RESUMEN
There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.
Asunto(s)
Ejercicios Respiratorios , Convulsiones , Humanos , Proyectos Piloto , Masculino , Femenino , Adulto , Convulsiones/fisiopatología , Convulsiones/terapia , Ejercicios Respiratorios/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Adolescente , Trastornos de Conversión/rehabilitación , Trastornos de Conversión/terapia , Estudios de SeguimientoRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
Asunto(s)
Trastorno Obsesivo Compulsivo , Selenio , Humanos , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Calidad de Vida , Magnesio/uso terapéutico , Selenio/uso terapéutico , Cisteína/uso terapéutico , Resultado del Tratamiento , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/diagnóstico , Suplementos Dietéticos , Zinc/uso terapéutico , Fosfatos/uso terapéutico , Piridoxal/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES(S): To characterise the clinical profile, aetiology and treatment responsiveness of 'Australian Lyme', or Debilitating Symptom Complexes Attributed to Ticks. METHODS: Single-centre retrospective case analysis of patients referred to the Infectious Diseases Unit at Austin Health - a tertiary health service in Heidelberg, Australia - between 2014 and 2020 for investigation and treatment of suspected Debilitating Symptom Complexes Attributed to Ticks. Patients were included if they had debilitating symptoms suggested by either themselves or the referring clinician as being attributed to ticks. RESULTS: Twenty-nine Debilitating Symptom Complexes Attributed to Ticks cases were included in the analysis. Other than Lyme disease (83%), the most common prior medical diagnoses were Epstein-Barr virus (38%), chronic fatigue syndrome (28%) and fibromyalgia (24%). Prior histories of anxiety (48%) and depression (41%) were common. The most frequently reported symptoms included fatigue (83%), headache (72%) and arthralgia (69%). National Association of Testing Authorities/Royal College of Pathologists of Australasia-accredited serology was not diagnostic of acute infective causes, including Lyme disease, in any patient. Of 25 cases with available data, 23 (92%) had previously been prescribed antimicrobials, with 53% reporting benefit from them. The most common diagnoses made by our hospital were chronic fatigue syndrome (31%), migraines (28%) and fibromyalgia (21%). Only one patient's symptoms were not accounted for by other diagnoses. CONCLUSION: This is the first case series of patients with Debilitating Symptom Complexes Attributed to Ticks. They had high rates of other medically unexplained syndromes, and no evidence of acute Lyme disease, or any common organic disease process. Debilitating Symptom Complexes Attributed to Ticks remains medically unexplained, and may therefore be due to an as yet unidentified cause, or may be considered a medically unexplained syndrome similar to conditions such as chronic fatigue syndrome.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Síndrome de Fatiga Crónica , Fibromialgia , Enfermedad de Lyme , Garrapatas , Animales , Australia/epidemiología , Síndrome de Fatiga Crónica/diagnóstico , Fibromialgia/diagnóstico , Herpesvirus Humano 4 , Humanos , Enfermedad de Lyme/complicaciones , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: Depression clinical trials are increasingly studying biomarkers to predict and monitor response to treatment. Assessment of biomarkers may reveal subsets of patients who are responsive to nutraceutical treatment, which may facilitate a personalized approach to treating depression. METHODS: This is a post hoc analysis of an 8-week, double-blind, randomized, controlled trial (n = 158) investigating a combination nutraceutical comprising Omega-3 (EPA 1 g/DHA 656 mg), SAMe, zinc, 5-HTP, folinic acid, and co-factors versus placebo for the treatment of Major Depressive Disorder. The study explored levels of polyunsaturated fatty acids, folate, vitamin B12, zinc, homocysteine, and BDNF as possible predictors and correlates of response to nutraceutical supplementation. RESULTS: Concentrations of EPA and DHA in red cell membranes increased in response to treatment and were significantly correlated with a decrease in depressive symptoms during active treatment (p = 0.003 and p = 0.029; respectively). Higher baseline levels of omega-6 fatty acid also correlated with depression reduction in the active treatment group ( p = 0.011). No other biomarkers were associated with a lessening of depressive symptoms. CONCLUSION: Changes in fatty acid levels resulting from a nutraceutical combination containing EPA and DHA provide a response biomarker in treating depression.
Asunto(s)
Trastorno Depresivo Mayor/dietoterapia , Suplementos Dietéticos , Ácidos Docosahexaenoicos/análisis , Ácido Eicosapentaenoico/análisis , Adulto , Biomarcadores/análisis , Método Doble Ciego , Membrana Eritrocítica/química , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. AIM: The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. METHODS: Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). RESULTS: The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). CONCLUSION: Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the pathophysiology of MDD.
Asunto(s)
Trastorno Depresivo Mayor/genética , Eritrocitos/metabolismo , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Estudios de Casos y Controles , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/metabolismo , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Familia de Multigenes , Victoria , Población BlancaRESUMEN
OBJECTIVE: We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment intervention. METHODS: We conducted one-to-one in-depth, semi-structured interviews with 13 people living in Australia affected by DSCATT. Interviews were transcribed and analysed using thematic analysis. RESULTS: Although participants attributed the origin of their illness to tick bites, not all were adamant they had Lyme disease. Negative experiences in conventional healthcare were marked and were reported to exacerbate the impact of the illness and affect mental health. Further, these negative experiences propelled participants to seek unapproved treatments (by Australian standards). The desire for the illness to be acknowledged and causative agents identified was pronounced among the participant group. CONCLUSIONS: Individuals with DSCATT experience significant challenges amid a contentious healthcare landscape surrounding chronic symptoms attributed to ticks in Australia. Our findings suggest the need for empathetic, supportive and patient-centred treatments for this cohort. IMPLICATIONS FOR PUBLIC HEALTH: DSCATT results in a considerable burden across multiple domains for those affected. Negative experiences with healthcare exacerbate the suffering of people with DSCATT in Australia. New approaches that acknowledge the illness experience of people with DSCATT, alongside evidence-based treatments that encompass biopsychosocial models of care, are needed to tackle this debilitating condition.
Asunto(s)
Entrevistas como Asunto , Investigación Cualitativa , Garrapatas , Humanos , Masculino , Femenino , Australia , Persona de Mediana Edad , Adulto , Animales , Anciano , Mordeduras de Garrapatas/psicologíaRESUMEN
Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments (d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.
RESUMEN
OBJECTIVE: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD. METHODS: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit. RESULTS: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment. CONCLUSION: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.
Asunto(s)
Acetilcisteína , Trastorno Obsesivo Compulsivo , Acetilcisteína/uso terapéutico , Método Doble Ciego , Humanos , Trastorno Obsesivo Compulsivo/terapia , Calidad de Vida , Resultado del TratamientoRESUMEN
Given the growing evidence that a range of lifestyle factors are involved in the etiology of depression, a 'lifestyle medicine' approach can be potentially safe and cost-effective to prevent or treat depression. To examine the effects and acceptability of a group-based, integrative lifestyle medicine intervention as a standalone treatment for managing depressive symptoms, a pilot randomized controlled trial (RCT) was conducted in a Chinese adult population in 2018. Participants (n = 31) with PHQ-9 score above the cut-off of ≥ 10, which was indicative of moderate to severe depression, were recruited from the general community in Hong Kong and randomly assigned to lifestyle medicine group (LM group) or care-as-usual group (CAU group) in a ratio of 1:1. Participants in the LM group received 2-hour group sessions once per week for six consecutive weeks, which covered diet, exercise, mindfulness, psychoeducation, and sleep management. Linear mixed-effects model analyses showed that the LM group had a significant reduction in PHQ-9 scores compared to the CAU group at immediate posttreatment and 12-week posttreatment follow-up (d = 0.69 and 0.73, respectively). Moreover, there were significantly greater improvements in anxiety, stress, and insomnia symptoms (measured by DASS-21 and ISI) at all time points in the LM group (d = 0.42-1.16). The results suggests that our 6-week group-based, integrative lifestyle intervention program is effective in lowering depressive, anxiety, stress, and insomnia symptoms in the Chinese population. Further studies in clinical populations with a larger sample size and longer follow-up are warranted.
Asunto(s)
Ansiedad/terapia , Depresión/terapia , Atención Plena , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Adulto , Ansiedad/epidemiología , Ansiedad/patología , Ansiedad/prevención & control , Análisis Costo-Beneficio , Depresión/epidemiología , Depresión/patología , Depresión/psicología , Terapia por Ejercicio , Femenino , Hong Kong/epidemiología , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Trastornos del Inicio y del Mantenimiento del Sueño/patología , Trastornos del Inicio y del Mantenimiento del Sueño/prevención & controlRESUMEN
RATIONALE: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy. OBJECTIVES: To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. METHODS: We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. RESULTS: A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated. CONCLUSIONS: Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. TRIAL REGISTRATION: ANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
Asunto(s)
Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , S-Adenosilmetionina/uso terapéutico , Adulto , Australia , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
Background: Metabolic syndrome and co-morbid physical health conditions are highly prevalent in people with a mental illness. Modifiable lifestyle factors have been targeted to improve health outcomes. Healthy Body Healthy Mind (HBHM) program was developed to provide an integrated evidence-based program incorporating practical diet and exercise instruction; alongside meditation and mindfulness strategies, and comprehensive psychoeducation, to improve the physical and mental health of those with a mental illness. Methods: We report on two data points: (1) Qualitative data derived from the first HBHM program (version 1) exploring its utility and acceptance according to patient feedback; (2) Biometric and mental health data collected on the modified and enhanced 12-week HBHM program (version 2) involving a pilot of 10 participants. Mental and physical health outcomes, weight, abdominal circumference, fasting glucose, cholesterol, and triglycerides were measured at program entry and completion. Results: Qualitative data from HBHM version 1 provided valuable feedback to redevelop and enhance the program. At the end of the HBHM (version 2) 12-week program, a significant mean weight loss of 2 kg was achieved, p = 0.023. There was also a significant reduction in abdominal circumference (mean = 2.55 cm) and a decrease in BMI of almost one point (mean = 0.96 kg/m2), p = 0.046 and p = 0.019, respectively. There were no significant changes in mental health measures or on any other biometrics. Conclusion: Pilot data from the HBHM program found significant reductions in weight and abdominal obesity. The HBHM program could benefit from further modifications, and study replication is required using a controlled design in a larger sample.
RESUMEN
Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900â¯mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (pâ¯=â¯0.73) nor insomnia severity on the Insomnia Severity Index (ISI; pâ¯=â¯0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; pâ¯=â¯0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISIâ¯≤â¯14; pâ¯=â¯0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.
Asunto(s)
Antidepresivos/farmacología , Trastornos de Ansiedad/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Glutamatos/farmacología , Evaluación de Resultado en la Atención de Salud , Preparaciones de Plantas/farmacología , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Adulto , Trastornos de Ansiedad/complicaciones , Disfunción Cognitiva/etiología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glutamatos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Preparaciones de Plantas/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/etiologíaRESUMEN
BACKGROUND: One of the most pressing questions in "Nutritional Psychiatry" is whether using combinations of different nutraceuticals with putative antidepressant activity may provide an enhanced synergistic antidepressant effect. METHODS: A phase II/III, Australian multi-site, 8-week, double-blind, RCT involving 158 outpatients with a DSM-5 diagnosis of MDD. The intervention consisted of a nutraceutical combination: S-adenosyl methionine; Folinic acid; Omega-3 fatty acids; 5-HTP, Zinc picolinate, and relevant co-factors versus placebo. The primary outcome was change in MADRS score. Hypothesis-driven analyses of potential moderators of response involving key SNPs, and BDNF were also conducted. RESULTS: Placebo was superior to the nutraceutical combination in reducing MADRS score (differential reduction -1.75 points), however a mixed linear model revealed a non-significant Group X Time interaction (pâ¯=â¯0.33). Response rates were 40% for the active intervention and 51% for the placebo; remission rates were 34% and 43% for active and placebo groups, respectively. No significant differences were found between groups on any other secondary depression, anxiety, psychosocial, or sleep outcome measures. Key SNPs and BDNF did not significantly moderate response. No significant differences occurred between groups for total adverse effects, aside from more nausea in the active group. LIMITATIONS: Very high placebo response rates suggest a placebo run-in design may have been valuable. INTERPRETATION: The adoption of a nutraceutical 'shotgun' approach to treating MDD was not supported, and appeared to be less effective than adding placebo to treatment as usual.
Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Suplementos Dietéticos , Adulto , Anciano , Australia , Factor Neurotrófico Derivado del Encéfalo/análisis , Método Doble Ciego , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , S-Adenosilmetionina/uso terapéutico , Adulto JovenRESUMEN
There has been increasing interest in nutraceutical augmentation strategies to boost the efficacy of antidepressants. This study assessed whether S-adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may be of such benefit. We conducted an 8-week, double-blind RCT in which 107 treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive Disorder (MDD) were randomized to either SAMe or placebo adjunctively to antidepressants. One-carbon cycle nutrients, pertinent single nucleotide polymorphisms (SNPs), and BDNF were also analysed as potential moderators of response. A linear mixed-effects model revealed a significant overall reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however there was no significant between-group difference observed (pâ¯=â¯0.51). Response rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect of SAMe was found on any secondary outcome. Differential response to SAMe was not modified by a range of key genotypes (e.g. COMT), nor reflected in a change of homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant adverse effects beyond placebo, however it was implicated in one case of serotonin syndrome-like symptoms. This study concludes that 800â¯mg/day of SAMe is not an effective adjunctive treatment in MDD, and no obvious biomarker reflected any differential response to treatment. Due to such a distinctly high placebo-response (despite rigorous screening), future studies should employ a placebo run-in period and other strategies to minimize placebo response.
Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/terapia , Suplementos Dietéticos , S-Adenosilmetionina/uso terapéutico , Adulto , Terapia Combinada , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , S-Adenosilmetionina/efectos adversos , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. METHODS: PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. RESULTS: Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400-3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. CONCLUSIONS: Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.
RESUMEN
Lifestyle-focused health programs are growing in interest throughout Western society, and a range of lifestyle factors are known to enhance both physical and mental health. However, it remains largely unknown as to whether this approach is salient for the Asian context. The major components of integrative lifestyle-focused health programs to enhance mental and physical health are considered to include the evidence-based adoption of physical activity and exercise, dietary modification, general psychoeducation, adequate relaxation/sleep and social interaction, use of mindfulness techniques, the reduction of substance use, attention of intersecting environmental factors, and the potential use of motivation and goal-setting techniques. This paper outlines an overview of the evidence underpinning these elements, and discusses potential barriers and challenges, and what logistical considerations may need to be addressed in the implementation of such programs within the context of Asian cultures.
Asunto(s)
Dietoterapia , Terapia por Ejercicio , Estilo de Vida , Trastornos Mentales/terapia , Atención Plena , Educación del Paciente como Asunto , Psicoterapia , Asia , HumanosRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. OBJECTIVE: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. METHODS: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. RESULTS: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20%) participants were considered 'responders' (YBOCS ≥35% reduction at endpoint) versus four (27%) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). CONCLUSION: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. TRIAL REGISTRATION: ACTRN12613000310763.