Reduction In MADRS Score Research Articles

Efficacy of extended release quetiapine fumarate monotherapy in elderly patients with major depressive disorder

This study evaluated extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD) according to baseline levels of anxiety, sleep disturbance, and pain. Post-hoc analyses of data from an 11-week (9-week randomized-treatment, 2-week post-treatment phase), double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) monotherapy in elderly (≥66 years) patients (n=338) with MDD were carried out. Outcomes included randomization to week 9 change in Montgomery Åsberg Depression Rating Scale (MADRS) score and week 9 response (≥50% MADRS score reduction) rates. Post-hoc analyses were carried out to assess subgroups of patients with MDD according to baseline levels in terms of the following: higher or lower anxiety (Hamilton Rating Scale for Anxiety total score≥20 or < 20, respectively); high or low sleep disturbance [Hamilton Rating Scale for Depression sleep disturbance factor (items 4+5+6) score≥5 or <5, respectively]; and pain visual analog scale total score 40 mm or higher or less than 40 mm. At week 9, quetiapine XR reduced the MADRS total score compared with placebo in the higher anxiety (least squares mean change -17.8 vs. -8.5; P<0.001) and lower anxiety (-14.8 vs. -8.8; P<0.001) subgroups. MADRS total score was also reduced with quetiapine XR compared with placebo in the high (-17.6 vs. -8.7; P<0.001) and low (-14.4 vs. -9.2; P<0.001) sleep disturbance subgroups, as well as in the pain visual analog scale subgroups [≥40 mm (-16.6 vs. -8.9; P<0.001) and <40 mm (-15.7 vs. -8.7; P<0.001)]. Quetiapine XR response rates were higher than those of placebo in all subgroups analyzed. In this study, quetiapine XR (50-300 mg/day) monotherapy was shown to be effective against depressive symptoms in elderly patients with MDD, irrespective of baseline levels of anxiety, sleep disturbance, and pain.

Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy

To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.

Vascular Endothelial Growth Factor (VEGF) serum concentration during electroconvulsive therapy (ECT) in treatment resistant depressed patients

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine, which induces vasopermeability and facilitates neurogenesis and synaptic plasticity in the adult brain. Expression studies in animal models have reported that brain VEGF is regulated by electroconvulsive seizures (ECS), which are used in an experimental paradigm similar to clinical electroconvulsive therapy (ECT) a treatment for drug resistant depressed (TRD) patients. The aim of this study was to investigate putative modulations of ECT on VEGF serum levels in TRD patients. Nineteen patients were enrolled in the study; illness severity and VEGF serum contents were assessed before the treatment (T0), the day after the end of ECT (T1) and one month later the end of ECT (T2). ECT treatment improved depression symptomatology as measured by MADRS scores (p<0.0001). No changes occurred in serum VEGF between T0 and T1, whereas a significant increase was observed between T0 and T2 (p=0.042). Moreover a significant correlation was observed between the VEGF increase at T2 and the reduction in MADRS scores (p=0.049). This study is the first to evaluate putative modulations of serum VEGF induced by ECT in TRD patients.

Five years of ECT: the relationship between consent status and treatment experiences.

ECT has received limited systematic study in the Irish setting. Amendments to the Mental Health Act (2001) propose limiting the use of ECT to patients who can provide written informed consent. We report on the use of ECT in Limerick specifically addressing the issue of patient consent and how it relates to response rate. Since 2003, the use of ECT within Limerick Mental Health Services has been monitored by a data gathering process that includes the documentation of mood disturbance before and after the procedure. In the five years between 2003 and 2007, 153 courses of ECT were given to 126 different patients (frequency 16.7/100,000; Female:Male = 2:1). The principal indication for ECT was depressive illness (95%). Bilateral electrode application was the preferred mode comprising 83% of use. A total of 60% experienced at least a 50% reduction in MADRS score over the course of ECT with 78% experiencing a reduction of 10 points or more on the MADRS. Higher response rate was linked to use of bilateral ECT (p = 0.007; 95% CI 1.3-13.6). A total of 14% of patients were unable to provide written informed consent and these patients had more severe depression at outset (p = 0.007; 95% CI 1.8-11.1) and a trend towards greater reduction in MADRS scores during ECT (p = 0.08). The commonest adverse incident associated with ECT was cognitive impairment (33 patients). The risk of cognitive problems was not related to age, ECT dose, number of treatments, severity of depressive symptoms, treatment response, or consent status. Frequency of use, response and adverse effect rates for ECT in Limerick Mental Health Services are similar to other centres. Cognitive impairment was the most frequent adverse event. The choice of electrode placement for ECT requires further consideration. Restricting ECT to patients that can provide written informed consent would prevent its use in many patients with severe illness who experience significant response to treatment.

P01-09 - Antidepressant monotherapy and combination of antidepressants in the treatment of resistant depression in current clinical practice. A retrospective study

Introduction and objectivesResistant depression is a long-term, disabling illness. The aim of this study was to compare the efficacy of antidepressant monotherapy (ADM) and combinations of antidepressants (CAD) in the treatment of resistant patient (≥1 unsuccessful antidepressant treatment) in current clinical practice.MethodsWe reviewed chart documents of resistant patients hospitalized at Prague Psychiatric Center for major depressive disorder (DSM IV) and had finished at least 4 - weeks of treatment with ADM or CAD. Clinical status was assessed using MADRS, CGI and BDI-S at baseline, after 2 weeks and in the end of treatment in the framework of regular evaluation during the hospitalization. Response to treatment was defined as a reduction of MADRS score ≥ 50%.Results: We analyzed 78 inpatients (CAD=27, ADM=51). Both groups were equal in baseline characteristics (number of previous treatments, severity of depression etc.) and in the length of index treatment. The CAD group was superior to ADM group in the MADRS score reduction (14.6 vs 10.2 pts, p=0.02) and the proportion of responders (67% vs. 39%, p=0.03) in the end of treatment. The post-hoc effect size of CAD compared to ADM was moderate (Cohen's d=0.54).Conclusion: The results of this study suggest that combinations of antidepressants may be more effective than a monotherapy in patients with resistant depression.This study was supported by a grants from Internal Grant Agency of Ministry of Health of Czech Republic No. NS 10368-3 and a grant from Ministry of Health of Czech Republic MZ0PCP2005.

Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose. On day 1, patients received a 40-min IV infusion of ketamine (.5 mg/kg) in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic effects and adverse events were recorded repeatedly. The primary efficacy measure was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If patients showed a > or =50% reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice-weekly for > or =4 weeks or until relapse. Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for >3 months. These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.

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Priming Stimulation Enhances the Effectiveness of Low-Frequency Right Prefrontal Cortex Transcranial Magnetic Stimulation in Major Depression

Low-frequency, right-sided repetitive transcranial magnetic stimulation (rTMS) to the prefrontal cortex has been shown to have antidepressant effects. Recent research has suggested that preceding low-frequency rTMS with a period of low-intensity, 6-Hz stimulation ("priming") enhances the physiological effects of low-frequency stimulation. The aim of this study was to investigate whether priming stimulation would enhance therapeutic response to low-frequency rTMS in patients with depression. The study consisted of a 2-arm, double-blind, randomized, controlled trial in 60 patients with treatment-resistant depression. Right 1-Hz rTMS was provided in one continuous, 15-minute train to all subjects. The priming stimulation (twenty 5-second, 6-Hz trains) or an equivalent, sham preceded 1-Hz stimulation. The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale (MADRS). There was a significant overall reduction in MADRS scores across the 4 weeks of the study and a significantly greater reduction in MADRS scores in the active-priming group compared with the sham-priming group. Low-intensity, high-frequency priming stimulation appears to enhance the response to low-frequency, right-sided rTMS treatment in patients with treatment-resistant depression.

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients.

Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.

L’escitalopram dans le traitement des épisodes dépressifs majeurs de l’adulte

Escitalopram is a selective serotonin reuptake inhibitor (SSRI); it is the therapeutically active S-enantiomer of the racemic mixture, citalopram. This review aimed to compare the efficacy and tolerability of escitalopram versus citalopram and several other SSRIs (citalopram, fluoxetine, paroxetine, sertraline), and a selective reuptake inhibitor of noradrenaline and serotonin, venlafaxine XR, for treatment of DSM IV (Diagnostic and Statistical Manual of mental disorders - fourth edition) major depressive disorder, based on the studies evaluated by the Commission de la Transparence de la R6publique Frangaise, and data from a pooled analysis presented in 2005 at the 158th annual congress of the American Psychiatric Association. Change from baseline to end-point on total MADRS (Montgomery-Asberg Depression Rating Scale--10 items, score range: 0-60) was the primary efficacy parameter; changes on HAM-D17 (Hamilton rating scale for depression--17 items), CGI-S and CGI-I (Clinical global Impression-Severity and-Improvement), and response rates (> or = 50% MADRS score reduction) and remissions (< 12 MADRS score) were the secondary efficacy parameters. Tolerability assessment was based on the numbers and rates of adverse events observed with treatment, and the DESS (Discontinuation Emergent Signs and Symptoms-43 items) scale was used for assessment of adverse events observed with treatment withdrawal. Analyses were based on intention to treat using the LOCF (last observation carried forward) method. Efficacy of escitalopram appeared to be at least equivalent to that of the active comparators in all cases. The difference between active compounds was more marked when depressive symptoms were more severe. From the point of view of tolerability, frequency of adverse effects occurring on treatment and the frequency of treatment discontinuations due to adverse effects were comparable with both escitalopram and the active comparators; however, the comparisons were mostly favourable to escitalopram, though differences were generally not statistically significant. In both studies of escitalopram versus venlafaxine XR, treatment discontinuations due to adverse events were less frequent on escitalopram than on venlafaxine XR (7.5% vs 11.2%, and 4.1% vs 16.0% respectively). With regard to adverse events associated with the withdrawal period, the signs and symptoms occurring on treatment discontinuation assessed after 1 week using the DESS scale were less frequent on escitalopram than on venlafaxine XR at 8 weeks and paroxetine at 24 weeks. Concerning suicide risk, a review of clinical trials involving 2277 patients on escitalopram and 1814 patients on placebo showed that this risk was minimal, and similar in both groups; moreover, no evidence was found suggesting that escitalopram might promote suicidal behaviour compared with placebo. These results suggest that escitalopram is suitable to be considered as a first-line drug treatment for major depressive disorder.

Multicenter double-blind randomized parallel-group clinical trial of efficacy of the combination clomipramine (150 mg/day) plus lithium carbonate (750 mg/day) versus clomipramine (150 mg/day) plus placebo in the treatment of unipolar major depression

Background: The therapeutic efficacy of adding lithium to an ongoing antidepressant in resistant depression is well known. However there is less data concerning the efficacy of giving lithium and antidepressant concurrently from the start of treatment. Methodology: The primary objective of this study was to compare the efficacy of a combination of clomipramine+lithium (C+L) with that of clomipramine+placebo (C+P) in-patients with unipolar major depression, during the first 11 days of treatment. Secondary objectives were the assessment of effectiveness after 6 weeks and assessment of the safety of the combination clomipramine and lithium carbonate. C+L and C+P groups were compared for 6 weeks in a multicenter randomized trial of 141 patients hospitalized with a DSM-IV diagnosis of major depression. Efficacy was evaluated using the standard MADRS and CGI scales. Results: Analysis of the ‘as treatment ITT’ population showed: the percentage reduction in MADRS scores between D0 and D11 in this population was better in the C+L group but not statistically significant (C+L: 32.1 vs. C+P: 27.4, P=0.07). Nevertheless, the comparison of mean MADRS scores showed a significant difference in the C+L group on days 4 (C+L: 25.1 vs. C+P: 27.8) and 7 (C+L: 18.6 vs. C+P: 21.5), P<0.05, and approaching significance on day 11 (C+L: 14.6 vs. C+P 17.2, P=0.054). On day 7, the number of patients in total remission was threefold higher in the C+L group than in the C+P group (15 vs. 4%, P<0.05) and twofold on day 11 (29 vs. 14%, P<0.05). CGI severity score showed C+L was superior to C+P on days 4, 7 and 11 and CGI improvement score was better in C+L group on day 11 ( P<0.05). After 6 weeks of treatment no statistical difference was found between the two groups from the clinical point of view. Safety based upon clinical and laboratory parameters was satisfactory in both groups during the 6 weeks of the study. Limitations: Patients with bipolar disorder, previously treated with clomipramine or with any other mood stabilizers during the previous week; or with suicide attempt during the current episode with a score ≥3 for item 10 of the MADRS were excluded from the study. Conclusion: The results of this study suggests that lithium slightly to moderately potentiates antidepressant treatment in unipolar non-refractory patients with severe major depression in the first days of treatment but not as significantly as for the bipolar population.

Efficacy of intravenous citalopram compared with oral citalopram for severe depression: Safety and efficacy data from a double-blind, double-dummy trial

Background: Intravenous administration is often beneficial in the treatment of severely depressed patients. It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously. However, these drugs have a less favourable safety profile than newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). Citalopram is the only SSRI that is available in a formulation for infusion. This double-blind, randomised, multicentre trial was designed to compare the efficacy and tolerability of citalopram infusion (40 mg per day) and citalopram tablet (40 mg per day). Methods: Patients were randomised to receive either placebo tablet plus citalopram infusion (the infusion group; n=135) or citalopram tablet plus placebo infusion (the tablet group; n=119). After receiving randomised treatment for eight days, all patients entered an open treatment phase, during which they received oral citalopram 40 mg per day for five weeks. Results: Although there was no difference in Montgomery–Åsberg Depression Rating Scale (MADRS) scores at the end of the randomised treatment period, by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group ( p=0.015). The infusion group also showed superior efficacy in Clinical Global Impressions assessments. Citalopram was equally well tolerated in both treatment groups. Conclusions: This trial confirmed the efficacy of citalopram 40 mg per day, and clearly supports the use of citalopram infusion in the treatment of severely depressed, hospitalised patients.

Should thyroid augmentation precede lithium augmentation – a pilot study

Background- It has not been investigated whether thyroid augmentation should precede lithium augmentation or vice versa. Methods- In 22 outpatients with major depression not responsive to 4 weeks of antidepressant treatment, the effect of subsequent 4 weeks of thyroxine administration followed by 4 weeks of lithium augmentation was compared with the effect of the same treatments in reverse order. Results- The percentage reduction in MADRS score was significantly greater in patients who started on thyroxine. Conclusions- Thyroxine augmentation should precede lithium augmentation. Limitations- We used relatively small doses of lithium. Clinical relevance- Thyroxine is effective in augmenting antidepressant responses.

Increased Platelet 5-HT2 Receptor Binding After Electroconvulsive Therapy in Depression

We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.

76-9 - Increased platelet 5-HT 2 receptor binding after electroconvulsive therapy in depression

We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.