Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features

The aim of this multicenter, randomized, double-blind, 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features. Patients with a baseline score of > or = 25 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to receive treatment with either mirtazapine (N = 78, 15-60 mg/day) or venlafaxine (N = 79, 75-375 mg/day, twice a day) in a rapid up-titration schedule. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Clinical Global Impression scale, and quality of life was assessed with the Quality of Life, Enjoyment, and Satisfaction Questionnaire and Quality of Life in Depression Scale. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Both drugs were effective in reducing overall symptoms of depression, showing substantial reductions in group mean MADRS scores (-20.1 for mirtazapine and -17.5 for venlafaxine) and HAM-D-17 scores (-17.1 for mirtazapine and -14.6 for venlafaxine) at the end of the treatment. Although not statistically significant, at all assessment times higher percentages of patients treated with mirtazapine were classified as responders (> or =50% reduction) on the HAM-D (at endpoint, 62% vs. 52%) and MADRS (at endpoint: 64% vs. 58%). Likewise were the percentages of remitters (HAM-D score < or =7; MADRS score < or =12) also higher in the mirtazapine group. A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points (p < or = 0.03). Both treatments were well tolerated. Although slightly more subjects treated with mirtazapine reported at least one adverse event, a statistically significantly higher percentage of patients treated with venlafaxine (15.3%) than mirtazapine (5.1%) dropped out because of adverse events (p = 0.037). Quality of life improved in both treatment groups. In this study, treatment with mirtazapine resulted in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events.     

米氮平与氟西汀治疗抑郁症的多中心对照研究

目的 :评价米氮平与氟西汀治疗抑郁症的有效性和安全性。方法 :采用DSM Ⅳ抑郁症的诊断标准 ,为期 6wk的观察。结果 :经 6wk治疗 ,米氮平组有效率和治愈率分别为 78%和 64% ,氟西汀组为 90 %和 55% (P >0 .0 5)。治疗 1wk后 ,米氮平组的有效率高于氟西汀组。 2组HAMD和MADRS总分治疗前后比较差异有显著意义 ,2组间差异无显著意义。治疗 1wk后 ,米氮平组HAMD总分和睡眠紊乱因子分的减分较氟西汀组明显。米氮平组主要不良反应是眩晕或 (和 )头昏等 ,与氟西汀组相比 ,米氮平组嗜睡发生率高 (P <0 .0 5)。结论 :米氮平是一种安全、有效的新型抗抑郁药物。起效较快 ,且有改善焦虑及睡眠作用     

A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression

Background: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline-controlled, 5 week clinical study. Method: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score ≥ 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. Results: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. Conclusion: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated.     

Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia

This was a 6-week, double-blind, randomized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia. Hospitalized and day care patients with DSM-IV major depression and melancholia and a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of > or = 25 were eligible. The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1-4, venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5-10, and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11-42. The intention-to-treat analyses included 55 patients on venlafaxine and 54 on fluoxetine. At the final evaluation, 70% of patients with venlafaxine and 66% with fluoxetine had > or = 50% reduction in the MADRS score, and 70% with venlafaxine and 62% with fluoxetine had a Clinical Global Impression (CGI) score of 1 or 2. A CGI improvement score of 1 was observed in 51% of patients with venlafaxine and 32% with fluoxetine (P = 0.018). A final Hamilton Depression Rating Scale (HAM-D) score < 7 was attained in 41% of venlafaxine-treated and 36% of fluoxetine-treated patients. Overall, 22% of patients in each group discontinued therapy, but only 5% on venlafaxine and 9% on fluoxetine discontinued for adverse events. Nausea was reported in 5.5% of venlafaxine-treated patients and 14.8% of fluoxetine-treated patients. Venlafaxine was effective and well tolerated for treating inpatients with major depression and melancholia. Based on remission criteria (HAM-D < 7 or CGI of 1), venlafaxine was superior to fluoxetine.     

Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: A four-week,randomized, double-blinded,placebo-controlled study

This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83–6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54–1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects.     

Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group

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.     

米氮平与氟西汀治疗伴有广泛焦虑障碍的抑郁症各35例的疗效比较

目的 :比较米氮平与氟西汀治疗伴有广泛焦虑障碍的抑郁症的疗效。方法 :70例同时符合DSM Ⅳ重症抑郁障碍及广泛焦虑障碍诊断标准的抑郁症病人随机分为 2组 ,米氮平组 35例 [男性 12例 ,女性 2 3例 ,年龄 (4 3±s 14 )a],予米氮平 15～4 5mg ,po ,qd。氟西汀组 35例 [男性 10例 ,女性 2 5例 ,年龄 (4 4± 12 )a],予氟西汀 2 0～ 6 0mg ,po ,qd ;均 8wk为一个疗程。结果 :米氮平组有效率为94 % (33/35 ) ,氟西汀组有效率为 89% (31/35 ) ,2组有效率比较差异无显著意义 (P >0 .0 5 )。结论 :米氮平治疗伴有广泛焦虑障碍的抑郁症 ,起效快、疗效与氟西汀相似     

Mirtazapine. A pharmacoeconomic review of its use in depression

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). The antidepressant efficacy of mirtazapine has been established in randomised, double-blind comparative studies. Mirtazapine has generally shown similar efficacy to other antidepressants. There is evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitors (SSRIs) on the basis of mean depression rating scale scores. Data from a long term (mean 240 days) clinical trial that was subsequently used in pharmacoeconomic analyses showed that mirtazapine was associated with significantly higher sustained remission rates and rates of discontinuation because of improvement than amitriptyline and placebo. Although differences were not statistically significant, mirtazapine had higher response rates at 6 weeks than the SSRI fluoxetine in an analysis that was also used as the basis of pharmacoeconomic studies. Mirtazapine improved quality of life to a similar extent to fluoxetine, citalopram and paroxetine in unpublished studies of 6 and 8 weeks' duration. Pooled analyses suggest that mirtazapine may be associated with greater improvement than fluoxetine and citalopram in quality of life after 2 and 4 weeks, although confirmation is required. In a decision analytical model of approximately 6 months' duration, mirtazapine was associated with a higher proportion of successfully treated patients and lower total direct costs than amitriptyline. The direct cost per successfully treated patient with mirtazapine was lower than that with amitriptyline by 33,112 Austrian schillings (S; year of costing not stated), 24,212 French francs (FF; 1995/1996 values), 13,851 Swedish kronor (SEK; 1997 values) and 553 Pounds (1997/1998 values) in Austrian, French, Swedish and UK analyses, respectively. Compared with fluoxetine, mirtazapine was associated with higher per-patient costs in all 4 countries but a higher proportion of successfully treated patients. Mirtazapine was more cost effective than fluoxetine: the direct cost per successfully treated patient was lower by S32,046 in Austria, FF25,914 in France, SEK9796 in Sweden and 327 Pounds in the UK. The additional cost of mirtazapine versus fluoxetine for each additional successfully treated patient at 6 months was S11,732, SEK17,229, 750 Pounds and FF3342 in the Austrian, Swedish, UK and French analyses, respectively. Mirtazapine was generally associated with lower indirect costs (for lost productivity of employed patients) than amitriptyline and similar indirect costs to fluoxetine in the analyses. CONCLUSIONS: Available data suggest that mirtazapine is a cost-effective alternative to amitriptyline and fluoxetine for the treatment of depression. Mirtazapine also has similar effects to SSRIs on quality of life with possibly a shorter time to onset of action, although published trial results are required to confirm these preliminary data.     

Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study

This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient.     

Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study

The nonselective serotonin (5-HT)-2A antagonists ritanserin, mianserin, and cyproheptadine were found efficacious in neuroleptic-induced akathisia (NIA). Mirtazapine is structurally and pharmacologically similar to mianserin, and the authors sought to determine its anti-NIA activity. Twenty-six neuroleptic-treated schizophrenic patients with DSM-IV diagnosis of NIA received add-on mirtazapine (15 mg/day) or placebo for 5 days in a double-blind design. Patients were assessed at baseline and days 3 and 5 with the Barnes Akathisia Scale (BAS), Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, and Simpson-Angus Scale for parkinsonism. Analysis of covariance with repeated measurements revealed significant group x time effects in favor of the mirtazapine group in both completers (n = 10 in each group) and intent-to-treat analysis (n = 13 in each group) for the BAS global subscale (F [1, 17] = 14.87, p = 0.001, and F [1, 23] = 13.24, p = 0.01, respectively) and objective subscale (F [1, 17] = 8.25, p = 0.011, and F [1, 23] = 7.35, p = 0.012, respectively) and borderline significant superiority for the BAS subjective subscale (F [1, 17] = 4.39, p = 0.051, and F [1, 23] = 4.12, p = 0.054, respectively) and distress subscale (F [1, 17] = 4.21, p = 0.056, and F [1, 23] = 3.80, p = 0.064, respectively). Significantly more mirtazapine-than placebo-treated patients (53.8% [7/13] vs. 7.7% [1/13], respectively; chi2 = 8.3, p = 0.004) met operational response criterion, a reduction of at least two points on the BAS global subscale. Mirtazapine treatment was associated with modest improvement of psychotic and parkinsonian symptoms. Mild sedation was the only side effect. Our study demonstrated that mirtazapine (15 mg/day) is an efficacious and well-tolerated therapeutic option in NIA. Marked 5HT2A/2C antagonistic activity of mirtazapine apparently accounts for its anti-NIA activity. The role of mirtazapine in the treatment of akathisia induced by atypical antipsychotic agents merits further investigation.     

Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder

Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.     

Effect of mirtazapine treatment on serotonin transporter in blood peripheral lymphocytes of major depression patients

Lymphocytes from human peripheral blood exhibit a series of markers of neurotransmitters, such as specific receptors and transporters. A reduction of serotonin transporters and an increase of them has been reported after treatment with fluoxetine in depressed patients. The aim of this study was to determine if the administration of an antidepressant with a different mechanism of action, such as mirtazapine, could produce a similar effect. Twenty eight patients (age 41.40+/-2.45) were diagnosed following the criteria for major depression by the Structured Clinical Interview for Disorders of Axis I of the American Psychiatric Association. Severity was measured by Hamilton Scale and by Beck Inventory for Depression, scores of 30.88+/-7.48 and 30.24+/-10.88, respectively, prior to treatment. Samples from control subjects were obtained alternating with patients before and after the administration of the antidepressant: twenty eight and twenty four, respectively (age 38.80+/-2.95). Mirtazapine was given in a dose of 30 mg/day for 6 weeks. Blood lymphocytes were isolated by density gradient from patients and controls before and after treatment. There was a partial response according to clinical evaluation and scores of the Scale and the Inventory. Serotonin transporters were labeled with [3H] paroxetine. Number of sites (B(max)) were 10.86+/-2.60 and 12.58+/-2.71 fmol/10(6) cells for both groups of controls. The depressed patients had a significant reduction of serotonin transporters in their lymphocytes before treatment and an increase after it, with B(max) values of 6.52+/-0.49 and 15.61+/-0.49 fmol/10(6) cells, respectively. There were no significant differences in the affinity for the ligand. Concentrations of serotonin or noradrenaline in lymphocytes were not modified before the treatment, although there was a significant decrease after taking 30 mg/day of the antidepressant for 6 weeks. Mirtazapine, not being a serotonin reuptake inhibitor, did increase the number of transporters in lymphocytes of major depression patients, indicating a complex mechanism, not only directly related to the transporter, but involved in the therapeutic response.     

Mirtazapine: a review of its use in major depression

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) which has predominantly been evaluated in the treatment of major depression. The drug had equivalent efficacy to tricyclic antidepressants and it was at least as effective as trazodone in the majority of available short term trials in patients with moderate or severe depression, including those with baseline anxiety symptoms or sleep disturbance and the elderly. A continuation study also showed that sustained remission rates were higher with mirtazapine than with amitriptyline and that the drugs had similar efficacy for the prevention of relapse. There is some evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Mirtazapine was more effective than the SSRI fluoxetine at weeks 3 and 4 of therapy and it was also more effective than paroxetine and citalopram at weeks 1 and 2, respectively, in short term assessments (6 or 8 weeks). Preliminary data suggest that the drug may be effective as an augmentation or combination therapy in patients with refractory depression. Anticholinergic events and other events including tremor and dyspepsia are less common with mirtazapine than with tricyclic antidepressants. There was a greater tendency for SSRI-related adverse events with fluoxetine than with mirtazapine, but, overall, mirtazapine had a similar tolerability profile to the SSRIs. Increased appetite and bodyweight gain appear to be the only events that are reported more often with mirtazapine than with comparator antidepressants. In vitro and in vivo data have suggested that mirtazapine is unlikely to affect the metabolism of drugs metabolised by cytochrome P450 (CYP)2D6, although few formal drug interaction data are available. CONCLUSIONS: Mirtazapine is effective and well tolerated for the treatment of patients with moderate to severe major depression. Further research is required to define the comparative efficacy of mirtazapine in specific patient groups, including the elderly and those with severe depression. Clarification of its efficacy as an augmentation therapy and in patients with refractory depression and its role in improving the efficacy and reducing the extrapyramidal effects of antipsychotic drugs would also help to establish its clinical value. The low potential for interaction with drugs that are metabolised by CYP2D6, including antipsychotics, tricyclic antidepressants and some SSRIs, may also make mirtazapine an important option for the treatment of major depression in patients who require polytherapy. Mirtazapine also appears to be useful in patients with depression who present with anxiety symptoms and sleep disturbance.     

Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study

The present study aimed to assess the safety and efficacy of mirtazapine in amphetamine detoxification in a 14-day randomized, placebo-controlled pilot trial in a Thai population. Subjects retained at a Specialized Probation Center, Department of Probation, Ministry of Justice, Thailand (n=20), who met DSM-IV criteria for amphetamine dependence and the inclusion criteria of the study, were randomized for either mirtazapine treatment or placebo. Efficacy was assessed by the Amphetamine Withdrawal Questionnaire (AWQ) for amphetamine withdrawal symptoms and the Montgomery-Asberg Depression rating scale (MADRS) for depression. Mirtazapine safety was assessed by interview during each follow-up period on days 3 and 14 after treatment. Nine subjects were randomized to the mirtazapine group and 11 to the placebo group. Among the initial 20 subjects, 16 (seven in the mirtazapine and nine in the placebo group) completed the study. There were significant improvements in the total AWQ score changes in the mirtazapine group versus placebo both at days 3 (P<0.005) and 14 (P<0.030). Significant improvements in favour of mirtazapine were also seen in the hyperarousal and the anxiety subscale score changes at days 3 (P<0.029) and 14 (P<0.018), respectively. No significant differences were seen (P>0.05) in the MADRS scores changes within or between the groups. Mild adverse events, such as headache, sedation, nausea and vomiting, were reported. In conclusion, despite its small sample size, this randomized, placebo-controlled pilot trial lends support to the hypothesis that mirtazapine may be an option in the meager armamentarium of amphetamine detoxification treatment.     

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients

Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.     

Effects of mirtazapine in patients with post-traumatic stress disorder in Korea: a pilot study

This study was aimed at testing the efficacy and tolerability of mirtazapine in the treatment of Korean patients with chronic post-traumatic stress disorder (PTSD). Mirtazapine was administered for 8 weeks using a flexible-dose regime in 15 Korean patients with PTSD based on the DSM-IV criteria. We evaluated the patients at baseline and at weeks 4 and 8 after treatment with the interviewer-administered structured interview for PTSD (SIP), short PTSD rating interview (SPRINT), impact of event scale-revised (IES-R) and the Montgomery Asberg depression rating scale (MADRS). Scores on the SIP, SPRINT, IES-R and MADRS had significantly reduced after 8 weeks treatment. In this pilot study, mirtazapine was found to be effective and well tolerated in the treatment of patients with PTSD. This calls for further evaluation of the effect of this drug on subjects with PTSD with randomized placebo-controlled studies.     

Comparison of efficacy and safety of milnacipran and fluoxetine in Korean patients with major depression

OBJECT: To compare efficacy and safety of milnacipran and fluoxetine in a population of Korean patients with major depression. RESEARCH DESIGN AND METHODS: The design was a multi-centre, randomised, comparative clinical study. Patients with major depression (DSM-IV diagnostic criteria) scoring over 17 points on the 17-item Hamilton Depression Scale (HAM-D) and over 21 points on the Montgomery-Asberg Depression Rating Scale (MADRS) were recruited and randomised to receive milnacipran (50 mg/day increasing after 1 week to 100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. All previous medication was stopped at least 7 days before entry into the study. Patients were evaluated (HAM-D, MADRS and clinical global impression scale, CGI) at baseline and after 1, 2, 4 and 6 weeks of treatment. All adverse events which developed during the study period were recorded. RESULTS: 70 patients (milnacipran 39; fluoxetine 31) were included in the study. Total score on both HAM-D, MADRS and CGI decreased significantly in both groups after 1 week and continued to decrease throughout the study. There was no significant difference between the two groups for any measurement at any time point. Both antidepressants were well tolerated. In the milnacipran group, 13 patients reported 28 adverse reactions, and in the fluoxetine group 11 patients reported 18 adverse reactions. Two patients discontinued due to adverse events in the milnacipran group and three in the fluoxetine group. There were no clinically significant modifications in vital signs, routine blood laboratory tests, biochemistry or ECG throughout the study. Nausea and headache were the most frequently reported adverse events with milnacipran while digestive disturbances, diarrhoea and insomnia were more common with fluoxetine. CONCLUSION: Milnacipran, like fluoxetine, was found to be effective and well tolerated for the treatment of major depression in this population of depressed Korean patients. Principal limitations of the study were its open design, its small sample size and its relatively short duration.     

Fluoxetine treatment of depressed patients with comorbid anxiety disorders

Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared to major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in severity of both depressive and anxiety symptoms in outpatients with major depression with comorbid anxiety disorder following fluoxetine treatment. We enrolled 123 outpatients (mean age 38.9 +/- 10.8 years; 49% women) with major depressive disorder accompanied by one or more current comorbid anxiety disorders in our study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks. Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression and Anxiety. The mood and anxiety disorder modules of the Structured Clinical Interview for DSM-III-R were administered at screen and endpoint. We used 'intent-to-treat' analysis in examining all patients assigned to treatment and completing the baseline visit. The mean number of comorbid anxiety disorders per patient was 1.5 +/- 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions-Severity scores decreased significantly from baseline to endpoint (week 8) following fluoxetine treatment (p < 0.0001). There were significant decreases in all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n = 65) were depression responders (i.e. > or = 50% decrease in HAM-D-17 score at endpoint) and 46% (n = 57) were remitters (HAM-D-17 < or = 7 at endpoint). Patients with panic disorder had significantly higher baseline HAM-D-17 scores compared to those without panic disorder (p < 0.01). Patients with comorbid obsessive-compulsive disorder (OCD) were significantly less likely to be responders to fluoxetine at endpoint (> or = 50% decrease in HAM-D-17) and to be remitters (HAM-D-17 score of s 7 at endpoint) compared to patients without comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical Interview for DSM-III-R modules for anxiety disorders were available, 49% (n = 20) no longer met criteria for one or more of their anxiety disorder diagnoses at endpoint. Our preliminary findings suggest that fluoxetine is effective in treating outpatients with major depression with comorbid anxiety disorders, with a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are required in larger samples to confirm our findings.     

Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home

OBJECTIVE: To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed, elderly nursing home residents, under naturalistic study conditions. METHODS: In this open-label 12-week study, mirtazapine orally disintegrating tablets (15-45 mg/day) were administered to patients > or =70 years old with physician-diagnosed depression and a Mini-Mental State Examination (MMSE) score > or =10. Patients with medical comorbidities, cognitive impairment and/or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and/or medication dosages that were considered stable. Assessments were performed at baseline by physicians and at days 14, 28, 56, and 84 (or early termination) by physicians or nurse coordinators using the Clinical Global Impression (CGI) scale, the 16-item Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item scale minus item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability was evaluated based on treatment-emergent adverse events. RESULTS: A total of 119 patients in the intent-to-treat (ITT) group were treated with mirtazapine orally disintegrating tablets (mean daily dose: 19.4 mg) and evaluated for efficacy. At endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16 responders (defined as decrease from baseline of at least 50% in Ham-D-16 total score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion. The decrease in Ham-D scores from baseline to day 84 was statistically significant (p < 0.0001). Mean changes from baseline to day 84 were -6.6 +/- 6.9 (CSDD score) and -7.9 +/- 7.4 (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group (11.3%) discontinued prematurely due to adverse events. The most frequently occurring adverse events were urinary tract infection (19%), accidental injury (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean body weight increased by 0.7 +/- 2.25 kg (1.54 +/- 5 lb) from baseline to day 28, and by 1.3 +/- 3.36 kg (2.86 +/- 7.4 lb) from baseline to day 84. CONCLUSIONS: The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities.     

米氮平与氟西汀治疗抑郁症的最小成本分析

目的:研究米氮平与氟西汀治疗抑郁症的经济学效果。方法:将63例抑郁症患者随机分为米氮平组与氟西汀组,2组疗程均为6wk,运用药物经济学原理进行最小成本分析。结果:米氮平组与氟西汀组的有效率分别为86.7%、90.9%(P>0.05),治疗成本分别为2948.58、2845.30元。结论:氟西汀治疗抑郁症的经济学效果优于米氮平。