Improvement In Depression Ratings Research Articles

Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study

Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3 “parent” studies could continue esketamine treatment, combined with an oral antidepressant, by enrolling in phase 3, open-label, long-term extension study, SUSTAIN-3. Based on their status at parent-study end, eligible participants entered a 4-week induction phase followed by an optimization/maintenance phase, or directly entered the optimization/maintenance phase of SUSTAIN-3. Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance. At the interim data cutoff (01 December 2020), 1148 participants were enrolled, 458 at induction and 690 at optimization/maintenance. Mean (median) cumulative duration of maintenance esketamine treatment was 31.5 (37.7) months (totaling 2769 cumulative patient-years). Common treatment-emergent adverse events (≥20%) were headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. Mean Montgomery–Åsberg Depression Rating Scale (MADRS) total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from the baseline to the endpoint of each phase: induction −12.8 [9.73]; optimization/maintenance +1.1 [9.93]), with 35.6% and 46.1% of participants in remission (MADRS total score ≤12) at induction and optimization/maintenance endpoints, respectively. Improvement in depression ratings generally persisted among participants who remained in maintenance treatment, and no new safety signal was identified during long-term treatment (up to 4.5 years) using intermittent-dosed esketamine in conjunction with daily antidepressant.

The Impact of Dorsal Root Ganglion Stimulation on Pain Levels and Functionality in Patients With Chronic Postsurgical Knee Pain

BackgroundChronic postsurgical pain is a considerable source of disabling neuropathic pain. Rates of knee replacement surgeries are increasing, and many patients report chronic postsurgical pain in their wake. When conventional therapies prove ineffective, neuromodulation options such as dorsal root ganglion stimulation (DRGS) may be used. However, little is known about the effect of DRGS on improvements in quantitative functional outcome parameters. Materials and MethodsIn a prospective observational study at two pain centers, patients with chronic postsurgical knee pain underwent implantation with a DRGS system after an interdisciplinary multimodal pain program. Ratings of pain, mood, quality of life, and function were captured at baseline and through 12 months of treatment. Quantitative measures (range of motion, walking distance, and pain medication usage) were also recorded. ResultsVisual analog scale ratings of pain decreased from 8.6 to 3.0 (p < 0.0001; N = 11), and other pain measures agreed. Quality of life on the 36-Item Short Form Health Survey questionnaire improved from 69.3 to 87.6 (p < 0.0001), whereas the improvement in depression ratings was nonsignificant. International Knee Documentation Committee questionnaire ratings of function improved from 27.7 to 51.7 (p < 0.0001), which aligned with other functional measures. On average, knee range of motion improved by 24.5°, and walking distance dramatically increased from 125 meters to 1481. Cessation of opioids, antidepressants, and/or anticonvulsants was achieved by 73% of participants. ConclusionsBoth subjective-based questionnaire and quantitative examination-based variables were in broad agreement on the value of DRGS in improving functionality and chronic postsurgical pain in the knee. Although this finding is limited by the small sample size, this intervention may have utility in the many cases in which pain becomes problematic after orthopedic knee surgery.

Cognitive outcomes are differentially associated with depression severity trajectories during psychotherapy treatment for late life major depressive disorder.

Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD. 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance. Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed. The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD.

Overweight in mood disorders: Effects on morbidity and treatment response

ObjectiveAs it is not clear how body-mass index (BMI) may relate to diagnosis, symptom-severity, illness-course, and treatment-response among psychiatric patients, we related BMI to psychiatric diagnosis and to selected clinical and demographic factors in major affective disorder subjects. MethodsWe analyzed mean BMI levels vs. diagnosis, and evaluated selected risk factors for association with overweight and obesity among subjects with DSM-5 major affective disorders. ResultsIn 1884 subjects, BMI ranged from 23.4 kg/m2 with anxiety disorders to 27.6 with psychotic disorders, and averaged 24.1 among 1469 affective disorder subjects. Mood-disorder subjects with BMI ≥ 25 (overweight/obese) were more likely: men, older, married, with more children and siblings, less education, lower socioeconomic status, engaged less in physical exercise, smoked more, and lived in less densely populated areas. They also were more likely to have: BD than MDD, familial mood disorders, no co-occurring ADHD, higher serum triglyceride levels, more time depressed and less improvement in depression ratings with treatment. ConclusionsRisk of being overweight or obese was greatest with psychoses, least with anxiety, personality, and minor depressive disorders, and intermediate with major mood disorders. Several plausible risk factors for high BMI were identified in mood disorder subjects, including male sex and with BD > MDD. Striking were selectively greater prospective morbidity and decreased treatment-response for depression vs. mania with BMI ≥ 25.

The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression.

We examined the short-term efficacies of three estrogen-like compounds under placebo-controlled conditions in women with perimenopause-related depression (PMD). Women with PMD were randomized in a double-blind parallel design to one of four treatments: transdermal 17-beta estradiol (TE) (100 mcg/d); oral raloxifene (60 mg/d); a proprietary phytoestrogen compound, Rimostil (1,000 mg twice/d); or placebo for 8 weeks. The main outcome measures were the Center for Epidemiology Studies Depression Scale, 17-item Hamilton Rating Scale for Depression (HRSD), and the Beck Depression Inventory completed at each clinic visit. Secondary outcomes included a visual analogue self-rating completed at each clinic visit, and daily self-ratings of hot flush severity. Cognitive tests were performed at pretreatment baseline and at the end of the trial. In the primary analysis, we obtained four repeated measures in each woman in the four treatment arms. Analyses were done with SAS Version 9.4 software (SAS Institute, Inc, Cary, NC), using PROC MIXED (for mixed models). All models included the following four explanatory variables, regardless of whether they were statistically significant: 1) treatment group (TE, raloxifene, Rimostil, placebo); 2) week (W2, W4, W6, W8); 3) treatment group-by-week interaction; and 4) baseline value of the measure being analyzed. The inclusion of additional variables was evaluated individually for each outcome measure. Sixty-six women were randomized into the trial, four women dropped out of the trial, and 62 women were included in the final data analysis. No effect of treatment group was observed in either the Center for Epidemiology Studies Depression Scale (P = 0.34) or Beck Depression Inventory (P = 0.27) scores; however, there was a difference in HRSD scores between treatment groups (P = 0.0037) that pair-wise comparisons of the combined weekly scores in each treatment demonstrated TE's beneficial effects on HRSD scores compared with Rimostil (P = 0.0005), and less consistently with placebo (P = 0.099). The average (SD) of the baseline scores for each treatment group on the HRSD was as follows: TE-15.3 (4.5), raloxifene-16.0 (3.7), Rimostil-14.0 (2.7), and placebo-15.2 (3.0). Whereas the HRSD scores after 8 weeks of treatment (least-square means) were TE-5.2(1.1), raloxifene-5.8(1.2), Rimostil-11.2(1.4), and placebo-7.8(1.1). No differences were observed between raloxifene and either TE or placebo in any scale score. HRSD scores in women assigned to TE were improved compared with those on Rimostil during weeks 6 and 8 (P values = 0.0008, 0.0011, respectively). Cognitive testing at week 8 showed that none of the three active treatment groups performed better than placebo. This study did not identify significant therapeutic benefits of TE, Rimostil, or raloxifene compared with placebo in PMD. However, improvements in depression ratings were observed between TE compared with Rimostil. Thus, our findings do not support the role of ERbeta compounds in the treatment of PMD (and indeed could suggest a more important role of ERalpha).

Urothelial toxicity of esketamine in the treatment of depression

RationaleKetamine is the first widely used substance with rapid-onset antidepressant action. However, there are uncertainties regarding its potential urothelial toxicity, particularly after repeated application. In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported. It is assumed that ketamine interacts with bladder urothelial cells and induces apoptosis.ObjectivesThis study aimed to assess whether single or repeated doses of esketamine used in an antidepressant indication are associated with urinary toxicity.MethodsWe included male and female inpatients with a current episode of depression and a diagnosis of recurrent depressive disorder, bipolar disorder or schizoaffective disorder according to ICD-10 criteria (n = 25). The esketamine treatment schedule involved a maximum of 3× weekly dosing at 0.25–0.5 mg/kg i.v. or s.c. The primary outcome was the change in urine toxicity markers (leukocytes, erythrocytes, protein and free haemoglobin). Description of demographic, clinical and laboratory data was conducted using means, standard deviations, frequencies and percentages. Changes in urinary toxicity markers over time were evaluated using linear mixed models with gender as a covariate.ResultsThe participants received an average of 11.4 (SD 8) esketamine treatments, and an average number of 11.2 (SD 8) urine samples were analysed over the course of treatment. Neither urinary leukocyte concentration (F(20; 3.0) = 3.1; p = 0.2) nor erythrocyte concentration (F(20;2.2) = 4.1; p = 0.2) showed a significant trend towards increase during the course of esketamine treatment. Similarly, free haemoglobin and protein concentrations, which were analysed descriptively, did not display a rise during treatment. There was a significant improvement in depression ratings after esketamine treatment (p < 0.001).ConclusionsThis study is, to the best of our knowledge, the first to focus on urothelial toxicity of esketamine used in antidepressant indication and dose. The results indicate that the use of single or repeated doses of esketamine is unlikely to cause urothelial toxicity. The results are in need of confirmation as sample size was small.

Efficacy of repetitive transcranial magnetic stimulation in the treatment of depression with comorbid anxiety disorders

BackgroundThe presence of comorbid anxiety is generally associated with poorer treatment outcomes in people with depression. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment resistant depression, but there has been little research examining rTMS in depressed patients with comorbid anxiety disorders. This study aimed to investigate the efficacy of rTMS in patients with treatment resistant Major Depressive Disorder (MDD) and comorbid anxiety disorders. MethodsThis study included 248 patients with treatment resistant MDD who were treated with rTMS. Of these, 172 patients had one or more comorbid anxiety disorders, so their outcomes were compared with patients who did not have comorbid anxiety. ResultsPatients both with and without comorbid anxiety disorders showed improvement in depression ratings after rTMS treatment, with no significant difference in remission rates between groups. In those with comorbid anxiety disorders, 23.3% met criteria for remission and 39.5% met response criteria. For each anxiety disorder diagnosis, there was a significant reduction in HAM-A, HAM-D21, MADRS and ZUNG scores (p = <0.001 for all). LimitationsThis was not a sham-controlled study, so placebo response rates are not known. Patients were referred by private psychiatrists so are not representative of all patients with depression. ConclusionOur study indicates that rTMS is an effective treatment for Major Depressive Disorder in people who have comorbid anxiety disorders.

A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder.

Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. The primary aim of this pilot study was to investigate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) monotherapy, compared to sertraline monotherapy, for patients with acute MDD. This open-label, nonrandomized controlled trial examined a MBCT cohort (N=23) recruited to match the gender, age, and depression severity of a depressed control group (N=20) that completed 8 weeks of monotherapy with the antidepressant sertraline. The 17-item clinician-rated Hamilton Depression Severity Rating Scale (HAMD-17) was the primary outcome measure of depression to assess overall change after 8 weeks and rates of response and remission. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) was the secondary outcome measure to further assess depression severity. Both cohorts were demographically similar and showed significant improvement in depression ratings. No difference was found in the degree of change in HAMD-17 scores (t(34) = 1.42, p = .165) between groups. Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 (t (32) = 4.39, p < 0.0001), with the MCBT group showing greater mean improvement. This study was limited by the small sample size and non-randomized, non-blinded design. Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and a viable alternative to antidepressant medication. Greater changes in the self-rated QIDS-SR16 for the MBCT cohort raise the possibility that patients derive additional subjective benefit from enhanced self-efficacy skills.

Neural Correlates of Rapid Antidepressant Response to Ketamine in Treatment-Resistant Unipolar Depression: A Preliminary Positron Emission Tomography Study

Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response. Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex. Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.

Serum BDNF levels before treatment predict SSRI response in depression

The "neurotrophin hypothesis" of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response. Thirty un-medicated depressed subjects were treated with escitalopram (N=16) or sertraline (N=14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects. Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p=0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p<0.001), and BDNF levels increased with treatment (p=0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p<0.01), and "Responders" to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did "Non-responders" (p<0.05). These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants.

Efficacy of ECT in Chronic, Severe, Antidepressant- and CBT-Refractory PTSD: An Open, Prospective Study

Treatment options are limited in patients with severe, chronic, posttraumatic stress disorder (PTSD). There is little information on the use of electroconvulsive therapy (ECT) for PTSD. Between January 1, 2005, and December 31, 2005, all consenting adults (n=20) with severe, chronic, extensively antidepressant-refractory PTSD were prospectively treated with a fixed course of 6 bilateral ECT treatments administered on an outpatient basis at a twice-weekly frequency. The primary outcome measure was improvement on the Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS). Baseline refractoriness was defined as a failure to respond to an adequate course of at least 4 different antidepressant drugs along with 12 sessions of cognitive behavior therapy. Response to ECT was defined as at least 30% attenuation of CAPS ratings, and remission as an endpoint CAPS score of 20 or less. After ECT, patients were prescribed sertraline (100-150 mg/day) or mirtazapine (15-30 mg/day). All but 3 patients completed the ECT course. An intent-to-treat analysis (n=20) showed statistically and clinically significant improvement in the sample as a whole: CAPS scores decreased by a mean of 34.4%, and depression scores by a mean of 51.1%. Most of the improvement in CAPS and depression ratings developed by the third ECT; that is, by day 10 of treatment, itself. The improvement in CAPS ratings was independent of the improvement in depression ratings; and improvement in CAPS did not differ significantly between patients with less severe vs more severe baseline depression. The response rate was 70%; no patient remitted. In the completer analysis (n=17), mean improvements were 40% and 57% for CAPS and depression ratings, respectively, and the response rate was 82%. Treatment gains were maintained at a 4-6 month follow-up. ECT may improve the core symptoms of PTSD independently of improvement in depression, and may therefore be a useful treatment option for patients with severe, chronic, medication- and CBT-refractory PTSD.

Escitalopram: An open-label study of bereavement-related depression and grief

Background Approximately 8 million Americans suffer the loss of an immediate family member each year. Chronic depression may develop following bereavement—about 15% of the bereaved are depressed at 1 year. Several studies of psychotropic medications have demonstrated improvement in depression ratings, but little data exists for selective serotonin reuptake inhibitor treatment in bereavement-related depression. Methods Thirty adults were treated with escitalopram for 12 weeks in open fashion for a major depressive episode following loss of a close family member (parent, sibling, child, or spouse/significant other). Main outcome measures were the Hamilton Depression Rating Scale, the Montgomery–Asberg Rating Scale, the Texas Revised Inventory of Grief, and the Inventory of Complicated Grief. Results Twenty-nine of thirty participants returned for at least one set of efficacy measures after starting medication. Nineteen subjects (66%) experienced a 50% or greater improvement on the Hamilton Depression Scale. Fifteen subjects (52%) achieved remission, defined as a final score of 7 or less on the Hamilton Depression Scale. Escitalopram significantly reduced depressive symptoms ( P < 0.001) over time. Subjects with uncomplicated grief and those with complicated grief improved similarly over time. Subjects with and without PTSD improved to a similar degree. Escitalopram was well tolerated. Limitations Open-label design, psychotherapy was not controlled, relatively short treatment period, variation in grief scales make comparisons to other studies difficult, all subjects with complicated grief also were clinically depressed, and gender discrepancy of sample. Conclusions Escitalopram improved depressive, anxiety, and grief symptoms in individuals experiencing a major depressive episode related to the loss of a loved one.

Perimenopausal Depression

Perimenopausal Depression

Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network

Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder. Prospectively collected life chart data from 63 outpatients with bipolar disorders, most recent episodes depressed, manic, or cycling, who received adjunctive quetiapine therapy as part of standard acute treatment were analyzed. Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes. Patients were grouped by baseline symptoms; depression only, mania only, or both mania and depression (cycling group). Owing to small mania and well groups (n=4), differences between depression and cycling groups were examined and mania and well groups excluded. Fifty-five patients were included in the analyses. The primary outcome measure was change in mood severity from baseline to change in treatment regimen, as measured by the NIMH Life Charting Method. Patients received adjunctive quetiapine for a mean of 122 (SD=149) days. Both groups showed significant improvement in depression ratings and time spent depressed by week 10. Both groups showed significant improvement in overall mood. No between-group differences in improvement were found. Adjunctive quetiapine may be useful as continuation treatment in bipolar populations with both pure depressive and cycling symptoms. Further controlled studies are warranted.

Behavioral Implications of Lowering Cholesterol Levels: A Double-Blind Pilot Study

The treatment of hypercholesterolemia may be associated with greater noncardiac mortality. This current pilot study sought to determine which behaviors, if any, are associated with decreases in cholesterol level. Twelve subjects received one of two cholesterol-reducing drugs or placebo. Cholesterol and behavioral ratings were measured at baseline, 4, and 52 weeks with standardized scales. Cholesterol levels markedly declined with concomitant significant increases in impulsivity ratings at 4 weeks. At 52 weeks, the increase in impulsivity ratings was no longer apparent, but depression ratings showed a significant improvement. This pilot study, although limited in size, raises the possibility that cholesterol-lowering drugs are associated with mild, time-limited increases in impulsivity and with mild, time-delayed improvements in depression ratings.

Antiglucocorticoid treatment of depression: double-blind ketoconazole

Background: Hypercortisolemia is frequently observed in major depression but its pathophysiologic significance is unknown. In patients in whom hypercortisolism contributes to depressive symptomatology, antiglucocorticoid agents should have antidepressant effects.Methods: Twenty medication-free depressed patients (eight of whom were hypercortisolemic and twelve of whom were not) received either the cortisol biosynthesis inhibitor, ketoconazole (400–800 mg/d p.o.) or placebo for 4 weeks in a double-blind manner, and behavioral ratings were performed weekly.Results: Ketoconazole, compared to placebo, was associated with improvements in depression ratings in the hypercortisolemic, but not in the non-hypercortisolemic patients. The hormonal changes seen (decreased dehydroepiandrosterone and testosterone levels and increased pregnenolone and pregnenolone-sulfate levels) are consistent with enzymatic blockade of C17,20-lyase, 11-hydroxylase, and 17-hydroxylase. Ketoconazole was generally well tolerated with no occurrence of significant side effects or laboratory abnormalities.Conclusions: This small-scale double-blind study suggests that antiglucocorticoids have antidepressant activity in hypercortisolemic depressed patients. The data are consistent with a causal role of adrenocortical dysfunction in some depressed patients and suggest the need for larger-scale trials.

Plasma noradrenaline response to electroconvulsive therapy in depressive illness.

Abnormalities of catecholaminergic function have been hypothesised to cause depressive illness. Plasma noradrenaline can be used as a marker of central noradrenergic activity. It is of interest to examine the change in resting plasma noradrenaline in patients with depressive illness over a course of electroconvulsive therapy (ECT) and relate this to their clinical state. Patients referred for ECT who suffered from DSM-III-R major depressive disorder or dysthymia were recruited. Blood samples were taken before and after each treatment, during a course of ECT, to measure plasma noradrenaline and cortisol. Clinical ratings were carried out weekly during the course of ECT. Plasma noradrenaline fell significantly in those patients with melancholic/psychotic depressions but increased in those with non-melancholic depressive illness. There was a strong trend indicating that a fall in plasma noradrenaline was associated with improvement in depression ratings in the melancholic/psychotic patients only. Electroconvlusive therapy decreases plasma noradrenaline in melancholic/psychotic depressive illness and this shows a trend associated with clinical improvement.

Dehydroepiandrosterone (DHEA) Treatment of Depression

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA and/or DHEA-S levels were openly administered DHEA (30–90 mg/d × 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months; her depression ratings improved 48–72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Dehydroepiandrosterone (DHEA) treatment of depression

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Reliability and validity of a health-related quality of life battery for evaluating outpatient antidepressant treatment.

This study was designed to evaluate the reproducibility, validity and responsiveness of a health-related quality of life (HRQOL) battery that was assembled for the evaluation of antidepressant therapy. The Montgomery-Asberg Depression Rating Scale was used to measure severity of depression. The HRQOL battery contained measures of energy and fatigue, social behaviour, cognitive function, home and work role function, and general well-being (i.e., health perceptions, life satisfaction) selected from previously developed and validated instruments. The clinical investigators and research nurses reported on difficulty in using the HRQOL battery. Most patients were able to complete the questionnaire without problems within 10 min. Reproducibility was very good with intraclass correlation coefficients ranging from 0.74 to 0.97. The HRQOL scales showed evidence of good concurrent validity. The scales were moderately correlated with MADRS scores (r = 0.30-0.62). The magnitude of these correlations indicate that HRQOL scales are related to depression measures, but they are not alternative measures of depression. Changes in MADRS scores were associated with changes in all scales, except for work behaviour, indicating that improvements in depression ratings also resulted in improvements in health status and well-being. The HRQOL scales included in this study were found to be reliable, reproducible, and valid and no appreciable burden was placed on patients or investigators participating in the study. With the exception of the Work Behaviour scale, the HRQOL scales were very responsive to changes in depression severity. This brief HRQOL instrument can provide a comprehensive assessment of the outcomes of antidepressant treatment.