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Patients' expectations and beliefs regarding the potential benefits and harms of medical interventions may induce placebo and nocebo effects, and affect the response to pain therapies. In a randomized clinical trial, we examined the effect of placebo and nocebo expectations on pain relief and adverse events (AEs) in association with a topical treatment among 65 cancer survivors experiencing chronic musculoskeletal pain. Participants received either a 1 % camphor-based topical pain patch or a placebo treatment for 14 days. We measured pain severity with the worst pain item of the Brief Pain Inventory (BPI) at baseline and 14 days and treatment expectations at baseline with validated expectation questionnaires. We found that high vs. low nocebo expectations decreased pain severity improvements by 2.5 points (95 % confidence interval [CI] −3.8 to −1.2; p<0.001) on a 0–10 numeric rating scale of the BPI and pain response rate by 42.7 % (95 % CI 0.2–0.6; p<0.001) at day 14, irrespective of placebo expectation status or treatment arms. Patients with high vs. low nocebo expectations in the true arm reported 22.4 % more unwanted AEs. High nocebo expectations were associated with increased AEs by 39.5 % (odds ratio: 12.0, 95 % CI 1.2, 145.5; p=0.029) and decreased pain response in the true arm vs. placebo. Our study demonstrated that nocebo expectations, rather than placebo expectations, elevate the risk of AEs and compromise the effect of topical pain interventions. The findings raise the possibility that nocebo expectations may worsen somatic symptoms through heightening central pain amplification and should be further investigated. [Display omitted] • This trial examined the role of nocebo expectations in topical pain relief among cancer survivors. • High vs. low nocebo expectation decreased the effect of a topical pain treatment on pain relief. • High vs. low nocebo expectation was associated with increased adverse events reported by patients. • Nocebo expectations may worsen somatic symptoms through heightening central pain sensitization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background : We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola rosea ( R. rosea) versus sertraline for mild to moderate major depressive disorder. Hypothesis : We hypothesize that R. rosea would have similar therapeutic effects as sertraline but with less adverse events. Study design : Phase II randomized placebo controlled clinical trial. Methods : 57 subjects were randomized to 12 weeks of standardized R. rosea extract, sertraline, or placebo. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores among groups were examined using mixed-effects models. Results : Modest, albeit statistically non-significant, reductions were observed for HAM-D, BDI, and CGI/C scores for all treatment conditions with no significant difference between groups ( p = 0.79, p = 0.28, and p = 0.17, respectively). The decline in HAM-D scores was greater for sertraline (−8.2, 95% confidence interval [CI], −12.7 to −3.6) versus R. rosea (−5.1, 95% CI: −8.8 to −1.3) and placebo (−4.6, 95% CI: −8.6 to −0.6). While the odds of improving (versus placebo) were greater for sertraline (1.90 [0.44–8.20]; odds ratio [95% CI]) than R. rosea (1.39 [0.38–5.04]), more subjects on sertraline reported adverse events (63.2%) than R. rosea (30.0%) or placebo (16.7%) ( p = 0.012). Conclusions : Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated. These findings suggest that R. rosea , although less effective than sertraline, may possess a more favorable risk to benefit ratio for individuals with mild to moderate depression. [ABSTRACT FROM AUTHOR]

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 . [ABSTRACT FROM AUTHOR]

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 . [ABSTRACT FROM AUTHOR]

Context: Racial pain disparities present challenges to cancer symptom management. Music therapy has demonstrated benefits for pain and is a promising treatment option for diverse populations due to music's multicultural presence. However, Black cancer patients are under-represented in music therapy trials.Objectives: This study compared pain severity, treatment approaches, and responses to music therapy between Black and white cancer patients. The findings will be used to generate hypotheses for future music therapy research to address racial disparities in pain management.Methods: We conducted a retrospective program evaluation of Black and white patients who received music therapy at an NCI-Designated Comprehensive Cancer Center. We used the Edmonton Symptom Assessment Scale (ESAS) to assess pain. We abstracted opioid use, music therapy referral reasons, and treatment approaches from the electronic health record.Results: Among 358 patients, 18% were Black, 42% reported moderate-to-severe pain, and 47% received opioids. Black patients reported higher baseline pain than white patients, but similar proportions of Black and white patients received opioids. Greater proportions of Black patients received music therapy referrals for pain (73% vs. 56%, P = 0.04) and engaged in active techniques (92% vs. 82%, P = 0.04). Black and white patients reported clinically meaningful pain reduction of similar magnitude after music therapy. Black patients discussed spirituality more commonly during music therapy, whereas white patients focused on family bonds.Conclusion: Black and white patients reported clinically meaningful pain reduction through varying music therapy approaches. Our findings may help inform cultural adaptations of music therapy to address racial pain disparities in oncology. [ABSTRACT FROM AUTHOR]