Montgomery-Asberg Depression Rating Scale Scores Research Articles

Repetitive transcranial magnetic stimulation in combination with citalopram in young patients with first-episode major depressive disorder: A double-blind, randomized, sham-controlled trial

To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery-Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color-Word Test (SCWT) were used to assess executive function. (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥ 20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ(2)=4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ(2)=0.295, p=0.586) or in remission rates (39% vs. 29%, χ(2)=0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. RTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.

Associations between Plasma Cytokines and Depressive Mood in Patients with Breast Cancer

The few studies on the associations between cytokines and depressive mood in patients with cancer have produced conflicting results. This study investigated the associations between plasma cytokines and depressive mood in patients with breast cancer using a large panel of pro-inflammatory, anti-inflammatory, and immune-modulating cytokines. We recruited 273 hospitalized patients with breast cancer awaiting surgery. Preoperative plasma samples were obtained for cytokine analysis, including pro-inflammatory (interleukin [IL]-2, IL-12, interferon [IFN]-gamma, and tumor necrosis factor [TNF-alpha]), anti-inflammatory (IL-4, IL-5, IL-10, and IL-13), and immune-modulating (granulocyte/macrophage colony-stimulating factor [GM-CSF]) cytokines. Depressive mood was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) at 2-5 days postoperatively, when the patients could cooperate. Covariates included various demographic and clinical characteristics. The association between the MADRS score and each cytokine level was estimated using linear regression models. Cytokine levels were significantly inter-correlated. Depressive mood was associated with lower levels of pro-inflammatory (IL-2, IL-12, and TNF-alpha), anti-inflammatory (IL-5, IL-10, and IL-13), and immune-modulating (GM-CSF) cytokines independent of potential covariates such as living area or functional level. The findings suggest that depressive mood is associated with a generally decreased inflammatory reaction or immune function in patients with breast cancer.

Differential pattern of response in mood symptoms and suicide risk measures in severely ill depressed patients assigned to citalopram with placebo or citalopram combined with lithium: Role of lithium levels

The assumption that antidepressants may reduce suicide risk by reducing depressive symptoms is not based on data. Further, it is unclear if the retrospectively based anti-suicidal effects of lithium can be prospectively evaluated using lithium as an augmenting agent to antidepressants. To verify our hypothesis, we designed and conducted an exploratory proof of concept trial of four weeks duration using a randomized, double-blind, parallel group method. Forty patients were assigned to citalopram + lithium and 40 were assigned to citalopram + placebo. The primary dependent measures were the Sheehan-Suicidality Tracking Scale (S-STS) and the Montgomery-Asberg Depression Rating Scale (MADRS). The reduction of S-STS scores was large (43%) and twice that seen in MADRS scores (25%) among the eighty patients included in the trial. Both response ( χ 2 = 8.8, p < 0.01) and remission ( χ 2 = 4.6, p = 0.03) rates showed similar patterns. There were no significant differences in mean total S-STS change scores among patients assigned to citalopram with placebo (4.8 ± 5.1) and patients assigned to citalopram with lithium (5.1 ± 5.2). When explored further, a subgroup of the patients assigned to citalopram and lithium achieved therapeutic serum levels and had significantly higher S-STS remission rates (45% compared to 19%, p < 0.05). There were no deaths by suicide or other causes indicating that trials enrolling acutely suicidal patients are feasible. These results suggest that citalopram may have a direct therapeutic effect on suicidal thoughts and behaviors. Further, lithium when used in therapeutic doses may augment such effects. These data warrant further exploration of lithium and an antidepressant combination for anti-suicidal effects.

Prospective cohort study of suicide attempters aged 70 and above: One-year outcomes

Most elderly persons who attempt suicide suffer from depression. This study aimed to investigate one-year outcomes in suicide attempters aged 70+, and to identify predictors of these outcomes. 101 persons (mean age 80) who were hospitalized after a suicide attempt were interviewed at baseline and followed for one year by record linkage. Face-to-face interviews were carried out with 71% of those who were alive after one year (60 out of 85). Outcome measures included major/minor depression, Montgomery-Asberg Depression Rating Scale (MADRS) score, repeat non-fatal/fatal suicidal behavior and all-cause mortality. One half (52%) of all those who were interviewed scored <10 on the MADRS at follow-up. Among those with major depression at baseline, two thirds (26 out of 39) no longer fulfilled criteria for this disorder. Factors associated with non-remission of major depression (MADRS ≥ 10) included higher baseline depression and anxiety scores, higher suicide intent and lower Sense of Coherence. There were two suicides and six non-fatal repeat attempts. The relative risk of death (any cause) was 2.53 (95% CI = 1.45-4.10, p<0.001). This is a naturalistic study; participants received non-uniform treatment as usual. The proportion with repeat suicidal behavior was lower than anticipated and the study was thus underpowered with regard to this outcome. Half of the surviving attempters were free from depressive symptoms at one-year follow-up and there were relatively few repeat attempts. However, all cause mortality remained high in this elderly cohort.

S29-02 A Pilot Trial of a Trauma-Focused, Cognitive-behavioural Intervention with Children Experiencing PTSD Following a Natural Disaster

Method: SAAD was a cross-sectional, observational study of depression in China, Korea, Malaysia, Singapore, Taiwan and Thailand. Participants were drug-free outpatients with depressed mood and/or anhedonia. Symptoms and clinical features were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R) and the Fatigue Severity Scale. Other measures included the Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36), the Sheehan Disability Scale (SDS) and the Multidimensional Scale of Perceived Social Support (MSPSS). Based on the MADRS scores, participants were classified into mild, moderate and severe depression subgroups. Results: A total of 547 outpatients with major depressive disorder were included in the analyses. Among MADRS symptom scores, ‘reported sadness’ and ‘reduced sleep’ had the highest means (3.4 for both). The mean SCL-90-R obsession-compulsion subscale score was high (1.9). The mean SF-36 subscale score for ‘pain’ (58.4) was the second highest among the eight domains. In comparison to other SDS subscores, the mean ‘work/school’ subscores were highest in all three severity groups (ranging from 4.2 to 7.5). Compared to the moderate group, the severe group had significantly lower mean MSPSS total, ‘friends’ and ‘significant others’ dimension scores. Conclusions: This study suggests that pain has a minimal impact on quality of life in Asian patients with depression. Noteworthy issues in this population may include insomnia, obsessive-compulsive symptoms, working/school disability and family support. Acknowledgements: This study is the work of the MD-RAN (The Mood Disorders Research: Asian & Australian Network), which comprises the following members (in alphabetical order of family name [in capital letters]): Jae Nam BAE (Korea), Dianne BAUTISTA (Singapore), Edwin CHAN (Singapore), Sung-man CHANG (Korea), Chia-hui CHEN (Taiwan), CHUA Hong Choon (Singapore), Yiru FANG (China), Tom GEORGE (Australia), Ahmad HATIM (Malaysia), Yanling HE (China), Jin Pyo HONG (Korea), Hong Jin JEON (Korea), Augustus John RUSH (Singapore), Tianmei SI (China), Manit SRISURAPANONT (Thailand), Pichet UDOMRATN (Thailand) and Gang WANG (China). This study was supported by unrestricted research grants from Lundbeck A/S and the Duke-National University of Singapore Office of Clinical Research.

Fluoxetine May Help Post-Stroke Recovery

Fluoxetine, in combination with physical rehabilitation, appears to boost motor recovery in patients who have had an acute ischemic stroke. The mechanism of the benefit isn't entirely clear and it should not be assumed that all selective serotonin-reuptake inhibitors would exert the same effect, Francois Chollet, MD, PhD, and his colleagues reported in the Lancet Neurology. “Selective serotonin-reuptake inhibitors are not a uniform category of drugs and further basic science and pharmacology studies will also be needed to increase understanding of their mechanisms of action,” wrote Dr. Chollet of the Centre Hospitalier Universitaire de Toulouse (France) and his coauthors (Lancet Neurol. 2011 Jan. 10 [doi:10.1016/S1474-4422(10)70314-8]). The FLAME trial randomized 118 patients with acute ischemic stroke to either placebo or 20 mg fluoxetine once daily for 3 months. All patients received standard-of-care physical rehabilitation treatment. The primary end point was a change in the Fugl-Meyer Motor Scale (FMMS), a 100-point scale that rates post-stroke motor recovery, with 0 being flaccid hemiplegia and 100 being normal movement. Secondary end points included the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), and the Montgomery Asberg depression rating scale (MADRS). The patients' averaged 66 years old. Men and women were similarly represented. Common comorbidities were hypertension, dyslipidemia, smoking, prior cardiac disease, and diabetes. Stroke location was in the carotid territory in more than 80% of patients. More than half of the group had severe post-stroke disability as measured by the mRS. There were only two dropouts in the fluoxetine group and four in the placebo group. By the end of 90 days, the mean total improvement in FMMS scores in the active group was significantly greater than in the placebo group (36 vs. 22). The difference remained significant after researchers controlled for treatment center, age, stroke history, and baseline FMMS score. Upper and lower limb scores made similar improvements. When the investigators analyzed the results of 76 patients who did not get thrombolytic therapy, the mean improvement in FMMS scores still was higher in the active group (38 vs. 24). At the end of follow-up, the total NIHSS score was not significantly different between the treatment groups, but the motor component was significantly better in the active group. The mRS improved in both treatment groups but, after adjustment, the between-group difference was not significant. After 90 days, the mean change in MADRS scores was significantly lower in patients who received fluoxetine than in those who received placebo. The frequency of clinical depression also was significantly lower in the active group (7% vs. 29%). However, the authors pointed out, this probably was not caused by the drug's antidepressant effects alone. “In a previous study, a single dose of fluoxetine improved hand motor function and increased activity in the motor cortex, compared with placebo in patients recovering from stroke, showing a specific motor effect, whereas a mood effect is unlikely after a single dose.” Adverse events included one death in each group; each was related to the stroke. Other adverse events found in each group were hyponatremia, gastrointestinal symptoms, liver enzyme abnormalities, and psychiatric disorders. There were two serious adverse events in the fluoxetine group (hyponatremia and partial seizure). No patient discontinued therapy because of an adverse event. Exactly how the antidepressant may benefit stroke patients remains unclear, the authors noted. Studies indicate that animals with a brain injury experience better functional recovery when treated with drugs that affect neurotransmitters. There is even evidence that such drugs might induce structural and physiologic brain changes after the insult. “One hypothesis is that a primary function of the brain serotoninergic system is to facilitate motor output, which emphasizes that the drug intake would be more efficient when paired with [physical] training,” the authors wrote. The study was sponsored by the French Ministry of Health. None of the authors declared any financial conflict. Michele G. Sullivan is with the Mid-Atlantic bureau of Elsevier Global Medical News. Many of us have long observed that, in general, post-stroke patients do better on antidepressants than not. While the neurochemistry has not been pinned down, this study gives us an additional rationale to consider, or even promote, antidepressant therapy in this population. This goes counter to our usual geriatrics mentality – it's better to take away a drug than add one – but we should give our stroke patients their best opportunity to make a meaningful recovery. Relating to depression, my admittedly unscientific observation is that residents getting strong family support and regular visitors also have much better outcomes after a stroke than do those with less support. –Karl Steinberg, MD, CMD Editor in Chief

A randomized, double-blind study comparing LY2216684 and placebo in the treatment of major depressive disorder

The efficacy, tolerability, and safety of LY2216684, a highly selective norepinephrine reuptake inhibitor, were studied in adult patients with major depressive disorder (MDD). This randomized, double-blind study compared flexible-dose LY2216684 6–18 mg once daily (N = 250) with placebo (N = 245) for 10 weeks acute therapy followed by 1 year LY2216684 treatment (results not reported here). Primary inclusion criteria consisted of GRID 17-item Hamilton Rating Scale for Depression total score ≥18 and Clinical Global Impressions-Severity score ≥4. The primary efficacy measure was the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Response was defined as a ≥50% reduction in MADRS score and remission as MADRS total score ≤10. Global functioning was assessed using the Sheehan Disability Scale (SDS). LY2216684-treated patients showed significant improvement from baseline on the MADRS total score compared with placebo-treated patients (−13.3 vs. −9.8, p < .001), and they had a significantly higher probability of achieving response (49.5%) and remission (29.7%) compared with placebo-treated patients (29.3% and 18.8%, respectively). For the SDS global functional impairment score, LY2216684 treatment resulted in significantly greater improvement compared with placebo treatment (p < .001). More LY2216684-treated than placebo-treated patients discontinued from the study because of an adverse event or death (9.6% vs. 1.6%, p ≤ .001). LY2216684 was associated with significant increases (p < .01) from baseline in systolic (3 mm Hg) and diastolic (4 mm Hg) blood pressure and pulse (10 bpm) compared with placebo. LY2216684 6–18 mg demonstrated significant efficacy and was tolerated in the treatment of MDD.

Development and preliminary validation of the PC‐SAD5, a screener‐derived short depression severity measure

The prevalence of depressive disorders is high among patients with skin disease. The PC-SAD is a 37-item self-administered depression screening questionnaire that has been validated in dermatological patients. The aim of this study was to develop and validate a brief depression severity instrument derived from the PC-SAD that can be used to assess severity and monitor ongoing clinical course. Two patient samples participated in the study: 72 adult dermatological inpatients and 73 adults attending six primary care practices. Psychiatric assessment included the Structured Clinical Interview for DSM-IV and an 18-item version of the PC-SAD; moreover, dermatological patients completed the Patient Health Questionnaire depression scale (PHQ-9), while primary care patients were administered the Montgomery-Asberg Depression Rating Scale (MADRS). A subset of five PC-SAD items showing the best psychometric properties were selected, and the reliability and validity of the resulting instrument (PC-SAD5) were examined. The PC-SAD5 showed satisfactory internal consistency in both samples. There was a high correlation between PC-SAD5 and PHQ-9 and MADRS scores. Multiple regression analysis revealed a gradient of PC-SAD5 scores from patients with no mental disorder, those with milder forms of depression, to those with Major Depressive Disorder. Similar results were observed for the 18-item version of the PC-SAD. The availability of valid and reliable continuous measures of depression severity derived from the PC-SAD extends its field of application from depression screening to use as a follow-up measure of depression severity in routine clinical practice. A validated very short instrument such as the PC-SAD5 may have substantial clinical value.

Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan disability scale

Relatively little research has focused on the relationship between functional remission and symptomatic remission in mood and anxiety disorders. This study investigates the relationship and synchrony between symptomatic and functional remission in outpatients with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Using data from three MDD (N=1419) and four GAD (N=1847) randomized, placebo-controlled duloxetine studies, we calculated the percentages of patients meeting symptomatic, functional, and combined functional-symptomatic remission criteria for each disorder. We also calculated mean depression [17-item Hamilton depression rating scale (HAMD₁₇), Montgomery-Asberg depression rating scale] scores and mean anxiety (Hamilton anxiety rating scale) scores for patients meeting Sheehan disability scale (SDS) functional remission and the mean SDS scores for patients with symptomatic remission. Among the patients with MDD, 38% achieved symptomatic remission (HAMD₁₇ ≤ 7), 32% achieved functional remission (SDS ≤ 6), and 23% achieved combined functional-symptomatic remission. Mean HAMD₁₇ and Montgomery-Asberg depression rating scale scores for patients with functional remission were approximately 6. Mean SDS total scores for patients with symptomatic remission were 7.1 (patients with HAMD₁₇ ≤ 7) and 8.6 (patients with Montgomery-Asberg depression rating scale ≤ 10). Among the patients with GAD, 30% achieved symptomatic remission (Hamilton anxiety rating scale ≤ 7), 45% achieved functional remission (SDS ≤ 6), and 25% achieved combined symptomatic-functional remission. The mean Hamilton anxiety rating scale score in GAD was approximately 8 for patients with functional remission and the mean SDS total score was approximately 4 in patients with symptomatic remission. The study shows that functional remission does not always move in tandem with symptom remission and provides useful anchor points or rules of thumb for evaluating symptomatic and functional remission in MDD and GAD.

Effect of augmentation with olanzapine in outpatients with depression in partial remission with melancholic features: Consecutive case series

The aim of the present 12-week, open-label study was to investigate the effect of olanzapine augmentation in outpatients with depression with melancholic features who demonstrated partial response to standard antidepressants but who were reluctant to change antidepressants. The subjects consisted of 22 outpatients meeting the DSM-IV-TR criteria for major depression. Olanzapine was initially added at 2.5 mg/day and the dose was adjusted according to the clinical condition. Data were analyzed using an intention-to-treat methodology. A paired t-test was used to compare total Montgomery Asberg Depression Rating Scale (MADRS) scores before treatment, at baseline (prior to olanzapine), and 4, 8, and 12 weeks after starting olanzapine. Of 22 enrolled patients, 20 completed the trial. The mean (±SD) MADRS score was 17.1 ± 1.0 at baseline and decreased significantly to 8.1 ± 3.2 at 4 weeks after the administration of olanzapine. This significant reduction continued until 12 weeks, when the mean MADRS score was 4.9 ± 2.9, indicating full remission. These results suggest that olanzapine augmentation may be useful for patients with depression in partial remission. A controlled, double-blind trial, however, is needed to confirm these preliminary findings.

Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression-Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Social Support Modifies the Relationship Between Personality and Depressive Symptoms in Older Adults

To explore the relationship between personality, social support, and depression in older adults, identify the personality trait and social support dimension most closely associated with depression, and determine whether the relationship between personality and depression varies by level of social support. Cross-sectional analysis within longitudinal study. Older patients originally diagnosed with major depression (n = 108) and never-depressed comparison group of older adults (n = 103). Patients sufficiently recovered from major depression and comparison participants were administered the NEO Personality Inventory. Social support was measured annually for both groups. Patients were administered the Montgomery-Asberg Depression Rating Scale (MADRS) every 3 months. Patients and comparison participants differed on four of the five NEO domains and all four social support dimensions, but personality did not significantly predict depression status (patient/comparison) in controlled analyses. Within the patient group, subjective social support was the only dimension correlated with MADRS score. In separate linear regression analyses among the patients, controlling for age, sex, and subjective social support, the domains of Neuroticism, Openness to Experience, Conscientiousness, and Extraversion were associated with MADRS score. For Neuroticism and Openness, the association varied by level of subjective social support. Our research confirmed that older patients differed from never-depressed older adults in dimensions of personality and social support, and the relationship between these variables differed by depression status. The relationship between personality, social support, and depressive symptoms in older adults recovering from depression is also complex, with subjective social support modifying the association between personality and depression.

A Pilot, 8-Week, Placebo Lead-In Trial of Quetiapine Extended Release for Depression in Midlife Women

Perimenopausal and early postmenopausal women have shown an increased risk for developing depression (new onset or recurrent); concomitant vasomotor and other menopause-related complaints significantly affect quality of life and overall functioning. This study examined the effects of quetiapine extended release (XR) in midlife women with major depressive disorder who also reported significant menopause-related symptoms. Forty eligible women with major depressive disorder entered a 2-week, placebo lead-in phase, followed by an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/d. The primary outcome measure (depressive symptoms) was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Other measures included menopause symptoms (Greene Climacteric Scale total scores and subscores) and the impact of hot flashes on functioning (Hot Flash-Related Daily Interference Scale). Weight, cholesterol, triglycerides, and glucose levels were monitored. Data from 24 subjects (modified intent-to-treat, last observation carried forward; quetiapine XR mean dose, 191 [SD, 55] mg/d) showed improvement in depressive and menopause-related symptoms, that is, reduction in MADRS, GCS, and Hot Flash-Related Daily Interference Scale scores (P < 0.01 for all comparisons). Seventeen subjects were considered responders (>50% reduction in MADRS scores); 15 achieved remission (MADRS<10). Main adverse effects included drowsiness and dry mouth. Based on these preliminary results, quetiapine XR should be further examined in larger, controlled trials for the management of depressed, symptomatic midlife women.

Efficacy and Safety of Duloxetine 60 mg and 120 mg Daily in Patients Hospitalized for Severe Depression

To assess whether hospitalized patients with severe depression and potential suicidal ideation/behavior have earlier and better response to duloxetine 120 mg daily than 60 mg daily. Adults from 34 sites in 4 countries with severe major depressive disorder, defined by DSM-IV criteria, who were demonstrating Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥ 30, 6-item Hamilton Depression Rating Scale (HDRS-6) scores ≥ 12, and Clinical Global Impressions-Severity of Illness scale (CGI-S) ≥ 4 and hospitalized ≥ 2 weeks underwent double-blind treatment with either duloxetine 60 mg (n = 167) or 120 mg (n = 171) daily for 8 weeks. Patients treated with 60 mg/d who did not respond had their doses titrated up to 120 mg/d. Primary outcome was the difference in baseline to week 4 change in MADRS scores between the groups. Secondary outcomes were baseline to week 8 changes in MADRS and HDRS-6 scores, response and remission, CGI-S scores, CGI-Improvement scores, Patient Global Impressions-Improvement, Hamilton Anxiety Rating Scale scores, and Reasons For Living inventory results. Safety was also assessed. The study was conducted between February 9, 2007, and August 26, 2008. There was no significant difference in mean baseline to week 4 MADRS score change between the 60-mg (-20.1) and 120-mg (-19.9) groups (P = .88). At week 4, 96/166 (60 mg) and 106/170 (120mg) patients responded and maintained responses at week 8 by further decreasing mean MADRS scores to 5.8 (60 mg) and 5.6 (120 mg). At week 8, 226/336 (67.3%) patients achieved remission, with no difference demonstrated between groups. Most secondary efficacy measures were significantly reduced from baseline to week 8 within each group and did not differ between groups. Treatment-emergent adverse events observed with > 10% frequency in both groups were headache and nausea. Duloxetine 60-mg and 120-mg doses were equally effective and demonstrated no significant differences in treating severe depressive symptoms in hospitalized patients. The safety and tolerability profile of duloxetine in both dosages did not differ and was similar to those reported in previous duloxetine studies. clinicaltrials.gov Identifier: NCT00422162.

Reduced Brain White Matter Integrity in Trichotillomania

Trichotillomania is an Axis I disorder characterized by repetitive, pathological hair pulling. To assess the integrity of white matter tracts in subjects with the disorder. Between-group comparison using permutation cluster analysis, with stringent correction for multiple comparisons. Academic psychiatry department. Eighteen volunteers meeting DSM-IV criteria for trichotillomania and 19 healthy control subjects. Fractional anisotropy (measured using diffusion tensor imaging), trichotillomania disease severity (Massachusetts General Hospital Hairpulling Scale score), and dysphoria (Montgomery-Asberg Depression Rating Scale score). Subjects with trichotillomania exhibited significantly reduced fractional anisotropy in anterior cingulate, presupplementary motor area, and temporal cortices. Fractional anisotropy did not correlate significantly with trichotillomania disease severity or depressive mood scores. These data implicate disorganization of white matter tracts involved in motor habit generation and suppression, along with affective regulation, in the pathophysiology of trichotillomania.

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 μg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group × block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group × block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block × gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment × block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block × gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

White Matter Hyperintensities, Medial Temporal Lobe Atrophy, Cortical Atrophy, and Response to Electroconvulsive Therapy in Severely Depressed Elderly Patients

Electroconvulsive therapy (ECT) is a valuable treatment option in severely depressed elderly patients. Structural abnormalities in the brain, such as white matter hyperintensities, medial temporal lobe atrophy (MTA), or global cortical atrophy, may influence therapeutic response. The respective value of these factors in response prediction is unclear. In a naturalistic clinical cohort of 81 elderly patients diagnosed with DSM-IV major depressive disorder, magnetic resonance imaging (MRI) was recorded and rated before ECT treatment. The study was conducted at the clinic for Geriatric Psychiatry of the VU University Medical Center/Stichting Buitenamstel Geestgronden, Amsterdam, The Netherlands, over a 5-year period (2001-2006). Severity of depressive symptoms was measured by using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to ECT was defined as a decrease of at least 50 percent on the MADRS, and remission was defined as a score below 10 points on the MADRS. Patients with moderate or severe MTA had a lower mean percentage decrease in MADRS scores after ECT (37.9% in those with MTA, compared to 66.2% in those without MTA, P = .008). Patients without MTA had a 3 times greater chance of remitting from their depression compared to patients with moderate or severe MTA, ie, the hazard ratio for remission was 3.22 (95% CI, 1.30 to 7.69, P = .01). In contrast, no differences in change in MADRS scores were found for white matter hyperintensities or global cortical atrophy. Medial temporal lobe atrophy--not white matter hyperintensities or global cortical atrophy--contributes to poor response to ECT in severely depressed elderly patients. These findings suggest that assessment of MTA in severely depressed elderly patients may be useful in the prediction of potential ECT response.

Detection of Subclinical Depression in Bipolar Disorder

The aim of this study was to assess the prevalence and the impact of depressive symptoms on the functional outcome of bipolar disorder outpatients in remission. A cross-sectional, prospective 16-week study of a cohort of 739 euthymic bipolar disorder patients (DSM-IV-TR criteria) recruited by 94 investigators was conducted. Clinical stability was assessed at baseline and at week 16 with the modified Clinical Global Impressions Scale-Bipolar Version, and depressive symptoms were assessed at baseline with the 17-item Hamilton Depression Rating Scale (HDRS-17 [primary endpoint measure]), the Montgomery-Asberg Depression Rating Scale (MADRS), and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). The study was conducted from April 2006 to March 2007. Subclinical depressive symptoms (SDS) were detected on the HDRS-17 in 16.9% of the sample. In symptom-free patients, the incidence of new SDS after 16 weeks was 20% (MADRS score > 7). At baseline, SDS patients compared to non-SDS patients presented with poorer social-occupational performance (SOFAS score mean difference, -11.9; 95% CI, -14.2 to -9.6) and poorer social adjustment (SASS score mean difference, -5.6; 95% CI, -7.1 to -4.1). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients, r = -0.54 (P < .0001), and MADRS-SASS correlation coefficients, r = -0.42 (P < .0001). The self-applied survey identified additional cases with depressive symptoms, showing an SDS total prevalence of 44.9%. Depressive symptoms in apparently remitted bipolar disorder outpatients are not rare and result in a decline in occupational outcome and social maladjustment.

Combination of Pharmacotherapy With Electroconvulsive Therapy in Prevention of Depressive Relapse

Relapse rates after electroconvulsive therapy (ECT) remain high with standard treatments. We aimed to test the efficacy of an early administered continuation pharmacotherapy (c-pharm early) strategy in prevention of post-ECT relapse. A 20-week, randomized, double-blind, placebo-controlled trial. Patients aged 18 to 65 years diagnosed with Diagnostic and Statistical Manual of Mental Disorders major depressive disorder, with or without psychotic features, with initial Montgomery-Asberg Depression Rating Scale scores higher than 22, underwent 8 bilateral ECT sessions (2 per week). Randomization to c-pharm early, c-pharm late, and placebo groups in 2:2:1, respectively, was performed at the completion of the fourth ECT session. After randomization, subjects in the c-pharm early group were given sertraline at 150 mg/d. Subjects in the c-pharm late group were first given placebo, which was substituted with sertraline at 150 mg/d at the completion of the eight ECT. Relapse was defined as a Montgomery-Asberg Depression Rating Scale score of 16 or higher. Seventy-three percent of the patients responded to the given treatment. The relapse rates were 12.5% in the c-pharm early group, 28% in the c-pharm late group, and 67% in the placebo group (P = 0.09). The c-pharm early strategy resulted in significantly lower relapse rates and longer well time compared with the placebo (P = 0.04). When the trend with the initiation of the c-pharm intervention was investigated in the 3 groups with equally spaced trend weights, the time of initiation was found to have a significant effect on the probability of the remaining well (P = 0.03). Comparative efficacy of c-pharm early and late strategies in providing improved protection against post-ECT relapse of major depressive disorder needs to be further explored.

Genome Search Reveals Clues to Antidepressant Response

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessGenome Search Reveals Clues to Antidepressant ResponseJun YanJun YanSearch for more papers by this authorPublished Online:7 May 2010https://doi.org/10.1176/pn.45.9.psychnews_45_9_004AbstractNumerous mutations, some of which were found in unexpected places in the genome, have been linked to therapeutic response to antidepressants among patients with depression, a new genomic study reported.Research in this area hopes to explain individual variations in patient response to different antidepressant drugs and one day help clinicians tailor the most effective treatment to each patient.This study, published online in AJP in Advance on April 1, was part of the larger Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a multinational collaboration by researchers in the United Kingdom, Poland, Croatia, Germany, Denmark, Italy, Belgium, Slovenia, Canada, and France.More than 800 adult patients with a diagnosis of moderate to severe unipolar depression participated in the intervention part of the study, and 706 of the patients provided DNA samples for analysis. All participants were of white European ancestry.Most of the participants were randomly assigned to receive either escitalopram or nortriptyline for 12 weeks on an open-label basis. A minority of patients who had contraindications to one of these antidepressants were assigned to the other drug.The two drugs were chosen for their different mechanisms of action: Escitalopram is highly selective for inhibiting the serotonin reuptake receptor with no binding to the norepinephrine reuptake receptor, while nortriptyline is a strong inhibitor of norepinephrine reuptake with very weak binding to the serotonin reuptake receptor. Among the patients who were included in the study, 394 received escitalopram and 312 received nortriptyline.To find genetic variations that may significantly influence patients' response to either antidepressant, the researchers tried two approaches to uncover ties between genetic variations and antidepressant response. In the first approach, they scanned the entire genome using more than half a million single nucleotide polymorphism (SNP) markers to pick up any signs of association. In the second approach, they focused on variants in 72 candidate genes and the DNA regions around these genes.The clinical response to either antidepressant was measured by the change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to the end of treatment.In the genomewide analysis, polymorphisms in the gene encoding for uronyl 2-sulphotransferase were significantly associated with patients' response to nortriptyline. This association was the strongest in the entire study. Uronyl 2-sulphotransferase is an enzyme involved in neurogenesis and the migration of neurons. The observation that the gene for this enzyme is associated with response to nortriptyline appears to corroborate the neurogenesis theory of antidepressant effects, the researchers pointed out.They also identified SNPs concentrated in two intergenic regions on chromosomes 1 and 10 as potentially associated with response to antidepressants. Intergenic regions are stretches of DNA that neither code for any genes nor regulate the expression of close-by genes. However, when DNA strands are folded, they may have a spatial or structural influence on the expression of certain genes that are linearly far away. These regions had not been associated with a clinical response to antidepressants in past research, and a possible mechanism for this connection is unknown.In addition, variants in the gene encoding for interleukin-11 (IL-11), a cytokine, were linked to response to escitalopram.The targeted analysis of 72 preselected candidate genes did not generate any strong association with antidepressant response. However, a potential but weak link was identified between response to escitalopram and the gene coding for interleukin-6, which is closely related to the gene for IL-11. This and the significant association with the IL-11 gene support the theory that inflammatory cytokines play a role in the therapeutic effect of antidepressants. Both cytokines are extensively expressed in the brain and have been shown to play a role in serotonin signaling.The authors noted that because the study sample was not large enough to provide sufficient statistical power, genes with moderate effects on the clinical response were likely to be missed by the analysis.The GENDEP project was supported primarily by a European Commission grant. GlaxoSmithKline and several U.K. organizations provided additional funding. Lundbeck, a Danish drug company, donated both study drugs.“Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project” is posted at <http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2009.09070932v1>. ISSUES NewArchived