Magnitude Of Symptom Reduction Research Articles

Effects of group trauma-sensitive yoga on inflammatory markers and psychological well-being in women veterans with PTSD: A randomized controlled trial

BackgroundLifetime prevalence of post-traumatic stress disorder (PTSD) is double among veterans compared to civilians and women compared to men. Inflammatory factors are increasingly implicated in symptoms of PTSD. Yoga shows promise to reduce psychological symptoms of PTSD and positively impact inflammatory responses. The present study aimed to examine the effectiveness of yoga to reduce symptoms of PTSD and depression in addition to investigating the impact of treatment on inflammatory markers in women veterans with PTSD secondary to military sexual trauma. MethodsWe collected dried blood spot samples, self-report and clinician administered measures of PTSD, and self-reported depression symptoms at baseline, 2 weeks, and 3 months post-intervention from a subset of women veterans diagnosed with PTSD (N = 27) who were randomized to either Trauma Center Trauma-Sensitive Yoga (TCTSY; a movement therapy) or cognitive processing therapy (CPT; a talk therapy) as part of a larger multisite RCT. Concentrations of interleukin (IL)-6, IL-10, and C-reactive protein (CRP) were measured using multiplex bead-based immunoassay at baseline and post-intervention (2 weeks and 3 months). Generalized estimating equations examined changes in symptoms of PTSD, depression, and inflammatory markers over time. We hypothesized decreases in IL-6 and CRP and increases in IL-10 in TCTSY participants compared to CPT participants and that PTSD and depression symptoms would improve over time in both groups. ResultsFrom baseline to 3 months post-intervention, IL-6 (β = 0.10, p < 0.05), IL-10 (β = 0.68, p < 0.05), and CRP (β = 0.77, p < 0.05) increased in TCTSY participants relative to those randomized to CPT. PTSD and depression symptoms reduced in both groups over time (CAPS-5 β = −3.96, PCL-5 β = −4.66, and BDI-II β = −2.70, all p < 0.05); groups did not differ in magnitude of symptom reduction. ConclusionsFindings indicate that TCTSY has the potential to improve symptoms of PTSD and depression and alter inflammatory markers. The findings are limited by our sample size and the immune factors we examined. Future directions for related research would benefit from measuring a wider array of stress response components.

Dosing transcranial magnetic stimulation in major depressive disorder: Relations between number of treatment sessions and effectiveness in a large patient registry

BackgroundThe number of sessions in an acute TMS course for major depressive disorder (MDD) is greater than in the earlier randomized controlled trials. ObjectiveTo compare clinical outcomes in groups that received differing numbers of TMS sessions. MethodsFrom a registry sample (N = 13,732), data were extracted for 7215 patients treated for MDD with PHQ-9 assessments before and after their TMS course. Groups were defined by number of acute course treatment sessions: 1–19 (N = 658), 20–29 (N = 616), 30–35 (N = 1375), 36 (N = 3591), 37–41 (N = 626), or >41 (N = 349) and compared in clinical outcomes at endpoint and at fixed intervals (after 10, 20, 30, and 36 sessions). The impact of additional treatments beyond 36 sessions was also examined. ResultsGroups that received fewer than 30 sessions had inferior endpoint outcomes than all other groups. PHQ-9 symptom reduction was greatest in the group that ended treatment at 36 sessions. The extended treatment groups (>36 sessions) differed from all other groups by manifesting less antidepressant response early in the course and had a slower but steady rate of improvement over time. Extending treatment beyond 36 sessions was associated with further improvement without evidence of a plateau. ConclusionsIn real-world practice, there are strong relations between the number of TMS sessions in a course and the magnitude of symptom reduction. Courses with less than 30 sessions are associated with diminished benefit. Patients with longer than standard courses typically show less initial improvement and a more gradual trajectory, but meaningful benefit accrues with treatment beyond 36 sessions.

Changes to Immunological Mechanisms and Symptoms of PTSD after Group Cognitive Processing Therapy vs. Trauma-Sensitive Yoga for Women Veterans with PTSD

Lifetime prevalence of post-traumatic stress disorder (PTSD) among Veterans is double that of civilians. Immunological mechanisms are implicated in PTSD, including cardiovascular and autoimmune consequences. Yoga shows promise to reduce psychological symptoms of PTSD and positively impact immunological mechanisms. We collected dried blood spot samples at baseline, 2 weeks, and 3 months post-intervention from women Veterans with PTSD (N=28), randomized to either cognitive processing therapy (CPT) or trauma-sensitive yoga. Concentrations of interleukin (IL)-6, IL-10, and C-reactive protein (CRP) were measured using multiplex bead-based immunoassay. The CAPS-5 measured PTSD symptoms. Generalized estimating equations modelled Time X Treatment to examine changes in immune factors and PTSD symptoms. We hypothesized baseline levels of immune factors would significantly improve over time (decreases in IL-6, CRP and increases in IL-10) in yoga participants compared to CPT participants and that PTSD symptoms would improve in both groups. IL-6 (b=.68, p<.01), IL-10 (b=.77, p=.02), and CRP (b=.10, p<.01) increased in all patients from baseline to 3 month follow-up and to a greater extent in patients who received yoga. PTSD symptoms reduced in both conditions over time (b=-3.93, p<.01); groups did not differ in magnitude of symptom reduction (b=-2.68, p=.25). Findings indicate CPT and yoga have the potential to alter immunological mechanisms and improve symptoms of PTSD, with additional long-term change for yoga participants. Future research should examine the health consequences of immunological changes following these interventions.

Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD

Fear extinction underlies prolonged exposure, one of the most well-studied treatments for posttraumatic stress disorder (PTSD). There has been increased interest in exploring pharmacological agents to enhance fear extinction learning in humans and their potential as adjuncts to PE. The objective of such adjuncts is to augment the clinical impact of PE on the durability and magnitude of symptom reduction. In this study, we examined whether hydrocortisone (HC), a corticosteroid, and D-Cycloserine (DCS), an N-methyl-D-aspartate receptor partial agonist, enhance fear extinction learning and consolidation in individuals with PTSD. In a double-blind placebo-controlled 3-group experimental design, 90 individuals with full or subsyndromal PTSD underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS−) with shock. Extinction learning occurred 72 h later and extinction retention was tested one week after extinction. HC 25 mg, DCS 50 mg or placebo was administered one hour prior to extinction learning. During extinction learning, the DCS and HC groups showed a reduced differential CS+/CS− skin conductance response (SCR) compared to placebo (b = −0.19, CI = −0.01 to −37, p = 0.042 and b = −0.25, CI = −08 to −0.43, p = 0.005, respectively). A nonsignificant trend for a lower differential CS+/CS− SCR in the DCS group, compared to placebo, (b = −0.25, CI = 0.04 to −0.55, p = 0.089) was observed at retention testing, one week later. A single dose of HC and DCS facilitated fear extinction learning in participants with PTSD symptoms. While clinical implications have yet to be determined, our findings suggest that glucocorticoids and NMDA agonists hold promise for facilitating extinction learning in PTSD.

Defining post-traumatic stress disorder recovery in veterans: Benchmarking symptom change against functioning indicators.

Improved metrics of Post-traumatic stress disorder (PTSD) treatment response that extend beyond a focus on symptom reduction to incorporate meaningful, patient-centred indicators of functioning are needed in veteran populations. The aim of this study was to extend previous research by investigating whether indicators of functioning can successfully distinguish against symptom response categories derived from the Post-Traumatic Stress Disorder Checklist (PCL-5) pre- and post- PTSD treatment. Participants were 472 veterans receiving hospital-based treatment for PTSD. In addition to the PCL-5, measures included quality of life, social relationships, physical health and psychological distress. Four mutually exclusive, progressive response categories were used to define treatment response including: No Response, Response, Response and Below Threshold, and Remission. PTSD symptom reductions were associated with corresponding improvements in broader indicators of functioning. However, it was only when the magnitude of symptom reduction placed the individual in the 'Response and Below Threshold' category that improvement on functioning measures achieved levels indicative of a good end state. Traditional metrics of treatment 'response' in PTSD treatment do not necessarily indicate recovery on important functioning indicators. Only when an individual both responds to treatment and drops below threshold for probable disorder are they likely to report having meaningful levels of functioning.

Does Early Low-Intensity Aerobic Exercise Hasten Recovery in Adolescents With Sport-Related Concussion?

Clinical Scenario: Low-intensity aerobic exercise (LIAEX) below the threshold of symptom exacerbation has been shown to be superior to rest for resolving prolonged (>4wk) symptoms following sport-related concussion (SRC), but the effects of LIAEX earlier than 4 weeks after SRC need to be elucidated. Focused Clinical Question: Does LIAEX within the first 4 weeks following SRC hasten symptom resolution? Summary of Key Findings: Two randomized controlled trials (RCT) and 1 nonrandomized trial involving adolescent athletes (10-19y) were included. One RCT reported faster recovery time with LIAEX versus placebo stretching. Likewise, recovery time was faster with LIAEX versus rest in the nonrandomized trial, but not in the underpowered RCT, although effect sizes were similar between these studies (0.5 and 0.4, respectively). All 3 studies reported a reduction in concussion symptom severity with LIAEX; however, the magnitude of symptom reduction across the recovery timeline was greater in the LIAEX group than the rest group in the nonrandomized trial, but not the 2 RCTs. Importantly, no adverse effects or incidence of delayed recovery from LIAEX were reported in any of the studies. Clinical Bottom Line: LIAEX initiated within 10 days after SRC may facilitate a faster recovery time versus placebo stretching or rest, although additional clinical trials are strongly advised to verify this. Strength of Recommendation: Level 1b and 2b evidence suggests subsymptom exacerbation LIAEX may decrease Postconcussion Symptom Scale scores and hasten symptom resolution in adolescent athletes following SRC.

T146. Anxiety-Potentiated Startle Reductions Correlate With Symptom Reduction by Sertraline in Premenstrual Dysphoric Disorder (PMDD)

Premenstrual dysphoric disorder (PMDD) affects millions of women worldwide, and is thought to reflect suboptimal sensitivity to the GABAergic progesterone metabolite allopregnanolone (ALLO). Anxiety-potentiated startle (APS), evoked by unpredictable threat, is mediated by the ALLO-sensitive bed nucleus of the stria terminalis (BNST), and is used in this study as a marker of GABAergic sensitivity. We hypothesized that luteal (L) phase sertraline treatment will reduce premenstrual mood symptoms, and the magnitude of symptom reduction will correlate with magnitude of APS reduction. We hypothesized that fear-potentiated startle (FPS) to predictable threat, which is not mediated by BNST, will not correspond to symptom reduction.

Assessing Suitability for Short-Term Cognitive-Behavioral Therapy in Psychiatric Outpatients with Psychosis

The Suitability for Short-Term Cognitive Therapy (SSCT) rating procedure has predicted outcome in depressed and anxious patients. This study examines its relevance in assessing patients with psychosis. Outpatients with psychosis (n=56), depression (n=93), and anxiety (n=264) received cognitive- behavioral therapy in a university hospital teaching unit (mean number of sessions=16, SD=11). Demographic, clinical, and suitability variables were assessed as potential predictors of dropout and success as measured by the Reliable Change Index. Despite lower suitability scores in the psychosis group, dropout and success rates were similar across groups, although the magnitude of symptom reduction was less in the psychosis group. Across diagnoses, dropout was predicted by unemployment and by reluctance to take personal responsibility for change. In the psychosis group only, dropout was predicted by hostility. Success of completed therapy was predicted by higher baseline agoraphobic anxiety and "responsibility for change" scores. Attention to hostility early in therapy may reduce dropout in psychotic patients. Fostering acceptance of responsibility for change may improve both treatment retention and success across diagnoses. Agoraphobic fear is associated with success, possibly reflecting the effectiveness of behavioral interventions in psychosis and anxiety alike.

A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression

BackgroundAlthough previous meta-analyses have examined effects of antidepressants, psychotherapy, and alternative therapies for depression, the efficacy of these treatments alone and in combination has not been systematically compared. We hypothesized that the differences between approved depression treatments and controls would be small.Methods and FindingsThe authors first reviewed data from Food and Drug Administration Summary Basis of Approval reports of 62 pivotal antidepressant trials consisting of data from 13,802 depressed patients. This was followed by a systematic review of data from 115 published trials evaluating efficacy of psychotherapies and alternative therapies for depression. The published depression trials consisted of 10,310 depressed patients. We assessed the percentage symptom reduction experienced by the patients based on treatment assignment. Overall, antidepressants led to greater symptom reduction compared to placebo among both unpublished FDA data and published trials (F = 38.5, df = 239, p<0.001). In the published trials we noted that the magnitude of symptom reduction with active depression treatments compared to controls was significantly larger when raters evaluating treatment effects were un-blinded compared to the trials with blinded raters (F = 2.17, df = 313, p<0.05). In the blinded trials, the combination of antidepressants and psychotherapy provided a slight advantage over antidepressants (p = 0.027) and psychotherapy (p = 0.022) alone. The magnitude of symptom reduction was greater with psychotherapies compared to placebo (p = 0.019), treatment-as-usual (p = 0.012) and waiting-list (p<0.001). Differences were not seen with psychotherapy compared to antidepressants, alternative therapies or active intervention controls.ConclusionsIn conclusion, the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls. These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program. Future research should consider whether certain patient profiles might justify a specific treatment modality.

Are Children Improving? Results from Outcome Measurement in a Large Mental Health System

Standardized outcome assessment was implemented in a large county mental health system. This study examines changes in children's emotional and behavioral problems after 6months of treatment and identifies factors associated with treatment improvement. Results from 3,215 youth indicated that externalizing and internalizing problems significantly decreased from intake to 6months and that ethnicity, gender, and age were associated with caregiver-reported changes in symptomatology. While there was improvement associated with entry into treatment, the magnitude of symptom reduction was small to medium and not associated with amount of care, providing only limited support for the impact of routine out-patient care.

Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizo-affective Disorder: Findings From the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders.

Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database.

Some studies suggest that more severely ill patients with depression respond well to antidepressants and poorly to placebo, whereas those who are mildly ill respond equally well to antidepressants and placebo. This notion has implications for the design of clinical trials. To further assess and substantiate these putative predictors of antidepressant and placebo response, we assessed the Food and Drug Administration database of 45 phase II and III antidepressant clinical trials. The frequency of statistically significant differences between antidepressants and placebo was higher in the trials that included patients with more severe depression. In the antidepressant-treated groups, the magnitude of symptom reduction was significantly related to mean initial Hamilton Rating Scale for Depression (HAM-D) score; the higher the mean initial HAM-D score, the larger the change. With placebo treatment, however, the higher the mean initial HAM-D score, the smaller the change. Early discontinuation was more frequent among patients whose mean initial HAM-D scores were higher. These data may help inform the design of future antidepressant clinical trials.