography. 1108 86


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