Reduction In Hamilton Depression Rating Scale Scores Research Articles

L-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial

BackgroundUnsatisfactory responses to major depressive disorder (MDD) therapeutics available necessitated up-to-date treatment approaches. This study sought to investigate the efficacy and tolerability of adjunctive l-theanine, a green tea constituent with neuropsychotropic effects, for MDD. MethodsSixty MDD (DSM-5) patients were equally assigned to receive sertraline (100 mg/d) plus either l-theanine (200 mg/d) or matched placebo in a six-week randomized, parallel-group, double-blind, placebo-controlled study. The participants were assessed using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. Changes in scores, early improvement, response and remission rates, and adverse events were compared between the groups. ResultsTwenty-five participants in each group, a total of 50 patients, completed the study. All baseline characteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p-value = 0.014), indicating more remarkable symptom improvement in the l-theanine group. A greater reduction in HDRS scores was observed in the l-theanine group from baseline to weeks 2, 4, and 6 (p-values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus l-theanine until week 6. l-theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p-values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups. LimitationsThe small sample size and short study period were the limitations. Conclusionsl-theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence.

Efficacy of Sertraline with Aripiprazole versus Paroxetine with Aripiprazole in Patient with Major Depressive Disorder

Background: Major Depressive Disorder (MDD) is the most severe form of depression and can be extremely debilitating for those afflicted. Treatment for MDD typically involves the use of antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, many patients do not respond adequately to these medications, leading to the use of adjunctive treatments, such as atypical antipsychotics. The combination of SSRIs and atypical antipsychotics has been found to be more effective than monotherapy with either medication alone. Aims: The Aim of this study is to compare the efficacy of two different combinations of antidepressants and atypical antipsychotics in the treatment of MDD: sertraline with aripiprazole, and paroxetine with aripiprazole. Study design and setting: Open-label trail. This study was conducted at Sir Cowasjee Jahangir Institute of Psychiatry & Behavioral Sciences, Hyderabad, Pakistan from October 2021 to October 2022. Materials and Methods: In this research trial, a total of 48 patients were randomized to receive either sertraline (100 mg/day) plus aripiprazole (5 mg/day) or paroxetine (20 mg/day) plus aripiprazole (5 mg/day) for a period of 6 weeks. The outcome measure was assessed by the change in Hamilton Depression Rating Scale (HDRS) score from baseline to 6 weeks. Data was analyzed statistically using SPSS version 26. Results: The overall mean age of patients with MDD was 36.52 ± 9.9 years; 56% female and 46% male were reported with MDD. There was a significant reduction in HDRS scores among both groups of drugs; however, no difference was found in terms of efficacy between the two groups. Conclusion: The combination therapy of aripiprazole augmentation, with the addition of either sertraline or paroxetine, was equally effective in patients with Major Depressive Disorder. Keywords: Major depressive disorder, MDD, Sertraline, Paroxetine, Aripiprazole, Augmentation therapy.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder

BackgroundGliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. MethodsA total of 41 subjects with treatment-resistant major depressive disorder underwent one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS). ResultsCumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively. ConclusionsCelecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO VT on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.

Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial

Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression. We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20-70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 μs) or LPW (210-450 μs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904. Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6-12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide. Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression. Alberta Innovates Health Solutions.

Comparison of efficacy and tolerability of escitalopram and venlafaxine in treatment-naïve patients with unipolar nonpsychotic depression: Is there a need to revisit the prescription patterns?

Background: Depression is a common mental illness for which guidelines recommend selective serotonin reuptake inhibitors as the first-line treatment. As per the Sequenced Treatment Alternatives to Relieve Depression trial, the first antidepressant needs to be chosen carefully so that the number of treatment changes and therefore treatment resistance can be reduced. This study compared the efficacy and tolerability of escitalopram and venlafaxine, in treatment-naive patients with first-episode, nonpsychotic unipolar depression. Methodology: In this prospective, randomized, open-label study, 77 patients with the International Classification of Disease-10 Diagnostic Criteria for Research diagnosis of depression were inducted and randomly assigned using a computer-generated random table to receive either escitalopram (10–20 mg/day) or venlafaxine (75–225 mg/day) in therapeutic range for a period of 12 weeks. The assessments included the Hamilton Depression Rating Scale (HDRS) and physical investigations at baseline and weeks 2, 6, and 12. A total of 60 patients completed the study and were included in the final analysis. Results: Thirty patients in each group (n = 60) enrolled with comparable baseline assessment except significantly higher HDRS in the venlafaxine group (29.87 ± 10.58) compared to escitalopram group (21.80 ± 4.41). At 12 weeks, the reduction in HDRS was significantly early and higher in the venlafaxine group (26.3 ± 9.7) than the escitalopram group (21.3 ± 4.2). Common adverse effects in the venlafaxine group included Gastrointestinal (GI) activation and vivid dreams which were seen till 2 weeks; the escitalopram group included sexual dysfunction which lasted till the end of the study. Conclusions: Both the molecules lead to significant reduction in HDRS scores across assessment. However, venlafaxine demonstrated superior efficacy and transient adverse effects compared to escitalopram, despite having higher HDRS scores at baseline. The results of the current study indicate that serotonin–norepinephrine reuptake inhibitors such as venlafaxine should be prescribed more often in routine clinical practice.

Does early response predict subsequent remission in bipolar depression treated with repeated sleep deprivation combined with light therapy and lithium?

BackgroundThe combination of three cycles of sleep deprivation (SD), light therapy (LT), and lithium has recently been proposed as a possible first-line treatment for bipolar depression. However, it is unclear whether early improvement predicts final response/remission in bipolar depression treated with this regimen. MethodWe studied 220 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder. The relation between response to first SD and response/remission at the end of the treatment (day 6) was analyzed using logistic regression analysis. Severity of depression was rated using the Hamilton Depression Rating Scale (HDRS). Clinical response was defined as a ≥50% reduction in HDRS scores, and remission was defined as an HDRS score of ≤7. ResultsAmong the 217 completers, 67.7% showed response and 54.4% reached remission at the end of the treatment. Multiple logistic regression analysis revealed that response after first recovery sleep (day 2) predicted final response and remission at the end of the treatment with high odds ratios (10.9 for response and 8.2 for remission); however, response immediately after the first SD (day 1) did not predict final response or remission. LimitationsWhether our results can be generalized to unipolar depression remains uncertain. ConclusionClinical status after first recovery sleep is a strong predictor of successful final outcome in patients with bipolar depression treated with the combination of repeated SD, LT, and lithium. Recovery sleep may play a role in inducing the antidepressant effect associated with the success of treatment.

Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression

BackgroundTranscranial direct current stimulation (tDCS) is a promising neuromodulation intervention for poor-responding or refractory depressed patients. However, little is known about predictors of response to this therapy. The present study aimed to analyze clinical predictors of response to tDCS in depressed patients. MethodsClinical data from 3 independent tDCS trials on 171 depressed patients (including unipolar and bipolar depression), were pooled and analyzed to assess predictors of response. Depression severity and the underlying clinical dimensions were measured using the Hamilton Depression Rating Scale (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis (bipolar/unipolar depression) were also investigated as predictors of response.Linear mixed models were fitted in order to ascertain which HDRS factors were associated with response to tDCS. ResultsAge, gender and diagnosis did not show any association with response to treatment. The reduction in HDRS scores after tDCS was strongly associated with the baseline values of “Cognitive Disturbances” and “Retardation” factors, whilst the “Anxiety/Somatization” factor showed a mild association with the response. LimitationsOpen-label design, the lack of control group, and minor differences in stimulation protocols. ConclusionsNo differences in response to tDCS were found between unipolar and bipolar patients, suggesting that tDCS is effective for both conditions. “Cognitive disturbance”, “Retardation”, and “Anxiety/Somatization”, were identified as potential clinical predictors of response to tDCS. These findings point to the pre-selection of the potential responders to tDCS, therefore optimizing the clinical use of this technique and the overall cost-effectiveness of the psychiatric intervention for depressed patients.

Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients.

ObjectivesWe investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients.MethodsIn an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up.Main outcome measuresClinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith–Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively.ResultsThe adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation.ConclusionBLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples.

Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM.

Background:Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.Methods:We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.Results:Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.Conclusions:The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.

Abstract W P125: Telephone versus In-person Psychosocial Behavioral Treatment in Post-Stroke Depression

Background: We previously showed that a brief psychosocial behavioral intervention delivered in-person by advanced practice nurses was effective in reducing post-stroke depression (PSD). Purpose: This randomized clinical trial compared a shortened (6 week) intervention by telephone or in-person to usual care in volunteers within 4 months of an ischemic or hemorrhagic stroke. Methods: 100 stroke survivors who screened positive for depression (Geriatric Depression Score &gt;11) were randomized to usual care (UC), telephone intervention (TI), or in-person intervention (IPI). Primary outcomes were percent reduction in the Hamilton Depression Rating Scale (HDRS) at 8 weeks, 21 weeks and 12 months following study entry. Outcome assessors were masked to randomization status. Results: All three groups had similar depression scores at baseline (HDRS mean 18 for UC and TI, 19 for IPI). The mean percent reduction in HDRS scores for telephone and in-person groups was 42% and 40% immediately following the intervention at 8 weeks compared to a 30% reduction in the usual care group. However the difference only trended toward significance, controlling for age, with older age associated with better response (p = 0.31). There was a greater early reduction in depression in the UC group than in our previous work (30% HDRS reduction vs 18% at 8 weeks). By 21 weeks and 12 months following entry there was no significant difference between groups in HDRS reduction (40% UC, 40% TI, 39% IPI and 37% UC, 42% TI and 44% IPI, respectively). Conclusions: A brief psychosocial intervention for PSD reduced depression somewhat more than usual care (p=.31) right after treatment but the difference between groups was even less at 21 weeks and one year following entry. The reduction in depression was slightly smaller than in our earlier study for the intervention groups, and the usual care group improved more. The comparability of telephone and in-person follow-up and treatment for depression is important given mandated post-hospital follow-up for comprehensive stroke centers. The improved response to brief therapy for older participants suggests tailoring of care to provide individualized follow-up.

Antidepressant and Group Psychosocial Treatment for Depression: A Rater Blind Exploratory RCT from a Low Income Country

Research in the West shows that group psychological intervention together with an antidepressant treatment leads to more effective treatment of a depressive disorder. There are no treatment trials from low income countries comparing the efficacy of antidepressant treatment with a group psychological intervention. To conduct a feasibility trial to compare the efficacy of an antidepressant to a group psychosocial intervention, for low income women attending primary health care in Karachi, Pakistan. This was a preliminary RCT in an urban primary health care clinic in Karachi, Pakistan. Consecutive eligible women scoring >12 on the CIS-R and >18 on Hamilton Depression Rating Scale (HDRS) (n = 66) were randomly assigned to antidepressants or a psychosocial treatment in group settings. The primary outcome measure was HDRS score; secondary outcome measures were disability and quality of life. More than half of the patients in both groups improved (50% reduction in HDRS scores); at end of therapy at 3 months 19 (59.4%) vs 18 (56.2%), and at 6-month follow-up 21(67.7%) vs 20(62.5%) for antidepressants and psychosocial intervention respectively. Although HDRS, BDQ and EQ5-D scores all improved considerably in both groups from start to end of treatment, and these improvements were largely maintained after a further 3 months, the differences between the two treatments were not statistically significant. Psychosocial intervention was as effective as antidepressants in reducing depression and in improving quality of life and disability at the end of therapy. However, these findings need further exploration through a larger trial.

Positive therapeutic and neurotropic effects of yoga in depression: A comparative study

Context:Therapeutic effect of yoga in depression is recognized. Neuroplastic effects of antidepressant therapies are inferred by elevations in brain-derived neurotrophic factor (BDNF). Role of yoga in both these effects has not been studied.Materials and Methods:Non-suicidal, consecutive out-patients of depression were offered yoga either alone or with antidepressants. The depression severity was rated on Hamilton Depression Rating Scale (HDRS) before and at 3 months. Serum BDNF levels were measured at the same time points. Repeated-measures analysis of variance was performed to look at change across groups with respect to HDRS scores and BDNF levels over 3 months of follow-up. Relationship between change in serum BDNF levels and change in HDRS scores was assessed using the Pearson's correlation coefficient.Results:Both yoga groups were better than drugs-only group with respect to reduction in HDRS scores. Serum BDNF rose in the total sample in the 3-month period. This was not, however, different across treatment groups. There was a significant positive correlation between fall in HDRS and rise in serum BDNF levels in yoga-only group (r=0.702; P=0.001), but not in those receiving yoga and antidepressants or antidepressants-alone.Conclusions:Neuroplastic mechanisms may be related to the therapeutic mechanisms of yoga in depression.

Repetitive Transcranial Magnetic Stimulation in the Treatment of depression: A Randomized, Double-blind, Placebo-controlled Trial

Background:The efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression has never been reported as yet in the Indian literature.Aims:To study the efficacy of rTMS in the treatment of depression and to evaluate its safety and tolerability.Settings and Design:A randomized, double-blind, sham-controlled trial was conducted at the Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore.Materials and Methods:23 patients with depression were randomized to receive either active (n=9) or sham (n=14) treatment with rTMS. Treatment consisted of six sessions of rTMS for 2 weeks (10 trains of pulses, intensity equal to motor threshold, 10 Hz frequency, train duration of 5 seconds, 1 minute inter-train duration). Response was assessed using Hamilton Depression Rating Scale (HDRS), Montgomery Åsberg Depression Rating Scale (MADRS) and Clinical Global Index (CGI). The safety and tolerability was assessed with side-effect checklist for electroconvulsive therapy. 50% reduction in HDRS scores from baseline was defined as treatment response. Outcome measures were analyzed by repeated measures analysis of variance. Chi-square test was used to analyze the categorical variables.Results:No statistical significance was seen on the baseline socio-demographic and illness characteristics (Pearson's Chi-square=0.5). Although HDRS (sham 22.0-12.4; active 22.8-12.7) and MADRS (sham 30.7-17.3; active 31.8-16.7) scores reduced by the end of 2 weeks treatment, it was not statistically significant. One patient developed manic symptoms early in the treatment.Conclusions:Treatment with rTMS did not show improvement at the end of 2 weeks. More studies with larger sample size and with higher rTMS dosages need to be done.

Efficacy and Tolerability of Antidepressants for Treatment of Depression in Coronary Artery Disease: A Meta-Analysis

Depression occurs in 18% to 45% of patients with coronary artery disease (CAD) where it is associated with an increased risk of acute coronary events and mortality. Our objective was to quantitatively summarize the data on the efficacy and tolerability of antidepressant (AD) treatment for depression in CAD. We performed a meta-analysis of randomized, placebo-controlled, double-blind trials with a database search of the English literature (to March 2008) and manual search of references. Four clinical trials with ADs (mirtazapine, citalopram, fluoxetine, and sertraline) of a 9- to 24-week duration involving 798 subjects (402 ADs, 396 placebo) with documented CAD and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for depression were included. ADs were superior to placebo for decreasing Hamilton Depression Rating Scale (HDRS) scores (402 ADs, 396 placebo; weighted mean difference 1.41, 95% CI 0.53 to 2.29, P = 0.002) and Beck Depression Inventory (BDI) scores (373 ADs, 369 placebo; weighted mean difference 2.27, 95% CI 0.60 to 3.94, P = 0.008). The proportion of patients (216 ADs, 213 placebo) who responded (a 50% or more reduction in HDRS scores, OR 1.72, 95% CI 1.17 to 2.54) and remitted (HDRS of 8 or less at final assessment, OR 1.80, 95% CI 1.18 to 2.74), were also significantly higher with AD, compared with placebo, with no significant differences between the 2 groups for overall dropouts (OR 0.84, 95% CI 0.42 to 1.68) or dropout owing to adverse events (OR 1.30, 95% CI 0.75 to 2.25). The combined studies were homogeneous except for overall dropout rate (P = 0.01). Treatment with ADs for depression in CAD results in significant therapeutic effects without substantially increased rates of discontinuation.

Modulation of cardiac autonomic functions in patients with major depression treated with repetitive transcranial magnetic stimulation

Background Sub clinical cardiac autonomic imbalance is associated with depression. Clinical improvement produced by antidepressant therapy might alter this autonomic balance. Objectives To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) therapy on autonomic functions measured by heart rate variability (HRV) in depression patients and compare it with selective serotonin re-up-take inhibitors (SSRI) therapy. Methods Consecutive drug-naïve patients of major depression based on DSM-IV-TR were recruited in this study ( n = 67). Basal Hamilton depression-rating scale (HDRS) and measures of cardiac autonomic function were recorded and compared with those after two weeks of therapy with rTMS ( n = 27) and one month after SSRI therapy ( n = 25). Results Both therapies produced comparable and significant reduction in HDRS scores. HRV measures indicated that rTMS produced significantly greater reduction in the sympathetic: parasympathetic ratio suggesting improvement in sympathovagal balance. Conventional cardiac autonomic function tests did not differentiate the two therapy effects. Conclusions rTMS not only produced antidepressant effects but also ‘‘corrected’’ the autonomic imbalance. SSRI was systemically administered and hence by direct cardiac effect, may have masked cardiac effects that would have occurred by the improvement in depression. Alternatively, the neurophysiological ‘‘correction’’ with drug therapy may have longer latency, just as with the therapeutic effects.

A Controlled Trial of Adinazolam versus Desipramine in Geriatric Depression

Thirty outpatients between the ages of 60 and 85 with DSM-III Major Depression entered an 8 week randomized, double-blind comparison of desipramine and adinazolam mesylate, a triazolobenzodiazepine derivative. Outcome was assessed on several measures including the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Rating Scale, Clinical Global Impressions (CGI), the 35-item Self-Rating Symptom Scale, and Carroll Depression Scale. Patients in both groups demonstrated a highly significant decrease in average HDRS scores (p less than 0.001) over the course of the study. Adinazolam was associated with significantly greater reduction in average HDRS scores by the third day. Repeated measures analysis of variance showed a significantly greater reduction in HDRS scores for adinazolam over the course of the study. The study medications were associated with distinct patterns of adverse reactions. Desipramine more often produced dry mouth, constipation and nervousness, while adinazolam was more likely to cause drowsiness and lightheadedness. Three of these elderly patients, all of whom were taking desipramine reported at least one fall during the study. Adinazolam may be a promising agent in the treatment of depression in the elderly.