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Background: It is not known whether common anxiety/mood comorbidities of panic disorder (PD) improve with panic-focused psychological treatment, nor whether there is differential efficacy between therapies in treating comorbidities., Methods: In a randomized controlled trial for PD with and without agoraphobia comparing Cognitive-Behavioral Therapy (CBT) and Panic-Focused Psychodynamic Psychotherapy (PFPP), symptomatic comorbidities of agoraphobia, MDD, GAD, and social anxiety disorder (SAD) were assessed pre-to-post treatment with the Anxiety Disorders Interview Schedule (ADIS). Comparative efficacy of CBT versus PFPP for treating comorbid disorders was tested at termination and 1 year's follow-up. Covariance between panic and comorbidity improvements was also analyzed., Results: Most treatment completers (n = 120) evidenced diagnostic remission of their comorbidity (range = 54-69%), which typically reflected a subclinical score on the ADIS (mean range = 1.3 to 1.8). These improvements were generally retained at follow-up. However, patients with MDD dropped out significantly more often (HR = 2.79). No significant symptom change or remission differences emerged between CBT and PFPP for any comorbidity at termination or at follow-up. Panic change was strongly related to improvements in agoraphobia (r = 0.70) and MDD (r = 0.53), moderately related for GAD (r = 0.31), and not significantly related for SAD (r = 0.20)., Discussion: Patients completing panic-focused psychotherapies often experience meaningful remission for diagnoses of agoraphobia, MDD, GAD, and SAD, with no detectable differences between treatments, although sample sizes for the MDD and SAD comparisons were small. In addition, additional efforts may be needed to keep MDD-comorbid patients in treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Dysfunctions in stress biology are hypothesized to contribute to anxiety disorders, and to be ameliorated during successful treatment, but limited clinical data exist to support this hypothesis. We evaluated whether increases in morning cortisol and the diurnal cortisol slope, markers of stress biology, are associated with clinical response to chamomile therapy among subjects with generalized anxiety disorder (GAD)., Methods: Among 45 subjects with DSM-IV diagnosed GAD in an open-label clinical trial of chamomile, salivary cortisol was assessed for three days each pre- and post-treatment, at 8am, 12pm, 4pm, and 8pm. Mixed model analyses assessed whether GAD symptom change predicted the degree to which cortisol levels changed during treatment., Results: Symptom improvement during treatment was significantly associated with pre-to-post treatment changes in cortisol. Subjects who experienced more symptomatic improvement experienced significant increases in their morning salivary cortisol (β = 0.48, p < 0.001), and a greater decrease in cortisol from morning to the rest of the day (β = 0.55, p < 0.001). In addition, at baseline a lower cortisol level (β = -0.24, p = 0.023) and a lesser decrease in cortisol after morning (β = 0.30, p = 0.003) were associated with greater symptomatic improvement., Conclusion: Increases in morning salivary cortisol and the diurnal cortisol slope are associated with symptom improvement in chamomile treatment of GAD. Response to treatment for GAD could partially stem from normalization of stress biology dysfunction, but further work involving establishing abnormalities within-sample, ruling out of confounds (e.g., sleep), and a placebo control is necessary to conclude an amelioration effect., Registration Code: NCT01072344. URL: https://clinicaltrials.gov/ct2/show/NCT01072344., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes., Methods: Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes., Results: Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient's predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = -0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = -0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306)., Conclusions: Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes., Registration: Trial Number NCT01072344 at ClinicalTrials.gov., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects., Purpose: To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse., Methods: Outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at ClinicalTrials.gov, identifier NCT01072344., Results: Between March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20-1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates., Conclusions: Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, but did not significantly reduce rate of relapse. Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding. Possible chamomile superiority over placebo requires further examination in large-scale studies., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD., Hypothesis: We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile., Study Design: We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD., Methods: Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined., Results: Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred., Conclusion: Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Since the introduction of Beck's cognitive theory of emotional disorders, and their treatment with psychotherapy, cognitive-behavioral approaches have become the most extensively researched psychological treatment for a wide variety of disorders. Despite this, the relative contribution of cognitive to behavioral approaches to treatment are poorly understood and the mechanistic role of cognitive change in therapy is widely debated. We critically review this literature, focusing on the mechanistic role of cognitive change across cognitive and behavioral therapies for depressive and anxiety disorders., (Copyright © 2016. Published by Elsevier Ltd.)

Recent randomized controlled trials (RCTs) suggest that psychodynamic therapy (PDT) may be useful in the treatment of anxiety disorders. This paper presents the most comprehensive meta-analysis to date examining the controlled effects of PDT for anxiety disorders. 14 RCTs totaling 1073 patients were included. PDT was found to be significantly more effective than control conditions (g=0.64). PDT did not differ significantly from alternative treatments at post-treatment (g=0.02), follow-up (FU) up to a year (g=-0.11), and FU past a year (g=-0.26). Medium-to-high levels of heterogeneity were detected, indicating significant differences between studies. Nevertheless, our findings remained unchanged when heterogeneity outliers were removed (termination g=-0.06/short FU g=-0.01/long FU g=-0.10). Power analyses indicated that large or medium effect size differences between PDT and other active treatments could be detected even with high heterogeneity. Exploratory moderator analyses found few significant predictors of effect (e.g., relative risk of dropout). No differences were found examining remission rates or relative risk of dropout. Overall, PDT was shown to be as efficacious as other active treatments that have been studied for anxiety disorders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)