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.

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 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.

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.

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.

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.

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.

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.

The empirical redefinition of the psychometric criteria for remission in bipolar disorder.

BACKGROUND: Current definitions of remission for mania and bipolar depression are convention-rather than empirically-based, and their clinical salience is unclear, as few studies have attempted to calibrate them against objective clinical criteria. This study aimed to determine equivalence scores on two widely used clinical rating scales, the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS), that corresponded with an objective global clinical measure of remission in bipolar disorder patients. METHODS: Data from four pharmacological randomised controlled trials in bipolar I disorder were analysed. Two trials were conducted for bipolar depression (N=410 and 833), and two for manic or mixed episodes (N=136 and 110). In this study, a Clinical Global Impression-Bipolar Version (CGI-BP) severity score of 1 (normal, not at all ill) was used as the primary comparative measure of remission. The mean total YMRS and MADRS scores in the mania and depression studies, respectively, that corresponded with a CGI-BP severity score of 1 were determined. RESULTS: The mean YMRS score that corresponded with a CGI-BP severity score of 1 was <4 in both trials (2.6 and 3.0, respectively), and the mean corresponding MADRS score was <5 (4.1 and 4.6, respectively). LIMITATIONS: Utilising a psychometric definition of remission. CONCLUSIONS: This study suggests that a cut-off score of <5 on the MADRS and <4 on the YMRS approximates a CGI-BP definition of complete remission. Although lower than conventional cut-off scores, these perhaps better represent clinical reality and patient expectations. In the context of clinical trials, study end-points may be more difficult to reach with lower cut-offs, but the outcomes achieved are more likely to be clinically meaningful.

Going up in smoke: tobacco smoking is associated with worse treatment outcomes in mania.

BACKGROUND: This study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials. METHODS: Post-hoc analysis was conducted on data collected from three double-blind, randomised controlled trials in bipolar mania that had similar inclusion criteria. Patients were randomised to olanzapine (N=70) or placebo (N=69) for 3 weeks in Trial 1, olanzapine (N=234) or haloperidol (N=216) for 12 weeks in Trial 2, and olanzapine (N=125) or divalproex (N=126) for 47 weeks in Trial 3. This study analysed the Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions scale for bipolar disorder (CGI-BP) mania severity scores between smokers and non-smokers for each trial and for the pooled data from all three trials, using a mixed-effects model repeated measures approach. RESULTS: For the pooled data, non-smokers showed superior treatment outcomes on both the YMRS (P=0.002) and CGI-BP (P<0.001), as well as longer time to discontinuation for any cause utilising Kaplan-Meier survival curves. For the individual trials, non-smokers showed greater improvement than smokers on both CGI-BP and YMRS in both treatment arms of Trial 2 (CGI-BP: haloperidol P=0.011, olanzapine P=0.042; YMRS: haloperidol P=0.010, olanzapine P=0.019), and in the olanzapine arm of Trial 3 (CGI-BP: P=0.002; YMRS: P=0.006). No significant difference in outcomes was found between smokers and non-smokers in Trial 1. LIMITATIONS: Post-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse. CONCLUSIONS: Smoking appears to be associated with worse treatment outcomes in mania.

Dual-dual action? Combining venlafaxine and mirtazapine in the treatment of depression.

OBJECTIVE: Venlafaxine and mirtazapine in combination are increasingly used in clinical practice to treat treatment-refractory depression. Putative efficacy for this combination of antidepressants, beyond that of monotherapy, stems from their synergistic actions. This paper describes a prospective case series that examined the efficacy of the venlafaxine-mirtazapine combination in the treatment of depressed patients who had failed at least one antidepressant trial. METHOD: Twenty-two depressed patients with major depression were treated with venlafaxine and mirtazapine in combination for an average of just under 8 weeks. Baseline ratings on the 17-item Hamilton Depression Rating Scale (HAM-D(17)), Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Severity Scale (CGI-S) were repeated at end-point, determined by the naturalistic termination of the depressive treatment episode or the discontinuation of the combination treatment due to adverse effects. The length of treatment until end-point was documented for each patient. Descriptive statistics were used on the collated data. RESULTS: At baseline, mean scores were 28.8 (SD=3.8) for HAM-D(17), 30.1 (SD=5.8) for MADRS, and 4.5 (SD=0.5) for CGI-S, reflecting a cohort at the moderate to severe end of the spectrum. At end-point, mean absolute scores were 10.2 (SD=4.7) for HAM-D(17), 10.8 (SD=4.6) for MADRS, and 2.3 (SD=0.6) for CGI-S. Mean change from baseline was 18.6 (SD=6.4) for HAM-D(17), 19.3 (SD=6.8) for MADRS, and 2.3 (SD=0.6) for CGI-S. Mean duration of treatment was approximately 8 weeks, producing a response rate of 81.8% and a remission rate of 27.3%. Only one patient was unable to tolerate the combination although nearly half (10) had significant side-effects during treatment. CONCLUSION: This study demonstrates relatively high response and remission rates that are encouraging and contribute to the efficacy database for this antidepressant combination. Further studies using randomized controlled designs are needed.

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.

The effects of physical activity in the acute treatment of bipolar disorder: a pilot study.

BACKGROUND: Physical activity has demonstrated efficacy in depression and anxiety, but its potential in the management of bipolar disorder is yet unexplored. This study is a pilot investigation into the effectiveness of an adjunctive walking program in the acute treatment of bipolar disorder. METHODS: This is a retrospective cohort study of all patients admitted over a 24-month period to a private psychiatric unit with a primary diagnosis of bipolar disorder (ICD-10). All patients were invited to participate voluntarily in a walking group during their admissions. Those who reliably attended the walking group (participants) were compared against those who did not attend (non-participants), using the clinician-rated Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scales and the self-reported 21-item Depression Anxiety Stress Scales (DASS) as primary outcome measures. RESULTS: There were 24 admissions for participants and 74 admissions for non-participants. The two groups did not differ significantly in patient demographics or admission CGI and DASS measures, except for a lower DASS Stress subscore for participants (p=0.049). At discharge, the inter-group differences in CGI measures remained non-significant, but participants had significantly lower scores than non-participants for DASS (p=0.005) and all its subscales (Depression p=0.048, Anxiety p=0.002, Stress p=0.01). LIMITATIONS: Methodological limitations include a retrospective design, small sample size, lack of randomisation or control, and indirect measure of manic symptoms. CONCLUSIONS: The results of this trial provide preliminary support for a therapeutic role of physical activity in bipolar disorder, and warrant further investigation with randomised controlled trials.

Effects of a walking program in the psychiatric in-patient treatment setting: a cohort study.

ISSUE ADDRESSED: To assess the effectiveness of a walking program in a psychiatric in-patient unit. METHOD: In-patients at a private psychiatric unit were offered the opportunity to participate in a daily morning 40- minute walk led by an activity supervisor. After discharge, outcomes for patients who had regularly participated in the walking group (n=35) and patients who had not participated (n=49) were compared for length of stay during their period of admission and Clinical Global Impression-Severity (CGI-S) and Depression Anxiety Stress Scales (DASS) scores measured at admission and discharge. This was a retrospective analysis of data collected routinely. RESULTS: There were no significant differences between the two cohorts on most primary outcome measures, including length of stay, DASS scores at admission and at discharge and CGI-S scores at admission. Patients who had not participated in the walking group had a significantly lower score on a single measure, the CGI-S, than patients who had participated (p=0.001). CONCLUSIONS: This study showed no evidence that in-patients benefited from participating in the physical activity program. However, this must be interpreted within the confines of a number of study limitations and, as such, the findings can neither support nor refute the effectiveness of physical activities.

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.

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.

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.