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Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.
Methods
We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.
Results
Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.
Conclusions
Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.
Having a relapse of schizophrenia or recurrent psychosis is feared by patients, can cause social and personal disruption and has been suggested to cause long-term deterioration, possibly because of a toxic biological process.
Aims
To assess whether relapse affected the social and clinical outcomes of people enrolled in a 24-month randomised controlled trial of antipsychotic medication dose reduction versus maintenance treatment.
Methods
The trial involved participants with a diagnosis of schizophrenia or recurrent, non-affective psychosis. Relapse was defined as admission to hospital or significant deterioration (assessed by a blinded end-point committee). We analysed the relationship between relapse during the trial and social functioning, quality of life, symptom scores (Positive and Negative Syndrome Scale) and rates of being in employment, education or training at 24-month follow-up. We also analysed changes in these measures during the trial among those who relapsed and those who did not. Sensitivity analyses were conducted examining the effects of ‘severe’ relapse (i.e. admission to hospital).
Results
During the course of the trial, 82 out of 253 participants relapsed. There was no evidence for a difference between those who relapsed and those who did not on changes in social functioning, quality of life, symptom scores or overall employment rates between baseline and 24-month follow-up. Those who relapsed showed no change in their social functioning or quality of life, and a slight improvement in symptoms compared to baseline. They were more likely than those who did not relapse to have had a change in their employment status (mostly moving out of employment, education or training), although numbers changing status were small. Sensitivity analyses showed the same results for those who experienced a ‘severe’ relapse.
Conclusions
Our data provide little evidence that relapse has a detrimental effect in the long term in people with schizophrenia and recurrent psychosis.
Psychotic disorders are known to be associated with elevated dopamine synthesis; yet, nondopamine factors may underlie the manifestation of some psychotic symptoms that are nonresponsive to dopamine-blocking agents. One under-explored nondopamine mechanism is neuroplasticity. We propose an account of the course of psychotic symptoms based on the extensive evidence for dopamine facilitation of Hebbian synaptic plasticity in cortical and subcortical memory systems. The encoding of psychotic experiences in autobiographical memory (AM) is expected to be facilitated in the hyperdopaminergic state associated with acute psychosis. However, once such ‘spurious AM of psychosis’ (SAMP) is encoded, its persistence may become dependent more on synaptic factors than dopamine factors. Under this framework, the involuntary retrieval of residual SAMP is postulated to play a key role in mediating the reactivation of symptoms with similar contents, as often observed in patients during relapse. In contrast, with active new learning of normalizing experiences across diverse real-life contexts, supported by intact dopamine-mediated salience, well-integrated SAMP may undergo ‘extinction’, leading to remission. The key steps to the integration of SAMP across psychotic and nonpsychotic memories may correspond to one’s ‘recovery style’, involving processes similar to the formation of ‘non-believed memory’ in nonclinical populations. The oversuppression of dopamine can compromise such processes. We synthesize this line of evidence into an updated dopamine-gated memory framework where neuroplasticity processes offer a parsimonious account for the recurrence, persistence, and progression of psychotic symptoms. This framework generates testable hypotheses relevant to clinical interventions.
Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.
Methods:
Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.
Results:
Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.
Conclusions:
A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.
Drug addiction is rife in Nepal, with a high relapse rate following treatment. Apart from basic psychosocial support, there are no evidence-based aftercare services for individuals in recovery. Recently, mindfulness-based interventions have shown promising results in preventing relapse. We discuss the context, challenges and opportunities of organising a 2-day intensive face-to-face mindfulness-based training for Nepalese mental health professionals to facilitate 8-week mindfulness-based relapse prevention (MBRP). Altogether, 24 participants completed the feedback questionnaire. Most were rehabilitation staff, along with a few psychologists and psychiatrists. Feedback suggested a high degree of satisfaction and provided comments to improve the programme. It has prompted us to design online MBRP training and set up a feasibility study for an MBRP programme in Nepal. If successful, this may help a huge number of individuals in recovery.
From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that N-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.
To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).
Methods:
This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.
Results:
1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.
Conclusion:
Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.
High-risk situations can be understood as events and situations that, if not effectively managed, pose a potential risk for relapse. What is important to note is that it is chiefly the individual’s subjective perception of “risk” that plays a significant role in whether a situation is high risk or not. A high-risk situation poses a threat to one’s perceived ability (what psychology calls “self-efficacy”) to handle the challenging situation at hand. Therefore, by developing more effective coping skills, thereby increasing perceived self-efficacy, one can learn to manage a high-risk situation without defaulting to substance use. This chapter provides practices that enables the reader to effectively deal with high-risk situations. The focus of this workbook is not to provide an exhaustive set of relapse prevention skills and tools but to help the reader to unlock their innate resilience through developing a Recovery Resilience Practice, so that they can effectively apply them.
Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies.
Methods
Probands and relatives with current DSM-IV BED (n = 156) from a family study of BED (‘baseline’) were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints.
Results
Of participants with follow-up data (n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables.
Conclusions
Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.
Studies investigating parenthood and how it affects long-term outcomes are lacking among individuals with schizophrenia spectrum disorders. This study aimed to examine the life of participants 20 years after their first diagnosis with a special focus on parenthood, clinical illness course, and family-related outcomes.
Methods
Among 578 individuals diagnosed with first-episode schizophrenia spectrum disorder between 1998 and 2000, a sample of 174 participants was reassessed at the 20-year follow-up. We compared symptom severity, remission, clinical recovery, and global functioning between 75 parents and 99 non-parents. Also, family functioning scored on the family assessment device, and the children's mental health was reported. We collected longitudinal data on psychiatric admission, supported housing, and work status via the Danish registers.
Results
Participants with offspring had significantly lower psychotic (mean (s.d.) of 0.89 (1.46) v. 1.37 (1.44), p = 0.031) negative (mean [s.d.] of 1.13 [1.16] v. 1.91 [1.07], p < 0.001) and disorganized symptom scores (mean [s.d.] of 0.46 [0.80] v. 0.85 [0.95], p = 0.005) and more were in remission (59.5% v. 22.4%, p < 0.001) and in clinical recovery (29.7% v. 11.1%, p = 0.002) compared to non-parents. When investigating global functioning over 20 years, individuals becoming parents after their first diagnosis scored higher than individuals becoming parents before their first diagnosis and non-parents. Regarding family-related outcomes, 28.6% reported unhealthy family functioning, and 10% of the children experienced daily life difficulties.
Conclusions
Overall, parents have more favorable long-term outcomes than non-parents. Still, parents experience possible challenges regarding family functioning, and a minority of their children face difficulties in daily life.
Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia.
Methods
This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK.
Results
Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%).
Conclusion
PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.
Body image concerns can be a significant barrier to treatment for individuals with eating disorders (EDs) and impact upon relapse risk. Body image difficulties can be challenging for clinicians and tend to be a lasting source of pain for ED patients. For ED with OCD, behaviors typically seen in ED presentations may be exacerbated. Body dissatisfaction and dysmorphia are common in EDs and often linked to sociocultural factors such as societal pressure and media representation. The media is heavily implicated in the prevalence of body dissatisfaction due to the amounts of misleading health advice and trends on social media which make people more anxious, aware, or insecure about their bodies. Media and political environments often underrepresent and stereotype women, people of color, and LGBTQ+ individuals, which can perpetuate negative stereotypes and biases that further marginalize people due to appearance. Given the widespread nature of body dissatisfaction and cultural messages that link a person’s worth to appearance, it is not surprising that people with OCD may become obsessed with these issues. This can make treatment more challenging, particularly when OCD and EDs are comorbid.
Relapse is a common phenomenon, and therefore relapse prevention plays a signficant part in addiction treatment. To effectively prevent relapse, it is important to understand how relapse happens and who is most susceptible to it. We now recognize relapse as a multi-stage process occuring over time, rather than a singular event. Multile intrapersonal and interpersonal factors have been identified that influence the risk of relapse. When creating a relapse prevention plan, these factors must be taken into consideration in order for the individual to be successful.
Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.
Method
One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.
Results
Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.
Conclusions
Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.
This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression.
Methods
An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months.
Results
Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse.
Conclusions
The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.
Some patients return for further psychological treatment in routine services, although it is unclear how common this is, as scarce research is available on this topic.
Aims:
To estimate the treatment return rate and describe the clinical characteristics of patients who return for anxiety and depression treatment.
Method:
A large dataset (N=21,029) of routinely collected clinical data (2010–2015) from an English psychological therapy service was analysed using descriptive statistics.
Results:
The return rate for at least one additional treatment episode within 1–5 years was 13.7%. Furthermore, 14.5% of the total sessions provided by the service were delivered to treatment-returning patients. Of those who returned, 58.0% continued to show clinically significant depression and/or anxiety symptoms at the end of their first treatment, while 32.0% had experienced a demonstrable relapse before their second treatment.
Conclusions:
This study estimates that approximately one in seven patients return to the same service for additional psychological treatment within 1–5 years. Multiple factors may influence the need for additional treatment, and this may have a major impact on service activity. Future research needs to further explore and better determine the characteristics of treatment returners, prioritise enhancement of first treatment recovery, and evaluate relapse prevention interventions.
Edited by
Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine,David Castle, University of Tasmania, Australia,Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
Cannabis use is highly prevalent among individuals presenting with their first episode psychosis (FEP), and a substantial proportion of individuals continue to use cannabis following the onset of the illness. Longitudinal research following up FEP patients has now started to explore in more detail the impact of cannabis use on long-term prognosis of psychosis, implicating continued cannabis use as a risk factor for an unfavourable illness course of psychosis. Since cannabis use is one factor amenable to treatment, it constitutes an attractive interventional target for early intervention. As such, a nuanced understanding of how exposure to cannabis affects the long-term course of psychosis is paramount, to help clinicians and carers to formulate the best possible treatment choices for individuals with a first episode psychosis. This chapter will focus in more detail on questions concerning the impact of cannabis use on the illness course of psychosis, including an overview of its effects on clinical and functional outcome dimensions, an assessment of causality, and a discussion on the interplay between cannabis use and other factors implicated in long-term prognosis of psychosis.
Nowadays, relapses are typical in patients with schizophrenia and may have serious implications due to most of them are caused by a lack of adherence to treatment.Therefore, numerous long-acting injectable antipsychotics (LAI) have been developed as aripiprazole depot who need a proper oral supplementation. Since November 2020, FDA approved a new treatment indication with a double injection start and a single dose of 20mg of oral aripiprazole, with the aim of avoiding oral supplementation during the next 14 days.
Objectives
The purpose of our study is to expose our experience with the new double injection start with aripiprazole LAI, regarding the rehospitalization rate.
Methods
A prospective study (n=17 patients) has been developed between November 2020 and October 2021 with the purpose of studying the rehospitalization and antipsychotic adherence after the new guideline of aripiprazole
Results
After an 11-month-follow-up, it is noticed a 65% non-rehospitalization rate and a 76% proper treatment persistence rate. The 94% did not present any kind of side effects, only one patient had a case report of bullous pemphigoid. Regarding the concomitant use of other antipsychotics, 82% of the patients remained in monotherapia. The average stay time was shortened (11 days) regarding the standard dose (14 days).
Conclusions
The new LAI regimen is well tolerated in our patients obtaining a high treatment persistence after several months of hospital discharge. It was already possible to shorten the time of rehospitalization, not having to add oral aripiprazole for 14 days. Most patients were discharged are on antipsychotic monotherapy and have not been rehospitalized in the short term.
Polypharmacy can be the cause of deliberate discontinuation of medication and consequent relapse of schizophrenia.
Objectives
To establish the one-year rate of relapse in the patients with schizophrenia with regard to monotherapy or polypharmacy.
Methods
The sample of all hospitalized patients with schizophrenia in a five-year period was analyzed. Descriptive statistics were used.
Results
Total of 87 participants (57 women), the median age was 43 years. Antipsychotic monotherapy was used in 31 (35.6%) of the participants. In one year period, 32 (36.8%) of all participants had a relapse. Prior to relapse, significantly more participants were treated with polypharmacy (p<0,05).
Conclusions
Antipsychotic polypharmacy is related to a higher rate of relapse in patients with schizophrenia.