Mirtazapine augmentation in the treatment of refractory depression

BACKGROUND: Pharmacotherapeutic strategies that target specific actions at multiple neuronal receptors or cellular components may offer a superior approach for treatment of refractory depression. Mirtazapine is a novel antidepressant which has a mechanism that involves the enhancement of noradrenergic and serotonergic neurotransmission via blockade of alpha2-adrenergic autoreceptors and heteroreceptors without activity at the serotonin transporter. Mirtazapine is thus a compelling candidate for augmentation treatment in patients who fail to achieve adequate response with other antidepressant medications. METHOD: Twenty patients with DSM-IV major depression or dysthmia who had persistent depressive syndromes despite at least 4 weeks of standard antidepressant pharmacotherapy were given augmentation with mirtazapine (15 to 30 mg p.o. q.h.s.) on an open-label basis. Clinical assessments of status at baseline, 2 weeks, and 4 weeks were used to rate response. RESULTS: Forty-five percent (N = 9) of the sample were responders at 2 weeks. At the 4 week follow-up, 55% (N = 11) were responders, 30% (N = 6) were nonresponders, and 15% (N = 3) had discontinued treatment owing to side effects. Common side effects included weight gain and sedation. CONCLUSION: These data suggest that the addition of mirtazapine may be beneficial for patients who have refractory depression, but side effects are prominent at the doses we used. Controlled trials to further evaluate the efficacy and safety of mirtazapine augmentation are needed.     

Mirtazapine for treatment-resistant depression: a preliminary report

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.     

Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study.

BACKGROUND: There is preliminary evidence that the atypical antipsychotic aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation strategy in treatment-resistant depression. METHOD: In this 4-week open-label non-randomized parallel-group study, the safety and efficacy of aripiprazole as add-on treatment strategy in patients suffering from non-delusional depression was investigated. Forty drug-free depressed inpatients without psychotic symptoms (13 men, 27 women), suffering from a major depressive episode or bipolar disorder, depressive state (DSM-IV criteria), were included in the study. The patients were treated either with mirtazapine monotherapy (45 mg/day) or combination therapy (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and efficacy were assessed weekly using the Hamilton Depression Rating Scale, the Simpson-Angus Scale and the Barnes Akathisia Scale. RESULTS: Mirtazapine monotherapy and combined treatment with mirtazapine and aripiprazole showed comparable antidepressant effects as assessed at the endpoint of the study period. However, additional administration of aripiprazole accelerated the onset of antidepressant action in patients suffering from treatment-resistant depression. Additive use of aripiprazole reduced the mirtazapine-induced increase in the body mass index. Moreover, mirtazapine had favourable effects on aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in the combination therapy group. CONCLUSION: Combined therapy with mirtazapine and aripiprazole is a safe and well-tolerated treatment option which may be useful especially in treatment-resistant depression. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole in depressed patients.     

Prevention and treatment of poststroke depression with mirtazapine in patients with acute stroke

BACKGROUND AND OBJECTIVE: Poststroke depression is one of the most frequent complications of stroke, affecting approximately 20% to 40% of all patients. In spite of the importance of this neuropsychiatric disorder, little attention has been given to the prevention of poststroke depression. The purpose of this study was to examine whether prophylactic treatment with the antidepressant mirtazapine in patients with acute stroke given from day 1 after the incidence prevents poststroke depression. METHOD: Patients with ischemic stroke received either 30 mg mirtazapine or no antidepressant medication from day 1 after the stroke in an open, randomized study design. Data were collected from August 2001 to December 2002. Seventy patients were enrolled in the study and were reexamined on days 7, 44, 90, 180, 270, and 360 using neurologic, functional, and depression rating scales. Those poststroke patients who developed depression (DSM-IV criteria) but had been randomly assigned to the nontreatment group were given the antidepressant mirtazapine after the diagnosis of depression had been established. RESULTS: Forty percent (14/35) of the nontreated patients and only 5.7% (2/35) of the patients who were treated with mirtazapine developed poststroke depression. Altogether, 16 patients developed poststroke depression, 15 of whom remitted after initiation of treatment with mirtazapine. CONCLUSION: Mirtazapine significantly reduced the rate of poststroke depression in patients with acute stroke. The study also demonstrated that this antidepressant was highly effective in treating poststroke depression.     

Effects of antidepressant pharmacotherapy after repetitive transcranial magnetic stimulation in major depression: an open follow-up study

An increasing number of clinical studies demonstrates antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, limited data are available so far concerning the stability of these effects and the efficacy of subsequent maintenance therapy. Therefore, we examined whether antidepressant pharmacotherapy can stabilize clinical improvement after rTMS monotherapy. Twenty-six drug-free patients suffering from a major depressive episode (DSM-IV criteria) participated in an open rTMS trial over two weeks (10-13 sessions, 10 Hz, left prefrontal stimulation at 100% motor threshold intensity). Subsequently, the patients were followed up during standardized antidepressant pharmacotherapy with mirtazapine for a further 4 weeks. The interval between the last rTMS and the first day of pharmacotherapy varied between one and five days. After two weeks of rTMS monotherapy 39% of the patients responded to rTMS by at least 50% reduction in their Hamilton Rating Scale for Depression (HRSD) scores. Treatment interruption after rTMS resulted in a significant increase in the HRSD score of rTMS responders. The degree of the deterioration was dependent on the length of interval without treatment. However, this deterioration was reverted and the further clinical course stabilized by subsequent mirtazapine treatment. The overall response rate after rTMS and mirtazapine treatment (alone or in combination) was 77%. Our results suggest that (1) antidepressant pharmacotherapy is able to further improve the clinical response to rTMS and (2) that responders to rTMS monotherapy should receive subsequent psychopharmalogical treatment without interruption in order to avoid a deterioration of symptoms.     

Sexual functioning in depressed outpatients taking mirtazapine.

OBJECTIVES: One-third of patients with untreated depression have sexual difficulties manifested by decreased libido, erectile dysfunction or delayed ejaculation. This dysfunction may be exacerbated by stimulation of post-synaptic serotonin 5HT2 receptors, a side-effect of most widely-used antidepressant medications, especially the selective serotonin reuptake inhibitors (SSRIs). Mirtazapine is an atypical antidepressant with alpha 2 adrenergic antagonist and serotonin 5-HT2 and 5-HT3 receptor-blocking activity. In theory, it should not worsen and perhaps may improve sexual function. This pilot study investigated sexual functioning and antidepressant activity in depressed patients taking mirtazapine. EXPERIMENTAL DESIGN: Twenty-five (F = 18, M = 7) sexually active adult outpatients with a DSM-IV-diagnosis of major depressive episode entered a 12-week, flexible-dosing, open-label pilot study. The Arizona Sexual Experiences Scale (ASEX) assessed sexual functioning and the Hamilton Depression Rating Scale (HAM-D) assessed depressive symptoms on a bimonthly basis. PRINCIPAL OBSERVATIONS: Desire, arousal/lubrication, and ease/satisfaction of orgasm improved (by 41%, 52%, and 48%, respectively) in the depressed women. In men, desire, arousal/erection, and ease/satisfaction of orgasm also improved (by 10%, 23% and 14%, respectively) but much more modestly. HAM-D, Clinical Global Impression (CGI) Sheehan Disability Scale (SDS), and Symptom Checklist-90 (SCL-90) scores improved in both groups. There was a 50% dropout rate among women before six weeks of treatment. However, the ASEX and HAM-D scores of the groups terminating before and after six weeks of treatment showed similar rates of improvement. CONCLUSIONS: Mirtazapine has a beneficial effect on sexual functioning in both depressed women and men. Longer-term double-blind research assessing sexual function during the administration of mirtazapine as well as other antidepressants is recommended.     

Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.

OBJECTIVE: Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase (8 weeks) and an extension phase (16 weeks). METHODS: Patients with major depression and without dementia, at least 65 years old, were eligible; they were randomized to mirtazapine or paroxetine once daily, with doses increasing over 42 days. Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and tolerability was assessed from adverse events. RESULTS: Of 255 patients randomized, 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis. Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score. Other significant differences were in the proportion of patients classified as responders (50% decrease from baseline Ham-D-17 scores) at Day 14 and in remission (Ham-D-17 score of 7 or less) at Day 42. The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group. The mirtazapine group also showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores. Efficacy of both drugs was maintained during the extension phase. Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events. CONCLUSION: During the first weeks of treatment, antidepressant effects were more pronounced in the mirtazapine group, suggesting that mirtazapine has an earlier onset of action. Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients.     

A double-blind,randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients

AIM: To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression. METHOD: 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group. RESULTS: Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog. CONCLUSION: Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study.     

Mirtazapine compared with paroxetine in major depression

BACKGROUND: The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine. METHOD: 275 outpatients with a diagnosis of major depressive episode (DSM-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (15-45 mg/day) or paroxetine (20-40 mg/day). Efficacy was assessed by the HAM-D-17, Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scales (Severity and Improvement), and analyses were performed on the intent-to-treat sample (127 mirtazapine-treated patients and 123 paroxetine-treated patients). RESULTS: Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine. Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out. Both drugs were equally effective in reducing symptoms of depression. At week 1, the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients (16.5 vs. 18.8, p = .0032). Similarly, significantly more mirtazapine-treated patients were HAM-D-17 responders (> or = 50% decrease from baseline) at weeks 1 (23.2% vs. 8.9%, p = .002) and 4 (58.3% vs. 44.5%, p = .04). Both treatments were equally effective in reducing anxiety. However, the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 (-5.1 vs. -3.5, p = .0435). Tolerability of both treatments was good, with more nausea, vomiting, tremor, and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group. CONCLUSION: Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated. A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression.     

Remission of mood disorder with psychotic features after treatment with mirtazapine

The antidepressant mirtazapine enhances both noradrenergic and serotonergic transmission by blocking α_2-adrenergic presynaptic auto- and heteroreceptors, respectively. We here report on three patients with mood disorders with psychotic features (two cases with depressive and one with bipolar disorder). Treatment with mirtazapine significantly improved not only their depression, but also their delusions. Depressive symptoms were only partially responsive and delusions unresponsive in all three patients to previous antidepressive and/or antipsychotic treatment, and only mirtazapine induced persistent improvement. These clinical cases suggest that mirtazapine can be a valid alternative for patients with depression with psychotic features and partial treatment-resistance.     

Residual symptoms in depressed patients who respond acutely to fluoxetine

BACKGROUND: Antidepressants have unequivocal efficacy as compared with placebo, but many patients have residual symptoms despite a robust response to antidepressant therapy. The purpose of this study is to assess residual symptoms in outpatients who respond acutely to fluoxetine. METHOD: Two hundred and fifteen outpatients with major depressive disorder as assessed with the Structured Clinical Interview for DSM-III-R (SCID-P) were treated openly with fluoxetine 20 mg/day for 8 weeks. One hundred and eight (50.2%) were considered full responders (final 17-item Hamilton Rating Scale for Depression [HAM-D] score < or =7). Percentages of full responders who continued to have subthreshold or full major depressive disorder symptoms were calculated. The relationship between residual symptoms and Axis I and Axis II (assessed with SCID-II for personality disorders) comorbidity was assessed. RESULTS: Of the 108 responders, 19 (17.6%) had no subthreshold or threshold SCID-P major depressive disorder symptoms, while 28 (25.9%) had 1 symptom, and 61 (56.5%) had 2 or more symptoms. No statistically significant relationships were found between number of residual symptoms and selected Axis I comorbid conditions or total number of Axis II disorders. CONCLUSION: Less than 20% of full responders to fluoxetine by HAM-D criteria were free of all SCID-P subthreshold and threshold major depressive disorder symptoms after 8 weeks of treatment. While depressed patients benefit from antidepressants, most continue to have some symptoms of depression. The high prevalence of residual symptoms among antidepressant responders suggests the need for further study including whether residual symptoms abate with longer treatment or increased dose of fluoxetine. Other strategies, such as cognitive behavioral therapy, may be needed to address residual symptoms.     

Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients

BACKGROUND: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. METHOD: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. RESULTS: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a newonset adverse event. CONCLUSION: Continuation-phase therapy with mirtazapine is effective and well tolerated.     

米氮平与氟西汀治疗抑郁症的疗效对比分析

目的　评价米氮平治疗抑郁症的临床疗效和安全性。方法　将符合CCMD - 3抑郁症诊断标准的 6 1例抑郁症患者随机分为米氮平组 (31例 )和氟西汀组 (30例 ) ,治疗 6周。用汉密顿抑郁量表 (HAMD)评定疗效 ,用副反应量表 (TESS)评定副反应。结果　米氮平组和氟西汀组的有效率分别为 78%和 77% ,二者比较差异无显著性 (P >0 0 5 ) ,但米氮平起效快 ,副反应轻。结论　米氮平是一种安全有效的新一代抗抑郁药。     

米氮平与氟西汀治疗抑郁症对照研究

目的：比较米氮平与氟西汀治疗抑郁症的临床疗效和安全性。方法：将60例抑郁症患者随机分为米氮平组和氟西汀组，分别给予米氮平和氟西汀治疗，疗程6周。采用汉密尔顿抑郁量表（HAMD）及治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：米氮平组和氟西汀组显效率分别为80．0％和76．7％，两组疗效相仿。但治疗1周后，米氮平组的有效率高于氟西汀组。结论：米氮平是一种起效较快，安全、有效的抗抑郁药。     

Two-year effects of quality improvement programs on medication management for depression

BACKGROUND: Significant underuse of evidence-based treatments for depression persists in primary care. We examined the effects of 2 primary care-based quality improvement (QI) programs on medication management for depression. METHODS: A total of 1356 patients with depressive symptoms (60% with depressive disorders and 40% with subthreshold depression) from 46 primary care practices in 6 nonacademic managed care organizations were enrolled in a randomized controlled trial of QI for depression. Clinics were randomized to usual care or to 1 of 2 QI programs that involved training of local experts who worked with patients' regular primary care providers (physicians and nurse practitioners) to improve care for depression. In the QI-medications program, depression nurse specialists provided patient education and assessment and followed up patients taking antidepressants for up to 12 months. In the QI-therapy program, depression nurse specialists provided patient education, assessment, and referral to study-trained psychotherapists. RESULTS: Participants enrolled in both QI programs had significantly higher rates of antidepressant use than those in the usual care group during the initial 6 months of the study (52% in the QI-medications group, 40% in the QI-therapy group, and 33% in the usual care group). Patients in the QI-medications group had higher rates of antidepressant use and a reduction in long-term use of minor tranquilizers for up to 2 years, compared with patients in the QI-therapy or usual care group. CONCLUSIONS: Quality improvement programs for depression in which mental health specialists collaborate with primary care providers can substantially increase rates of antidepressant treatment. Active follow-up by a depression nurse specialist in the QI-medications program was associated with longer-term increases in antidepressant use than in the QI model without such follow-up.     

Influence of mirtazapine on urinary free cortisol excretion in depressed patients

Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol secretion in depressed patients is not necessarily correlated with a favorable therapeutic response.     

Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs.

BACKGROUND: The significant morbidity and mortality associated with severe depression and its psychotic or melancholic subtypes necessitate effective and well-tolerated therapy. This review evaluates antidepressant treatments for patients with severe depression. DATA SOURCES: Comparative clinical trials conducted on patients with severe depression were found by an English-language MEDLINE search (1985 to present). Additional studies were identified in article bibliographies. Search terms included depressive disorders, depression and severe, hospitalized, melancholic or melancholia, psychotic, and endogenous. STUDY FINDINGS: Evidence for efficacy of SSRIs in severe or melancholic depression comes from a small but growing number of controlled studies with adequate samples, as well as meta-analyses and retrospective subgroup analysis of premarketing trials. In studies that defined response as a 50% or greater reduction in Hamilton Rating Scale for Depression (HAM-D) scores, response rates ranged from 53% to 64% for SSRIs and 43% to 70% for TCAs. In separate trials on severe depression, venlafaxine and mirtazapine were both more effective than placebo and an active comparator. Nefazodone and bupropion were each found to be more effective than placebo in studies of severe depression. Venlafaxine and mirtazapine have been found to be more effective than fluoxetine. CONCLUSION: SSRIs and TCAs are comparably effective for the treatment of severe or melancholic depression. SSRIs and other newer agents appear to be better tolerated than TCAs, specifically lacking adverse anticholinergic and cardiovascular effects that may limit the use of TCAs. Emerging data with venlafaxine and mirtazapine in severely depressed patients with or without melancholia support the efficacy of these treatments. Nefazodone and bupropion were found to be effective in hospitalized depressed patients. Electroconvulsive therapy (ECT) or combined antidepressant therapy may be useful in some patients with severe depression. Patients with severe psychotic depression may respond better to an antipsychotic-antidepressant combination.     

Reboxetine addition in patients with mirtazapine-resistant depression: a case series

OBJECTIVES: Treatment-resistant depression is a common occurrence in clinical practice as well as combination treatment with 2 different antidepressants. In the present case series, we study the effectiveness of the addition of reboxetine, during 12 weeks, to 14 outpatients diagnosed with major depressive disorder, according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria, who had previously failed to respond or who had only responded partially, over a period of 6 weeks, to conventional treatment with mirtazapine. METHODS: Evaluation of antidepressant efficacy was carried out through the application of the 21-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). RESULTS: The percentages of responders (HDRS>or=50%), patients in remission (HDRS相似文献   

A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report

OBJECTIVE: Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant (nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder. METHOD: Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks (first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone (second step), adult outpatients (N=235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day) (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom remission, was defined a priori as a total exit score of /=50% reduction in score from baseline). RESULTS: For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16) response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events. CONCLUSIONS: Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder.     

Influence of mirtazapine on salivary cortisol in depressed patients

Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2)-receptors, at postsynaptic 5-HT2 and 5-HT3 receptors, and at histaminergic H1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients (4 men, 8 women) suffering from major depression according to DSM-IV criteria. Patients were treated with mirtazapine for 3 weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45 mg per day from day 2 up to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. 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 08.00 until 20.00 h. The area under the curve values served as parameter for the salivary cortisol secretion. Following analysis of variance with a repeated measures design, tests with contrasts revealed a significant reduction of cortisol concentrations already after 1 day of mirtazapine treatment that was comparable in responders and nonresponders. In addition to new pharmacological approaches such as CRH1 receptor antagonists, mirtazapine therefore appears to be an effective strategy to decrease hypercortisolism and restore HPA system dysregulation in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified.