Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features. Continuity is the main challenge in treating major depressive disorder in psychiatric care. Two-year prospective naturalistic study of remission from major depressive disorder as a function of personality disorder comorbidity. Exercise and Pharmacotherapy in Patients With Major Depression: One-Year Follow-Up of the SMILE Study Specific characteristics of the pain/depression association in the general population. The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey. Diagnostic consistency of major depression with psychosis across 10 years. Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies. Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder Three-Year long-term outcome of 458 naturalistically treated inpatients with major depressive episode: severe relapse rates and risk factors Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). The natural course and outcome of major depressive disorder in primary care: the PREDICT-NL study Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial. Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: an open label trial. A pilot study to evaluate symptom-oriented selection of antidepressants in patients with cancer.
Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD .  SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram OBJECTIVE Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features ( MD-Psy ) . We assessed the extent to which the  pharmacotherapy  received by patients with MD-Psy under usual care conforms to these recommendations . METHOD We assessed the  pharmacotherapy  received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD ( Study of the Pharmacotherapy of Psychotic Depression ) , a 12-week r and omized , controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo . Our assessment took place from January 2003 to May 2004 . The strength of antidepressant trials was rated using the Antidepressant Treatment History Form ( ATHF ) . The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF . We also determined whether the strength of antipsychotic or combination trials was associated with age , the duration of the current depressive episode , medical burden , cognitive status , or the severity of depressive or psychotic symptoms . RESULTS Most patients with MD-Psy were treated with antidepressants ( N = 82 , 82 % ) or antipsychotics ( N = 65 , 65 % ) . About half of the patients ( N = 48 , 48 % ) received therapeutic doses of an antidepressant ; 10 % ( N = 10 ) received an intermediate dose of an antipsychotic , and 6 % ( N = 6 ) received a high dose . Overall , only 5 % ( N = 5 ) received a combination of an adequate dose of an antidepressant and a high dose of an  antipsychotic .  The strength of both antipsychotic trials ( p = .021 ) and combination trials ( p = .039 ) was significantly associated only with a longer duration of the current depressive episode . CONCLUSIONS These findings show a persisting low use of  antipsychotics  in the treatment of MD-Psy . Given the high morbidity rates associated with MD-Psy , it is important to continue to educate clinicians regarding its identification and treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00056472 OBJECTIVE Several evidence -based treatment guidelines for major depressive disorder ( MDD ) have been published . However , little is known about how recommendations for treatment are adhered to by patients in current usual psychiatric practice . METHOD The Vantaa Depression Study is a prospect i ve , naturalistic cohort study of 269 psychiatric patients with a new episode of DSM-IV MDD who were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and Structured Clinical Interview for DSM-III-R Personality Disorders between February 1 , 1997 , and May 31 , 1998 , and again at 6 and 18 months . Treatments provided , as well as adherence to and attitudes toward both antidepressants and psychotherapeutic support/psychotherapy , were investigated among the 198 unipolar patients followed for 18 months . RESULTS Most depression patients ( 88 % ) received antidepressants in the early acute phase , but about half ( 49 % ) terminated treatment prematurely . This premature termination was associated with worse outcome of major depressive episodes , and with negative attitudes , mainly explained by fear of dependence on or side effects of antidepressants . Nearly all patients ( 98 % ) received some  psychosocial treatment  in the acute phase ; about one fifth ( 16 % ) had weekly psychotherapy  during the follow-up . About a quarter of patients admitted nonadherence to ongoing treatments . CONCLUSION Problems of psychiatric care seem most related to continuity of treatment . While adequate treatments are provided in the early acute phase , antidepressants are terminated too soon in about half of patients , often following their autonomous decisions . From a secondary and tertiary preventive point of view , improving continuity of treatment would appear a crucial task for improving the outcome of psychiatric patients with MDD In this study , the authors examined prospect ively the 24-month natural course of remission from major depressive disorder ( MDD ) as a function of personality disorder ( PD ) comorbidity . In 302 participants ( 196 women , 106 men ) , psychiatric and PDs were assessed  at baseline with diagnostic interviews , and the course of MDD was assessed with the Longitudinal Interval Follow-Up Evaluation at 6- , 12- , and 24-month follow-ups .  Survival analyses revealed an overall 24-month remission rate of 73.5 % for MDD that differed little by gender . Participants with MDD who had certain forms of coexisting PD psychopathology ( schizotypal , borderline , or avoidant ) as their primary PD diagnoses had a significantly longer time to remission from MDD than did patients with MDD without any PD . These PDs emerged as robust predictors of slowed remission from MDD even when controlling for other negative prognostic predictors Objective : To examine a 1-year follow-up of a 4-month , controlled clinical trial of exercise and antidepressant medication in patients with major depressive disorder ( MDD ) . Methods : In the original study , 202 sedentary adults with MDD were r and omized to : a ) supervised exercise ; b ) home-based exercise ; c ) sertraline ; or d ) placebo pill . We examined two outcomes measured at 1-year follow-up ( i.e. , 16 months post r and omization ) : 1 ) continuous Hamilton Depression Rating Scale score ; and 2 ) MDD status ( depressed ; partial remission ; full remission ) in 172 available participants ( 85 % of the original cohort ) . Regression analyses were performed to examine the effects of treatment group assignment , as well as follow-up antidepressant medication use and self-reported exercise ( Godin Leisure-Time Exercise Question naire ) , on the two outcomes . Results : In the original study , patients receiving exercise achieved similar benefits compared with those receiving sertraline . At the time of the 1-year follow-up , rates of MDD remission increased from 46 % at post treatment to 66 % for participants available for follow-up . Neither initial treatment group assignment nor antidepressant medication use during the follow-up period were significant predictors of MDD remission at 1 year . However , regular exercise during the follow-up period predicted both Hamilton Depression Rating Scale scores and MDD diagnosis at 1 year . This relationship was curvilinear , with the association concentrated between 0 minute and 180 minutes of weekly exercise . Conclusion : The effects of aerobic exercise on MDD remission seem to be similar to sertraline after 4 months of treatment ; exercise during the follow-up period seems to extend the short-term benefits of exercise and may augment the benefits of antidepressant use . Trial Registration : clinical trials.gov Identifier : NCT00331305 . MDD = major depressive disorder ; HAM-D = Hamilton Depression Rating Scale ; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition Axis I Disorders ; PSSS = Perceived Social Support Scale OBJECTIVE To evaluate how the presence of a chronic painful physical condition ( CPPC ) lasting 6 months or more influences the frequency and severity of depressive symptoms in subjects with major depressive disorder ( MDD ) . METHOD R and om sample s of 18,980 subjects aged between 15 and 100 years who were representative of the general population of 5 European countries ( the United Kingdom , Germany , Italy , Portugal , and Spain ) were interviewed by telephone  between 1994 and 1999 . Subjects answered a series of questions that allowed positive and differential diagnosis of DSM-IV mental disorders . The question naire also included a series of questions about painful physical conditions , medical treatment , consultations , and hospitalizations for medical conditions and a list of diseases . RESULTS A total of 4 % ( 95 % CI = 3.7 % to 4.3 % ) of the sample had MDD at the time of the interview . Nearly half of subjects with MDD ( 43.4 % ) also reported having a CPPC . Compared with MDD subjects without chronic pain , MDD subjects with a CPPC had a longer duration of depressive symptoms ( 7 months longer ) and were more likely to report severe fatigue ( OR = 5.4 ) , insomnia nearly every night ( OR = 3.3 ) , severe psychomotor retardation ( OR = 3.3 ) , weight gain ( OR = 2.3 ) , severe difficulty concentrating ( OR = 1.7 ) , and severe feelings of sadness or depressed mood ( OR = 1.8 ) . CONCLUSION A CPPC was present in nearly half of subjects with MDD . CPPCs increased the severity of physical symptoms of depression ( fatigue , insomnia , psychomotor retardation , weight gain ) . Moreover , CPPCs affected the duration of depressive episodes and their recurrence . Physicians should consider CPPCs as a major factor in the expression and evolution of MDD . They must remember that MDD patients tend to amplify physical symptoms , to the detriment of their depressive symptomatology In order to estimate the prevalence of affective disorders in Hungary a sample of the Hungarian adult population ( 18 - 64 years ) selected at r and om was interviewed using the Diagnostic Interview Schedule ( DIS ) which generated DSM-III-R diagnoses . The lifetime rate for Major Depressive Disorder ( MDD ) was 15.1 % , and for Bipolar Disorders ( BD ) 5.1 % . The female-to-male ratio was 2.7 for MDD and nearly equal for BD . The 1-year and 1-month period prevalence rates were 7.1 % and 2.6 % for MDD and 0.9 % and 0.5 % for manic episodes . A higher rate of divorced or separated persons was found among individuals with a lifetime diagnosis of MDD . Besides these , the lifetime diagnosis of BD coexisted with higher rates of the never-married state . The highest hazard rate for the development of BD or MDD was in the range 15 - 19 years but in MDD another peak was also found in the range 45 - 50 years . The first peak was characteristic of the recurrent , and the other one of the single form of MDD . Insomnia , loss of energy , decreased interest , concentration problems were the most common symptoms during the depressive episode , independent of polarity . Higher rates of lifetime diagnosis of dysthymia and all kinds of anxiety disorder were revealed among persons with MDD . BD was associated with GAD ( Generalized Anxiety Disorder ) , and panic disorder more often than chance OBJECTIVE The present study investigates how consistently DSM-IV major depressive disorder ( MDD ) with psychosis was diagnosed by research consensus across 10 years and the association of clinical characteristics with diagnostic consistency . METHOD The sample included 146 participants , part of a larger first-admission cohort ( N = 628 ) presenting to a psychiatric inpatient facility with psychosis , who were diagnosed with psychotic depression at least once across 4 assessment s spanning 10 years ( after first admission and at 6-month , 24-month , and 10-year follow-ups ) . The primary outcome of this prospect i ve epidemiologic study was retention of the best-estimate consensus diagnosis at each assessment . Diagnoses at each assessment were determined from semistructured interviews , medical records , and informant reports . The participants were recruited from 1989 to 1995 . RESULTS Fifty-five of the 146 participants ( 37.7 % ) were diagnosed with psychotic depression at each available assessment ; 13 ( 8.9 % ) switched from MDD to bipolar disorder , 24 ( 16.4 % ) switched from MDD to schizophrenia or schizoaffective disorder , and the remaining 54 ( 37.0 % ) had other patterns of diagnostic change . Only 47 of 80 participants ( 58.8 % ) diagnosed with MDD at baseline retained a mood disorder diagnosis 10 years later ( 36 [ 45.0 % ] had MDD and 11 [ 13.8 % ] had bipolar disorder ) , while 16 of 52 participants ( 30.8 % ) who ended the study with MDD were initially misdiagnosed . Compared to participants who were consistently diagnosed with MDD , those switching from MDD to bipolar disorder had better premorbid adjustment , more first-degree relatives with MDD , better functioning , and fewer negative symptoms at baseline , whereas those shifting to the schizophrenia spectrum had a more insidious onset , longer initial hospital stays , worse functioning , and more negative symptoms ( all P values < .05 ) . CONCLUSIONS The diagnosis of MDD with psychosis among in patients showed poor long-term consistency . For clinicians , results indicate that the diagnosis of MDD with psychosis based on a single assessment should be considered provisional BACKGROUND Major depressive disorder ( MDD ) is a common , chronic illness associated with substantial disability and economic burden . Although a number of effective antidepressants are available , the need for new medications that are effective and well tolerated remains . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/d with placebo for MDD . A post hoc pooled analysis was conducted to evaluate this study in the context of all similarly design ed , completed studies with the 2 doses . METHODS This was an 8-week , Phase III , r and omized , double-blind , duloxetine-referenced , placebo-controlled , parallel-group trial conducted in 21 centers across the United States .  Duloxetine was included for assay sensitivity as a positive control ; the study was not design ed or powered to compare desvenlafaxine with duloxetine .  Participants were out patients aged > or = 18 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition-defined MDD and a 17-item Hamilton Rating Scale for Depression ( HAM-D(17 ) ) score > or = 20 . Patients were r and omly assigned at baseline to fixed-dose desvenlafaxine ( 50 or 100 mg/d ) , fixed-dose duloxetine ( 60 mg/d ) , or placebo . The primary outcome measure was HAM-D(17 ) total score at the final evaluation . Additional measures included the Clinical Global Impressions-Improvement ( CGI-I ) score , Montgomery Asberg Depression Rating Scale ( MADRS ) score , Clinical Global Impressions-Severity ( CGI-S ) score , and 6-item Hamilton Rating Scale for Depression , Bech version ( HAM-D(6 ) ) . Tolerability assessment s included discontinuation rates , adverse events ( AEs ) , vital signs , and laboratory tests . The post hoc pooled analysis was performed using data from the current study and 2 previously published , positive studies that compared the efficacy and tolerability of desvenlafaxine 50 and 100 mg/d with placebo for MDD . The design and method ologies of the 2 studies were similar to the methodology of the current trial , other than not including a reference compound . RESULTS Of the 925 patients who were screened , 287 did not meet entry criteria , and 638 patients enrolled in the study ; the intent-to-treat ( ITT ) population included 615 patients who were evaluated for efficacy ( mean [ SD ] age range , 38.8 - 40.7 [ 12.1 - 13.2 ] years ; mean weight range , 83.3 - 87.0 [ 22.8 - 23.9 ] kg ; female sex , 398 [ 64.7 % ] ; white race , 458 [ 74.5 % ] ) . The primary end point did not reach significance based on the global F test for controlling multiplicity of the desvenlafaxine doses . Based on pairwise comparison , significantly greater improvements on the HAM-D(17 ) were observed in the desven-lafaxine 100 mg/d ( -10.5 ; P = 0.028 , unadjusted for multiple comparisons ) and duloxetine 60 mg/d groups ( -10.3 ; P = 0.047 ) compared with placebo ( -8.7 ) . Desvenlafaxine 100 mg/d and duloxetine 60 mg/d were associated with significantly better scores compared with placebo on the CGI-I , MADRS , CGI-S , and HAM-D(6 ) . No significant differences were observed in any scale between the desvenlafaxine 50 mg/d and placebo groups . Discontinuation rates due to AEs were 5 % , 7 % , 13 % , and 6 % for the desvenlafaxine 50-mg/d , desvenlafaxine 100-mg/d , duloxetine 60-mg/d , and placebo groups , respectively . The ITT population from all 3 studies in the pooled analysis consisted of 1388 patients ( mean [ SD ] age range , 38.8 - 45.7 [ 12.1 - 12.6 ] years ; mean weight range , 73.1 - 87.0 [ 17.6 - 23.9 ] kg ; female sex , 896 [ 64.6 % ] ; white race , 1136 [ 81.8 % ] ) . Significantly greater improvements on the HAM-D(17 ) were observed for desvenlafaxine 50 mg/d ( -11.5 ; P < 0.001 ) and 100 mg/d ( -11.8 ; P < 0.001 ) versus placebo ( -9.6 ) . Both doses were significantly better than placebo on the CGI-I , MADRS , and HAM-D(6 ) . CONCLUSIONS The current study failed to meet its primary efficacy end point based on the a priori analysis plan . Desvenlafaxine was generally well tolerated . A post hoc pooled analysis of this trial and 2 previously published trials with both desvenlafaxine 50 and 100 mg/d found both doses to be effective for MDD compared with placebo . Clinical Trials.gov Identifier : 00384033 Objective : To assess whether patients receiving aerobic exercise training  performed either at home or in a supervised group setting achieve reductions in depression comparable to st and ard antidepressant medication ( sertraline ) and greater reductions in depression compared to placebo controls . Methods : Between October 2000 and November 2005 , we performed a prospect i ve , r and omized controlled trial ( SMILE study ) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital . A total of 202 adults ( 153 women ; 49 men ) diagnosed with major depression were assigned r and omly to one of four conditions : supervised exercise in a group setting ; home-based exercise ; antidepressant medication ( sertraline , 50–200 mg daily ) ; or placebo pill for 16 weeks . Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale ( HAM-D ) . Results : After 4 months of treatment , 41 % of the participants achieved remission , defined as no longer meeting the criteria for major depressive disorder ( MDD ) and a HAM-D score of < 8 . Patients receiving active treatments tended to have higher remission rates than the placebo controls : supervised exercise = 45 % ; home-based exercise = 40 % ; medication = 47 % ; placebo = 31 % ( p = .057 ) . All treatment groups had lower HAM-D scores after treatment ; scores for the active treatment groups were not significantly different from the placebo group ( p = .23 ) . Conclusions : The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD . Placebo response rates were high , suggesting that a considerable portion of the therapeutic response is determined by patient expectations , ongoing symptom monitoring , attention , and other nonspecific factors . BDI = Beck Depression Inventory ; CI = confidence interval ; HAM-D = Hamilton Depression Rating Scale ; ITT = intention-to-treat ; MDD = major depressive disorder ; SD = st and ard deviation ; SSRIs = selective serotonin reuptake inhibitors ; TSH = thyroid stimulating hormone In r and omized controlled trials , maintenance treatment for relapse prevention has been proven to be efficacious in patients responding in acute treatment , its efficacy in long-term outcome in “ real-world patients ” has yet to be proven . Three-year long-term data from a large naturalistic multisite follow-up were presented . Severe relapse was defined as suicide , severe suicide attempt , or rehospitalization . Next to relapse rates , possible risk factors including antidepressant medication were identified using univariate generalized log-rank tests and multivariate Cox proportional hazards model for time to severe relapse . Overall data of 458 patients were available for analysis . Of all patients , 155 ( 33.6 % ) experienced at least one severe relapse during the 3-year follow-up . The following variables were associated with a shorter time to a severe relapse in univariate and multivariate analyses : multiple hospitalizations , presence of avoidant personality disorder , continuing antipsychotic medication  , and no further antidepressant treatment . In comparison with other studies , the observed rate of severe relapse during 3-year period is rather low . This is one of the first reports demonstrating a beneficial effect of long-term antidepressant medication on severe relapse rates in naturalistic patients . Concomitant antipsychotic medication may be a proxy marker for treatment resistant and psychotic depression CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result Purpose To examine the natural course and outcome of major depressive disorder ( MDD ) in primary care over 39 months . Methods Prospect i ve cohort study of 1,338 consecutive attendees with follow-up after 6 , 12 , and 39 months with DSM-IV MDD using the Composite International Diagnostic Interview ( CIDI ) . We measured severity of depressive symptoms  ( Patient Health Question naire 9 )  , somatic symptoms ( Patient Health Question naire  15 ) , and mental and physical function ( Short Form 12 , mental and physical component summary ) . Analysis of variance and r and om coefficient models were performed . Results At baseline , 174 people ( 13 % ) had MDD of which 17 % had a chronic and 40 % had a fluctuating course , while 43 % remitted . Patients with chronic courses had more severe depressive symptoms ( mean difference 6.54 ; 95 % CI 4.38–8.70 ) , somatic symptoms ( mean difference 3.31 ; 95 % CI 1.61–5.02 ) , and greater mental dysfunction ( mean difference −10.49 ; 95 % CI −14.42 to −6.57 ) at baseline than those who remitted from baseline , independent of age , sex , level of education , presence of a chronic disease , and a lifetime history of depression . Conclusions Although 43 % of patients with MDD attending primary care recover , this leaves a majority of patients ( 57 % ) who have a chronic or intermittent course . Chronic courses are associated with higher levels of depressive symptoms and somatic symptoms and greater mental dysfunction at baseline 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 BACKGROUND With a lifetime risk for major depressive disorder of up to 50 % , depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated . We investigated the potential of a fully automated , internet-based , cognitive behavioural therapy programme , Deprexis , to reduce depressive symptoms in patients with multiple sclerosis . METHODS For this r and omised controlled trial , we recruited patients from an outpatient clinic in Hamburg , Germany . Patients aged 18 - 65 years were eligible for inclusion if they had multiple sclerosis and self-reported depressive symptoms . By use of a computer-generated r and omisation sequence , we allocated 90 patients ( 1:1 ; no blocking or stratification ) to either the intervention group or a waitlist control group for 9 weeks . The primary endpoint was the Beck Depression Inventory ( BDI ) , as assessed by an intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT01663649 . FINDINGS 71 patients completed the trial : 35 patients in the intervention group and 36 patients in the control group . During the intervention , BDI scores decreased in the Deprexis group and increased in the control group , yielding a positive effect of Deprexis relative to the waitlist group ( mean group difference -4·02 points [ 95 % CI -7·26 to -0·79 ] , p=0·015 , effect size d=0·53 ) . Worsening of depressive symptoms from below to above the clinical cutoff ( BDI > 13 ) occurred in three ( 7 % ) of 45 patients in the control group and no patients in the Deprexis group . We noted no adverse events with respect to new occurrence of suicidal ideation during the trial . INTERPRETATION Psychological online-intervention programmes could be suitable for patients with multiple sclerosis who are unable to regularly attend therapeutic sessions because of mobility impairments . FUNDING European Union and the Deutsche Forschungsgemeinschaft BACKGROUND Major depressive disorder ( MDD ) is a significant cause of worldwide disability and treatment resistance is common . High-frequency repetitive transcranial magnetic stimulation ( HF-rTMS ) has emerged as a treatment for MDD , and while efficacious , the daily commitment for typical 4 - 6 weeks of treatment poses a significant challenge . We aim ed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD . METHODS In this naturalistic trial , 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS ( 10 Hz ) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks ( 60,000 pulses ) . The primary outcomes were rates of clinical remission and response ( 16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6 , and ≥ 50 % reduction , respectively ) . Secondary outcomes were self-reported anxious symptoms , depressive symptoms and quality of life , and dropout rates as a proxy for acceptability . RESULTS Ten ( 37.0 % ) patients met criteria for clinical remission and 15 ( 55.6 % ) were classified as responders , with comparable outcomes for both moderate and severe MDD . Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms , as well as quality of life . No patient discontinued treatment . LIMITATIONS This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness , limited duration of follow-up , small sample size , and an open-label design requiring r and omized controlled replication . CONCLUSION An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD , and had excellent acceptability . Additional research is required to optimize accelerated rTMS treatment protocol s and determine efficacy using sham-controlled trials BACKGROUND Major depressive disorder ( MDD ) is a common and debilitating illness in patients with cancer . However , the optimal treatment of depression in these patients remains uncertain , with limited evidence to support the use of pharmacologic therapy . We conducted a pilot study to evaluate the feasibility of an antidepressant clinical trial in the oncology population and the process of symptom-oriented selection of antidepressants ( citalopram or mirtazapine ) in patients with cancer and MDD . METHODS This was a single center , two-arm , nonr and omized , open-label , nine-week pilot study of mirtazapine or citalopram in cancer patients with MDD . The primary endpoint was the feasibility to recruit and to retain patients . Secondary outcomes included changes in Patient Health Question naire-9 ( PHQ-9 ) ( depression ) , Functional Assessment of Cancer Therapy-General ( FACT-G ) ( quality of life ) , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) ( fatigue ) , and Pittsburgh Sleep Quality Index ( PSQI ) ( sleep ) . We conducted descriptive statistics and responder analyses . RESULTS Of 21 patients , 18 ( 86 % ) successfully completed the study . An average of 2.8 subjects were enrolled per month . Mean scores on the PHQ-9 improved overall by 6.4 points ( 95 % confidence interval [ CI ] 3.6 - 9.2 ) . Additionally , mean FACT-G , FACIT-Fatigue , and PSQI scores improved in both study arms . CONCLUSION Conducting antidepressant clinical trials is challenging in the oncology population . We approached but did not meet our feasibility goals . Depression and quality of life ( QOL ) scores improved with both mirtazapine and citalopram , but evidence -based pharmacologic treatments for depression in cancer patients are needed
There were some beneficial effects compared to placebo or antidepressants but tolerability was worse .
Quetiapine was more effective than placebo treatment .
Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo .
Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people .
Most SGAs showed worse tolerability
BACKGROUND Major depressive disorder ( MDD ) is a common condition with a lifetime prevalence of 15 % to 18 % , which leads to considerable suffering and disability .
Some antipsychotics have been reported to induce remission in major depression , when added to an antidepressant .
OBJECTIVES To evaluate the effects of second-generation antipsychotic ( SGA ) drugs ( alone or augmentation ) compared with placebo or antidepressants for people with MDD or dysthymia .