Reduction In Hamilton Rating Scale For Depression Score Research Articles

What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol

ObjectiveReanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and related publications.DesignThe study was open label and...

A randomized, double-blind, placebo-controlled proof-of-concept study of ondansetron for bipolar and related disorders and alcohol use disorder

Bipolar disorder is associated with high rates of alcohol use disorder. However, little is known about the treatment of this dual diagnosis population. Previous studies suggest that ondansetron decreases alcohol use, particularly in people with specific single nucleotide polymorphism (SNP) alleles. A 12-week, randomized, double-blind, placebo-controlled trial of ondansetron was conducted in 70 outpatients with bipolar spectrum disorders and early onset alcohol use disorder. Outcome measures included alcohol use, assessed with the Timeline Followback method, Penn Alcohol Craving Scale (PACS), Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology–Self-report, and Young Mania Rating Scale. SNPs rs1042173, rs1176713 and rs1150226 were explored as predictors of response. Participants had a mean age of 44.9 ± 9.4 years, were mostly men (60.0%), and African American (51.4%). Mean ondansetron exit dose was 3.23 ± 2.64 mg. No significant between-group differences in alcohol use measures were observed. However, a significant reduction in HRSD scores was observed (p = 0.045). Inclusion of SNPs increased effect sizes for some alcohol-related outcomes and the HRSD. Ondansetron was well tolerated. This proof-of-concept study is the first report on ondansetron in bipolar people with bipolar disorders and alcohol use disorder. Alcohol use did not demonstrate a significant between-group difference. However, the findings suggest that ondansetron may be associated with reduction in depressive symptom severity in persons with bipolar illnesses and alcohol use disorder. A larger trial is needed to examine the effects of ondansetron on bipolar depression.

Percutaneous mastoid electrical stimulator improves Poststroke depression and cognitive function in patients with Ischaemic stroke: a prospective, randomized, double-blind, and sham-controlled study

BackgroundPoststroke depression can lead to functional dependence, cognitive impairment and reduced quality of life. The aim of this study was to evaluate the effects of a percutaneous mastoid electrical stimulator (PMES) plus antidepressants on poststroke depression and cognitive function.MethodsThis study was a prospective, randomized, double-blind, and sham-controlled study. A total of 258 clinically depressed ischaemic stroke patients within 14 days of index stroke were randomly assigned to the PMES plus antidepressant (PMES group, N = 125) and sham plus antidepressant (sham group, N = 133) groups. All patients underwent the Montreal Cognitive Assessment (MoCA) and Hamilton Rating Scale for Depression (HRSD) test at 2 weeks (baseline), and 6 months(M6) after ischaemic stroke. Primary outcomes were the percentage of patients showing a treatment response (≥50% reduction in HRSD score) and depression remission (HRSD score ≤ 9) at 6 months. The secondary outcome was the percentage of patients with a MoCA score < 26.ResultsThe percentages of patients showing a treatment response and depression remission were significantly higher in the PMES group than in the sham group (57.60% vs 41.35%, P = 0.009; 44.00% vs 29.32%, P = 0.014 respectively). The mean value of the HRSD score change [M (month)6-baseline] was significantly higher in the PMES group than in the sham group at 6 months (− 11.93 ± 5.32 vs − 10.48 ± 6.10, P = 0.036, respectively). The percentage of patients with MoCA scores < 26 was lower in the PEMS group than in the sham group (12.0% vs 24.06%, P = 0.012,respectively), and the mean value of the MoCA score change (M6-baseline) was higher in the PMES group than in the sham group (3.50 ± 2.55 vs 2.72 ± 2.52, P = 0.005, respectively).ConclusionThese findings demonstrate that PMES adjunctive to antidepressant therapy is effective in reducing depression, achieving remission in the short term, and improving cognition.Trial registrationThis trial was retrospectively registered (registration number: ChiCTR1800016463) on 03 June 2018.

Med Check: Sage’s Treatment; Cannabidiol Products; Pimavanserin; Cognitive Supplements

Med Check: Sage’s Treatment; Cannabidiol Products; Pimavanserin; Cognitive Supplements

Rostral anterior cingulate glutamate predicts response to subcallosal deep brain stimulation for resistant depression

BackgroundDeep brain stimulation (DBS) of the subcallosal cingulate (SCC) provided benefit for treatment-resistant depression (TRD) in open-label studies but failed in a recent randomized sham-controlled trial. Informed patient selection, based on reliable biomarkers, is needed to optimize outcome. We investigated if rostral anterior cingulate (rACC) glutamate/glutamine concentration could serve as a potential biomarker of response. MethodsSixteen adults with TRD (Major Depression; MDD = 14; Bipolar Depression; BD =2) underwent proton magnetic resonance spectroscopy using a short-echo proton spectroscopy with a voxel placed in the rACC, prior to DBS. Improvement in depression was assessed using the 17-item Hamilton Rating Scale for Depression (HDRS). Glutamate and glutamine concentrations at baseline in the rACC were examined in relation to clinical outcomes at six months. ResultsLower baseline glutamate predicted significant reduction in HDRS scores in all TRD patients (p = 0.018), and predicted both HDRS reduction (p = 0.002) and 6-month response outcome in MDD-TRD patients (p = 0.013). Neither baseline glutamine nor glutamine/glutamate ratio significantly related to outcome or symptom improvement. LimitationsOur study was limited by sample size, though it is large for a DBS study. We measured from a single voxel in the brain, so we cannot be certain our findings are specific to the rACC. ConclusionsThese preliminary results suggest that baseline rACC-glutamate concentration could serve as a response-predictive biomarker for SCC-DBS, particularly in patients with resistant major depression. If our findings are replicated and validated, rACC-glutamate may provide a basis to prospectively select TRD patients to improve likelihood of response to SCC-DBS.

Estimating outcome probabilities from early symptom changes in cognitive therapy for recurrent depression.

Acute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD) producing benefits comparable to pharmacotherapy, but not all patients respond or remit. The purpose of the current analyses was to estimate CT patients' probability of nonresponse and remission from symptom improvement early in treatment. Data from 2 clinical trials of acute-phase CT for recurrent depression were pooled for analysis (N = 679). Adult outpatients received 16- or 20-session CT protocols. Symptoms were measured repeatedly with the clinician-report Hamilton Rating Scale for Depression (HRSD) and Inventory of Depressive Symptomatology-Self-Report (IDS-SR). Outcomes at exit from CT were nonresponse (<50% reduction in HRSD scores) and remission (no MDD and HRSD score ≤6). The nonresponse rate was 45.7%, and the remission rate was 33.4%. In logistic regression models, improvements on the HRSD or IDS-SR from intake to CT Sessions 3, 5, 7, 9, or 11 significantly predicted both outcomes, with prediction gaining in accuracy in later sessions. Clinician and self-report assessments yielded similar results. Prediction of outcomes replicated across data sets. Patients with no symptom improvement by CT Session 9 (Week 5) had ≤10% probability of remission and >75% probability of nonresponse. Outcomes of CT for depression are predictable from early symptom changes. Clinicians may find nonresponse and remission probability estimates useful in the informed consent process and in choosing whether to continue, augment, or switch treatments for CT patients with recurrent MDD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Effect of Synbiotic as an Adjuvant Therapy to Fluoxetine in Moderate Depression: A Randomized Multicenter Trial

Background: Depression is a serious and burdensome disorder in modern societies, with lifetime prevalence of about 16%. Disturbed immune responses in the gut and immune-privileged sites including the central nervous system might occur subsequent to dysbiosis of gut microbiome. In this study we aimed at assessing the efficacy of 6 weeks synbiotic supplementation in the treatment of moderate depression in a double-blind, placebo-controlled, multi-center, and randomized trial. Methods: A total of 40 adult outpatients, who met the diagnostic and statistical manual of mental disorders fifth edition for moderate depression, were recruited based on the structured interview for DSMV. Recruited patients had a Hamilton rating scale for depression (HAM-D) score of 17 to 23 at baseline. All patients received fluoxetine (20 mg/d) for 4 weeks. Then, either a synbiotic capsule (plus fluoxetine) or placebo (plus fluoxetine) was added to the therapy for 6 weeks. Results: The mean age of the participants in the synbiotic treated group was 34.45 years and it was 35.50 years in the placebo group. Following the adjustment of ANCOVA models for gender, age, and BMI at baseline, there was a greater reduction in HAM-D score in synbiotic treated patients (Mean ± SD = -19.25 ± 1.71) compared to placebo taking group (Mean ± SD = -17.75 ± 2.05; P = 0.024). At the end of the 10th week of the intervention and after applying ANCOVA adjusted for the mentioned variables as well as baseline HAM-D score, it was found that the synbiotic group had a significantly decreased HAM-D score compared to the placebo (3.65 vs. 4.80, P = 0.013). Conclusions: The results of the current study revealed the efficacy of synbiotic as an adjuvant therapy in moderate depression.

Anti-Inflammatory May Benefit Treatment-Resistant Depression

Anti-Inflammatory May Benefit Treatment-Resistant Depression

Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode

IntroductionRole of l-5-hydroxytryptophan (l-5-HTP) in depression is relatively less studied but the literature has shown its robust role in depression. The present randomized double blind study was undertaken to assess the role of l-5-HTP as an antidepressant and to compare its antidepressant efficacy with fluoxetine in first depressive episode patients of Indian population. MethodsA total of 70 patients of first depressive episode, all of whom were diagnosed with ICD-10 criteria, were recruited but only 60 patients completed the study and were randomly divided into two groups, receiving l-5-HTP and fluoxetine, respectively, for a period of 8weeks. All patients were administered Hamilton Rating Scale for Depression (HAM-D) to assess severity of depression at baseline, 2weeks, 4weeks and 8weeks. The efficacy of treatment was assessed by comparing HAM-D scores obtained at these examinations with the baseline examination; final evaluation of both efficacy and tolerance was assessed using the Clinical Global Impression (CGI) scale at the end of study. ResultsBoth treatment groups showed significant and nearly equal reduction in HAM-D scores beginning at week two and continuing through week eight. Twenty-two patients (73.33%) in the l-5-HTP group and 24 patients (80%) in the fluoxetine group showed positive response at the end of the study. Conclusionl-5-HTP has definitely got antidepressant effect in patients of depression. Antidepressant effect was seen within 2weeks of treatment and was apparent in all degrees of depression. The therapeutic efficacy of l-5-HTP was considered as equal to that of fluoxetine.

Post-dexamethasone cortisol as a predictor for the efficacy of electroconvulsive therapy in depressed inpatients

Background Although several variables have been studied as a possible predictor for the efficacy of ECT, results regarding hypercortisolism have been inconsistent. This prospective study evaluates the relation between pre-treatment cortisol levels and the efficacy of ECT in a population of drug-free inpatients with severe major depression. Methods At the inpatient depression unit, 18 patients meeting the DSM-IV criteria for depressive disorder, and with scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D), were treated with bilateral ECT twice weekly. The HAM-D evaluated depression severity and was performed within 3 days prior to ECT, weekly during the course of ECT, and within 3 days after the last treatment. The outcome criterion was defined a priori as the change on the HAM-D score. Salivary cortisol was assessed within 3 days prior to ECT at two time points, followed by 0.5 mg dexamethasone ingestion. The following day, salivary cortisol was again assessed at two time points. The generalized linear model was used to assess the relation between salivary cortisol levels and reduction in HAM-D score as continuous variables. Results Higher levels of salivary cortisol at 9 AM after 0.5 mg dexamethasone ingestion are associated with a greater reduction in HAM-D score ( B = −0.279, 95% CI: −0.557 to −0.01, s.e. = 0.13, p = 0.049; R square = 0.23; adjusted R square = 0.13). Conclusion This study suggests that higher levels of post-dexamethasone salivary cortisol at 9 AM are predictive of ECT efficacy.

Pregnenolone for cognition and mood in dual diagnosis patients

Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition. In a proof-of-concept investigation, 70 participants with bipolar disorder or recurrent major depressive disorder and history of substance abuse/dependence (abstinent for ≥14days prior to enrollment) were randomly assigned to receive pregnenolone (titrated to 100mg/day) or placebo for 8weeks. Participants were assessed using the Mini International Neuropsychiatric Interview, Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT-B), and Stroop Test. Mood was assessed bi-weekly, while cognition was evaluated at baseline, and weeks 4 and 8. Groups were compared using a random regression analysis that used all of the available data. The pregnenolone group showed trends toward greater improvement, relative to placebo, on the HRSD and YMRS. A post hoc analysis of completers found a statistically significant reduction in HRSD scores with pregnenolone as compared to placebo. Pregnenolone appeared to be safe and well tolerated. Findings suggest that pregnenolone use may be associated with some improvement in manic and depressive symptoms, but not cognition in depressed patients with a history of substance use. Larger trials examining the impact of pregnenolone on mood in more narrowly defined populations may be warranted.

Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure

Objective The purpose of this study is to compare the effectiveness of a combined 12-week home-based exercise (EX)/cognitive behavioral therapy (CBT) program ( n=18) with CBT alone ( n=19), EX alone ( n=20), and with usual care (UC, n=17) in stable New York Heart Association Class II to III heart failure (HF) patients diagnosed with depression. Methods Depressive symptom severity [Hamilton Rating Scale for Depression (HAM-D)], physical function [6-min walk test (6MWT)], and health-related quality of life (HRQOL) (Minnesota Living with Heart Failure Questionnaire) were evaluated at baseline (T1), after the 12-week intervention/control (T2), and following a 3-month telephone follow-up (T3). A repeated measures analysis of variance was used to determine group differences. Depression severity was dichotomized as minor (HAM-D, 11–14) and moderate-to-major depression (HAM-D, ≥15), and group intervention and control responses were also evaluated on that basis. Results The greatest reduction in HAM-D scores over time occurred in the EX/CBT group (−10.4) followed by CBT (−9.6), EX (−7.3), and UC (−6.2), but none were statistically significant. The combined group showed a significant increase in 6-min walk distance at 24 weeks ( F=13.5, P<.001). Among all groups with moderate-to-major depression, only those in CBT/EX had sustained lower HAM-D scores at 12 and 24 weeks, 6MWT distances were significantly greater at 12 ( P=.018) and 24 ( P=.013) weeks, and the greatest improvement in HRQOL also occurred. Conclusions Interventions designed to improve both physical and psychological symptoms may provide the best method for optimizing functioning and enhancing HRQOL in patients with HF.

Onset of Clinical Effects and Plasma Concentration of Fluvoxamine in Japanese Patients

It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder.

A Randomized, Double-Blind, Placebo-Controlled Study of Testosterone Treatment in Hypogonadal Older Men With Subthreshold Depression

Hypogonadism and subthreshold depression are common conditions in elderly men. The objective of this study was to examine the effect of testosterone treatment in older, hypogonadal men with subthreshold depression. A randomized, double-blind, placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older (N = 33) with screening total testosterone levels of <or= 280 ng/dL and subthreshold depression (dysthymia or minor depression, according to DSM-IV). Recruitment for the study was conducted from November 2002 through May 2005. Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks, followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel. The primary outcome measure was the change in the Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of the double-blind phase. Secondary outcome measures were remission of subthreshold depression (defined a priori as a HAM-D score <or= 7) and changes in the Hopkins Symptom Checklist depression scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the short-form 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. At the end of the double-blind phase, testosterone-treated men had a greater reduction in HAM-D scores (p = .024) and a higher remission rate of subthreshold depression (52.9% vs. 18.8%, p = .041) than did placebo-treated men, but there were no differences in other secondary outcome measures between groups. At the end of the open-label phase, the testosterone group had sustained improvement, the control group improved, and there were no differences between groups in any outcome measures. These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism. Larger studies are needed to corroborate these findings. clinicaltrials.gov Identifier: NCT00202462.

Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis

Hypericum perforatum is a medicinal plant with established antidepressant properties. The aim of this meta-analysis was to compare the efficacy and tolerability of this antidepressant with selective serotonin reuptake inhibitors (SSRIs) as a group of standard antidepressants. For this purpose, Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies comparing efficacy and/or tolerability of Hypericum with SSRIs in the management of major depressive disorder (MDD). The search terms were: “Hypericum” or “St. John's wort” and “fluoxetine”, “paroxetine”, “citalopram”, “serteraline”, “escitalopram”, or “fluvoxamine”. Data were collected from 1966 to 2008 (up to June). “Clinical response”, “remission”, “mean reduction in Hamilton Rating Scale for Depression (HAMD) score from baseline”, “total adverse events”, and “withdrawals due to adverse events” were the key outcomes of interest. Thirteen randomized placebo controlled clinical trials met our criteria and were included. Comparison of SSRIs with placebo yielded a significant relative risk (RR) of 1.22 (95% confidence interval: 1.03–1.45, P = 0.02) for clinical response ( n = 4), a non significant RR of 0.96 (95% CI: 0.71–1.29, P = 0.76) for remission ( n = 4), and a significant effect size [weighted mean difference (wmd+)] of 1.33 (95% CI: 1.15–1.51, P < 0.0001) for mean reduction in HAMD score from baseline ( n = 3). Comparison of Hypericum with SSRIs yielded a non significant relative risk (RR) of 0.99 (95% confidence interval: 0.91–1.08, P = 0.83) for clinical response, a non significant RR of 1.1 (95% CI: 0.90–1.35, P = 0.35) for remission, and a non-significant wmd+ of 0.32 (95% CI: − 1.28–0.64, P = 0.52) for mean reduction in HAMD score from baseline, a non significant RR of 0.85 (95% CI: 0.7–1.04, P = 0.11) for any adverse events, and a significant RR of 0.53 (95% CI: 0.35–0.82, P = 0.004) for withdrawals due to adverse events. Hypericum does not differ from SSRIs according to efficacy and adverse events in MDD. Lower withdrawal from study due to adverse events by Hypericum is an advantage in management of MDD.

Partial clinical response to 2 weeks of 2 Hz repetitive transcranial magnetic stimulation to the right parietal cortex in depression

The aim of this treatment study was to evaluate the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) over the right parietal cortex in depression. In a double-blind, sham-controlled design ten consecutive sessions of 2 Hz rTMS (inter-pulse interval 0.5 s) at 90% motor threshold to the right parietal cortex (2400 pulses per session) were applied to 34 patients with the primary diagnosis of DSM-IV depression and a score of > or =15 on the 17-item Hamilton Rating Scale for Depression (HAMD). The primary outcome measures were the percentage change from baseline on the 17-item HAMD scores after ten sessions, and the percentage of clinical (defined as > or =50% reduction in HAMD score) and partial clinical (defined as > or =30% reduction in HAMD score) responders. Reduction of HAMD scores in the real rTMS treatment (mean real+/-S.D., -19.9+/-32.5%) was not statistically different from the sham rTMS treatment (mean sham+/-S.D., -5.6+/-28.4%), and the number of clinical responders did not differ between treatments. However, a significant greater number of partial clinical responders were observed in the real (43.8%) compared to the sham rTMS treatment (6.3%). This study provides the first evidence showing that 2 Hz rTMS over the right parietal cortex may have antidepressant properties, and warrants further research.

An Open-Label, Prospective Study of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Long-Term Treatment of Refractory Depression

Several studies have assessed the acute antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), and many have revealed positive results. However, the impact of rTMS throughout the long course of major depressive disorder (MDD) and the efficacy of rTMS in the treatment of depressive relapses still remain to be elucidated. Sixteen medication-free patients with refractory MDD (diagnosed according to DSM-IV) who initially had clinically significant antidepressant responses to a 10-day course of 10-Hz rTMS were consecutively admitted to the protocol from 1997 to 2001 and were followed for 4 years. The cohort was studied during a total of 64 episodes of depressive relapse. Severity of depression was evaluated with the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI) prior to and after completion of each rTMS treatment course. Clinically significant response was defined as a reduction in HAM-D score of at least 50%. Safety was assessed by serial neurologic examinations and neuropsychological evaluations. Approximately one half of the patients individually sustained a clinically significant response to the repeated courses of rTMS; the mean +/- SD decrease in HAM-D scores was 64.8% +/- 12.6% (p < .0001), and, in BDI scores, 60.4% +/- 20.6% (p < .0001). Despite the lack of adjuvant antidepressant medication, the mean interval between treatment courses was approximately 5 months, and the medication-free period ranged from 26 to 43 months. Transcranial magnetic stimulation was well tolerated, and evaluations regarding the safety of the repeated applications of rTMS revealed no findings of concern. Repeated rTMS applications have demonstrated a reproducible antidepressant effect in patients with refractory depression who initially showed a clinically significant benefit. The duration of effect varied across patients, but benefits were sustained for a mean of nearly 5 months. Further studies with larger cohorts will be useful in determining the long-term effectiveness of rTMS maintenance therapy.

Efficacy of Imipramine in Psychotic Versus Nonpsychotic Depression

The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features. A total of 112 patients diagnosed with major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82 without psychotic features) received treatment with imipramine for 6 weeks after a washout period of 7 days. Imipramine doses were adjusted to attain a predefined fixed plasma level. Treatment response was assessed with the Hamilton Rating Scale for Depression (HAM-D). A logistic regression analysis showed a significantly larger reduction in HAM-D score in the sample with psychotic features compared with the nonpsychotic sample (regression coefficient, -3.47; SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the change in HAM-D score, imipramine was significantly more effective in the sample with psychotic depression compared with the nonpsychotic depressed patients. The contradiction between our results and those of several previous studies may be due to the fixed plasma level dosing of imipramine refraining from concurrent psychotropic medication or limiting our patient sample to patients with mood-congruent psychotic features.

The effectiveness of carbamazepine in unipolar depression: A double-blind, randomized, placebo-controlled study

Our previous studies have shown the effectiveness of carbamazepine (CBZ) in the treatment of bipolar depression. This double-blind, randomized, placebo-controlled study was designed to further evaluate the efficacy of CBZ in unipolar depressed subjects who never received antidepressant and other psychotherapeutic treatment. A total of 89 patients who had at least two major depressive episodes, but never experienced mania or hypomania, were randomly assigned to treatment with immediate-release CBZ 300–800 mg/daily ( n = 51) or placebo ( n = 38) for 12 weeks. The primary efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery–Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). The mean final CBZ dose of CBZ-treated patients was 461.6 mg/day. CBZ treatment yielded significantly greater improvements on the three efficacy measures at week 8 through endpoint compared to placebo. Patients assigned to CBZ treatment also had a significantly higher clinical response rate than placebo (74% vs. 42%, p < 0.001), as defined for ≥ 50% reduction in HAMD score. Based on the results of our present and previous studies, we suggest that CBZ might be considered an alternative in the management of certain conditions in major depressive disorder.

Efficacy of paroxetine in treating major depressive disorder in persons with multiple sclerosis

Objective The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS). Method In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life. Results Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls ( P=.073). Conclusion Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals.