Response to 4-month treatment with reboxetine in Parkinson's disease patients with a major depressive episode

OBJECTIVE: The aim of this study is to evaluate response to reboxetine in a 4-month follow-up study on depression in Parkinson's disease (PD), and to assess its tolerability profile. METHODS: A prospective 4-month follow-up study was performed in 17 PD patients with a major depressive episode. The intensity of depressive symptoms was evaluated mainly with the Hamilton Rating Scale for Depression (HAM-D), and PD was assessed with the Unified Parkinson Disease Rating Scale (UPDRS). RESULTS: Reboxetine causes a progressive decrease in depressive symptoms in PD patients; the initial score of 16.76 (2.68) on HAM-D decreased to 5.85 (2.42) at 4 months (P < .002). Mean UPDRS scores did not show a statistically significant increase: 18.18 (2.6) at the beginning and 18.25 (2.4) at the end of the follow-up period (P = .8). CONCLUSIONS: Reboxetine, as first choice treatment for major depressive episodes in PD patients, seems to be effective in progressively improving depressive symptoms over the first 4 months of treatment until complete remission. Reboxetine does not seem to increase PD symptoms, whereas patients' quality of life improves.     

Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder

Aims: The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode. Methods: A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables. Results: Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI. Conclusion: Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.     

Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression

BACKGROUND: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) are effective when used alone in the treatment of unipolar depression with psychotic features. The purpose of the present study was to examine the response to sertraline for patients with and without psychotic features using standard criteria such as recovery and remission. METHOD: An 8-week open-label trial of sertraline in depressed inpatients was conducted. Twenty-five subjects had DSM-IV major depressive disorder with psychotic features, and 25 had DSM-IV major depressive disorder without psychotic features. After a 1-week open washout, all subjects were rated using the Hamilton Rating Scale for Depression (HAM-D) and Brief Psychiatric Rating Scale (BPRS) at baseline. The HAM-D was administered weekly, and the BPRS was administered again only at the end of the 8-week trial. Medication dosage was started at 50 mg/day, increased to 100 mg/day after 1 week, and then increased up to 200 mg/day if subjects had not remitted. RESULTS: Depressed patients without psychosis responded significantly better than did depressed patients with psychosis using the criteria of remission (HAM-D score - 7; p =.001), response (HAM-D score - 50% of baseline score; p =.011), referral for electroconvulsive therapy (HAM-D score >/= 15; p =.011), or change in HAM-D scores (p =.016). Baseline HAM-D score and psychosis independently predicted response, whereas baseline BPRS scores did not, regardless of whether psychotic status was entered into the analyses. CONCLUSION: Psychotic depression responds more poorly than depression without psychosis to sertraline alone. Psychosis was a predictor of response independent of degree of depression and general psychopathology. Limitations due to an open-label design are discussed, as are differences between this study and others using SSRIs for psychotic depression.     

Predictors for the efficacy of electroconvulsive therapy: chart review of a naturalistic study

BACKGROUND: Several variables have been suggested that can predict the efficacy of electro-convulsive therapy (ECT) in patients suffering from depression. The results of studies into these predictors for ECT efficacy are not consistent. METHOD: In a retrospective chart review of patients suffering from major depressive disorder and bipolar disorder according to DSM-IV criteria who have been given ECT in a psychiatric hospital in the Netherlands, predictors for ECT efficacy were explored. Information was gathered for predictors including sex, age, diagnosis, presence of psychosis, duration of index episode, medication treatment failure prior to ECT, medication during ECT course, and ECT variables. ECT was given twice weekly from November 1997 to June 2002. The 17-item Hamilton Rating Scale for Depression (HAM-D) was applied at baseline and weekly during the course. RESULTS: Seventy-three patients suffering from unipolar or bipolar depression were given ECT in the study period, with 56 patients (77%) meeting antidepressant treatment history form criteria for medication treatment failure. With remission defined as a reduction of depressive symptoms of at least 60% from baseline and a HAM-D end score of less than 8, 48 patients (65.8%) remitted. Forward stepwise logistic regression analysis selected only duration of index episode as a significant predictor for ECT efficacy. Medication treatment failure was not found to be a significant predictor. The concurrent use of psychotropic medication during ECT did not influence the efficacy. CONCLUSION: Duration of index episode was the only variable found to significantly predict the efficacy of ECT.     

Subsyndromal depression is associated with functional impairment in patients with bipolar disorder

BACKGROUND: The purpose of this study was to assess whether a relationship exists between mild depressive symptoms and overall functioning in subjects with bipolar disorder. METHOD: Twenty-five male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined using the Structured Clinical Interview for DSM-III-R, were evaluated for degree of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis V). RESULTS: GAF scores were significantly negatively correlated with HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a HAM-D score high enough to be considered clinically depressed. CONCLUSION: The results of this study support a relationship between subsyndromal depressive symptoms and functional impairment in bipolar subjects, despite their not meeting threshold criteria for a major depressive episode. These findings raise the possibility that in some patients with bipolar disorder subsyndromal depressive symptoms might contribute to ongoing functional impairment.     

Differences between minimally depressed patients who do and do not consider themselves to be in remission

OBJECTIVE: We recently derived a cutoff on a self-report scale corresponding to the most commonly used definition of remission in depression treatment studies (i.e., Hamilton Rating Scale for Depression [HAM-D] score < or = 7). However, recent research has suggested that use of this cutoff on the HAM-D to define remission is overinclusive. The goal of the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project was to examine how many depressed patients in ongoing treatment who are considered to be in remission by a self-report equivalent of the HAM-D definition of remission nonetheless do not consider themselves to be in remission. METHOD: Five hundred thirty-five psychiatric outpatients treated for a DSM-IV major depressive episode were asked whether they considered themselves to be in remission and completed the Clinically Useful Depression Outcome Scale (CUDOS), a measure of the severity of the DSM-IV symptoms of depression. The study was conducted from August 2003 until July 2004. RESULTS: Nearly one quarter of the patients who met the remission threshold on the CUDOS (55/249) did not consider themselves to be in remission. Among the CUDOS remitters, the total score on the CUDOS was significantly lower (p < .001) in patients who considered themselves to be in remission than in patients who did not indicate that they were in remission. Examination of specific symptoms revealed greater appetite disturbance and hypersomnia in the patients who did not think they were in remission. CONCLUSIONS: Our results suggest that heterogeneity of clinical status exists even among patients who are minimally depressed and considered to be in remission according to contemporary definitions on symptom severity scales.     

Predictors of remission after electroconvulsive therapy in unipolar major depression

CONTEXT: Electroconvulsive therapy (ECT) is the most effective biological treatment for major depression. However, there is little agreement about clinically useful predictors of acute ECT outcomes. OBJECTIVE: To assess whether age, sex, burden of comorbid physical illness, age at onset, history of recurrence, episode duration, chronic depression or comorbid dysthymia, melancholic features, episode severity, and medication resistance are predictors of remission after an acute course of ECT. DESIGN: We performed an analysis using data gathered prospectively in 328 patients with unipolar major depression (according to Research Diagnostic Criteria) treated with ECT. The study was conducted from 1993 through 1999. Patients had a pretreatment score of 21 or higher on the 24-item Hamilton Rating Scale for Depression (HAM-D). Treatment history was assessed using the Antidepressant Treatment History Form. Remission was defined as a 24-item HAM-D score of 10 or less and a 60% or more relative reduction of the HAM-D score. RESULTS: On univariate logistic regression, statistically significant predictors of nonremission were chronic depression/dysthymia, medication resistance, longer episode duration, and younger age. On backward elimination logistic regression, only medication resistance (OR = 1.67, 95% CI = 1.05 to 2.67) and chronic depression/ dysthymia (OR = 1.84, 95% CI = 1.06 to 3.21) were statistically significant predictors of nonremission. CONCLUSIONS: In patients with major depression, lower rates of remission after acute ECT are associated with medication resistance and chronicity, but not with age or burden of physical illness.     

Positive correlation between anxiety severity and plasma levels of dehydroepiandrosterone sulfate in medication-free patients experiencing a major episode of depression

Although numerous studies have identified a correlation between dehydroepiandrosterone sulfate (DHEAS) levels and anxiety or depression, those findings remain controversial. The purpose of the present study was to determine whether a correlation exists between depression severity and anxiety severity and serum DHEAS concentrations in medication-free patients experiencing a major depressive episode. Twenty-eight medication-free major depressive outpatients (Hamilton Rating Scale for Depression 17 [HAM-D 17] score >or=17) were enrolled consecutively. Plasma DHEAS levels of all subjects were measured. Blood from subjects was drawn at 0900-1100 h Depression severity was assessed with the HAM-D 17 and the Hospital Anxiety and Depression Scale (HADS) depression subscale. Anxiety was assessed using the HADS anxiety subscale. Serum concentrations of DHEAS were measured immediately following the HAM-D 17 and HADS assessments. A significant, positive correlation was identified between HADS anxiety subscale total score and morning serum DHEAS concentration (P = 0.013) after controlling for age, gender and body mass index (BMI). No statistically significant correlations were found between depression ratings and morning serum DHEAS concentrations. This preliminary study provides pilot data indicating that morning serum DHEAS concentrations were positively correlated with HADS anxiety subscale score (anxiety severity) after controlling for age, gender and BMI in medication-free outpatients experiencing a major depressive episode. It is not known if morning serum DHEAS levels would show similar or dissimilar changes in non-depressed subjects. The present result needs subsequent replication.     

Pharmacotherapy plus psychotherapy for treatment of depression in active injection drug users

CONTEXT: Depressive disorders are common among opiate abusers and are associated with detrimental behavioral effects. However, there is little precedent for offering active drug users complex treatments for depression. OBJECTIVE: To determine whether combined psychotherapy and pharmacotherapy treatment reduces reported depressive symptoms compared with an assessment-only condition among out-of-treatment drug injectors. DESIGN: Randomized controlled trial. SETTING: Research office located at an academic medical center. PATIENTS: Active injection drug users with a DSM-IV diagnosis of major depression, dysthymia, substance-induced mood disorder with symptoms persisting for at least 3 months, or major depression plus dysthymia, and a Modified Hamilton Rating Scale for Depression (HAM-D) score greater than 13. INTERVENTION: Combined psychotherapy (8 sessions of cognitive behavior therapy) plus pharmacotherapy (citalopram). MAIN OUTCOME MEASURES: Modified HAM-D scale scores at the end of 3 months of combined treatment. RESULTS: The 109 study subjects were 64% male and had a mean age of 36.7 years and a mean baseline HAM-D score of 20.7. Depression subtypes included major depression only (63%), substance-induced depression (17%), and major depression plus dysthymia (17%). In the intent-to-treat analysis, participants in treatment averaged 2.11 HAM-D points greater improvement than control subjects (P=.08), and 26.1% of combined treatment patients (n=53) compared with 12.5% of control patients (n=56) were in remission (P=.047). Nearly 40% of fully adherent subjects (receiving >75% of either psychotherapy or pharmacotherapy) were in remission at follow-up (odds ratio, 3.6; P=.04). CONCLUSIONS: Combined treatment for depression is significantly superior to a control condition (assessment only) in proportion of patients in remission, but not in HAM-D improvement among drug injectors. Full adherence to treatment is associated with the largest treatment effects. Our findings demonstrate that active drug users with dual diagnoses are able to participate in conventional treatment.     

Symptomatic recovery and social functioning in major depression

OBJECTIVE: To determine whether social functional recovery precedes, runs in parallel with, or lags behind symptomatic recovery from major depressive episodes. METHOD: Psychiatric out-patients or in-patients aged 18 years or over, diagnosed with unipolar major depressive disorder according to DSM-IV, and who had received no antidepressant medication in the preceding 3 months were identified at 23 collaborating centres from all over Japan (n=95). They were rated with the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment Scale (GAS) monthly, and with the Social Adjustment Scale-Self Report (SAS-SR) 6-monthly. Remission was defined as 7 or less on the HRSD and recovery as 2 or more consecutive months of remission. RESULTS: The GAS ratings showed continuous amelioration from baseline to remission, remission to recovery, and after sustained recovery. The same trends were observed for SAS-SR scores. CONCLUSION: We can expect further amelioration in social adjustment after symptomatic remission and recovery of major depressive episodes.     

Residual symptoms in bipolar disorder: the effect of the last episode after remission

In this study it is aimed to assess interepisode residual symptoms in remitted bipolar disorder patients with a hypothesis that the last episode recovered has implications on residual symptomatology. The study was carried out with 23 bipolar patients diagnosed as mania (BP-M) and 20 bipolar patients diagnosed as depression (BP-D) in their last episode, and with 22 healthy controls in a university hospital clinic. All patients were in remission for at least 6 months. In the assessment Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Stroop Test, Auditory Verbal Learning Test (AVLT), increased latency positive-evoked potentials (P300), Global Assessment of Functioning Scale (GAF), and Social Functioning Scale (SFS) were used cross-sectionally. In affective symptomatology, the BP-M group had higher YMRS scores, and the BP-D group had higher HAM-D scores compared to the controls. P300 test results revealed low amplitude in the BP-D group. In the AVLT, verbal learning and delayed recall were significantly lower in the two bipolar groups. The Stroop tasks were not different in the groups. Concerning the SFS, social withdrawal was impaired in the two bipolar groups, whereas dependency-competency was impaired in the BP-M and employment/occupation was impaired in the BP-D group. As a conclusion, bipolar patients recovering from depressive episode may experience more impairment in daily functioning due to residual depressive symptoms and impairment of attention and memory.     

艾司西酞普兰治疗抑郁症伴焦虑的疗效分析

目的评价国产艾司西酞普兰片治疗抑郁症伴焦虑的疗效及安全性。方法本研究为6周的多中心开放性研究,共入组符合CCMD-3诊断标准的抑郁症(同时HAMD≥17分、HAMA≥14分)患者173例,服用国产艾司西酞普兰片的剂量为10mg-20mg/d,分别在治疗前及第1、2、4、6周末以汉密尔顿抑郁量表17项(HAMD)、汉密尔顿焦虑量表(HAMA)和临床总体印象量表CGI(包括病情严重程度评分CGI-SI、疗效评分CGI-GI)评定疗效,以不良事件记录表、体格检查、实验室检查评估用药安全性。结果共169例患者完成研究,经6周治疗后显示,HAMD、HAMA、CGI-SI评分呈现一致的减分趋势,各时点HAMD-17、HAMA、CGI-SI的总分与治疗前比较,差异均有显著性(P<0.05),总体有效率为81.1%、痊愈率是63.9%。不良反应发生率为10.06%,一般可以耐受。结论国产艾司西酞普兰片治疗抗抑郁及焦虑作用确切,可用于治疗抑郁症伴焦虑障碍。     

重度抑郁症症状缓解前后海马局部一致性研究

目的观察静息态下发作期重度抑郁症患者的海马功能,以及其在抗抑郁药物治疗达临床痊愈后的变化。方法对20例24项汉密尔顿抑郁量表(HAMD24)总分35分的重度抑郁症患者在治疗前、治疗8周达临床痊愈(HAMD24减分率≥75%)后进行静息态fMRI扫描,以性别、年龄、受教育程度匹配的20名正常人做对照组。采用局部一致性(regional homogeneity,ReHo)作为海马功能的测量指标。结果治疗前患者组较正常对照组左海马ReHo值增高,差异具有统计学意义(P0.05);但患者组治疗前与治疗后、治疗后与正常对照组的左海马ReHo值的差异均无统计学意义(P0.05)。患者组治疗前、治疗后、正常对照组中每两组间右海马ReHo值的差异均无统计学意义(P0.05)。结论重度抑郁症患者海马功能受损,存在侧化现象,经短期系统的抗抑郁药物治疗达临床痊愈后,这种损伤未见有效逆转。     

Subjective quality of life in first episode schizophrenia spectrum disorders with comorbid depression

Previous studies have reported high prevalence rates of depressive symptoms or syndromes in subjects with first episode psychosis, but data are lacking on the quality of life (QOL) in these subjects. This cross-sectional study seeks to compare the subjective QOL of these individuals with and without a comorbid depressive syndrome at baseline. Using the Structured Clinical Interview to Diagnose DSM IV-Axis I Disorders, the Scale to Assess Unawareness of Mental Disorders (SUMD), Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAM-D), and the World Health Organization Quality of Life-Bref Scale (WHOQOL-BREF), we evaluated 66 consecutive subjects with first episode schizophrenia spectrum disorders (schizophrenia, schizoaffective and schizophreniform disorders) in our Early Psychosis Intervention Program. We found that subjects with a comorbid depressive syndrome had greater awareness of their mental illness, its social consequences and treatment efficacy, but poorer overall QOL, especially in the physical, psychological health, social relationships and environmental domains. The poorer QOL in subjects with a comorbid depressive syndrome may be explained by the greater degree of insight in these patients and their attributing their troubles to poor health, unsatisfactory social support and negative environment. Alternative explanations are also possible, providing possible foci for psychological support and intervention.     

Partial remission in major depression: a two-phase, 12-month prospective study

We conducted an interview-based survey to predict the clinical course of major depressive disorder during a follow-up period of 12 months. Altogether 86 patients were investigated. A SCID I interview for DSM-III-R axis-I diagnosis was conducted at baseline and a SCID II interview for personality disorders at the 6-month follow-up. Beck Depression Inventory scores indicated the level of depression and were compiled at baseline and at 6 and 12 months. A BDI score between 9 and 14 was considered to indicate partial remission, and score of 0-8 indicated remission. At the 6-month assessment 33% of the patients had remission, 20% were in partial remission, and 47% were in the depressive phase. Older age, personality disorder, and alexithymia were associated with poor response at 6 months. At 12 months 37% had remission, 28% were in partial remission, and 35% were still in the depressive phase. Treatment at the early stage should be effective enough to achieve remission. If the response is not satisfactory within 6 months, a renewed search should be conducted for factors hindering recovery. Comorbid personality disorder is the main factor predicting a poor short-term response in major depressive disorder.     

The impact of medical comorbidity on acute treatment in major depressive disorder

OBJECTIVE: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (>/=50% reduction in score) and clinical remission (score 相似文献   

Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder

BACKGROUND: A subset of patients with comorbid major depressive disorder and generalized anxiety disorder (GAD) was examined from a double-blind. placebo-controlled study comparing the efficacy and safety of venlafaxine extended release (XR) and fluoxetine. METHOD: From a total of 368 patients, 92 patients meeting DSM-IV criteria for major depressive disorder who also had comorbid GAD were identified. The comparison group comprised 276 evaluable noncomorbid patients. Patients received venlafaxine XR (75-225 mg/day), fluoxetine (20-60 mg/day), or placebo for 12 weeks. Efficacy evaluations included Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions (CGI) scale. RESULTS: By the final assessment at week 12, comorbid patients in the venlafaxine XR group, but not in the fluoxetine group, showed a significantly greater decrease than those in the placebo group in the primary efficacy variables of mean HAM-D and HAM-A total scores (p < .05, pairwise comparison). In comorbid patients, significant pairwise differences were noted between venlafaxine XR and placebo at week 12 for the secondary variables of HAM-D anxiety-somatization and retardation factors, HAM-D depressed mood item. HAM-A psychic anxiety factor, the Hospital Anxiety and Depression scale (HAD) anxiety subscale score, and the Covi Anxiety Scale score. Fluoxetine was significantly different from placebo only on the HAD depression subscale score. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Onset of efficacy appeared to be slower in comorbid than in noncomorbid patients. CONCLUSION: This is the first evidence from a controlled study of the effectiveness of pharmacotherapy in patients with comorbid major depressive disorder and GAD. The delayed improvement in comorbid patients compared with noncomorbid patients suggests that a longer treatment period may be necessary in comorbid patients.     

Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression

Objectives:  The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects.
Methods:  Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day.
Results:  All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: F  =   22.36, p < 0.0001; F  =   12.66, p < 0.0001; and F  =   10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of ≥50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score ≤ 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: F  =   0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment.
Conclusions:  Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.     

Beneficial effect of pramipexole for motor function and depression in Parkinson’s disease

We examined whether pramipexole (PPX) can influence depressive scale in normal and mild depressive parkinsonian patients. In an open study of PPX as an add-on to L-dopa therapy or single administration, 36 nondemented outpatients with Parkinson’s disease (PD) were entered first. All were in the stage II or III of Hoehn and Yahr scale (H&Y). PPX were started at 0.125 mg/day and daily doses were increased to 1.5 mg/day. At 3 months after PPX treatment, patients were re-evaluated. Hamilton Depression Rating Scale (HAM-D), Unified Parkinson’s Disease Rating Scale III, H&Y stage, and freezing of gait questionnaire were compared in patients before and after PPX treatment. These scores were significantly improved after PPX administration. There were no correlations between HAM-D and those motor functions. We suggest that PPX treatment has antidepressant effects in depressive PD patients and also ameliorates HAM-D score in nondepressive PD patients in addition to motor function.     

Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial

BACKGROUND/OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been mainly studied as adjunctive treatment for drug-resistant patients. We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients. We also evaluated if, among the 3 antidepressants administered, one had a better synergy with rTMS. METHOD: In this 5-week, double-blind, randomized, sham-controlled study, we recruited 99 inpatients suffering from a major depressive episode (DSM-IV criteria). They were randomly assigned to receive venlafaxine, sertraline, or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were gathered from February 2004 to June 2005. RESULTS: The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D) scores compared with the sham group (p = .0029). The response and remission rates were significantly greater in the active rTMS group after the stimulation period (p = .002 and p = .003, respectively), but not at the endpoint. We found no significant difference in HAM-D score reduction among the 3 drugs administered, either in the active or in the sham group. CONCLUSION: These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder. The effect of rTMS seems to be unaffected by the specific concomitantly administered drug.