MDMA-assisted psychotherapy for post-traumatic stress disorder: The devil is in the detail.

Recent years have seen escalating media, public and scientific interest in psychedelic medicine. Australia and New Zealand have been late to this research; however, in the past 2 years, rapid developments suggest that this is changing. Here, we argue for the need to critically review existing evidence in this field to guide future directions. We focus on (±)3,4-methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder, currently the most advanced area of clinical psychedelic research. Food and Drug Administration approval of this approach is likely in 2023, based on a series of promising findings. We provide a detailed overview of Phase 2 and 3 studies published to date. We identify several concerns related to this body of evidence, including methodological/design limitations and broader factors - such as robust involvement of advocacy groups in research and reliance on non-government financing leading to simplistic public messaging - that compound the methodological issues identified. We propose steps for future improvement, including the need for large, high-quality, independent efficacy trials with design enhancements, effectiveness trials and for researchers to consider their own engagement with media and public messaging around these modalities. We argue that, notwithstanding promising findings to date, rigorous and dispassionate science is needed to move the field forward and safeguard the welfare of participants.

Ill-defined: Concepts of mental health and illness are becoming broader, looser, and more benign.

OBJECTIVES: We argue that mental health-related concepts have become degraded within professional circles and in the wider community. We identify three trends: concept creep, the rise of broad umbrella concepts (e.g. distress and trauma), and the conflation of mental health with well-being, which marginalises serious mental illness. We speculate on the causes of these trends, including cultural shifts towards greater sensitivity to harm and the rise of wellness industries. Contributing factors within psychiatry include overdiagnosis, dimensional models and transdiagnostic perspectives. CONCLUSIONS: These trends may lead to inflated demands on services from those at the milder end of the psychopathological spectrum. We set out seven measures that mental health professionals can take to resist trends towards broad concepts of mental illness and limit some of their adverse consequences.

Personality disorder increases risk of low quality of life among women with mental state disorders.

BACKGROUND: Limited data are available examining the relationship between mental state disorders (mood, anxiety, substance use, eating disorders), their co-occurrence with personality disorder (PD), and quality of life among women. We aimed to investigate these relationships in a sample of women from the community. METHOD: Women from the Geelong Osteoporosis Study (n = 717) were administered the Structured Clinical Interview for DSM-IV (SCID-I/NP and SCID-II) and the World Health Organisation Quality of Life scale (WHOQOL-BREF). Weight and height were measured and lifestyle and demographic factors were self-reported. Logistic regression models (odds ratios with 95% confidence intervals) were undertaken to investigate associations among groups (mental state disorders, co-occurring mental state disorders with PD, and controls) and the WHOQOL-BREF domains (physical, psychological, social, and environmental health) while testing for potential confounding. RESULTS: Results indicated that mental state disorders were associated with increased risk of low quality of life in physical, psychological, social, but not environmental domains, compared to controls. This risk was increased among women with co-occurring PD across all domains compared to both controls and those with mental state disorders. CONCLUSION: These findings add evidence suggesting poor quality of life is experienced by those with mental state disorders, and that this is worsened by the experience of co-occurring PD.

Individual placement and support for vocational recovery in first-episode psychosis: randomised controlled trial.

BACKGROUND: High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).AimsTo examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370). METHOD: Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations. RESULTS: At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17-9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12- and 18-month follow-up points. There was no difference at any time point on educational outcomes. CONCLUSIONS: This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.Declaration of interestNone.

The prevalence, age distribution and comorbidity of personality disorders in Australian women.

OBJECTIVE: We aimed to describe the prevalence and age distribution of personality disorders and their comorbidity with other psychiatric disorders in an age-stratified sample of Australian women aged ⩾25 years. METHODS: Individual personality disorders (paranoid, schizoid, schizotypal, histrionic, narcissistic, borderline, antisocial, avoidant, dependent, obsessive-compulsive), lifetime mood, anxiety, eating and substance misuse disorders were diagnosed utilising validated semi-structured clinical interviews (Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition and Structured Clinical Interview for DSM-IV Axis II Personality Disorders). The prevalence of personality disorders and Clusters were determined from the study population ( n = 768), and standardised to the Australian population using the 2011 Australian Bureau of Statistics census data. Prevalence by age and the association with mood, anxiety, eating and substance misuse disorders was also examined. RESULTS: The overall prevalence of personality disorders in women was 21.8% (95% confidence interval [CI]: 18.7, 24.9). Cluster C personality disorders (17.5%, 95% CI: 16.0, 18.9) were more common than Cluster A (5.3%, 95% CI: 3.5, 7.0) and Cluster B personality disorders (3.2%, 95% CI: 1.8, 4.6). Of the individual personality disorders, obsessive-compulsive (10.3%, 95% CI: 8.0, 12.6), avoidant (9.3%, 95% CI: 7.1, 11.5), paranoid (3.9%, 95% CI: 3.1, 4.7) and borderline (2.7%, 95% CI: 1.4, 4.0) were among the most prevalent. The prevalence of other personality disorders was low (⩽1.7%). Being younger (25-34 years) was predictive of having any personality disorder (odds ratio: 2.36, 95% CI: 1.18, 4.74), as was being middle-aged (odds ratio: 2.41, 95% CI: 1.23, 4.72). Among the strongest predictors of having any personality disorder was having a lifetime history of psychiatric disorders (odds ratio: 4.29, 95% CI: 2.90, 6.33). Mood and anxiety disorders were the most common comorbid lifetime psychiatric disorders. CONCLUSIONS: Approximately one in five women was identified with a personality disorder, emphasising that personality disorders are relatively common in the population. A more thorough understanding of the distribution of personality disorders and psychiatric comorbidity in the general population is crucial to assist allocation of health care resources to individuals living with these disorders.

Delusional infestation: the case for improved mental state testing.

OBJECTIVES: Delusional infestation may present as a primary disorder or secondary to another disorder (e.g. schizophrenia). In this report we focus on the issue of inadequacies in mental state examinations leading to diagnostic uncertainty. METHODS: Case studies were identified for this review through searching the academic databases MedLine, PSYCInfo and PubMed. We developed a template that contained 36 headings and independently examined each case study report. Our percentage agreement for the first 42 case studies we reviewed was 91%. RESULTS: We identified diagnostic uncertainty due to inadequacies in the reporting of mental state examinations. CONCLUSIONS: Clinicians need to provide mental state information to an adequate standard that would allow confirmation of a diagnosis of delusions of infestation or exclude other possibilities.

Therapy contamination as a measure of therapist treatment adherence in a trial of cognitive behaviour therapy versus befriending for psychosis.

BACKGROUND: High quality randomized controlled trials (RCT) of psychotherapeutic interventions should ensure that the therapy being tested is what is actually delivered. However, contamination of one therapy into the other, a critical component of treatment adherence, is seldom measured in psychotherapy trials of psychosis. AIMS: The aim of the study was to determine whether a purpose-designed measure, the ACE Treatment Integrity Measure (ATIM) could detect therapy contaminations within a controlled trial of cognitive behavioural therapy (CBT) versus Befriending for first-episode psychosis and to compare the ATIM to a more traditional adherence measure, the Cognitive Therapy Scale (CTS). METHOD: Therapy sessions were audio-recorded and at least one therapy session from 53 of the 62 participants in the RCT was rated by an independent rater using the CTS and ATIM. RESULTS: Ninety-nine therapy sessions were rated. All Befriending sessions and all but three CBT sessions were correctly identified. The ATIM showed that 29 of the 99 (29%) sessions were contaminated by techniques from the other therapy. Within the CBT sessions, 19 of the 51 sessions (37%) were contaminated by one or more Befriending techniques. Of the Befriending sessions, 10 of 48 (21%) were contaminated by ACE techniques. The mean CTS score was higher in the CBT than the Befriending group. CONCLUSIONS: The ATIM was able to detect contaminations and revealed more meaningful, fine-grained analysis of what therapy techniques were being delivered and what contaminations occurred. The study highlights the benefit of employing purpose-designed measures that include contamination when assessing treatment adherence.

Social relationships and quality of life moderate distress associated with delusional ideation.

PURPOSE: In a previous study, individuals who followed a particular new religious movement (NRM) reported significantly less distress even though they reported similar levels of delusional ideation when compared with individuals diagnosed with psychotic disorders. Protective factors such as social relationship quality and quality of life (QOL) were hypothesized to explain attenuated distress associated with delusional ideation. METHODS: NRM individuals (n = 29), individuals diagnosed with psychotic disorders (n = 25), and control individuals (n = 63) were recruited. Psychotic symptoms, delusion-proneness, and facets of social relationships quality and QOL were examined across group. Potential moderators of the relationship between group membership and distress were further examined in multiple regression models. RESULTS: NRM participants reported more social relationships that were of higher quality (as demonstrated by more crisis supports, unique and overlap supports, more helpful supports and more reciprocated supports) than individuals with psychotic disorders. NRM participants also reported significantly higher QOL than individuals with psychotic disorders. Furthermore, NRM participants reported more distinct and less reciprocated supports, and significantly higher psychological, environmental, and total QOL, when compared with control participants. The relationship between group membership, delusional ideation, and distress was moderated by relationship reciprocity as well as by total QOL. CONCLUSIONS: Findings highlight the importance of establishing healthy reciprocal social relationships and improving QOL in people diagnosed with psychotic disorders, as these factors may act as a buffer against distress associated with delusional beliefs.

An analysis of real-time suicidal ideation and its relationship with retrospective reports among young people with borderline personality disorder.

INTRODUCTION: This study aimed to analyze the real-time variability of suicidal ideation intensity and the relationship between real-time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). METHODS: Young people (15-25-year olds) with BPD (N = 46), recruited from two government-funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. RESULTS: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real-time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. CONCLUSION: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week.

Tobacco smoking predicts depression and poorer quality of life in heart disease.

BACKGROUND: We report on the prospective association between smoking and depression and health-related quality of life (HRQOL) in patients with coronary artery disease (CAD). METHODS: Prospective study of 193 patients with assessment of depression occurring 3-, 6- and 9- months (T1, 2, and 3, respectively) following discharge from hospital for a cardiac event. HRQOL was assessed at T3. T1 depression was assessed by clinical interview; T2 and T3 depression was assessed by self-report. Smoking at time of cardiac event was assessed by self-report. Multivariate analyses controlled for known demographic, psychosocial and clinical correlates of depression. RESULTS: Smoking at the time of index cardiac event increased the likelihood of being diagnosed with Major Depressive Disorder (MDD) at T1 by 4.30 [95% CI, 1.12-16.46; p < .05]. The likelihood of receiving a diagnosis of minor depression, dysthymia or MDD as a combined group was increased by 8.03 [95% CI, 2.35-27.46; p < .01]. Smoking did not reliably predict depression at T2 or T3 and did not reliably predict persistent depression. Smoking increased the likelihood of being classified as depressed according to study criteria at least once during the study period by 5.19 [95% CI, 1.51-17.82; p < .01]. Smoking independently predicted worse mental HRQOL. CONCLUSIONS: The findings support a role for smoking as an independent predictor of depression in CAD patients, particularly in the first 3 months post-cardiac event. The well-established imperative to encourage smoking cessation in these patients is augmented and the findings may add to the evidence for smoking cessation campaigns in the primary prevention of depression.

The jumping-to-conclusions bias in new religious movements.

The jumping-to-conclusions bias has not been examined in a new religious movement (NRM) group. Twenty-seven delusion-prone NRM individuals were compared with 25 individuals with psychotic disorders and 63 non-delusion-prone individuals on four probabilistic inference tasks, together with measures of psychotic symptoms and delusion proneness. The NRM individuals requested significantly less evidence when compared with the control individuals on both meaningful and nonmeaningful tasks. The NRM individuals requested significantly more evidence on a difficult meaningful task when compared with the individuals with psychotic disorders. A specific reasoning style but not a general reasoning style differentiates the NRM individuals from the individuals with psychotic disorders. These findings may be specific to NRM individuals and may not be generalized to other delusion-prone groups.

Childhood trauma increases the risk of post-traumatic stress disorder in response to first-episode psychosis.

OBJECTIVE: To investigate the relationship between childhood trauma, post-traumatic stress symptoms due to the experience of childhood trauma, and post-traumatic stress symptoms due to the experience of psychosis. METHOD: The current study assessed childhood trauma and post-traumatic stress disorder (PTSD) symptoms as a result of both childhood trauma and psychosis using the Impact of Events Scale - Revised, in a group of 36 people with first-episode psychosis. RESULTS: Reported rates of clinical level post-psychotic PTSD symptoms, childhood trauma and childhood trauma-related clinical level PTSD symptoms were 47% (95% CI 31-64%), 64% (95% CI 48-80%) and 39% (95% CI 23-55%), respectively. Reporting childhood trauma increased the risk of developing post-psychosis PTSD 27-fold (95% CI 2.96-253.80, p = 0.01). Having childhood trauma-related PTSD increased the risk of developing post-psychosis PTSD 20-fold (95% CI 3.38-123.25, p = 0.01). These risks were not explained by illness factors such as duration of untreated psychosis, age of onset or severity of psychotic symptoms. Those without post-psychotic PTSD symptoms at clinical levels were unlikely to report childhood trauma (6%; 95% CI 3-8%). CONCLUSIONS: These results suggest the cognitive, social and biological consequences of childhood trauma can prevent effective recovery from the trauma of acute first-episode psychosis resulting in post-psychotic PTSD. Treatment strategies for post-psychotic PTSD must address childhood trauma and related PTSD.

Source monitoring and proneness to auditory-verbal hallucinations: a signal detection analysis.

INTRODUCTION: It has been suggested that a bias to misattribute self-generated thoughts to a nonself source underlies the experience of auditory-verbal hallucinations (AVH). We tested this hypothesis with healthy participants prone or not prone to AVH. METHOD: Participants (N=133) were presented with 96 words for subsequent recognition (half positively, half negatively valenced). For self-generated trials, participants generated a sentence containing the word. For other-generated trials, participants heard a prerecorded sentence containing the word. At test, studied words were re-presented visually, intermixed with 96 matched lures. Participants indicated the study status (old or new) and source (self or other) for each item. Sensitivity and bias measures were derived for item and source memory using signal detection theory. The 20 participants scoring highest on questions relating to AVH from the revised Launay-Slade Hallucination Scale formed the high-AVH group and the 20 scoring lowest formed the low-AVH group. RESULTS: ANOVAs revealed no significant differences between the two participant groups in sensitivity or bias of source memory, regardless of item valence. There was a trend for the sensitivity of item memory to be lower in the high-AVH group, compared with the low-AVH group. The bias of item memory was not significantly different between groups. CONCLUSIONS: Although we found no evidence that source-monitoring problems underlie the experience of AVHs in the general population, we recommend that signal detection measures be applied in future investigations of source monitoring in at-risk and clinical populations.

Hearing voices inside and outside the head: spatial source monitoring in participants prone to auditory hallucinations.

INTRODUCTION: Previous studies of source monitoring and auditory hallucinations (AH) have often conflated spatial source (internal-external) with source agency (self-other). Other studies have used suboptimal manipulations of auditory space (e.g., imagine saying vs. saying aloud). We avoided these problems by presenting experimenter-generated stimuli over headphones in the voice of another person so that the location of the voice sounded either internal or external to the participant's head. METHODS: Participants (N=121) studied 96 words and indicated for each whether it was presented internally or externally (online spatial source monitoring). At test, studied words were presented visually, intermixed randomly with 96 unstudied words. Participants indicated whether each item was old or new (item memory) and whether it was presented internally or externally during study (spatial source memory). Independent measures of memory accuracy and response bias were derived for online source monitoring, item memory and source memory using signal detection theory. Performance on these measures was compared between two groups of 30 participants who scored low or high on a measure of AH proneness. RESULTS: ANOVAs revealed no differences between the high- and low-AH groups in online spatial source monitoring, item memory, or spatial source memory. CONCLUSIONS: We found no evidence that proneness to AH in a sample of healthy volunteers was related to any of the measures of spatial source monitoring performance. We recommend that the methods introduced be applied to future investigations of spatial source monitoring with patient groups and with individuals at-risk for psychosis.

Predictors of vocational recovery among young people with first-episode psychosis: findings from a randomized controlled trial.

OBJECTIVE: The current study sought to examine demographic and clinical predictors of vocational recovery among young people with first-episode psychosis who participated in a randomized controlled trial (RCT) investigating the effectiveness of the supported employment model among this population. METHOD: Our original RCT compared Individual Placement and Support + treatment as usual (n = 20) with treatment as usual alone (n = 21) (Killackey, Jackson, & McGorry, 2008). A series of logistic regression analyses were conducted to assess the predictive power of demographic and clinical factors on the vocational recovery of young people with first-episode psychosis. RESULTS: Vocational recovery (defined as securing a position in competitive employment or attending a course of education at any point during the 6-month follow-up period) was predicted by participating in the vocational intervention (OR = 14.17, p = .001), having never been married (compared to those married/de facto: OR = 6.56, p = .044), and the instrumental role functioning subscale from the Quality of Life scale (OR = 1.21, p = .037). When considered together, only treatment group remained significant: Participants randomized to the vocational intervention were 16.26 times more likely to obtain work or study during the follow-up period compared to participants randomized to treatment as usual. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: It is critical that vocational services are introduced as part of an evidence-based, multidisciplinary approach in routine clinical care at early psychosis services. Further replication of these findings is indicated with a larger sample, particularly with the addition of cognitive training interventions to further improve vocational outcomes for young people with first-episode psychosis.

Psychometric properties of a brief, self-report measure of social inclusion: the F-SIM16.

AIMS: A disproportionate number of people with mental ill-health experience social exclusion. Appropriate measurement tools are required to progress opportunities to improve social inclusion. We have developed a novel measure, the Filia Social Inclusion Measure (F-SIM). Here we aimed to present a more concise, easy-to-use form, while retaining its measurement integrity by (i) refining the F-SIM using traditional and contemporary item-reduction techniques; and (ii) testing the psychometric properties of the reduced measure. METHODS: Five hundred and six participants completed the F-SIM, younger and older groups of people with serious mental illness (including psychosis, mood, anxiety disorders) and same-aged community counterparts. The F-SIM was completed at baseline and 2-week follow-up, alongside other measures (including social inclusion, loneliness). The F-SIM was refined using multidimensional scaling network analysis, confirmatory factor analysis and item response theory. The psychometric evaluation included assessment of dimensionality, internal consistency, test-retest reliability, discriminant ability and construct validity. RESULTS: The F-SIM was reduced from 135-items to 16; with 4-items in each domain of housing and neighbourhood, finances, employment and education and social participation and relationships. Psychometric properties were sound, including strong internal consistency within domains (all α > 0.85) and excellent overall (α = 0.92). Test-retest reliability was also high (γ = 0.90). Differences between groups were observed; clinical subgroups consistently reported lower levels of social inclusion compared to community counterparts. CONCLUSIONS: The F-SIM16 is a sound, reliable, brief self-report measure of social inclusion suitable for use in clinical and research settings. It has the potential to evaluate the effectiveness of interventions, and aid in fostering targeted and personalised needs-based care.

Selective attention to threat bias in delusion-prone individuals.

The study examined the selective attention to threat bias in delusion-prone individuals recruited from New Religious Movements (NRMs). Twenty-seven delusion-prone NRM individuals were compared with 25 individuals with psychotic disorders and 63 non-delusion-prone individuals on a Stroop task, together with psychotic and delusion proneness measures. NRM individuals showed significantly lower levels of selective attention to threat bias compared with individuals with psychotic disorders but not with non-delusion-prone individuals. Selective attention to threat bias was also not correlated with distress associated with delusional ideation. These findings may be specific to delusion-prone NRM individuals. The absence of the selective attention to threat bias may be related to levels of safety and security among members of NRMs.

INdividual Vocational and Educational Support Trial (INVEST) for young people with borderline personality disorder: study protocol for a randomised controlled trial.

BACKGROUND: The clinical onset of borderline personality disorder (BPD) usually occurs in young people (aged 12-25 years) and commonly leads to difficulty achieving and maintaining vocational (education and/or employment) engagement. While current psychosocial interventions lead to improvements in psychopathology, they have little effect upon functioning. Individual Placement and Support (IPS) is a client-driven model that assists individuals with severe mental illness to engage with education and/or employment appropriate to their personal goals, and that provides ongoing support to maintain this engagement. The objective of the INdividual Vocational and Educational Support Trial (INVEST) is to evaluate the effectiveness of adding IPS to an evidence-based early intervention programme for BPD, with the aim of improving vocational outcomes. METHODS/DESIGN: INVEST is a single-blind, parallel-groups, randomised controlled trial (RCT). The randomisation is stratified by gender and age and uses random permuted blocks. The interventions are 39 weeks of either IPS, or 'usual vocational services' (UVS). Participants will comprise 108 help-seeking young people (aged 15-25 years) with three or more DSM-5 BPD features and a desire to study or work, recruited from the Helping Young People Early (HYPE) early intervention programme for BPD at Orygen, in Melbourne, Australia. All participants will receive the HYPE intervention. After baseline assessment, staff who are blind to the intervention group allocation will conduct assessments at 13, 26, 39 and 52 weeks. At the 52-week primary endpoint, the primary outcome is the number of days in mainstream education/employment since baseline. Secondary outcomes include the cost-effectiveness of the intervention, quality of life, and BPD severity. DISCUSSION: Current treatments for BPD have little impact on vocational outcomes and enduring functional impairment is prevalent among this patient group. IPS is a targeted functional intervention, which has proven effective in improving vocational outcomes for adults and young people with psychotic disorders. This trial will investigate whether IPS is effective for improving vocational (employment and educational) outcomes among young people with subthreshold or full-syndrome BPD. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12619001220156 . 13 September 2019.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial.

OBJECTIVE: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). METHODS: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. RESULTS: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). CONCLUSION: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. CLINICAL TRIAL REGISTRATION: ACTRN12612000283875.