Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients Association study of the serotonin transporter promoter polymorphism and mirtazapine antidepressant response in major depressive disorder Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Add-on mirtazapine improves orgasmic functioning in patients with schizophrenia treated with first-generation antipsychotics Mirtazapine Orally Disintegrating Tablets Versus Venlafaxine Extended Release: A Double-blind, Randomized Multicenter Trial Comparing the Onset of Antidepressant Response in Patients With Major Depressive Disorder The Use of Antidepressants for Physical and Psychological Symptoms in Cancer. FKBP5 polymorphisms and antidepressant response in geriatric depression Efficacy and safety of add on low-dose mirtazapine in depression Mirtazapine Orally Disintegrating Tablet Versus Sertraline: A Prospective Onset of Action Study Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Treatment of Post-Myocardial Infarction Depressive Disorder: A Randomized, Placebo-Controlled Trial With Mirtazapine Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients. Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential Different effects of mirtazapine and venlafaxine on brain activation: an open randomized controlled fMRI study. Comparisons of the Efficacy and Tolerability of Extended-Release Venlafaxine, Mirtazapine, and Paroxetine in Treatment-Resistant Depression: A Double-Blind, Randomized Pilot Study in a Chinese Population Prevention and treatment of poststroke depression with mirtazapine in patients with acute stroke. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Neural correlates of treatment outcome in major depression. Open trial of mirtazapine in patients with fibromyalgia. Depressed in-patients respond differently to imipramine and mirtazapine. Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based?
BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action Abstract Introduction : Depression is a major global problem associated with large medical , sociological and economic burdens . Mirtazapine ( Remeron ® , Organon NV , The Netherl and s ) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression . However , this agent has not yet been tested in patients with severe depression alone . Objective : To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression ( ≥25 points on the first 17 items of the Hamilton Depression Rating Scale [ HDRS-17 ] ) . Methods : In this double-blind study , 297 severely depressed patients were r and omised to receive mirtazapine 15–60 mg/day ( n = 147 ) or fluoxetine 20–40 mg/day ( n = 152 ) for 8 weeks . 294 subjects were actually treated and 292 included in the intent-to-treat population . Symptom severity was measured by the HDRS-17 , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) rating scale . Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Question naire and the Quality of Life , Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study . Results : No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point ; both treatments were associated with large ( ∼15 points ) decreases by study end . However , more mirtazapine-treated patients tended to exhibit a ≥50 % decrease in HDRS score ( significant at day 7 ; 9.0 % vs 0.7 % , p = 0.002 ) . Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores ( −10.9 vs −8.5 , p = 0.006 ) and the proportion of patients with ≥50 % decrease in MADRS score ( 21.4 % vs 10.9 % , p = 0.031 ) . On the CGI , the proportion of ‘ much/very much improved ’ patients tended to be greater with mirtazapine ( significant at day 7 ; 9.7 % vs 3.4 % , p = 0.032 ) . No significant between-group differences were observed for the majority of quality -of-life measures . However , mirtazapine produced significantly better improvements on ‘ sleeping assessment 1 ’ ( 14.9 ± 5.2 vs 13.7 ± 5.4 , p = 0.028 ) and ‘ sleeping assessment 2 ’ ( p = 0.013 ) than fluoxetine . Both agents were generally well tolerated  but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7 kg compared with a mean decrease in weight of 0.4 ± 2.1 kg for fluoxetine-treated patients ( p < 0.001 ) . Conclusions : Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants , and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene ( 5-HTTLPR ) . Mirtazapine has a dual-action profile , combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes . The goal of this study was to eluci date whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder ( MDD ) . One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment . The severity of depression was assessed with the 21-item Hamilton Depression Rating scale , and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction . Our results showed that responses at the 2nd and 4th weeks were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers . These results support our hypothesis that the response to noradrenergic and specific serotonergic antidepressants is significantly associated with the 5-HTTLPR polymorphism 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 r and omized 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 r and omized , 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 Abstract Aim : Sexual dysfunction , common in schizophrenia , may be further exaggerated by antipsychotics , especially those of First Generation ( FGAs ) , and antidepressants , such as Selective Serotonin Reuptake Inhibitors ( SSRs ) . Mirtazapine , an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants , may improve SSRI-induced sexual dysfunction in patients with depression . It is unknown , however , whether mirtazapine improves sexual functioning in schizophrenia . Methods : This study r and omly assigned FGA-treated patients with schizophrenia to receive either an add-on  mirtazapine ( n = 20 )  or a placebo  ( n = 19 ) for 6 weeks . Sexual functioning was prospect ively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale ( UKU-SERS ) . Results : Orgasmic function improved with statistical significance in the mirtazapine group ( p = .03 ) , with no changes in any other sexual functions in either group . Conclusion : Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia This r and omized , multicenter , double-blind study was design ed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets ( ODT ) with venlafaxine extended-release ( XR ) formulation in out patients with major depression . Both treatments were administered in a rapidly escalating dosing regimen . Target doses ( mirtazapine ODT , 45 mg OD ; venlafaxine XR , 225 mg OD ) were reached by day 6 of treatment . On the primary efficacy parameter [ the average of the change in HAM-D ( 17-item ) total score on days 5 , 8 , 11 , and 15 ] , mirtazapine ODT was significantly superior to venlafaxine XR ( P = 0.008 ) . In addition , calculating the HAM-D score without the sleep items result ed in significant reductions in favor of mirtazapine ODT on days 8 ( P = 0.006 ) and 11 ( P = 0.037 ) . The proportion of responders ( HAM-D decrease of ≥50 % from baseline ) was higher in the mirtazapine ODT group on all assessment days , being significant on days 8 ( P = 0.002 ) , 11 ( P = 0.004 ) , and 22 ( P = 0.027 ) . More patients in the mirtazapine ODT group achieved remission ( HAM-D total score of ≤7 ) up to day 29 , and the difference was statistically significant on day 15 ( P = 0.016 ) . Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 ( P = 0.019 ) , 11 ( P = 0.004 ) , and 15 ( P = 0.031 ) , and the CGI of severity on days 8 ( P = 0.014 ) and 11 ( P = 0.033 ) . Both treatments were well tolerated . These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy  than venlafaxine XR in patients with major depressive disorder , and that this effect is independent of its sleep-improving properties Cancer patients are commonly associated with various physical and psychological symptoms . In palliative setting , the aims are to relieve those symptoms , improve quality of life , and increase medication adherence among cancer patients . Antidepressants are generally accepted for the treatment of depression among patients with or without cancer . Some other potential benefits of the antidepressants have been reported in cancer patients . OBJECTIVE This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients . RESULTS Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients . These studies are categorised according to the hierarchy of evidence from high to low level , namely r and omised controlled trials , cohort studies , case-control studies , case series , case reports , as well as other type of publications . The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression , anxiety , hot flashes and other symptoms such as sexual dysfunction , fatigue , nicotine dependence , vasomotor symptoms , executive functions , sleep problems , pruritus , as well as for hypochondriasis . While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron , mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients . CONCLUSION More research studies with adequate statistical power are warranted to vali date the use of antidepressants among cancer patients in treating these physical and psychological symptoms Genetic variation at the FKBP5 locus has been reported to affect clinical outcomes in patients treated with antidepressant medications  in several studies . However , other reports have not confirmed this association . FKBP5 may regulate the sensitivity of the hypothalamic – pituitary – adrenal axis . We tested two  FKBP5 single nucleotide polymorphisms ( rs1360780 and rs3800373 ) in a sample of 246 geriatric patients treated for 8 weeks in a double‐blind r and omized comparison trial of paroxetine and mirtazapine .  These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine , and those treated with mirtazapine , an agent with both serotonergic and noradrenergic actions . However , we found no significant associations between these FKBP5 genetic variants and clinical outcomes . Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by FKBP5 genetic variation . These results suggest that FKBP5 is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients . © 2009 Wiley‐Liss , Objectives : Although antidepressant medications are effective , they have a delayed onset of effect . Mirtazapine , an atypical antidepressant is an important option for add-on therapy in major depression . There is insufficient data on mirtazapine in Indian population ; hence this study was design ed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors ( SSRIs ) in major depressive disorder ( MDD ) in Indian population . Material s and Methods : In an open , r and omized study , 60 patients were divided into two groups . In Group A ( n=30 ) patients received conventional SSRIs for 6 weeks . In Group B ( n=30 ) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks . Patients were evaluated at baseline and then at 1 , 2 , 3 , 4 , 5 , and 6 weeks . Results : There was significant improvement in Hamilton Depression Rating Scale ( HDRS ) , Montgomery and Asberg depression rating scale ( MADRS ) scores ( P<0.05 ) in both groups . Mirtazapine in low dose as add on therapy showed improvement in scores , had earlier onset of action , and more number of responders and remitters as compared to conventional treatment ( P<0.05 ) . No serious adverse event was reported in either of the groups . Conclusion : Low-dose mirtazapine as add-on therapy has shown better efficacy , earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients This multinational , r and omized , double-blind study was specifically design ed to prospect ively 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 . Assessment s 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 assessment s 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 , ≥50 % reduction in HAMD total score from baseline ) , HAMD remission rate ( HAMD total score of ≤7 ) , and the Montgomery-Åsberg 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 prospect i ve 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 OBJECTIVE Various classes of antidepressant medications generally induce remission of major depressive disorder  in only about one-third of patients . In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation , the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone . In this double-blind study , the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation . METHOD Patients ( N=105 ) meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive , from treatment initiation , either fluoxetine monotherapy ( 20 mg/day ) or mirtazapine ( 30 mg/day ) in combination with fluoxetine ( 20 mg/day ) , venlafaxine ( 225 mg/day titrated in 14 days ) , or bupropion ( 150 mg/day ) for 6 weeks . The primary outcome measure was the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS The overall dropout rate was 15 % , without notable differences among the four groups . Compared with fluoxetine monotherapy , all three combination groups had significantly greater improvements on the HAM-D. Remission rates ( defined as a HAM-D score of 7 or less ) were 25 % for fluoxetine , 52 % for mirtazapine plus fluoxetine , 58 % for mirtazapine plus venlafaxine , and 46 % for mirtazapine plus bupropion . Among patients who had a marked response , double-blind discontinuation of one agent produced a relapse in about 40 % of cases . CONCLUSIONS The combination treatments were as well tolerated as fluoxetine monotherapy and more clinical ly effective . The study results , which add to a growing body of evidence , suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication Objective : To examine the antidepressant efficacy of a dual-acting antidepressant ( mirtazapine ) in patients with post-myocardial infa rct ion ( MI ) depressive disorder . Antidepressants used in post MI trials with a r and omized , double-blind , placebo-controlled design have been restricted to selective serotonin reuptake inhibitors ( SSRIs ) . Antidepressant effects have been limited . Methods : In a prospect i ve multicenter study , 2177 patients with MI were evaluated for depressive disorder during the first year post MI . Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) criteria for major or minor depressive disorder were r and omized to a 24-week , double-blind , placebo-controlled trial . Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach , with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale ( Ham-D ) , and secondary outcomes the Beck Depression Inventory ( BDI ) and depression subscale of the Symptom Check List 90 items ( dSCL-90 ) as well as the Clinical Global Impression ( CGI ) scale . Results : Using the “ last observation carried forward ” ( LOCF ) method , mirtazapine did not show to be superior to placebo on the Ham-D , but did on the BDI , dSCL-90 , and CGI scale over the acute treatment phase of 8 weeks ( n = 91 ) . Using mixed models analysis over the entire 24 weeks of treatment ( n = 40 ) , we did find a significant difference favoring mirtazapine to placebo on the Ham-D , BDI , and CGI , but on the dSCL-90 , this difference was not significant . Conclusions : This trial shows efficacy of mirtazapine on primary and secondary depression measures . Mirtazapine seems to be safe in the treatment of post-MI depression . MI = myocardial infa rct ion ; RCT = r and omized controlled trial ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders ; CAD = coronary artery disease ; SSRI = selective serotonin reuptake inhibitors ; TCA = tricyclic antidepressant ; Ham-D = Hamilton-Depression Rating Scale ; BDI = Beck Depression Inventory ; CGI = Clinical Global Impression ; dSCL-90 = Symptom Check List 90 items , depression subscale ; SES = st and ardized effect size BACKGROUND The necessity of antidepressant continuation-phase therapy following acute-phase response has result ed in the need to characterize the longer-term efficacy and safety of all new medications . Previous studies using " extension " protocol s 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 , r and omized , 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 r and omly 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 ABSTRACT Introduction :  Chronic breathlessness  is a common and distressing symptom of advanced disease with few effective treatments . Central nervous system mechanisms are important in respiratory sensation and control . Consequently , drugs which may modify processing and perception of afferent information in the brain may have a role . Antidepressants have been proposed ; however , current evidence is limited . Of potentially suitable antidepressants , mirtazapine is an attractive option given its tolerability profile , low cost , and wide availability , along with additional potential benefits . Areas covered : The paper provides an overview of the physiology of breathlessness , with an emphasis on central mechanisms , particularly the role of fear circuits and the associated neurotransmitters . It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease . The evidence was identified by a literature search performed in PubMed through to October 2018 . Expert opinion : Currently , there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease . Mirtazapine is a promising c and i date to pursue , with definitive r and omized controlled trials required to determine its efficacy and safety in this setting OBJECTIVE Antidepressants with different mechanisms of action might have different effects on brain functions . The aim of the study was therefore to investigate effects of 2 antidepressants on brain activation and to identify predictors for therapy response . METHOD Twenty-four untreated patients with major depressive disorder ( according to Structured Clinical Interview for DSM-IV ) were enrolled in a prospect i ve , r and omized , 4-week trial with mirtazapine and venlafaxine . Functional magnetic resonance imaging ( fMRI ) was performed at baseline and after 4 weeks in the patients and in 15 healthy controls . The primary outcome measure was fMRI blood-oxygen-level dependence ( BOLD ) activation .  The patients were recruited in 2007 and 2008 . RESULTS Comparison between patients and controls revealed that emotional face matching elicited enhanced activation in the anterior cingulate cortex ( ACC ) , dorsomedial prefrontal cortex , dorsolateral prefrontal cortex , and basal ganglia in patients . During treatment , a significant decrease of BOLD responses was seen in the hippocampus , basal ganglia , thalamus , and cerebellum of venlafaxine-treated patients , and a significant increase in BOLD responses was seen in the middle cingulate gyrus and supplementary motor area of mirtazapine-treated patients ( P < .05 , family wise error [ FWE ] cluster-level corrected ) . Larger BOLD responses in the left fusiform gyrus at baseline predicted a better response to venlafaxine , and smaller BOLD responses in the right rol and ic operculum at baseline predicted a better response to mirtazapine ( P < .05 , FWE cluster-level corrected ) . CONCLUSIONS These fMRI results indicate that antidepressants with different mechanisms of action have different effects on brain function . It therefore seems that fMRI can be used for therapy evaluation and response prediction and can facilitate the development of new pharmaceuticals To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine ( venlafaxine-XR ) , mirtazapine , and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials . One hundred fifty adult patients with treatment-resistant depression according to their medical records and /or response to current treatments were r and omly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d ( n = 50 ) , mirtazapine 45 mg/d ( n = 55 ) , or paroxetine 20 mg/d ( n = 45 ) for 8 weeks . The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) . Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50 % reduction or greater on the HRSD-17 total score , and the improvement of patients ' general health functions . The completion rates were 82 % for venlafaxine-XR , 81.8 % for mirtazapine , and 82.2 % for paroxetine . Only one patient in paroxetine arm discontinued the study owing to an adverse event . The remission rates based on the HRSD-17 were 42.0 % for venlafaxine-XR , 36.4 % for mirtazapine , and 46.7 % for paroxetine . There were no statistical significance s between treatment arms in remission rates . Similarly , there were also no significant differences between groups in secondary outcome measure .  Venlafaxine-XR , mirtazapine , and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments . Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients 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 , r and omized 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 r and omly 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 OBJECTIVE Few controlled studies have addressed the issue of which antidepressant medications should be recommended for out patients 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 prospect i ve , 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 out patients ( N=235 ) with nonpsychotic major depressive disorder were r and omly 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 < /=7 on the 17-item Hamilton Rating Scale for Depression . The 16-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR(16 ) ) , obtained at treatment visits , provided secondary outcomes of remission ( score < /=5 at exit ) and response ( > /=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 result ed in low remission rates ( < 20 % ) among patients with major depressive disorder There is a need to identify clinical ly useful biomarkers in major depressive disorder ( MDD ) . In this context the functional connectivity of the orbitofrontal cortex ( OFC ) to other areas of the affect regulation circuit is of interest . The aim of this study was to identify neural changes during antidepressant treatment and correlates associated with the treatment outcome . In an exploratory analysis it was investigated whether functional connectivity measures moderated a response to mirtazapine and venlafaxine .  Twenty-three drug-free patients with MDD were recruited from the Department of Psychiatry and Psychotherapy of the Ludwig-Maximilians University in Munich . The patients were subjected to a 4-wk r and omized clinical trial with two common antidepressants , venlafaxine or mirtazapine .  Functional connectivity of the OFC , derived from functional magnetic resonance imaging with an emotional face-matching task , was measured before and after the trial . Higher OFC connectivity with the left motor areas and the OFC regions prior to the trial characterized responders ( p<0.05 , false discovery rate ) . The treatment non-responders were characterized by higher OFC-cerebellum connectivity . The strength of response was positively correlated with functional coupling between left OFC and the cau date nuclei and thalami . Differences in longitudinal changes were detected between venlafaxine and mirtazapine treatment in the motor areas , cerebellum , cingulate gyrus and angular gyrus . These results indicate that OFC functional connectivity might be useful as a marker for therapy response to mirtazapine and venlafaxine and to reconstruct the differences in their mechanism of action BACKGROUND Some positive therapeutic effects in fibromyalgia syndrome ( FS ) were reported with both tricyclic and new antidepressant drugs as well as serotonergic agents ( 5HT2 and 5HT3 receptor blockers ) . METHODS In the present study , a novel antidepressant drug mirtazapine , 15 - 30 mg/day , has been used in 29 patients with FS in an open trial . RESULTS Twenty-six patients completed the six-week study . Ten ( 38 % ) were considered responders on account of the reduction of > or = 40 % on pain , fatigue and sleep disturbances and remission of depressive symptoms at the end of study . Eighteen patients had at least moderate depression before mirtazapine treatment and 8 patients presented mild depressive symptoms .  Reduction on main symptoms of FS after 6 weeks of mirtazapine treatment significantly correlated with the reduction in depression . However , the percentage of responders and patients with > or = 40 % reduction on main symptoms of fibromyalgia was similar in high and low depression groups . CONCLUSIONS The results obtained suggest that mirtazapine may be promising method of FS treatment . Further double-blind placebo-controlled studies are required to confirm these results 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 r and omly 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 result ed 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 Major depression ( MD ) is underdiagnosed and undertreated in patients with temporal lobe epilepsy ( TLE ) . Side effects of some antidepressants , like increased risk of seizures and drug-drug interactions with anticonvulsants , contribute to undertreatment of MD in patients with TLE . We analyzed post hoc the data from 2 years of treatment of in patients with MD and TLE . Seventy-five patients received st and ard treatment with citalopram , mirtazapine , or reboxetine , respectively , at recommended dosage . Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20 - 30 weeks . Plasma levels of anticonvulsants were examined at admission and discharge . Seizures were documented . The antidepressive treatment was efficacious in all antidepressant groups . No case of serious adverse event or drug interaction occurred . There was no increase in frequency or severity of seizures . At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram . Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4 Major depression disorder is most commonly treated with antidepressants . However , due to their side effects clinicians seek non-pharmacologic options , and one of these is exercise . The literature on the benefits of exercise for depression is extensive . Nevertheless , two recent review s focusing on antidepressants vs. other therapies as a basis for clinical practice guidelines recommended mainly antidepressants , excluding exercise as a viable choice for treatment of depression . The aim of this perspective is to analyze the literature exploring the reasons for this discrepancy . Two categories of publications were examined : r and omized controlled trials ( RCTs ) and meta-analyses or systematic review s. Based on this re assessment , RCTs comparing exercise to antidepressants reported that exercise and antidepressants were equally effective . RCTs comparing exercise combined with antidepressants to antidepressants only reported a significant improvement in depression following exercise as an adjunctive treatment . Almost all the review s examining exercise vs. other treatments of depression , including antidepressants , support the use of exercise in the treatment of depression , at least as an adjunctive therapy . The two review s examining pharmacologic vs. non-pharmacologic therapies as a basis for clinical practice guidelines examined limited evidence on exercise vs. antidepressants . In addition , it is possible that academics and health care practitioners are skeptical of viewing exercise as medicine . Maybe , there is a reluctance to accept that changes in lifestyle as opposed to pharmacological treatment can alter biological mechanisms . Longitudinal studies are needed for assessing the effectiveness of exercise in real clinical setting s , as well as studies exploring dose-response relationship between exercise and depression
Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor ( venlafaxine only , two trials , n = 415 ) at two weeks ( OR 2.29 , 95 % CI 1.45 to 3.59 ) and at the end of acute-phase treatment ( OR 1.53 , 95 % CI 1.03 to 2.25).In terms of dropouts , there was no robust evidence to detect a difference between mirtazapine and other antidepressants .
Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction .
AUTHORS ' CONCLUSIONS Some statistically significant and possibly clinical ly meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression .
Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment .
Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants , although the adverse event profile of mirtazapine is unique
BACKGROUND Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice .
OBJECTIVES The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults .