title: A multisite trial of mifepristone for the treatment of psychotic depression: a site-by-treatment interaction. A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients The validity of major depression with psychotic features based on a community study. A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients Clinical and Biological Effects of Mifepristone Treatment for Psychotic Depression Citalopram versus nortriptyline in late‐life depression: a 12‐week randomized single‐blind study Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome. Placebo response rates in psychotic and nonpsychotic depression.
abstract: Major Depression with Psychotic Features ( psychotic depression ) is a common , debilitating psychiatric disease . We hypothesized that mifepristone , a cortisol receptor ( GRII ) antagonist , would significantly reduce psychotic symptoms in psychotic depression . Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were r and omized to mifepristone or placebo for 7 days . The primary outcome was rapid and sustained response , defined as a 50 % or greater decrease in Brief Psychiatric Rating Scale - Positive Symptom Subscale scores at the end of treatment ( day7 ) and 49 days later ( day 56 ) . Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site . Exploratory analyses compared response of patients with mifepristone plasma concentrations of > or = 1800 ng/ml to placebo . The primary endpoint was not statistically significant . However , the Breslow-Day test indicated a statistically significant site-by-treatment interaction . Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset ( p<.05 ) , whereas no difference was observed at the nine sites added late in the trial . Patients with  mifepristone plasma levels > or = 1800 ng/ml were significantly more likely to respond than placebo patients ( Intent-to-Treat : OR=2.4 , p=.03 ; Initial 20 sites : OR=4.1 , p=.002 ) . The results of this trial are instructive in two respects . First , while statistical adjustments for [ corrected ] site are common in multisite clinical trials , this study reminds trialists to formally evaluate the interaction of site by treatment . Second , the association between increased  mifepristone plasma concentration levels and greater clinical response , detected despite the site-by-treatment interaction , suggests that higher plasma levels may be needed for maximizing the probability of a positive response Objective To compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients This article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV Antidepressant effects of mirtazapine and imipramine were compared in a r and omized , double blind , fixed blood-level study with in- patients in a single centre . Patients with a DSM-III-R diagnosis of major depression and a Hamilton ( 17-item ) score of ≥18 were selected . After a drug-free and a placebowashout period of 7 days in total , 107 patients still fulfilling the HRSD criterion of ≥18 , started on active treatment . The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine . Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms . Eight patients dropped out and two were excluded from analyses because of non-compliance ; 97 completed the study . According to the main response criterion ( 50 % or more reduction on the HRSD score ) 11/51 ( 21.6 % ) patients responded on mirtazapine and 23/46 ( 50 % ) on imipramine after 4 weeks ' treatment on the predefined blood level . Such a dramatic difference in efficacy between antidepressants has not often been reported before . The selection of ( severely ill ) in- patients , including those with suicidal or psychotic features , may have significance in this respect . Optimization of treatment with the reference drug imipramine through blood level control , exclusion of non-compliance for both drugs , exclusion of most concomitant medication and a low drop-out rate may also have contributed . It is concluded that imipramine is superior to mirtazapine in the patient population studied Psychotic major depression ( PMD ) is found to be a relatively common psychiatric condition that affects up to nearly 20 % of patients with major depression . Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone , in addition to restoring a more normal afternoon cortisol release . The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed . In total , 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a r and omized double-blind manner . The Hamilton Depression Rating Scale ( HDRS ) and the Brief Psychiatric Rating Scale ( BPRS ) were administered at baseline and again after 8 days of treatment . Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment . Significantly , more patients in the mifepristone group ( seven of 15 ) showed a 50 % or greater decline on the BPRS positive symptom subscale , an index of psychotic symptoms , as compared to the placebo group ( two of 15 ) . Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo , but these differences were not statistically significant . In addition , mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo . Clinical and biological effects of mifepristone were comparable among males and females . Age was found to significantly and positively correlate with changes in cortisol and ACTH . These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis . Additional blinded studies are warranted Objective : The aim of this single‐blind study was to examine the efficacy and tolerability of citalopram compared to nortriptyline in moderate to severe major depressive patients aged 60 years or over In a multicenter , double-blind , parallel group trial , the efficacy of risperidone ( RIS ) was compared with a combination of haloperidol and amitriptyline ( HAL/AMI ) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder , depressive type , a major depression with psychotic features , or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria . A total of 123 patients ( 62 RIS ; 61 HAL/AMI ) were included ; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI .  Efficacy results for those 98 patients ( 47 RIS ; 51 HAL/AMI ) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale ( RIS 37 % ; HAL/AMI 51 % ) and the Bech-Rafaelsen Melancholia Scale total scores ( RIS 51 % ; HAL/AMI 70 % ) . The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group ( p < 0.01 ) , mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features , whereas treatment differences in the other diagnostic subgroups were not significant . The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS ( 37 % ) than under HAL/AMI ( 31 % ) . Adverse events were reported by 66 % of RIS and 75 % of HAL/AMI patients . The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms . However , subgroup differences have to be considered The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline . Using a 14-day drug-free ' wash-out ' period , they found that the  placebo response rates were 0 % for psychotic depressives and 13.3 % for nonpsychotic depressives .  Amitriptyline  was significantly superior to placebo for both psychotic ( P less than or equal to 0.05 ) and nonpsychotic ( P less than or equal to 0.05 ) depressed patients
target: Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo .
  Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone
background: BACKGROUND Evidence is limited regarding the most effective pharmacological treatment for psychotic depression :  combination of an antidepressant plus an antipsychotic , monotherapy with an antidepressant or monotherapy with an antipsychotic .
  This is an up date of a review first published in 2005 and last up date d in 2009 .
  OBJECTIVES 1 .
  To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression :  antidepressant monotherapy , antipsychotic monotherapy and the combination of an antidepressant plus an antipsychotic , compared with each other and /or with placebo.2 .
  To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment .