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Objective: The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS). Methods: This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers. Results: In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023). Conclusion: Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes. [ABSTRACT FROM AUTHOR]

Background. When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. Method. We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. Results. An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01-1.01, p = 0.047, I² = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00-1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. Conclusions. There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas. [ABSTRACT FROM AUTHOR]

RATIONALE: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into 'aqueous' extracts of Kava. OBJECTIVE: [...]

Psychopharmacol [...], OBJECTIVE: We report the first randomised controlled trial (RCT) using a combination of St. John's wort (SJW) and Kava for the treatment of major depressive disorder (MDD) with comorbid anxiety. METHODS: Twentyeight adults with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of 4 weeks. The primary analyses used intention-to-treat and completer analyses. RESULTS: On both intention-to-treat (p = 0.047) and completer analyses (p = 0.003), SJW and Kava gave a significantly greater reduction in self-reported depression on the Beck Depression Inventory (BDI-II) over placebo in the first controlled phase. However, in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life. CONCLUSION: There was some evidence of antidepressant effects using SJW and Kava in a small sample with comorbid anxiety. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava.

Objective: The aim of this study was to examine whether gender differences may have affected treatment response to S-adenosyl methionine (SAMe) in a recent failed randomized clinical trial (RCT) for adults with major depressive disorder. Methods: Data from a 2-site, 12-week, doubleblind RCT (n = 189) assessing the efficacy of SAMe vs. placebo and a comparator selective serotonin reuptake inhibitor (escitalopram) were subjected to post-hoc analyses to evaluate effects of patient gender on treatment response. Results: When assessing the efficacy outcomes within each gender separately, SAMe was superior to placebo among males (n = 51), but not among females (n = 62). Males showed a significant reduction of depression severity from baseline to study endpoint on the 17-item Hamilton Depression Rating Scale (4.3 point difference; p = 0.034; d = 0.95), while females did not show significant change. This finding emerged despite equivalence on baseline measures of depression severity between the gender groups. Conclusion: Results of this secondary data analysis suggest that gender might impact the antidepressant efficacy of SAMe, with greater therapeutic effect found in males. The underlying mechanism is still relatively unknown. Further work is needed to replicate this observation in independent samples. Clinicaltrials.gov identifier: NCT00101452 [ABSTRACT FROM AUTHOR]

The influence of the exciting frequency on crack detection by eddy current thermography is investigated experimentally. The performance of a coil designated C16 with exciting frequency 32 kHz in the detection of eight cracks in circular aluminium plates, at various positions and orientations, is compared with the performance of two coils (designated C8 and C15) with exciting frequency 50 Hz. Crack detection is based not only on the thermograms but also on data processing techniques. The coil C16 proved to be the most effective as it detected seven cracks out of the eight, whereas the C8 coil detected five cracks and the C15 four. Furthermore, in most cases, it gave sharper images of the crack. Elevated heating rates are induced by higher exciting frequencies, resulting in elevated values of current density and heat flow. Therefore, wider detection regions and longer detection periods may be achieved. [ABSTRACT FROM AUTHOR]

Overview:Increasing concerns over the potentially impairing effects of prescriptive sedative drugs such as benzodiazepines on driving have been raised. However, other alternatives such as natural medicines may also carry similar risks with respect to driving safety. Kava (Piper methysticum) is a psychotropic plant commonly used both recreationally and medicinally in the United States, Australia, and the South Pacific to elicit a physically tranquilizing effect. To date no controlled study has tested a medicinal dose of kava versus placebo and a standard sedative drug on driving ability and driving safety. Objective:Due to the need to establish the safety of kava in operating a motor vehicle, we compared the acute effects of the plant extract versus the benzodiazepine oxazepam and placebo using a driving simulator. Methods:A driving simulator (AusEd) was used by 22 adults aged between 18 and 65 years after being randomly administered an acute medicinal dose of kava (180 mg of kavalactones), oxazepam (30 mg), or placebo one week apart in a crossover design trial. Results:No impairing effects on driving outcomes were found after kava administration compared to placebo. Results on specific driving outcome domains revealed that the oxazepam condition had significantly slower braking reaction time compared to the placebo condition (p =.002) and the kava condition (p =.003). The kava condition had significantly fewer lapses of concentration compared to the oxazepam condition (p =.033). No significant differences were found between conditions for steering deviation, speed deviation, and number of crashes. Results were not modified by driving experience. On the Bond-Lader visual analogue sub-scale of alertness, a significant Treatment × Time interaction (p =.032) was found, with a significant reduction over time for oxazepam decreasing alertness (p <.001), whereas no significant reduction was found in the kava or placebo conditions. Conclusion:The results indicate that a medicinal dose of kava containing 180 mg of kavalactones does not impair driving ability, whereas 30 mg of oxazepam shows some impairment. Research assessing larger recreational doses of kava on driving ability should now be conducted. [ABSTRACT FROM PUBLISHER]

Introduction: Hypericum perforatum (St John's wort: SJW) has been extensively studied as an antidepressant in short-term trials, however little research has been conducted on longer-term efficacy. Methods: Our objective was to analyze the continuation data from a 26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline and placebo in major depressive disorder. 124 participant "responders" continued treatment after week 8, until week 26. They continued randomly assigned SJW (900-1 500 mg), sertraline (50-100 mg) or matching placebo. Results: At week 26, on the primary outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW (6.6 ± 4.5), sertraline (7.1 ± 5.4) and placebo (5.7 ± 5.4) with a significant effect for time ( p = 0.036). Comparisons between all treatments were however non-significant ( p = 0.61). This effect was mirrored on the other outcomes: the BDI, CGI-severity, CGI-improvement, and on intention-to-treat analyses. Conclusion: While the continuation data re vealed an equivocal outcome between treatments at week 26, both SJW and sertraline were still therapeutically effective, with a pronounced "placebo-effect" impeding a significant result at week 26. [ABSTRACT FROM AUTHOR]

Aim: To develop a new optical device (prostate optical device, POD) for assessment of prostate tissue stiffness and evaluate its sensitivity and specificity in prostate cancer detection. Patients and Methods: POD was tested in prostate phantoms and in patients with indications for prostate biopsy. Its sensitivity and specificity were compared to digital rectal examination (DRE) and transrectal ultrasonography (TRUS). Results: POD was able to identify stiffness differences on each prostate phantom. 45 patients were included in the study. Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%) (p = 0.000 and p = 0.003, respectively). There was no statistical difference between POD and DRE (p = 0.221). The combination of POD and DRE showed the highest sensitivity (88.6%), positive predictive value (81.6%), and negative predictive value (42.9%) among all diagnostic tests. Conclusions: POD identified prostatic stiffness differences with the same sensitivity of DRE performed by an experienced urologist providing an objective indication for prostate biopsy and early prostate cancer detection. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Clinical depression has a major impact on individuals and society, often presenting the clinician with a significant challenge. Recent evidence suggests that synthetic antidepressants- although effective in the treatment of severe depressed mood-may have only a weak effect against mild-moderate forms of depression. In such cases, nonpharmaceutical options may be indicated. Furthermore, research findings suggest that select natural products are effective adjuvants when combined with synthetic antidepressants. Research concerning the treatment of depression emphasizes individual monotherapies, which is often incongruent with clinical reality. In practice, clinicians often use a variety of interventions; however, this approach may not be systematic, and many interventions used may not be based on strong evidence. Primary objective This article proposes an evidence-based prescriptive clinical model based on the biopsychosocial model to treat unipolar depression. The 'Antidepressant-Lifestyle- Psychological-Social (ALPS) depression treatment model' integrates nonpharmacological interventions (such as complementary medicines, lifestyle advice, and psychosocial techniques) for use by clinicians. Results Initially a review of nonpharmacological mood-elevating interventions was undertaken. Evidentiary support was revealed for use of psychological techniques such as cognitive and behavioral medicine and interpersonal therapy, St John's wort, S-adenosyl methionine, and aerobic and anaerobic exercise. There were inconsistent research findings for acupuncture, omega-3 fish oils, and L-tryptophan for depressed mood. From these evidencebased interventions an integrative model was formed. Clinical recommendations in addition to a practical stepped-care decision tree are outlined. Conclusion The ALPS model has the potential to improve treatment outcomes and reduce relapse rates in clinical depression and warrants research using rigorous and appropriate methodology. [ABSTRACT FROM AUTHOR]

Many randomised controlled trials (RCT) have been conducted using Piper methysticum (kava), however no qualitative research exploring the experience of taking kava during a clinical trial has previously been reported. Patients and methods: A qualitative research component (in the form of semi structured and open ended written questions) was incorporated into an RCT to explore the experiences of those participating in a clinical trial of kava. The written questions were provided to participants at weeks 2 and 3 (after randomisation, after each controlled phase). The researcher and participants were blinded as to whether they were taking kava or placebo. Two open ended questions were posed to elucidate their experiences from taking either kava or placebo. Thematic analysis was undertaken and researcher triangulation employed to ensure analytical rigour. Key themes after the kava phases were a reduction in anxiety and stress, and calming or relaxing mental effects. Other themes related to improvement in sleep and in somatic anxiety symptoms. Results: Kava use did not cause any serious adverse reactions although a few respondents reported nausea or other gastrointestinal side effects. This represents the first documented qualitative investigation of the experience of taking kava during a clinical trial. The primary themes involved anxiolytic and calming effects, with only a minor theme reflecting side effects. Our exploratory qualitative data was consistent with the significant quantitative results revealed in the study and provides additional support to suggest the trial results did not exclude any important positive or negative effects (at least as experienced by the trial participants). [ABSTRACT FROM AUTHOR]

No studies to date have evaluated SLC6A2 and SLC6A4 genetic polymorphisms influencing antidepressant response to desvenlafaxine. We conducted an 8-week, open-label, prospective pilot study in 35 patients with major depressive disorder to assess the effects of genetic variations in SLC6A2 and SLC6A4 on both efficacy and side effect profile of desvenlafaxine. Results revealed that homozygotes for the SLC6A4 HTTLPR S allele showed a 33 % HDRS reduction compared to a 58 % reduction for L allele carriers (p = 0.037). No results survived adjustments for covariates or multiple comparisons. While these results need to be interpreted cautiously, they provide preliminary support for the SLC6A4 HTTLPR polymorphism as potential modifier of desvenlafaxine efficacy. [ABSTRACT FROM AUTHOR]

Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into “aqueous” extracts of Kava. The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day. The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by −9.9 (CI = 7.1, 12.7) vs. −0.8 (CI = −2.7, 4.3) for placebo and in the second controlled phase by −10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = −6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant ( p < 0.0001), with a substantial effect size ( d = 2.24, $$ \eta_{\text{p}}^2 = 0.428 $$). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery–Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity. The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety. [ABSTRACT FROM AUTHOR]