Do benzodiazepines reduce the efficacy of transcranial magnetic stimulation?

OBJECTIVE: To investigate the effect of concomitant use of benzodiazepines on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant major depressive disorder (TR-MDD). METHODS: This is a retrospective study comparing rTMS treatment outcomes between patients taking benzodiazepines (n = 59) and those who were not (n = 136). Participants completed the HAM-A, HAM-D17, MADRS and ZUNG at baseline and at the end of treatment. RESULTS: Patients taking benzodiazepines during rTMS treatment did not show any difference in partial response, response or remission rates compared to patients not treated with benzodiazepines. There was a significant decrease (p < .0001) in depression and anxiety scores from baseline to post-treatment among both groups. CONCLUSIONS: Concomitant benzodiazepine treatment had no effect on the efficacy of rTMS treatment of TRD, contrary to previous research.

Revisiting the effectiveness of repetitive transcranial magnetic stimulation treatment in depression, again.

Following on from the publication of the Royal Australian and New Zealand Journal of Psychiatry Mood Disorder Clinical Practice Guidelines (2020) and criticisms of how these aberrantly addressed repetitive transcranial magnetic stimulation treatment of depression, questions have continued to be raised in the journal about this treatment by a small group of authors, whose views we contend do not reflect the broad acceptance of this treatment nationally and internationally. In fact, the evidence supporting the use of repetitive transcranial magnetic stimulation treatment in depression is unambiguous and substantial, consisting of an extensive series of clinical trials supported by multiple meta-analyses, network meta-analysis and umbrella reviews. Importantly, the use of repetitive transcranial magnetic stimulation treatment in depression has also been subject to a series of health economic analyses. These indicate that repetitive transcranial magnetic stimulation is a cost-effective therapy and have been used in some jurisdictions, including Australia, in support of public funding. An argument has been made that offering repetitive transcranial magnetic stimulation treatment may delay potentially effective pharmacotherapy. In fact, there is considerably greater danger of the opposite happening. Repetitive transcranial magnetic stimulation is as, if not more effective, than antidepressant medication after two unsuccessful medication trials and should be a consideration for all patients under these circumstances where available. There is no meaningful ongoing debate about the use of repetitive transcranial magnetic stimulation treatment in depression - it is a safe, effective and cost-effective treatment.

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial.

INTRODUCTION: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. METHODS: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4. RESULTS: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p = 0.180) or remission (p = 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub- and supra-threshold intensities were not significantly different (p = 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p = 0.680). CONCLUSION: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub- and supra-threshold accelerated bilateral TBS.

Treatment approaches of palliative medicine specialists for depression in the palliative care setting: findings from a qualitative, in-depth interview study.

BACKGROUND: Treatment of depression in the palliative care setting is complicated by varied treatment preferences, a small body of research, and unique challenges associated with the end-of-life. Little is known about the treatment practices of medical practitioners in this setting. OBJECTIVE: This study aimed to investigate and characterise the treatment approaches of palliative medicine specialists for depression. DESIGN: Semistructured, in-depth interviews were conducted to explore explanatory models of depression from palliative medicine specialists, including a focus on treatment. Verbatim interview transcripts were analysed for themes. SETTING/PARTICIPANTS: Palliative medicine specialists practising in Australia were recruited and purposively sampled. Nine participants were interviewed to reach data saturation. RESULTS: Five themes were identified in relation to treatment of depression: (1) guiding principles of treatment; (2) treatment approaches; (3) factors underpinning treatment decisions; (4) difficulties arising in treatment; and (5) interdisciplinary roles. Participants described five distinct treatment approaches, consisting of biological orientation, psychosocial orientation, combination approach, undifferentiated approach and ambivalence. Treatment decisions were contingent on patient, depression, clinician and sociocultural factors. Difficulties included discomfort with treating depression, being inadequately equipped and confronting therapeutic limitations. Treating depression was considered to require multidisciplinary team effort. CONCLUSIONS: Palliative medicine specialists' treatment approaches are linked to their concepts of and causal explanations for depression. Future treatment guidelines could aim to consider specific varieties of depression, be more differentiated in treatment modality and type, and consider decision-shaping factors. Continuing mental health education and the incorporation of psychiatry and psychology into palliative care services may have enduring benefits.

Palliative medicine specialists' causal explanations for depression in the palliative care setting: a qualitative in-depth interview study.

OBJECTIVE: Medical practitioners have different causal explanations for depression, and may have greater difficulty in explaining causality of depression in the palliative care setting. The objective of this study was to investigate and describe the causal explanations of depression in the palliative care setting, from the perspective of palliative medicine specialists. METHODS: Palliative medicine specialists practising in Australia were recruited and purposively sampled. Individual semistructured, in-depth interviews were conducted to explore their explanatory models of depression, including a focus on causal explanations. Nine participants were interviewed to reach data saturation. Interview transcripts were analysed for themes. RESULTS: Six themes for causal explanations of depression were identified: (1) Depression is inexplicable; (2) Biological explanations-primarily neurotransmitter depletion; (3) Psychological explanations-including reaction to circumstances, inability to accept illness and dying, diminished self, and coping mechanisms; (4) Social explanations-including inadequate social support, and contribution from modern medicine and societal norms; (5) Interrelationships between causal factors-mainly multifactoriality; (6) Different explanation for de novo and pre-existing depressions. Participants also articulated a link between causal explanations and clinical interventions. CONCLUSIONS: Palliative medicine specialists hold causal explanations of depression that align with the biopsychosocial and vulnerability-stress models. They use multiple individual explanations with diverse theoretical underpinnings, and largely view depression as multifactorial in causality. Given that causal explanations are linked to clinical interventions, these findings have implications for clinical practice and medical education.

Is death our business? Philosophical conflicts over the end-of-life in old age psychiatry.

OBJECTIVES: Old age psychiatrists work with end-of-life (EOL) issues and encounter patient deaths, but death and dying have received limited focus in old age psychiatry training and research. This qualitative study explores old age psychiatrists' experience of and approach to working with patients at the EOL. METHOD: Australian old age psychiatrists were purposively sampled and interviewed in-depth. Data saturation was achieved after nine participant interviews. Verbatim transcripts were analysed for themes, which were independently verified. RESULTS: Two dichotomous overarching themes were identified. Death is not our business reflected participants' experience of working in a mental health framework and incorporated four themes: death should not occur in psychiatry; working in a psychiatric treatment model; keeping a distance from death and unexpected death is a negative experience. Death is our business reflected participants' experience of working in an aged care context and incorporated four themes: death is part of life; encountering the EOL through dementia care; doing EOL work and expected death is a positive experience. CONCLUSION: Participants reported conflict because of the contradictory domains in which they work. They were comfortable working with patients at the EOL when death was expected, particularly in dementia. By contrast, they struggled with death as an adverse outcome in circumstances influenced by mental health culture, which was characterised by risk management, suicide prevention and a focus on recovery. This study has implications for models of care underpinning old age psychiatry. An integrated person-centred model of care may provide a contextually appropriate approach for practice.

Depression means different things: A qualitative study of psychiatrists' conceptualization of depression in the palliative care setting.

OBJECTIVE: Medical practitioners conceptualize depression in different ways, which adds to the challenges of its diagnosis and treatment, as well as research in the palliative care setting. Psychiatric assessment is often considered the "gold standard" for diagnosis, therefore how psychiatrists conceptualize depression in this setting is pertinent. Our study aimed to investigate this issue. METHOD: Psychiatrists working in palliative care in Australia were individually interviewed using a semistructured approach. Nine participants were interviewed to reach data saturation. Interview transcripts were analyzed for themes. RESULTS: Three overarching themes were identified: (1) depression means different things; (2) depression is conceptualized using different models; and (3) depression is the same concept within and outside of the palliative care setting. Participants explicitly articulated the heterogeneous nature of depression and described a different breadths of concepts, ranging from a narrow construct of a depressive illness to a broader one that encompassed depressive symptoms and emotions. However, depressive illness was a consistent concept, and participants considered this in terms of phenotypic subtypes. Participants used three models (spectral, dichotomous, and mixed) to relate various depressive presentations. SIGNIFICANCE OF RESULTS: Psychiatrists did not subscribe to a unitary model of depression but understood it as a heterogeneous concept comprised of depressive illness and other less clearly defined depressive presentations. Given the influence of psychiatric opinion in the area of depression, these findings may serve as a platform for further discussions to refine the concepts of depression in the palliative care setting, which in turn may improve diagnostic and treatment outcomes.

The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression. METHOD: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. RESULTS: The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F1,520.9 = 1.98, P = .067), and the groups did not separate at week 12 (t360.3 = -1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t221.03 = -2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. CONCLUSIONS: Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary. TRIAL REGISTRATION: www.anzctr.org.au Identifier: ACTRN12607000134426.

How do palliative medicine specialists conceptualize depression? Findings from a qualitative in-depth interview study.

BACKGROUND AND OBJECTIVE: Different professional conceptualizations of depression may complicate the clinical approach to depression in the palliative care setting. This study aimed to explore and characterize how palliative medicine specialists conceptualize depression. METHODS: Palliative medicine specialists (i.e., consultants/attending physicians in palliative medicine) practicing in Australia were recruited. Participants were purposively sampled. Individual semi-structured, in-depth interviews were conducted to explore their conceptualizations of depression. Nine participants were interviewed to reach data saturation. Interview transcripts were analyzed for themes. RESULTS: Four main themes were identified in relation to the conceptualization of depression: (1) depression is a varied concept--it was variously considered as abnormal, a medical problem, an emotional experience, a social product, and an action-oriented construct; (2) depression has unclear boundaries, with differentiation between depression and sadness being especially challenging; (3) depression is different in the palliative care setting--it was seen as more understandable, and distinct from depression that predates life-limiting illnesses; and (4) depression is a challenging issue. CONCLUSIONS: Depression is conceptualized by palliative medicine specialists in divergent, ontologically heterogeneous and ill-defined ways. A unitary concept of depression was not evident in this study. The concepts of depression need to be actively debated and refined in clinical practice, medical education, and research in order for more sophisticated and consistent models to be developed. The distinction of de novo depression from recurrent or persistent forms of depression also warrants further study.

Palliative medicine practitioners' views on the concept of depression in the palliative care setting.

BACKGROUND: Despite its clinical importance in palliative care, depression remains an ambiguous concept. OBJECTIVE: The purpose of this study was to explore how medical practitioners working in palliative care conceptualize depression in that setting. DESIGN: Medical practitioners who attended a palliative medicine conference (N=185) were invited to respond to a questionnaire, which explored their views on the concept of depression in the palliative care context. Descriptive statistics were used to summarize responses, and comparison between groups was conducted using nonparametric statistics. Themes in free-text comments were identified. RESULTS: Seventy-nine responses were obtained (response rate 43%). Depression was not a unified concept, but was generally considered to be an illness with psychological, spiritual, and existential causes. Respondents were more uncertain about depression being an illness in the palliative care setting compared with other settings, and were ambivalent about its causality. Treatment preferences leaned towards psychological interventions. Depression being different in the palliative care setting was a theme. It was considered to be more prevalent, different in quality, harder to define, and associated with greater barriers to diagnosis and treatment. Conceptual differences were associated with the respondents' area of work, work position, duration of practice, and previous mental health training. CONCLUSIONS: Depression in the palliative care setting is a variable concept for palliative medicine practitioners. The conceptual diversity and complexities of depression in this setting must be acknowledged and further explored in order to develop nuanced approaches in clinical practice and in research.

Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia.

OBJECTIVE: The pharmacokinetic profile of a drug often gives little indication of its potential therapeutic application, with many therapeutic uses of drugs being discovered serendipitously while being studied for different indications. As hypothesis-driven, quantitative research methodology is exclusively used in early-phase trials, unexpected but important phenomena may escape detection. In this context, this study aimed to examine the potential for integrating qualitative research methods with quantitative methods in early-phase drug trials. To our knowledge, this mixed methodology has not previously been applied to blinded psychopharmacologic trials. METHOD: We undertook qualitative data analysis of clinical observations on the dataset of a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) in patients with DSM-IV-TR-diagnosed schizophrenia (N = 140). Textual data on all participants, deliberately collected for this purpose, were coded using NVivo 2, and emergent themes were analyzed in a blinded manner in the NAC and placebo groups. The trial was conducted from November 2002 to July 2005. RESULTS: The principal findings of the published trial could be replicated using a qualitative methodology. In addition, significant differences between NAC- and placebo-treated participants emerged for positive and affective symptoms, which had not been captured by the rating scales utilized in the quantitative trial. Qualitative data in this study subsequently led to a positive trial of NAC in bipolar disorder. CONCLUSIONS: The use of qualitative methods may yield broader data and has the potential to complement traditional quantitative methods and detect unexpected efficacy and safety signals, thereby maximizing the findings of early-phase clinical trial research. TRIAL REGISTRATION: www.anzctr.org.au Identifier: ACTRN12605000363684.

The relationship between substance use and posttraumatic stress disorder in a methadone maintenance treatment program.

INTRODUCTION AND AIMS: Posttraumatic stress disorder (PTSD) is frequently linked with substance abuse. The self-medication hypothesis suggests that some people may use illicit substances in an attempt to self-treat psychiatric symptoms. This study explores the relationship between substance abuse and PTSD symptom clusters in a methadone maintenance population. DESIGN AND METHODS: Clients of a methadone maintenance program at a public Drug and Alcohol Service were invited to complete the PTSD Checklist-Civilian Version, a screening tool for PTSD. Information about their history of substance use was also collected. RESULTS: Eighty clients (43 female, 37 male), aged 35 ± 8.0 years (mean ± SD), participated in the study, of which 52.7% screened positive for PTSD. Severity of marijuana use was significantly associated with a number of reexperiencing and hyperarousal symptoms and with overall severity of PTSD symptoms. Opiate, amphetamine, and benzodiazepine use did not appear to be related to PTSD symptoms. DISCUSSION AND CONCLUSIONS: In this sample, marijuana may be used to self-treat certain PTSD symptoms, supporting the self-medication hypothesis. Further research is required to confirm the association between a diagnosis of PTSD and substance use. Given the high prevalence of PTSD in the substance-using population, routine PTSD screening in the substance abuse treatment setting may be justified.

Do we need to flick the switch? The need for a broader conceptualization of iatrogenic course aggravation in clinical trials of bipolar disorder.

The term 'switching' is often used in bipolar disorder when describing polarity changes in bipolar disorder, but this term is ambiguous and imprecise, and is sometimes used interchangeably with the term 'cycling'. Furthermore, polarity changes in bipolar disorder can be understood in different ways, because their clinical manifestations range from the emergence of subthreshold symptoms to a full episode of the opposite pole. Besides the need to tighten the meaning of the term 'switching', this paper also argues that switching does not adequately describe the complex phenomena that occur with course aggravation of bipolar disorder, such as alteration in episode frequency or amplitude. A more-fine grained approach to course aggravation in bipolar disorder is proposed, which incorporates trans-polar switching, index polarity aggravation, as well as alterations in episodic amplitude, episodic duration, and inter-episode length. This approach has the potential to capture a broader, more fine-grained and clinically relevant picture of the process of aggravation of the bipolar cycle.

The utility of the Mood Disorders Questionnaire as a screening tool in a methadone maintenance treatment program.

Abstract Objective. Comorbid mental illness amongst methadone maintenance therapy clients may be common and screening may be warranted. The Mood Disorders Questionnaire (MDQ) is a screening tool for bipolar disorder that has been validated in other treatment settings. Its utility for patients with substance use disorders is assessed in this study. Methods. Clients of a methadone maintenance program were invited to complete the MDQ when they attended a public Drug and Alcohol Service for their regular scheduled appointments. Information about their history of substance use was also collected. Results. Eighty clients (43 females, 37 males) aged 35 ± 8.0 years (mean ± SD) participated in the study. Seventy-four clients completed the MDQ of which 36 (48.6%) obtained a positive screen. A check of client files suggested that only three of the 74 participants had a current working diagnosis of bipolar disorder. These three participants had screened positive on the MDQ. Conclusions. There was a high prevalence of manic symptoms reported by participants, suggesting that screening for bipolar disorder in this population may be warranted. However, there is a risk of false positives with the MDQ, as it does not clearly differentiate between symptoms of mania and drug intoxication.

The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments.

OBJECTIVES: Safety monitoring is an important aspect of bipolar disorder treatment, as mood-stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost-effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder. METHODS: These guidelines were developed by an ISBD workgroup, headed by the senior author (MB), through an iterative process of serial consensus-based revisions. After this, feedback from a multidisciplinary group of health professionals on the applicability of these guidelines was sought to develop the final recommendations. RESULTS: General safety monitoring recommendations for all bipolar disorder patients receiving treatment and specific monitoring recommendations for individual agents are outlined. CONCLUSIONS: These guidelines are derived from evolving and often indirect data, with minimal empirical cost-effectiveness data available to provide guidance. These guidelines will therefore need to be modified to adapt to different clinical settings and health resources. Clinical acumen and vigilance remain critical ingredients for safe treatment practice.

Client-reported reasons for non-engagement in drug and alcohol treatment.

INTRODUCTION AND AIMS: To examine client-reported reasons for missed early appointments at a drug and alcohol treatment service and to compare characteristics of those who missed appointments with those who attended. DESIGN AND METHODS: Clients who missed a first or second appointment between 1 May and 31 August 2007 at a public community-based outpatient treatment facility were invited to participate in a semistructured telephone interview. This consisted of an open-ended question asking the reason(s) for nonattendance, followed by a questionnaire of items for therapeutic alliance and service satisfaction, perceived impact of substance use and previous treatment experience, mostly rated on Likert scales. Database information on demographic and clinical variables was gathered for all clients who were accepted for treatment within the study time frame. Characteristics of those who missed a first or second appointment (n = 66) were compared with those who attended at least their first two appointments (n = 97). RESULTS: Of clients who missed their appointments, 80.6% provided reasons for nonattendance, which included extraneous factors (50.0%), service shortcomings (29.7%), no further need for service (16.2%) and motivational ambivalence (4.1%). They generally had high ratings of therapeutic alliance and service satisfaction and identified their substance use as having a negative impact on their lives. Clients who missed appointments were more likely to be male, unmarried and have a history of polysubstance use. DISCUSSION AND CONCLUSIONS: Extraneous issues relating to the client may be a dominant obstacle in early treatment engagement. Efforts to overcome these issues may therefore improve early engagement.

Tobacco smoking as a risk factor for major depressive disorder: population-based study.

BACKGROUND: Smoking is disproportionately prevalent among people with psychiatric illness. AIMS: To investigate smoking as a risk factor for major depressive disorder. METHOD: A population-based sample of women was studied using case-control and retrospective cohort study designs. Exposure to smoking was self-reported, and major depressive disorder diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP). RESULTS: Among 165 people with major depressive disorder and 806 controls, smoking was associated with increased odds for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03-2.07). Compared with non-smokers, odds for major depressive disorder more than doubled for heavy smokers (>20 cigarettes/day). Among 671 women with no history of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed de novo major depressive disorder during a decade of follow-up. Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93, 95% CI 1.02-3.69); this was not explained by physical activity or alcohol consumption. CONCLUSIONS: Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women.

Is this D vitamin to worry about? Vitamin D insufficiency in an inpatient sample.

OBJECTIVE: The aim of the present study was to investigate the relationship between reduced serum vitamin D levels and psychiatric illness. METHOD: This study was an audit of serum 25-hydroxyvitamin D (25-OHD) levels measured routinely in a sample of 53 inpatients in a private psychiatric clinic. These levels were compared with those of controls without psychiatric illness. RESULTS: The median levels of serum 25-OHD were 43.0 nmol L(-1) (range 20-102 nmol L(-1)) in the patient population, 46.0 nmol L(-1) (range 20-102 nmol L(-1)) in female patients (n =33) and 41.5 nmol L(-1) (range 22-97 nmol L(-1)) in male patients (n =20). The proportion of vitamin D insufficiency (serum 25-OHD < or =50 nmol L(-1)) in this patient population was 58%. Furthermore, 11% had moderate deficiency (serum 25-OHD < or =25 nmol L(-1)). There was a 29% difference between mean levels in the patient population and control sample (geometric mean age- and season-adjusted levels: 46.4 nmol L(-1) (95% confidence interval (CI) =38.6-54.9 nmol L(-1)) vs 65.3 nmol L(-1) (95%CI =63.2-67.4 nmol L(-1)), p <0.001). CONCLUSION: Low levels of serum 25-OHD were found in this patient population. These data add to the literature suggesting an association between vitamin D insufficiency and psychiatric illness, and suggest that routine monitoring of vitamin D levels may be of benefit given the high yield of clinically relevant findings.

Glutathione: a novel treatment target in psychiatry.

There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target.