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Relapse in schizophrenia: Definitively not a bolt from the blue
Abstract
Background:
Detailed study of the period before schizophrenic relapse when early warning signs (EWS) are present is crucial to effective pre-emptive strategies.
Aims:
To investigate the temporal properties of EWS self-reported weekly via a telemedicine system.
Method:
EWS history was obtained for 61 relapses resulting in hospitalization involving 51 patients with schizophrenia. Up to 20 weeks of EWS history per case were evaluated using a non-parametric bootstrap test and generalized mixed-effects model to test the significance and homogeneity of the findings.
Results:
A statistically significant increase in EWS sum score was detectable 5 weeks before hospitalization. However, analysis of EWS dynamics revealed a gradual, monotonic increase in EWS score across during the 8 weeks before a relapse.
Conclusions:
The findings - in contrast to earlier studies - suggest that relapse is preceded by a lengthy period during which pathophysiological processes unfold; these changes are reflected in subjective EWS.
Supplementary resource (1)
... Most mental disorders, especially severe ones, are associated with a high risk of relapse (Murray et al., 2001;Spaniel et al., 2018). Patients suffering from SMDs experience frequent relapses during their life. ...
... Its web-based interface offers the authorized physician a longitudinal analysis of the dynamics and development of possible prodromes (Choi et al., 2016;Koblauch et al., 2018). Several studies worldwide have investigated the effectiveness of ITAREP in reducing the relapse among patients who live with SMDs (Gumley et al., 2022;Spaniel et al. 2018;Ybarra et al., 2019). However, there have been no randomized clinical trials on the effectiveness of ITAREP in reducing relapse among psychiatric patients in Iran. ...
... The social worker referred the patients to a psychiatrist in case of crisis (Spaniel et al., 2008(Spaniel et al., , 2018 and facilitated and advocated for setting an appointment to visit the psychiatrist and involved the caregiver to make sure that the patient will meet the psychiatrist. The psychiatrist visited the patients and decided about changing the dosage of drugs, issuing an order to admit the patient to the hospital in the shortest possible time, etc. ...
Background
Severe Mental Disorders (SMDs) cause mental health worldwide challenges because of several relapses and extensive recovery periods of hospitalization, which put a lot of economic and social burden on families and governments. Therefore, interventions are necessary to decrease the relapse of these disorders.
Aim
This study was conducted to investigate the effect of Information Technology Assisted Relapse Prevention Program (ITAREP) on relapse among people who live with SMDs.
Method
This study was a randomized clinical trial with intervention and control groups. ITAREP is a remote intervention based on monitoring the Early Warning Signs (EWS) to decrease the number of potential relapses. Using convenience sampling, people with SMDs admitted to Sina Juneqan Psychiatric Hospital and their caregivers were recruited in this study and randomly allocated to the control and intervention groups. Two checklists of the EWS for the patient and the patient’s caregiver were used for monitoring the relapse signs. Data were collected at baseline and 90 days after discharge and were analyzed using t-test and Chi-square statistical tests and linear regression in SPSS software.
Results
Fifty-two patients who lived with SMDs participated in this study (26 in the intervention group and 26 in the control group). The two groups were homogeneous regarding age, gender, type of mental disorder, and duration of the disorder. Forty-two males and ten females participated in this research. Most of the participants were diagnosed with schizophrenia. The results showed that the number of relapses in the intervention group was significantly lower than in the control group in the post-test.
Conclusion
Social workers, as the case managers and a member of the interdisciplinary psychiatric team, can actively perform follow-up measures after discharge using ITAREP, and it can be expected that these interventions will reduce the number of relapses among patients who live with SMDs.
... The information provided by EMA could be useful in clinical settings aiming to detect symptom increases that signal impending relapse or to track recovery during high-risk periods (i.e., after hospitalizations). New approaches using weekly assessments of aggregate warning signs collected via mobile SMS (25,26) have demonstrated that rather than occurring in a 2-4 week period as has been previously hypothesized, patients report gradual increases that begin 2 months before a relapse (27). Few studies have assessed changes in individual symptoms that precede and follow relapses with mobile devices. ...
... In addition to symptoms of psychosis, EMA items also assessed overall mental health (e.g., stress, depression, hopefulness, calmness, clarity of thought), and functioning (e.g., socialization, sleep). For the present study, we identified five variables based on research (11,12,27) suggesting that negative mood, anxiety, hallucinations, and delusions are elevated in assessments that precede relapses. Two of those items-persecutory ideation, and self-reported sleep quality-were assessed with a single item, while three-negative mood (average of the "depression" item and reverse-coded "hopefulness" item), anxiety ("stress" item and reverse-coded "calm" item), and hallucinations (average of "seeing things" and "voices" items)-were assessed as composite scores. ...
... Thus, model coefficients indicated the rate of change in symptoms per week during the pre or post relapse period, and the amount of sudden change in symptoms when transitioning from pre relapse to post relapse (beyond what was attributable to the gradual change over time trajectories). Because our analyses aimed to examine gradual changes over periods consistent with previous research (27), our models included EMA data within 100 days before or after relapse. ...
Theoretical views and a growing body of empirical evidence suggest that psychiatric relapses in schizophrenia-spectrum disorders (SSDs) have measurable warning signs. However, because they are time- and resource-intensive, existing assessment approaches are not well-suited to detect these warning signs in a timely, scalable fashion. Mobile technologies deploying frequent measurements—i.e., ecological momentary assessment—could be leveraged to detect increases in symptoms that may precede relapses. The present study examined EMA measurements with growth curve models in the 100 days preceding and following 27 relapses (among n = 20 individuals with SSDs) to identify (1) what symptoms changed in the periods gradually preceding, following, and right as relapses occur, (2) how large were these changes, and (3) on what time scale did they occur. Results demonstrated that, on average, participants reported elevations in negative mood (d = 0.34), anxiety (d =0.49), persecutory ideation (d =0.35), and hallucinations (d =0.34) on relapse days relative to their average during the study. These increases emerged gradually on average from significant and steady increases (d = 0.05 per week) in persecutory ideation and hallucinations over the 100-day period preceding relapse. This suggests that brief (i.e., 1–2 item) assessments of psychotic symptoms may detect meaningful signals that precede psychiatric relapses long before they occur. These assessments could increase opportunities for relapse prevention as remote measurement-based care management platforms develop.
... Concerning mobile applications, a recent study found that a questionnaire embedded in an app was able to effectively monitor the longitudinal variation of mood instability in the long-term and to discriminate between BD and borderline personality disorders patients [26]. Similarly, in SCZ patients there is evidence that electronic home telemonitoring via a PC-to-phone SMS platform was able to identify prodromal symptoms of relapse, to enable early intervention and prevent unnecessary hospitalizations through a longitudinal analysis of the dynamics and development of possible prodromes [27,28]. ...
... Mounting evidence has shown the potential of digital and electronic monitoring tools in SCZ. Indeed, electronic or information technology aided monitoring has been proven effective in the area of relapse prevention [28,[41][42][43][44][45], of treatment adherence [47], and of illness severity in general [46,48,53], as well as in the early phase of illness [49]. ...
... The analysis of the temporal properties of early warning signs collected weekly ITAREPS, showed that relapse was preceded by a lengthy period during which pathophysiological processes unfold. An increase in patient-reported early warning signs was detected as early as 5 weeks before hospitalization [28] 5 patients with SCZ Smartphone-based CrossCheck, and a multimodal data collection system Digital self-reports provided a clear and potentially actionable description of symptom exacerbation prior to hospitalization 17 treated patients with SCZ Smartphone-based Statistical approach based on weighted resampling of observed trajectories to impute the gaps Testing for changes in mobility patterns and social behavior over time for up to 3 months using a smartphone app in SCZ patients was effective in identifying statistically significant behavioral anomalies in the days prior to psychotic relapse. The rate of behavioral anomalies detected in the two weeks prior to relapse was 71% higher than the rate of anomalies during other time periods [44] 52 patients with SCZ Employs a case management system and follows several thousand individuals in both inpatient and outpatient settings. ...
There is an increasing interest in the development of effective early detection and intervention strategies in severe mental illness (SMI). Ideally, these efforts should lead to the delineation of accurate staging models of SMI enabling personalized interventions. It is plausible that big data approaches will be instrumental in describing the developmental trajectories of SMI by facilitating the incorporation of data from multiple sources, including those pertaining to the biological make-up of affected subjects. In this review, we first aimed to offer a perspective on how big data are helping the delineation of personalized approaches in SMI, and, second, to offer a quantitative synthesis of big data approaches in metabolomics of SMI. We finally described future directions of this research area.
... Concerning mobile applications, a recent study found that a questionnaire embedded in an app was able to effectively monitor the longitudinal variation of mood instability in the long-term and to discriminate between BD and borderline personality disorders patients [26]. Similarly, in SCZ patients there is evidence that electronic home telemonitoring via a PC-to-phone SMS platform was able to identify prodromal symptoms of relapse, to enable early intervention and prevent unnecessary hospitalizations through a longitudinal analysis of the dynamics and development of possible prodromes [27,28]. ...
... Mounting evidence has shown the potential of digital and electronic monitoring tools in SCZ. Indeed, electronic or information technology aided monitoring has been proven effective in the area of relapse prevention [28,[41][42][43][44][45], of treatment adherence [47], and of illness severity in general [46,48,53], as well as in the early phase of illness [49]. ...
... The analysis of the temporal properties of early warning signs collected weekly ITAREPS, showed that relapse was preceded by a lengthy period during which pathophysiological processes unfold. An increase in patient-reported early warning signs was detected as early as 5 weeks before hospitalization [28] 5 patients with SCZ Smartphone-based CrossCheck, and a multimodal data collection system Digital self-reports provided a clear and potentially actionable description of symptom exacerbation prior to hospitalization 17 treated patients with SCZ Smartphone-based Statistical approach based on weighted resampling of observed trajectories to impute the gaps Testing for changes in mobility patterns and social behavior over time for up to 3 months using a smartphone app in SCZ patients was effective in identifying statistically significant behavioral anomalies in the days prior to psychotic relapse. The rate of behavioral anomalies detected in the two weeks prior to relapse was 71% higher than the rate of anomalies during other time periods [44] 52 patients with SCZ Employs a case management system and follows several thousand individuals in both inpatient and outpatient settings. ...
There is increasing interest in the development of effective early detection and intervention strategies in severe mental illness (SMI). Ideally, these efforts should lead to the delineation of accurate staging models of SMI enabling personalized interventions. It is plausible that big data approaches will be instrumental in describing the developmental trajectories of SMI by facilitating the incorporation of data from multiple sources,
including those pertaining to the biological make-up of affected subjects. In this review, we first aimed to offer a perspective on how big data are helping the delineation of personalized approaches in SMI, and, secondly, to offer a quantitative synthesis of big data approaches in metabolomics of SMI. We finally described future directions of this research area.
... Concerning mobile applications, a recent study found that a questionnaire embedded in an app was able to effectively monitor longitudinal variation of mood instability in the long-term and to discriminate between BD and borderline personality disorders (BPD) patients [25]. Similarly, in SCZ patients there is evidence that electronic home telemonitoring via a PC-to-phone SMS platform was able to identify prodromal symptoms of relapse, to enable early intervention and prevent unnecessary hospitalizations through a longitudinal analysis of the dynamics and development of possible prodromes [26,27]. ...
... Mounting evidence has shown the potential of digital and electronic monitoring tools in SCZ. Indeed, electronic or information technology aided monitoring has been proven effective in the area of relapse prevention [27,[39][40][41][42][43], of treatment adherence [44], and of illness severity in general [45][46][47], as well as in the early phase of illness ...
... Of interest, the analysis of the temporal properties of early warning signs collected weekly ITAREPS, showed that relapse was preceded by a lengthy period during which pathophysiological processes unfold [27]. ...
Abstract: There is increasing interest in the development of effective early detection and intervention strategies in severe mental illness (SMI). Ideally, these efforts should lead to the delineation of accurate staging models of SMI enabling personalized interventions. It is plausible that big data approaches will be instrumental in describing the developmental trajectories of SMI by facilitating the incorporation of data from multiple sources, including those pertaining to the biological make-up of affected subjects. Here, we first aimed to offer a perspective on how big data are helping the delineation of personalized approaches in SMI, and, secondly, to offer a quantitative synthesis of big data approaches in metabolomics of SMI. We finally offer a perspective on future directions of this research area.
Keywords: machine learning; metabolite; digital monitoring; accuracy; personalized medicine
... We identified significantly increased use of words belonging to the swear, anger, and negative emotion categories in the period of time preceding a relapse hospitalization consistent with escalating irritability and depression known to be associated with emerging relapse. 50,71 We also found increased use of words belonging to the hear and feel categories in the month preceding a relapse hospitalization, consistent with emerging perceptual disturbances, commonly experienced by individuals with psychosis. 50,51,71 This is also consistent with prior work in those at risk for developing psychosis, suggesting that words related to auditory perception, such as voices and sounds, predicted conversion to psychosis. ...
... 50,71 We also found increased use of words belonging to the hear and feel categories in the month preceding a relapse hospitalization, consistent with emerging perceptual disturbances, commonly experienced by individuals with psychosis. 50,51,71 This is also consistent with prior work in those at risk for developing psychosis, suggesting that words related to auditory perception, such as voices and sounds, predicted conversion to psychosis. 62 Consistent with prior studies, we found increased use of firstperson pronouns, 59,63 but also second-person pronouns, which may be indicative of changes in the way an individual thinks about him/herself in relation to others, in-line with the social changes prominent in individuals experiencing worsening symptoms of psychosis. ...
... 62 Consistent with prior studies, we found increased use of firstperson pronouns, 59,63 but also second-person pronouns, which may be indicative of changes in the way an individual thinks about him/herself in relation to others, in-line with the social changes prominent in individuals experiencing worsening symptoms of psychosis. 50,51,71 Increased use of first-person pronouns may also be indicative of emerging self-referential thinking, a common psychotic experience contributing to delusions, whereby neutral environmental stimuli are perceived to be personally meaningful. 37 In contrast to those at risk for developing psychotic disorders, we did not find that the use of determiners 60 or possessive pronouns 61 were associated with psychotic symptom exacerbation, which may represent linguistic differences among individuals who develop a psychotic disorder compared to those who relapse, or more likely, differences in the way individuals communicate through speech versus Facebook. ...
Although most patients who experience a first-episode of psychosis achieve remission of positive psychotic symptoms, relapse is common. Existing relapse evaluation strategies are limited by their reliance on direct and timely contact with professionals, and accurate reporting of symptoms. A method by which to objectively identify early relapse warning signs could facilitate swift intervention. We collected 52,815 Facebook posts across 51 participants with recent onset psychosis (mean age = 23.96 years; 70.58% male) and applied anomaly detection to explore linguistic and behavioral changes associated with psychotic relapse. We built a one-class classification model that makes patient-specific personalized predictions on risk to relapse. Significant differences were identified in the words posted to Facebook in the month preceding a relapse hospitalization compared to periods of relative health, including increased usage of words belonging to the swear (p < 0.0001, Wilcoxon signed rank test), anger (p < 0.001), and death (p < 0.0001) categories, decreased usage of words belonging to work (p = 0.00579), friends (p < 0.0001), and health (p < 0.0001) categories, as well as a significantly increased use of first (p < 0.0001) and second-person (p < 0.001) pronouns. We additionally observed a significant increase in co-tagging (p < 0.001) and friending (p < 0.0001) behaviors in the month before a relapse hospitalization. Our classifier achieved a specificity of 0.71 in predicting relapse. Results indicate that social media activity captures objective linguistic and behavioral markers of psychotic relapse in young individuals with recent onset psychosis. Machine-learning models were capable of making personalized predictions of imminent relapse hospitalizations at the patient-specific level.
... While rehabilitation has been noted to have promising outcomes with regard to prevention of multiple relapses, assertive community treatment has been noted to reduce the relapse risk at 6 months, even as the case management had confidence intervals that included probability of no dissimilarity with normal treatment. The above observations are consistent with earlier findings of reviews that disclosed that assertive community treatment was effective in the prevention of multiple relapses in schizophrenia, even as case management did not prefer any protective effect [85,86]. Other notable psychosocial interventions were not effective in reducing the relapse risk in schizophrenia. ...
In persons with schizophrenia, multiple relapses depict the course of illness, yet the nature of these episodes has not been extensively researched and clinicians may not always be aware of important implications. Most individuals living with schizophrenia experience multiple relapses in the course of their lifetimes. While behaviors may precede the relapses, it has been disclosed that 71% of the behavioral changes may be noticed two weeks prior to the relapses compared to the anomaly rates at other times. Moreover, almost 3 out of every five individuals with schizophrenia experience a relapse in their symptoms after commencing treatment/medication. In most instances, the multiple relapses are increasingly distressing to the patients, their families, and their societies, and not only disrupt the recovery process but also increase the risk of treatment resistance. The objective of this systematic review is, therefore, to evaluate the causes of multiple relapses in patients with schizophrenia, and identify effective ways to prevent the relapses. This study reviewed selected literature concerning the nature and possible causes of multiple relapses in schizophrenia patients and the prevention of relapse. The findings have shown that the key causes of multiple relapses in patients with schizophrenia include non-adherence to treatment, lack of effective social support, substance use and abuse, mental illness-associated stigma, unavailability of essential psychotic medications, and delays in care seeking. The findings of this systematic review indicate that multiple relapse rates are increasingly higher in schizophrenia patients in instances where the treatments have been discontinued, even following a single psychotic episode and that prolonged treatment duration before discontinuation does not result in a reduction in multiple relapse risks. Despite of, timely and effective detection of the relapses and the taking of effectual preventive measures against the potential causative factors are vital for improved prognosis of multiple relapse in schizophrenia patients. Given the inefficiencies of various treatments to prevent full-blown relapse and the possible adverse outcomes, medication adherence and various factors predisposing to multiple relapses need to be the key focus in the management of schizophrenia. Keywords Schizophrenia; Multiple relapses; Antipsychotics; Discontinuation
... While rehabilitation has been noted to have promising outcomes with regard to prevention of multiple relapses, assertive community treatment has been noted to reduce the relapse risk at 6 months, even as the case management had confidence intervals that included probability of no dissimilarity with normal treatment. The above observations are consistent with earlier findings of reviews that disclosed that assertive community treatment was effective in the prevention of multiple relapses in schizophrenia, even as case management did not prefer any protective effect [85,86]. Other notable psychosocial interventions were not effective in reducing the relapse risk in schizophrenia. ...
In persons with schizophrenia, multiple relapses depict the course of illness, yet the nature of these episodes has not
been extensively researched and clinicians may not always be aware of important implications. Most individuals living
with schizophrenia experience multiple relapses in the course of their lifetimes. While behaviors may precede the
relapses, it has been disclosed that 71% of the behavioral changes may be noticed two weeks prior to the relapses
compared to the anomaly rates at other times. Moreover, almost 3 out of every five individuals with schizophrenia
experience a relapse in their symptoms after commencing treatment/medication. In most instances, the multiple
relapses are increasingly distressing to the patients, their families, and their societies, and not only disrupt the
recovery process but also increase the risk of treatment resistance. The objective of this systematic review is, therefore,
to evaluate the causes of multiple relapses in patients with schizophrenia, and identify effective ways to prevent the
relapses. This study reviewed selected literature concerning the nature and possible causes of multiple relapses in
schizophrenia patients and the prevention of relapse. The findings have shown that the key causes of multiple
relapses in patients with schizophrenia include non-adherence to treatment, lack of effective social support, substance
use and abuse, mental illness-associated stigma, unavailability of essential psychotic medications, and delays in care
seeking. The findings of this systematic review indicate that multiple relapse rates are increasingly higher in
schizophrenia patients in instances where the treatments have been discontinued, even following a single psychotic
episode and that prolonged treatment duration before discontinuation does not result in a reduction in multiple
relapse risks. Despite of, timely and effective detection of the relapses and the taking of effectual preventive measures
against the potential causative factors are vital for improved prognosis of multiple relapse in schizophrenia patients.
Given the inefficiencies of various treatments to prevent full-blown relapse and the possible adverse outcomes,
medication adherence and various factors predisposing to multiple relapses need to be the key focus in the
management of schizophrenia.
... Of these, EMA has been extensively studies in the last 20 years, initially via text messaging approaches and later via mobile apps (Buck et al., 2021;Š paniel et al., 2008). Several subtle warning signs such as poor sleep and irritability are reported as early as five weeks prior to relapse (Herz and Melville, 1980;Spaniel et al., 2018). However, the warning signs that rely on patient reports have poor sensitivity (with a median of 61 %), as these features are often ignored by patients until it is too late (Eisner et al., 2013). ...
... Of these, EMA has been extensively studies in the last 20 years, initially via text messaging approaches and later via mobile apps (Buck et al., 2021;Španiel et al., 2008). Several subtle warning signs such as poor sleep and irritability are known to occur as early as five weeks prior to relapse (Herz & Melville, 1980;Spaniel et al., 2018). However, the warning signs that rely on patient reports have poor sensitivity (with a median of 61%), as these features are often ignored by patients until it is too late (Eisner et al., 2013). ...
... Family members point out that the presence of psychotic symptoms, irritability, agitation, aggressiveness, unwillingness to live, forgetfulness and disorganized behavior (e.g., soliloquies and unmotivated laughter) were suggestive signs of the occurrence of psychotic relapses. Other investigations that listed EWS of psychotic relapse pointed similar factors, some of which are changes in behavior, change in sleep pattern, irritability, anxiety, agitation, difficulty concentrating, distraction, disorganization in behavior, and return or worsening of psychotic symptoms (Birchwood et al., 2000;Spaniel et al., 2018). Importantly, although many patients can recognize changes that precede a relapse episode, some patients may not be able to recognize the EWS alone (Eisner et al., 2014). ...
This qualitative study was carried out with 10 dyads of patients-family members to explore their perception about psychotic relapses. Data were collected through a semi-structured interview from April to August 2019, in Brazil, and analyzed using the thematic analysis proposed by Braun & Clark. Four main themes emerged from the interviews: (1) defining and describing the psychotic relapses; (2) risk factors for psychotic relapse; (3) protective factors for psychotic relapse; and (4) early warning signs: identification of an episode of psychotic relapse. Exploring the perception of patients with psychotic disorders and their families about relapse is fundamental for the development of relapse risk assessment tools and to guide further research on this topic.
... 50 Relapse in psychosis is now understood to be the end point of a process of change associated with early signs including changes in affect and incipient psychotic experiences. 50 EWS may be identifiable for as long as 5-8 weeks prior to a relapse, 51 creating significant opportunity for early intervention. However, review evidence suggests considerable variation in the proportion of relapses correctly predicted by EWS (sensitivity 10-80%, median 60%) and non-relapses correctly predicted (specificity 38-100%, median 81%), with more frequent monitoring and the inclusion of both affective and psychosis symptoms found to improve prediction. ...
Background
Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse.
Objective
How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse?
Design
A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up.
Settings
Glasgow, UK, and Melbourne, Australia.
Participants
Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user.
Interventions
The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted.
Main outcome measures
The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse.
Results
We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference –4.29, 95% confidence interval –7.29 to –1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained.
Limitations
This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness.
Conclusions
A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible.
Future work
A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3–0.4).
Trial registration
This trial is registered as ISRCTN99559262.
Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).
... Continuous antipsychotic therapy has been recommended to avoid relapse [7]. High relapse rates [8] and decompensations because of poor medication adherence can affect long-term outcomes [9,10]. Patient adherence to medication is important for controlling symptoms and relapse rates and preventing deterioration. ...
Treatment of schizophrenia Schizophrenia therapy requires long-term medication to prevent relapses. Treatment non-adherence may increase the risk of relapses, leading to increased hospitalizations and emergency room (ER) visits. Long acting injectable (LAI), such as paliperidone palmitate have improved treatment adherence, consequently improving symptoms. However, real-world studies comparing 3-monthly LAI formulations with other LAIs, and oral antipsychotic (OA) drugs are scarce. The objective of this study was to investigate and compare the clinical effectiveness of paliperidone palmitate LAIs monthly (PP1M, Xeplion®) and 3-monthly (PP3M, Trevicta®) to LAI monthly aripiprazole (AM, Abilify Maintena®) and to OA in Spain.
Methods: Retrospective, observational study including 2275 adult patients with schizophrenia schizophrenia patients in Spanish population. Data from hospital, primary care, and pharmacy dispensation electronic medical records were obtained between January 2017- February 2018. Main outcomes included psychiatric hospitalizations and ER visit rates, days on treatment and treatment persistence.
Results: PP3M patients had a significantly lower mean hospitalization rate (Mean, SD: 0.00046 (0.00181); p<0.0001) compared to other treatment groups. Kaplan-Meier curves revealed that 92.0% and 88.4% of PP3M patients remained hospitalization-free by 12 and 18 months, respectively. All treatment groups had at least a 2-fold significantly higher risk of psychiatric hospitalizations compared to PP3M and compared to OA, hospitalization risk among the PP3M group was significantly lower [(HR=0.46, (95% CI: 0.31-0.67; p<0.0001)]. The risk of ER visits was significantly lower among both PP3M and PP1M compared to OA, although lower among the PP3M [(HR = 0.462, (95% CI: 0.29-0.62); and HR= 0.833, p=0.03 (95% CI: 0.59-0.97), respectively]). Time until treatment switch. Treatment persistence with PP3M was high, with more than 86.5% remaining on treatment by 18 months.
Conclusions: PP3M was more effective than OA and monthly LAIs in improving clinical outcomes for patients with schizophrenias patients in a real-world setting in Spain.
... EWS can be used to avoid relapse in a timely manner (Gumley et al., 2020), and must be present prior to relapse for successful early intervention. A statistically signifi cant rise in EWS total score might be seen 5 to 8 weeks before relapse (Spaniel et al., 2018). Many individuals relapse shortly aft er treatment reduction and/or cessation; the change from remission to relapse may be rapid (Emsley et al., 2013). ...
Maintaining remission and improving quality of life for individuals with schizophrenia can encourage them to return to work, participate in volunteer opportunities, and establish healthy intimate relationships. The purpose of the current review was to explore the impacts of using relapse prevention interventions on maintaining remission and minimizing relapse rate for individuals with schizophrenia. A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines to screen 134 studies published between 2010 and 2020. A total of 14 articles met eligibility criteria. Included studies showed that intervention strategies tailored to meet the needs of individuals with schizophrenia must be developed and applied in different psychiatric settings to maintain remission and minimize relapse rate. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].
... Recent literature has begun to recognize the importance of timesensitive monitoring of subtle changes in cognition, energy level, social and physical activities, sleep patterns and perception (Birchwood et al., 2000;Eisner et al., 2013;Gleeson et al., 2005;Spaniel et al., 2018) in relapse prediction. However, conventional clinical evaluations at mental health facilities do not allow for timely, sensitive detection of the abovementioned factors. ...
Background
Psychotic disorders are associated with a high rate of relapse. In addition to medication non‐adherence, some psychosocial factors have been found to be predictive of relapse (e.g., poor premorbid adjustment, high expressed emotion and substance misuse). Impairments in cognitive functions including general memory functioning, set shifting, attention, processing speed and working memory have also been indicative of a subsequent psychotic episode. As clinical appointments do not always allow for timely or accurate detection of these early warning signs, the ReMind app is developed to explore potential relapse predictors and enhance the process of relapse monitoring.
Aim
The ReMind app aims (1) to assess whether verbal or visual working memory predicts psychotic relapse in 1 year and (2) to determine whether social factors such as stressful life events, level of expressed emotion and medication adherence also predict relapse in 1 year.
Methods
This is a one‐year prospective follow‐up study involving 176 remitted patients diagnosed with schizophrenia or non‐affective psychoses. Monthly relapse predictor assessments will be conducted via ReMind throughout the one‐year study duration. These assessments include neurocognitive tasks and psychosocial questionnaires.
Results
Recruitment began in August 2017 and is still ongoing. Preliminary user feedback suggested an overall positive experience with the app.
Conclusion
The ReMind app presents a step forward to the identification and sensitive detection of reliable psychosis relapse predictors. With its anticipated success, it may offer an alternative means of monitoring relapse for the Chinese‐speaking population in the future.
... Psychotic patients were faced to the significant risk of relapse. Long-term follow-up of those patients suffering from schizophrenia was indispensable [4][5][6]. Their access to health care is often limited because of social stigmatization and discrimination, but also of questions relating to the development of mental health departments in the context of public health services [7]. Nancy Coover Andreasen [8][9][10] made a significant contribution to the better management of those patients, inaugurating the pathway of integrated psychological therapies [11]. ...
... EWS can be used to avoid relapse in a timely manner (Gumley et al., 2020), and must be present prior to relapse for successful early intervention. A statistically signifi cant rise in EWS total score might be seen 5 to 8 weeks before relapse (Spaniel et al., 2018). Many individuals relapse shortly aft er treatment reduction and/or cessation; the change from remission to relapse may be rapid (Emsley et al., 2013). ...
... Relapse prevention is a major challenge for the patient, family and mental health service providers (Sariah et al., 2014); 52% of PDwS after discharge experienced at least one relapse episode within a year (Matsuda & Kohno, 2016). Of them, 30%-40% frequently suffered from relapse, even if they adhered to their medication treatment (Sariah et al., 2014;Spaniel et al., 2016). ...
... Relapse prevention is a major challenge for the patient, family and mental health service providers (Sariah et al., 2014); 52% of PDwS after discharge experienced at least one relapse episode within a year (Matsuda & Kohno, 2016). Of them, 30%-40% frequently suffered from relapse, even if they adhered to their medication treatment (Sariah et al., 2014;Spaniel et al., 2016). ...
Background
Schizophrenia is one of the most complicated psychiatric disorders, and, although medication therapy continues to be the core treatment for schizophrenia, there is a need for psychotherapy that helps in providing patients comprehensive mental health care. Psychoeducation is one of the most recognized psychosocial interventions specific to schizophrenia. Further knowledge about the impact of this type of intervention on patients diagnosed with schizophrenia needs to be acquired.
Aim
This review aimed to explore the effects of psychoeducational interventions on improving outcome measures for patients diagnosed with schizophrenia.
Methods
The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline was used in this systematic review. Two reviewers were involved in screening articles for inclusion and in the data extraction process. The selected studies were assessed for quality using the ‘Consolidated Standards of Reporting Trial (CONSORT)’ checklist. Out of the 441 records identified, 11 papers were considered for full review (from 2000 to 2018).
Results
The psychoeducational interventions showed a consistent improvement in many outcome measures. Most of the reviewed studies focused on outpatients and the method of delivering the psychoeducational interventions was mostly in lecture format.
Conclusion
This systematic review of randomized controlled trial studies emphasizes the positive impact of psychoeducational interventions for patients diagnosed with schizophrenia concerning various outcome measures. The findings of this review have important implications for both nursing practice and research, as the information presented can be used by the administrators and stakeholders of mental health facilities to increase their understanding and awareness of the importance of integrating psychoeducational interventions in the routine care of patients diagnosed with schizophrenia.
... These early warning signs (EWSs) include affective changes and incipient psychosis. These EWSs can be detected as early as 8 weeks before rehospitalization [15]. A systematic review [16] found that the sensitivity of early signs to relapse (proportion of relapses correctly predicted) ranged from 10% to 80% (median 61%) and specificity (proportion of nonrelapses correctly identified) ranged from 38% to 100% (median 81%). ...
Background
Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions.
Objective
This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial.
Methods
We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants’ own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support.
Results
Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation.
Conclusions
The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial.
Trial Registration
International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262
International Registered Report Identifier (IRRID)
DERR1-10.2196/15058
... These early warning signs (EWSs) include affective changes and incipient psychosis. These EWSs can be detected as early as 8 weeks before rehospitalization [15]. A systematic review [16] found that the sensitivity of early signs to relapse (proportion of relapses correctly predicted) ranged from 10% to 80% (median 61%) and specificity (proportion of nonrelapses correctly identified) ranged from 38% to 100% (median 81%). ...
BACKGROUND
Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions.
OBJECTIVE
This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial.
METHODS
We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants’ own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support.
RESULTS
Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation.
CONCLUSIONS
The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial.
CLINICALTRIAL
International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262
... None of those studies described having undertaken adverse events monitoring. We identified nine further studies of mHealth for psychosis that either did not meet the inclusion criteria for the Bell et al. (2017) review or which were published subsequent to the review (Ainsworth et al., 2013;Barnett et al., 2018;Bucci et al., 2018;Kumar et al., 2018;Meyer et al., 2018;Niendam et al., 2018;Palmier-Claus et al., 2012;Spaniel et al., 2018) Of these just one described adverse event monitoring and in that instance it was limited to the identification of serious adverse events, 1 with none noted over the twelve-month period of the Actissist trial (Bucci et al., 2018). There was no indication of whether non-serious events were monitored or whether the relatedness of events to the digital intervention was assessed. ...
... Existing early signs studies have typically used pen and paper questionnaires (Birchwood et al., 1989;Gaebel et al., 1993;Riesbeck, 2007, 2014;Gleeson et al., 2005;Gumley et al., 2015;Hirsch and Jolley, 1989;Jørgensen, 1998;Malla and Norman, 1994;Marder et al., 1991;Marder et al., 1994;Subotnik and Neuchterlein, 1988;Tait et al., 2002;Tarrier et al., 1991) or text message systems (Spaniel et al., 2018;Spaniel et al., 2007;Spaniel et al., 2008) to examine the predictive value of conventional early signs of relapse. Compared to these methods, smartphone apps have a number of advantages: apps can be accessed at the individual's convenience (Ben-Zeev et al., 2013), decreasing participant burden and increasing ecological validity ; apps can automatically supply surveys and securely upload responses; finally, apps are more acceptable to individuals with psychosis than text message systems (Ainsworth et al., 2013). ...
Background
Psychosis relapses are common, have profound adverse consequences for patients, and are costly to health services. ‘Early signs’ have been used to predict relapse, in the hope of prevention or mitigation, with moderate sensitivity and specificity. To improve predictive power, we investigated adding ‘basic symptoms’ to conventional early signs and using a smartphone app to facilitate prompt identification of these.
Methods
Individuals who had experienced a relapse of psychosis within the past year (n=22) took part in a screening interview. Those with at least one basic symptom emerging prior to a previous relapse (n=19; 86%) were eligible for the longitudinal feasibility study. Consenting participants (n=18) were asked to use a smartphone app (‘ExPRESS’) weekly for six months to report early signs, basic symptoms and psychotic symptoms. When app responses indicated an increase in psychotic symptoms above a pre-defined threshold, the researcher conducted the PANSS positive symptoms interview over the telephone to assess whether the symptom increase was indicative of relapse (in combination with a management change, evidenced by casenote review). On completion of, or dropout from, the app-use phase, participants were invited to give their views on the acceptability of the app and study procedures in a qualitative interview.
Results
Participants completed 65% of app assessments and 58% of telephone interviews over the 6-month follow-up period. Completion of app assessments declined as the study progressed (OR=0.89 per week follow-up; p<0.001). Percentage app completion was significantly and inversely correlated with baseline depression (ρ=-0.56, p=0.015) and fear of relapse (ρ=-0.58, p=0.014). App items showed high concurrent validity with researcher-rated psychotic symptoms (ρ range 0.80 to 0.87, p<0.001) and basic symptoms (ICC=0.76, p<0.001) over six months. There was excellent agreement between telephone call and face-to-face assessed psychotic symptoms (ICC range 0.94 to 0.96, p<0.001). The primary relapse definition, based on telephone assessment and casenotes, compared well with a casenote-only definition but had better specificity (κ=0.76, p=0.003). Mixed-effects models (>200 observations) provided preliminary evidence of predictive validity: early signs and basic symptoms were associated with most app-assessed psychotic symptom variables the same week and three weeks later and adding basic symptoms to early signs improved model fit in most cases. Qualitative interviews indicated that both the app and study procedures were acceptable to patients with psychosis.
Discussion
This study demonstrates that weekly app-based monitoring is feasible, valid and acceptable over a six-month period. It also provides a novel approach to operationally defining relapse by using a combination of telephone interviews and casenotes. We suggest that remote relapse assessment is more easily integrated into participants’ everyday lives, decreasing both participant and researcher burden; this is likely to increase engagement and allow more frequent and long-term monitoring.
... Existing early signs studies have typically used pen and paper questionnaires (Birchwood et al., 1989;Gaebel et al., 1993;Riesbeck, 2007, 2014;Gleeson et al., 2005;Gumley et al., 2015;Hirsch and Jolley, 1989;Jørgensen, 1998;Malla and Norman, 1994;Marder et al., 1991;Marder et al., 1994;Subotnik and Neuchterlein, 1988;Tait et al., 2002;Tarrier et al., 1991) or text message systems (Spaniel et al., 2018;Spaniel et al., 2007;Spaniel et al., 2008) to examine the predictive value of conventional early signs of relapse. Compared to these methods, smartphone apps have a number of advantages: apps can be accessed at the individual's convenience (Ben-Zeev et al., 2013), decreasing participant burden and increasing ecological validity ; apps can automatically supply surveys and securely upload responses; finally, apps are more acceptable to individuals with psychosis than text message systems (Ainsworth et al., 2013). ...
Background:
Psychosis relapses are common, have profound adverse consequences for patients, and are costly to health services. 'Early signs' have been used to predict relapse, in the hope of prevention or mitigation, with moderate sensitivity and specificity. We investigated the feasibility and validity of adding 'basic symptoms' to conventional early signs and monitoring these using a smartphone app.
Methods:
Individuals (n = 18) experiencing a relapse within the past year were asked to use a smartphone app ('ExPRESS') weekly for six months to report early signs, basic symptoms and psychotic symptoms. Above-threshold increases in app-reported psychotic symptoms prompted a telephone interview (PANSS positive items) to assess relapse.
Results:
Participants completed 65% app assessments and 58% telephone interviews. App items showed high concurrent validity with researcher-rated psychotic symptoms and basic symptoms over six months. There was excellent agreement between telephone call and face-to-face assessed psychotic symptoms. The primary relapse definition, based on telephone assessment and casenotes, compared well with a casenote-only definition but had better specificity. Mixed-effects models provided preliminary evidence of concurrent and predictive validity: early signs and basic symptoms were associated with most app-assessed psychotic symptom variables the same week and with a number of psychotic symptoms variables three weeks later; adding basic symptoms to early signs improved model fit in most of these cases.
Conclusions:
This is the first study to test a smartphone app for monitoring early signs and basic symptoms as putative relapse predictors. It demonstrates that weekly app-based monitoring is feasible, valid and acceptable over six months.
SARS-CoV-2 is a growing field of research and mental health in long COVID is one of its interesting domains. This scoping review aims at studying the outcomes of mental health in patients already known for psychiatric illness. This was done by researching the literature in two databases (Embase and PubMed) for articles studying mental health consequences of long COVID in patients already known for psychiatric history. Eleven studies were included. 6/11 studies found an effect of long COVID, with varying severity of outcomes studied, with either a worsening in length or severity. 4/11 did not find any correlation between worsening symptoms and psychiatric history. The methods for assessing which psychiatric symptoms to include and how to determine prior history were heterogeneous, making direct comparison sometimes difficult. The data seem to show worse effects of long COVID on mental health of patients with prior mental illness, with limitations regarding the heterogeneity of the studies’ designs and focuses. It also highlights how neglected this population of patients is in the current state of research.
Aim:
Early psychosis may be a critical time at which clinical trajectories are still evolving, and sleep interventions hold promise to improve outcomes at this stage. Although cognitive behavioural therapy (CBT) for insomnia shows promise in psychosis, there has been limited evaluation of delivery within current care. This study aims to evaluate the feasibility and acceptability of providing fully-automated digital CBT for insomnia (CBT-I) within an early intervention in psychosis service.
Methods:
We will conduct a single-arm feasibility trial within an early psychosis intervention service, and up to 40 individuals experiencing a first episode of psychosis and with evidence of insomnia can be enrolled (May 2021 - August 2022). Additional service user inclusion criteria are capacity to consent and access to a suitable technological device to access digital CBT. Participants will be offered access to a fully-automated digital CBT-I program (Sleepio) delivered using web and/or mobile app. The study comprises pre- and post- intervention questionnaire assessments and interviews with service users and staff to provide initial outcome signals.
Results:
Quantitative questionnaire data will be analysed descriptively, alongside rates of eligibility, consent, uptake and completion. Qualitative data will be analysed using thematic analysis. Results will be used to develop a logic model describing feasibility and implementation.
Conclusions:
From this study, we hope to better understand how to deliver digital CBT for insomnia within an early intervention in psychosis service. This study will help inform further research, including how best to support staff in using Sleepio, and inform the design of subsequent trials in this area.
Digital acquisition of patients’ self-reports on individual risk factors and symptom severity represents a promising, cost-efficient, and increasingly prevalent approach for standardized data collection in psychiatric clinical routine. Yet, studies investigating digital data collection in patients with a schizophrenia spectrum disorder (PSSDs) are scarce. The objective of this study was to explore the feasibility of digitally acquired self-report assessments of risk and symptom profiles at the time of admission into inpatient treatment in an age-representative sample of hospitalized PSSDs. We investigated the required support, the data entry pace, and the subjective user experience. Findings were compared with those of patients with an affective disorder (PADs). Of 82 PSSDs who were eligible for inclusion, 59.8% (n=49) agreed to participate in the study, of whom 54.2% (n=26) could enter data without any assistance. Inclusion rates, drop-out rates, and subjective experience ratings did not differ between PSSDs and PADs. Patients reported high satisfaction with the assessment. PSSDs required more support and time for the data entry than PADs. Our results indicate that digital data collection is a feasible and well-received method in PSSDs. Future clinical and research efforts on digitized assessments in psychiatry should include PSSDs and offer support to reduce digital exclusion.
Abstract
Background: Positive and negative symptoms of schizophrenia contribute substantially to
poor functional outcomes and poor quality of life. Aim of study: Was to examine the relationship
between positive, negative symptoms and quality of life among schizophrenic patients. Research
design: A descriptive correlational design was utilized in this study. Setting: The study conducted
at Psychiatric and Mental Health Hospital in Benha City in Qalyubia Governorate. Subject: A
convenient sample consisted of 100 schizophrenic patients. Tools of data collection: Four tools
were used for data collection, I: A structured Interview Questionnaire included socio demographic
and clinical data of the studied patients. II: Scale for the Assessment of Positive Symptoms. III:
Scale for the Assessment of Negative Symptoms and IV: Structured Interview Self-Report Quality
of Life. Results: More than half of the studied patients had severe level of positive symptoms, more
than half had severe level of negative symptoms and half of them had poor level of quality of life.
Also, there were highly statistically significant negative correlations between total positive,
negative symptoms and total quality of life among the studied patients. Conclusion: Patients had
severe levels of positive and negative symptoms are more likely to have poor level of quality of life.
Recommendation: Psycho-educational programs should be established for patients with
schizophrenia to enhance their coping skills, social skills, problem solving skills and emotion
focused coping strategies that hence their quality of life and alleviate positive and negative
symptoms.
Context: Schizophrenia is one of the most severe mental disorders that affect all aspects of a patient's lives. Telemedicine can be helpful for this population. Objectives: This study aimed to review the studies for investigating the applications and outcomes of telemedicine in providing healthcare services for patients with schizophrenia. Evidence Acquisition: We searched PubMed and Scopus databases to find relevant studies in July 2020. The combination of two “Schizophrenia” AND “Telemedicine” keywords were used to search databases. Original observational and interventional studies, which have used a telemedicine service in schizophrenia disease, were included in this review. Results: Of 309 gathered studies, 26 studies were entered into this research. The synchronous modality and videoconference communication were used in most studies. Most studies (84.5%) have shown that telemedicine was a beneficial method. More than half of the studies (58%) had therapeutic goals. The rest of the studies were for diagnostic (19%), educational (11.5%), and both therapeutic and educational (11.5%) purposes. Only one study (4%) showed that telemedicine was not cost-effective. In nine studies (34.5%), users were satisfied with the use of telemedicine services. Conclusions: Telemedicine is a useful method for the management of patients with schizophrenia, especially to improve treatment adherence and prevent relapse. It would be better to pay more attention to the educational issues because of the positive impact on adherence to treatment and prevent relapse.
Introduction:
The course of schizophrenia illness is characterised by recurrent relapses which are associated with adverse clinical outcomes such as treatment-resistance, functional and cognitive decline. Early identification is essential and relapse prevention remains a primary treatment goal for long-term management of schizophrenia. With the ubiquity of devices such as smartphones, objective digital biomarkers can be harnessed and may offer alternative means for symptom monitoring and relapse prediction. The acceptability of digital sensors (smartphone and wrist-wearable device) and the association between the captured digital data with clinical and health outcomes in individuals with schizophrenia will be examined.
Methods and analysis:
In this study, we aim to recruit 100 individuals with schizophrenia spectrum disorders who are recently discharged from the Institute of Mental Health (IMH), Singapore. Participants are followed up for 6 months, where digital, clinical, cognitive and functioning data are collected while health utilisation data are obtained at the 6 month and 1 year timepoint from study enrolment. Associations between digital, clinical and health outcomes data will be examined. A data-driven machine learning approach will be used to develop prediction algorithms to detect clinically significant outcomes. Study findings will inform the design, data collection procedures and protocol of future interventional randomised controlled trial, testing the effectiveness of digital phenotyping in clinical management of individuals with schizophrenia spectrum disorders.
Ethics and dissemination:
Ethics approval has been granted by the National Healthcare Group (NHG) Domain Specific Review Board (DSRB Reference no.: 2019/00720). The results will be published in peer-reviewed journals and presented at conferences.
Trial registration number:
NCT04230590.
The use of internet and cellular based interventions to prevent relapse schiophrenia has not been found. The purpose of this article was to identify mobile apps and mobile web that were used to relapse prevention. The method of writing was systematic review by searching articles using electronic databases, namely: ProQuest, Wiley Online, Sage publications, ScienceDirect, dan Springer Link. The key word used were ((Mobile apps) OR (Mobile web)) AND (Relapse Prevention) AND (Schizophrenia). The inclusion criteria used were: use english, mobile apps or mobile web that foccused on schizophrenia relapse prevention, research area was in psychiatric field, published in the span of 2015 to 2020. And open access. The extraction results obtained 13 relevant articles. The author identified 11 applications and web that can be used to prevent relapse in schizophrenic clients. Most applications and web used the features of assessment, intervention, and implementation. It was expected to mental health service, especially nursing staff can develop mobile apps or mobile web to prevent relapse in schizophrenic clients based on a comprehensive nursing process. Keywords:Mobile apps; mobile web; relapse prevention; schizophrenia ABSTRAK Penggunaan intervensi berbasis internet dan seluler untuk mencegah kekambuhan klien skizofrenia dapat meningkatkan keefektifan biaya dan pelayanan serta dapat dikontrol dari jarak jauh, namun belum pernah digunakan di Indonesia. Tujuan artikel ini adalah untuk mengidentifikasi mobile apps dan mobile web yang digunakan untuk mencegah kekambuhan klien skizofrenia. Metode penulisan adalah systematic Review dengan melakukan pencarian artikel menggunakan database elektronik yaitu: ProQuest, Wiley Online, Sage publications, ScienceDirect, dan Springer Link. Kata kunci yang digunakan adalah ((Mobile apps) OR (Mobile web)) AND (Relapse Prevention) AND (Schizophrenia). Kriteria inklusi meliputi: studi menggunakan bahasa Inggris, mobile apps atau mobile web yang berfokus pada pencegahan kekambuhan skizofrenia, area penelitian dalam bidang psikiatrik, diterbitkan dalam rentang tahun 2015 sampai tahun 2020, dan dapat diakses secara terbuka. Hasil ekstraksi didapatkan 13 artikel yang relevan. Penulis mengidentifikasi terdapat 11 aplikasi dan web yang dapat digunakan untuk mencegah kekambuhan klien skizofrenia. Sebagian besar aplikasi dan web sudah menggunakan fitur pengkajian, intervensi dan implementasi. Diharapkan pelayanan kesehatan jiwa di Indonesia khususnya tenaga keperawatan dapat mengembangkan mobile apps atau mobile web dalam mencegah kekambuhan klien skizofrenia berdasarkan proses keperawatan yang komprehensif. Kata kunci: Mobile apps; mobile web; pencegahan kekambuhan; skizofrenia
Having a good understanding of the natural history of schizophrenia, admittedly an abstraction, allows clinicians to make a correct diagnosis based on the longitudinal history. In this chapter, I describe the clinical phases of schizophrenia that need to be recognized, particularly the prodromal phase of schizophrenia that often begins with non-specific symptoms several years before schizophrenia declares itself with the onset of frank psychosis. A corresponding phase exists in chronic patients, where an impending relapse is heralded by non-specific early warning sign. This chapter also discussing the problem of prognostication as schizophrenia has many possible outcomes, ranging from a restitutio ad integrum in about 20–30% of cases to severe, unremitting illness in 10% of cases. For most patients treated schizophrenia is a manageable illness, particularly if help is provided when needed.
Patient monitoring:
SMARTPHONES CAN TRACK SCHIZOPHRENIA-RELATED SLEEP ABNORMALITIES: Smartphones may one-day offer accessible, clinically-useful insights into schizophrenia patients' sleep quality. Despite the clinical relevance of sleep to disease severity, monitoring technologies still evade convenience and reliability. In search of a preferential method, a group of Harvard University researchers led by Patrick Staples investigated the validity of data collected via patients' own mobile phones. The team, with a cohort of 17 schizophrenia patients, compared the quality of data produced by smartphone sensors and smartphone-delivered questionnaires to that of an in-clinic evaluation. The results significantly showed that smartphone monitoring could generate information that approached the accuracy of in-clinic assessments. The team noted some areas for improvement; however, this study provides convincing justifications for further research into this non-invasive, low-cost, scalable method to monitor the sleep quality of schizophrenic patients.
Objective:
This purpose of this study was to describe and demonstrate CrossCheck, a multimodal data collection system designed to aid in continuous remote monitoring and identification of subjective and objective indicators of psychotic relapse.
Method:
Individuals with schizophrenia-spectrum disorders received a smartphone with the monitoring system installed along with unlimited data plan for 12 months. Participants were instructed to carry the device with them and to complete brief self-reports multiple times a week. Multimodal behavioral sensing (i.e., physical activity, geospatials activity, speech frequency, and duration) and device use data (i.e., call and text activity, app use) were captured automatically. Five individuals who experienced psychiatric hospitalization were selected and described for instructive purposes.
Results:
Participants had unique digital indicators of their psychotic relapse. For some, self-reports provided clear and potentially actionable description of symptom exacerbation prior to hospitalization. Others had behavioral sensing data trends (e.g., shifts in geolocation patterns, declines in physical activity) or device use patterns (e.g., increased nighttime app use, discontinuation of all smartphone use) that reflected the changes they experienced more effectively.
Conclusion:
Advancements in mobile technology are enabling collection of an abundance of information that until recently was largely inaccessible to clinical research and practice. However, remote monitoring and relapse detection is in its nascence. Development and evaluation of innovative data management, modeling, and signal-detection techniques that can identify changes within an individual over time (i.e., unique relapse signatures) will be essential if we are to capitalize on these data to improve treatment and prevention. (PsycINFO Database Record
A relapse prevention program called the Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) has been developed and is reported to be highly effective. However the effectiveness was influenced by user adherence to the protocol of the program, the exact effectiveness and the role of the ITAREPS have been partially uncertain.
The purpose of this study is to evaluate the effectiveness of the ITAREPS excluding the effect of user adherence to the protocol of the program.
We attempted to perform a randomized controlled trial by the devised method with visiting nurse service. Outpatients with schizophrenia were randomized to the ITAREPS (n=22) or control group (n=23) and were observed for 12months.
The risk of rehospitalization was reduced in the ITAREPS group (2 [9.1%]) compared with the control group (8 [34.8%]) (hazard ratio=0.21, 95% CI 0.04-0.99, p=0.049; number needed to treat (NNT)=4, 95% CI 2.1-35.5). The mean number of inpatient days was significantly lower in the ITAREPS group (18.5days) compared with the control group (88.8days) (p=0.036). The ratio of the number of rehospitalizations to that of relapses was significantly lower (p=0.035) and the mean change in total BPRS scores at relapse from baseline was significantly less in the ITAREPS group (p=0.019).
The relapse prevention effectiveness of the ITAREPS was high, and we confirmed that the ITAREPS, i.e., detecting signs of relapse and increasing medication during the warning state, is an effective intervention during the early stages of relapse.
Mobile health (mHealth) describes the use of portable electronic devices with software applications to provide health services and manage patient information. With approximately 5 billion mobile phone users globally, opportunities for mobile technologies to play a formal role in health services, particularly in low- and middle-income countries, are increasingly being recognized. mHealth can also support the performance of health care workers by the dissemination of clinical updates, learning materials, and reminders, particularly in underserved rural locations in low- and middle-income countries where community health workers deliver integrated community case management to children sick with diarrhea, pneumonia, and malaria.
Our aim was to conduct a thematic review of how mHealth projects have approached the intersection of cellular technology and public health in low- and middle-income countries and identify the promising practices and experiences learned, as well as novel and innovative approaches of how mHealth can support community health workers.
In this review, 6 themes of mHealth initiatives were examined using information from peer-reviewed journals, websites, and key reports. Primary mHealth technologies reviewed included mobile phones, personal digital assistants (PDAs) and smartphones, patient monitoring devices, and mobile telemedicine devices. We examined how these tools could be used for education and awareness, data access, and for strengthening health information systems. We also considered how mHealth may support patient monitoring, clinical decision making, and tracking of drugs and supplies. Lessons from mHealth trials and studies were summarized, focusing on low- and middle-income countries and community health workers.
The review revealed that there are very few formal outcome evaluations of mHealth in low-income countries. Although there is vast documentation of project process evaluations, there are few studies demonstrating an impact on clinical outcomes. There is also a lack of mHealth applications and services operating at scale in low- and middle-income countries. The most commonly documented use of mHealth was 1-way text-message and phone reminders to encourage follow-up appointments, healthy behaviors, and data gathering. Innovative mHealth applications for community health workers include the use of mobile phones as job aides, clinical decision support tools, and for data submission and instant feedback on performance.
With partnerships forming between governments, technologists, non-governmental organizations, academia, and industry, there is great potential to improve health services delivery by using mHealth in low- and middle-income countries. As with many other health improvement projects, a key challenge is moving mHealth approaches from pilot projects to national scalable programs while properly engaging health workers and communities in the process. By harnessing the increasing presence of mobile phones among diverse populations, there is promising evidence to suggest that mHealth can be used to deliver increased and enhanced health care services to individuals and communities, while helping to strengthen health systems.
Data are presented on the 15-year natural course of schizophrenia and other nonaffective functional psychoses in a cohort of 82 first-contact cases from a circumscribed area in the Netherlands. The subjects were suffering from functional psychosis with International Classification of Diseases-Ninth Revision (ICD-9) diagnoses 295, 297, or 298.3–9 (broad definition of schizophrenia) on entry. Standardized assessments of psychopathology, psychological impairments, negative symptomatology, social disability, and use of mental healthcare were used. The study reveals a pattern of chronicity and relapses with a high risk of suicide: Two-thirds of the subjects had at least one relapse and after each relapse 1 of 6 subjects did not remit from the episode; 1 of 10 committed suicide; and 1 of 7 had at least one episode with affective psychotic symptoms that started on average 6 years after the onset of the schizophrenic disorder. Diagnoses were reclassified in five patients, according to DSM-III-R criteria for a bipolar disorder. The predictive power—in terms of time in psychosis and in partial or full remission—of demographic, illness, and treatment variables at onset of the illness was very limited. Insidious onset and delays in mental health treatment are risk factors that predict a longer duration of first or subsequent episodes. The importance of mental health treatment in regard to outcome is probably subject to change because an early warning and intervention strategy could prevent further damage and deterioration. Our data support the need for an adequate relapse prevention program as a priority for our mental health services.
GAMLSS is a general framework for fitting regression type models where the distribution of the response variable does not have to belong to the exponential family and includes highly skew and kurtotic continuous and discrete distribution. GAMLSS allows all the parameters of the distribution of the response variable to be modelled as linear/non-linear or smooth functions of the explanatory variables. This paper starts by defining the statistical framework of GAMLSS, then describes the current implementation of GAMLSS in R and finally gives four different data examples to demonstrate how GAMLSS can be used for statistical modelling.
A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia.
To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment.
Case-control study of in vivo striatal dopaminergic function.
Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging.
Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms.
These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.
Decreasing a number of hospital admissions is important for improving outcomes for people with schizophrenia. The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) programme enables early pharmacological intervention in psychosis by identification of prodromal symptoms of relapse using home telemonitoring via a phone-to-PC SMS platform.
This study was a 1-year extension of a previously published mirror-design follow-up evaluation of programme clinical effectiveness. In total, 73 patients with psychotic illness (45 patients from original sample and 28 newly added subjects) collaborating with 56 family members participated in the clinical evaluation.
There was a statistically significant 77% decrease in the number of hospitalisations during the mean 396.8 +/- 249.4 days of participation in ITAREPS, compared with the same time period before participation in ITAREPS (Wilcoxon-signed ranks test, p < 0.00001), as well as significantly reduced number of hospitalisation days when in the ITAREPS (2365 hospitalisation days before and 991 days after ITAREPS enrolment respectively, Wilcoxon-signed ranks test, p < 0.003).
The ITAREPS programme represents an effective tool in the long-term treatment of patients with psychotic disorders.
Longitudinal studies of schizophrenia based on at least 70 subjects and a minimum five-year follow-up period are reviewed in respect of the requirements of adequate method. A cohort of 121, PSE-diagnosed, schizophrenic admissions from a defined population was identified. The sex-distribution of the subjects was almost equal. Forty per cent were first admissions; 65% of the men and 24% women were unmarried; the mean age of onset for men was 28.6 years, for women 33.2 years. Almost half (48%) were continuously employed (including house and child care) for 2 years prior to admissions. First rank symptoms of schizophrenia were present in 79% of the men and 86% of the women. Comprehensive, standardized assessments of clinical state and social function were made on discharge from hospital and at follow-up by home interview of patient and relative(s). Outcome was also assessed by duration and frequency of readmission and by duration of employment. First admissions were analysed separately from the whole cohort. There were 49 first admissions generating an incidence of 7.4 per 100,000 general population per annum. Sixty-nine per cent of men and 13% of women were unmarried. The mean age of admission for men was 30.8 years, women 40.3 years and the mean age of onset 30.7 and 38.6 respectively. After 5 years first rank symptoms were present in 46% of the males and 35% of the females. The proportion showing depressive symptoms fell from 39% at intake to 22% at five years. In terms of a combination of symptoms and readmissions there was a good outcome in 50% of men and 65% of women, a trend comparable to that found in the whole cohort. For the whole cohort a combination of the number of symptoms and admissions disclosed a good outcome for 48%. The mean total duration of readmissions during the five years for men was 76 weeks and for women 27 weeks. Depressive symptoms were present in 38% at intake and 21% after 5 years. An overall rating of social functioning at 5 years showed no more than mild impairment for 47% of men and 74% of women, although individual items were more impaired. However, 38% of the group showed no more than mild impairment in any aspect of social functioning rated. Clinical and social outcome were, in general, closely correlated. The difference in outcome between men and women and the relations between clinical and social outcome are discussed. By means of an application of measures of association between independent and dependent variables to the onset data the clinical and social categories of pathology and impairment at 5 years were forecast.(ABSTRACT TRUNCATED AT 400 WORDS)
Six-week periods prior to 17 psychotic relapses and to 10 relapses characterized by depression and/or hostility were examined for 23 recent-onset schizophrenic outpatients. These prodromal periods were compared with periods that did not precede relapse for the same patients and for 27 schizophrenic patients who did not relapse. The Brief Psychiatric Rating Scale (BPRS) was used to assess symptomatology. Psychotic relapse was defined as an elevation to severe or extremely severe from nonpathological levels on one or more of the BPRS items: Hallucinations, Unusual Thought Content, and Conceptual Disorganization. Nonpsychotic relapses were similarly defined using the Depression and Hostility items of the BPRS. Even small elevations in odd thought content, unusual perceptual experiences, depression, somatic concern, and guilt above the levels usually present for a given patient may presage psychotic relapse during the 6 to 8 weeks prior to its occurrence. When compared with nonprodromal periods of other patients, periods before relapse were found to show significantly higher levels of hostility and grandiosity in addition to higher levels of unusual thought content and perceptual abnormalities. For relapses characterized by depression and hostility, an elevation of activation was found in the prodromal period.
The purpose of this study was to develop a model based on the authors' previous studies to identify which neuroleptic-treated schizophrenic patients are at risk of early relapse following drug withdrawal.
Clinical and CSF monoamine-related variables obtained for 50 male haloperidol-treated, schizophrenic patients were used in a logistic regression model to identify those who relapsed (N = 24) within 6 weeks after placebo substitution and those who did not (N = 26).
The oral dose of haloperidol, weight, CSF norepinephrine, 3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By including the interactions of paranoia subscale by CSF norepinephrine and anxiety by CSF norepinephrine, the model correctly identified 20 relapsers and 23 nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively.
Increased noradrenergic activity during chronic dopamine blockade may be an episode marker and may predict relapse within 6 weeks following haloperidol withdrawal in schizophrenia. Effective relapse prediction models have important practical implications for the treatment of schizophrenia and the understanding of the psychotic relapse process.
Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia.
To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables.
Historic prospective study. Standardised assessments of course and outcome.
About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery.
A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.
Six-week periods prior to 17 psychotic relapses and to 10 relapses characterized by depression and/or hostility were examined for 23 recent-onset schizophrenic outpatients. These prodromal periods were compared with periods that did not precede relapse for the same patients and for 27 schizophrenic patients who did not relapse. The Brief Psychiatric Rating Scale (BPRS) was used to assess symptomatology. Psychotic relapse was defined as an elevation to severe or extremely severe from nonpathological levels on one or more of BPRS items: Hallucinations, Unusual Thought Content, and Conceptual Disorganization. Nonpsychotic relapses were similarly defined using the Depression and Hostility items of the BPRS. Even small elevations in odd thought content, unusual perceptual experiences, depression, somatic concern, and guilt above the levels usually present for a given patient may presage psychotic relapse during the 6 to 8 weeks prior to its occurrence. When compared with nonprodromal periods of other patients, periods before relapse were found to show significantly higher levels of hostility and grandiosity in addition to higher levels of unusual thought content and perceptual abnormalities. For relapses characterized by depression and hostility, an elevation of activation was found in the prodromal period.
Objective:
Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question.
Methods:
The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years.
Results:
Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity.
Conclusions:
Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.
Background:
Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine ((18)F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.
Methods:
(18)F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.7±4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean±SD age = 24.5±4.5 years).
Results:
Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum.
Conclusions:
The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.
To evaluate the effectiveness of the Information Technology-Aided Program of Re lapse Prevention in Schizophrenia (ITAREPS).
Relapse-prone outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n=75) or control group (n=71). In the active arm, according to the protocol, investigators were prompted to increase the antipsychotic dose upon occurrence of a pharmacological inter vention requiring event (PIRE) detected by ITAREPS.
Intention-to-treat (ITT) analysis found no between-group difference in the hospitalization-free survival rate at 12 months. However, the trial suffered from high non-adherence of investigators in the active group, with no antipsychotic dose increase in 61% of PIREs. Furthermore, Cox regression analysis showed a 11-fold increased risk of hospitalization in the absence of pharmacological intervention following a PIRE (hazard ratio [HR]=10.8; 95% confidence interval [CI] 1.4-80.0; p=0.002). Therefore, a post-hoc as-treated analysis was performed, which demonstrated a nine-fold reduction in the risk of hospitalization in ITAREPS Algorithm-Adherers (IAAs, n=25) compared with the ITAREPS Non-interventional group (INIs, n=70; Kaplan-Meier survival analysis, HR=0.11, 95% CI 0.05-0.28, p=0.009; number needed to treat [NNT]=4, 95% CI 3-10). A significant difference in favor of the IAA group was seen in the number of inpatient days (p<0.05) and costs (p<0.05).
Future ITAREPS trials should target the underlying mechanisms that cause low investigator adherence to the program. Trial registration: Clinical Trials NCT00712660.
Of 61 schizophrenic outpatients in remission, 33 who had relapses within the past 20 months were retrospectively examined for prodromal symptoms of relapse. Four weeks prior to the relapse, 63.6% manifested 4 prodromal symptoms, which were somatic concern, feeling of tiredness, anxiety and depressive mood. Contrarily, with the GAS evaluation, no significant deterioration was recognized until one week before the relapse. Subsequently, a prospective observation of symptoms in 43 patients was conducted for 7 months to determine whether therapeutic intervention at the time of the manifestation of prodromal symptoms could be effective in the prevention of relapses and the improvement of outcome of relapses, and to consider the therapeutic use of this method.
A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y, as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.
Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues.
We searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and ClinicalTrials.gov for those before June 8, 2011. We also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. Our primary outcome was relapse between 7 and 12 months. We also examined safety and various functional outcomes. We used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses.
We identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27%vs placebo 64%; risk ratio [RR] 0·40, 95% CI 0·33-0·49; number needed to treat to benefit [NNTB] 3, 95% CI 2-3). Fewer patients given antipsychotic drugs than placebo were readmitted (10%vs 26%; RR 0·38, 95% CI 0·27-0·55; NNTB 5, 4-9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0·62, 95% CI -1·15 to -0·09) and fewer aggressive acts (2%vs 12%; RR 0·27, 95% CI 0·15-0·52; NNTB 11, 6-100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10%vs 6%; RR 2·07, 95% CI 2·31-3·25), had movement disorders (16%vs 9%; 1·55, 1·25-1·93), and experienced sedation (13%vs 9%; 1·50, 1·22-1·84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0·31, 95% CI 0·21-0·41) more than did oral drugs (0·46, 0·37-0·57; p=0·03); depot haloperidol (RR 0·14, 95% CI 0·04-0·55) and fluphenazine (0·23, 0·14-0·39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0·26, 0·17-0·39) than in most blinded studies (0·42, 0·35-0·51; p= 0·03). In a meta-regression, the difference between drug and placebo decreased with study length.
Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side-effects. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality of these drugs.
German Ministry of Education and Research.
Current drug treatments for schizophrenia are inadequate for many patients, and despite 5 decades of drug discovery, all of the treatments rely on the same mechanism: dopamine D(2) receptor blockade. Understanding the pathophysiology of the disorder is thus likely to be critical to the rational development of new treatments for schizophrenia.
To investigate the nature of the dopaminergic dysfunction in schizophrenia using meta-analysis of in vivo studies.
The MEDLINE, EMBASE, and PsycINFO databases were searched for studies from January 1, 1960, to July 1, 2011.
A total of 44 studies were identified that compared 618 patients with schizophrenia with 606 controls, using positron emission tomography or single-photon emission computed tomography to measure in vivo striatal dopaminergic function.
Demographic, clinical, and imaging variables were extracted from each study, and effect sizes were determined for the measures of dopaminergic function. Studies were grouped into those of presynaptic function and those of dopamine transporter and receptor availability. Sensitivity analyses were conducted to explore the consistency of effects and the effect of clinical and imaging variables.
There was a highly significant elevation (P.<001) in presynaptic dopaminergic function in schizophrenia with a large effect size (Cohen d=0.79). There was no evidence of alterations in dopamine transporter availability. There was a small elevation in D(2/3) receptor availability (Cohen d=0.26), but this was not evident in drug-naive patients and was influenced by the imaging approach used.
The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic, which affects dopamine synthesis capacity, baseline synaptic dopamine levels, and dopamine release. Current drug treatments, which primarily act at D(2/3) receptors, fail to target these abnormalities. Future drug development should focus on the control of presynaptic dopamine synthesis and release capacity.
Treatment guidelines provide evidence-based recommendations to assist practitioners in specific clinical situations. They are a major tool to assure and enhance treatment quality and to overcome existing disparities. However, guideline quality itself varies and needs to be considered. Based on a former review, schizophrenia guidelines with high methodological quality were identified and examined regarding updated versions. Five guidelines were selected, of which three updates have been newly evaluated with the AGREE instrument. In addition, clinical content regarding seven core topics in schizophrenia treatment decisions was compared. Guideline quality on average is good, with highest AGREE scores for the NICE guideline. Updating of the German guideline resulted in noticeable quality improvements. Regarding content, recommendations largely correspond in five areas across guidelines, whereas discrepancies or vagueness exist in two areas due to newly emerging (drug choice) or still restricted evidence (duration of antipsychotic treatment). There are increasing efforts to develop guidelines with improved quality. Also, there is a need to equalize and improve healthcare quality across countries. Since many formal and content-related issues are 'universal', development of trans-national guidelines seems indicated. Nevertheless, core guideline recommendations should be adapted to regional conditions using available tools for adaptation.
SUMMARY A method of devising stepwise multiple testing procedures with fixed experimentwise error is presented. The method requires
the set of hypotheses tested to be closed under intersection. The method is applied to the problem of comparing many treatments
to one control and to ordered analysis of variance.
The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.
The underlying mechanisms explaining brain volume changes in schizophrenia are not yet understood, but psychosis might be related to these changes. Forty-eight patients with first-episode schizophrenia underwent Magnetic Resonance Imaging brain scanning at inclusion and after five years. An association was found between longer duration of psychosis, larger gray matter volume decrease and larger ventricular volume increase. These findings strongly suggest that psychosis contributes to brain volume reductions found in schizophrenia.
This report describes the use of several analytical methods to provide a single composite reference analyte value for split-sample method comparison studies. The statistical techniques necessary to analyze the data are slightly more complicated than least-squares linear regression. A potentially appropriate technique is principal component analysis (PCA) using two components-the first measures analyte concentration, and the second measures aggregate interaction (errors). We applied PCA to glucose measurements performed on 130 blood sera by six glucose methods. Two methods, which have been shown to have large interferences, deviated significantly from composite values, although they were permitted to influence them. These experimental conclusions were in fair agreement with those obtained using modeled data that had been constructed to simulate known specific experimental conditions, i.e., interferences and imprecision.
Fifty-six patients who were hospitalised for a schizophrenic episode were followed up for nine months after discharge. The Psychiatric Assessment Scale (PAS, Krawiecka et al., 1977) was administered at monthly intervals during this period. Twenty-three patients relapsed of which data were available for sixteen. In these sixteen patients who relapsed comparisons were made of the PAS symptoms between the month prior to relapse and the month preceding this. Sixteen patients who did not relapse were randomly matched with the relapsing patients and an index point comparable in time to relapse onset in the matched relapsed patient was identified. Comparisons were made on the PAS symptoms using a repeated measures ANOVA to compare relapsers and non relapsers on the month prior to relapse and the month which preceded this. Discriminant function analysis was used to predict relapse by analysis of those PAS symptoms which showed an increase in the month before relapse. This suggested that the measures of depression and hallucinations significantly increased in the month prior to relapse compared to the preceding month in relapsers but not non-relapsers. The results of this study closely agree with previous published results even though there were some differences between studies in the patient samples.
Thirty-two male DSM-III diagnosed schizophrenic patients received a lumbar puncture (LP) during chronic haloperidol treatment that was followed by replacement with placebo for up to 6 weeks. Fourteen patients relapsed on placebo within 6 weeks. Patients received a second LP at the time of relapse or at the end of 6 weeks if they had not relapsed. Bunney-Hamburg Global Psychosis Ratings of the day and the hours of sleep of the night before the LP were obtained, as were the Brief Psychiatric Ratings Scale (BPRS) ratings during the week of the LPs. CSF norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5 HIAA) concentrations were measured with high-pressure liquid chromatography (HPLC). Patients who relapsed had significantly higher CSF NE levels on and off haloperidol than patients who did not relapse. CSF MHPG was higher in the relapsers in the drug-free condition only, but CSF HVA and 5-HIAA were not significantly different in either condition. In the drug-free relapsed patients, CSF NE correlated significantly with the psychosis ratings of the day and hours of sleep the night prior to the LP. Our data indicate that elevated CSF NE levels during neuroleptic treatment may predict behavioral decompensation after discontinuing the medication.
Synopsis
Recognition of prodromal symptoms of schizophrenia offers the potential of early intervention to avert relapse and re-hospitalization (Carpenter & Heinrichs, 1983). The present study investigated how a strategy to detect prodromal signs might be effectively applied in the clinical setting. A standard monitoring system was developed involving completion of a new early signs scale (ESS) measuring changes in key symptoms phenomenologically (self-report) and behaviourally (observer report). The ESS was subject to rigorous psychometric evaluation and tested in a prospective pilot investigation. The ESS reliably identified early signs and predicted relapse with an overall accuracy of 79%. Several different patterns of relapse were identified. Observer reports compensated for loss of insight in some patients. In two cases where early signs indices were detected, prompt increases in medication appeared to arrest relapse and avert readmission. The ESS offers itself as a reliable, valid and administratively feasible measure and demonstrates considerable potential as a cost-effective procedure for secondary prevention.
Although schizophrenia is a chronic illness with exacerbations and remissions, there has been surprisingly little systematic study of early signs of relapse. The authors gave 145 chronic schizophrenic patients and 80 family members a structured interview regarding early signs of relapse and other information related to the relapse period. Most patients and family informants were aware of a prodromal period during which patients experienced such symptoms as having trouble sleeping, having trouble concentrating, loss of appetite, and feeling depressed. The authors discuss the implications of these findings for the treatment of chronic schizophrenic patients.
This paper describes a prospective study of the relationship between non-psychotic prodromal symptoms and psychotic symptoms in 55 schizophrenic (DSM-III-R) out-patients. Once a month, a number of non-psychotic symptoms generally regarded as prodromal symptoms in schizophrenia were assessed, as well as psychotic symptoms, with standardised self-administered instruments and rating scales for a minimum of 12 months (range 12-29). The data were analysed for each patient using a longitudinal correlational design with a 1-month lag between the prodromal and psychotic symptoms over the total period. Results showed that in less than one-fifth of subjects did any of the prodromal symptoms, individually or in combination, show a significantly positive correlation with the subsequent level of psychotic symptoms. Such relationships were significant in an even smaller proportion of subjects when the confounding effect of concurrent psychotic symptoms on prodromal symptoms was partialled out. High levels of prodromal symptoms appeared to have adequate specificity but low sensitivity in their power to predict high levels of subsequent psychotic symptoms. There were no differences in age, gender, medication levels, and the number of previous admissions between the subjects who did or did not show a relationship between putative prodromal symptoms and psychotic symptoms.
All recently completed controlled two-year studies on intermittent, early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention. The reason for this failure is still unclear. Therefore the implicit, but as yet unproven, hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study. Results demonstrate that this is not the case. Possible reasons for and clinical implications of this negative finding are discussed.
For the majority of patients, schizophrenia is a chronic recurrent disease that leads to significant residual morbidity which occurs through a process of behavioral deterioration. The factors that influence the course of schizophrenia after its onset and the ability of treatment to modify the effects of the patient's illness are not well understood. This article examines specific clinical and biological variables that are associated with treatment response and outcome. These variables, which are both trait and state dependent, include premorbid adjustment, age and mode of onset of illness, gender, duration of psychosis, schizophrenia subtype, primary negative symptoms, and extrapyramidal signs including tardive dyskinesia and plasma HVA and brain pathomorphology. In addition, the chronic effects of antipsychotic drug treatment may influence illness course both favorably and adversely as well as potentially altering the neurobiological substrates that mediate expression of the illness and treatment response. Finally, the question of whether the active phase of the illness involves a pathologic process that leads to illness progression is discussed. In light of this discussion, we can speculate that although certain aspects of the illness in terms of its severity and course may be, to an extent, predetermined, a number of factors can exert favorable and unfavorable effects on the course of the illness and its ultimate outcome. One question for the field is to develop therapeutic strategies that minimize the morbidity of the illness in a way that does not introduce iatrogenic consequences to the patient.
People with schizophrenia are at high risk of psychotic relapse. The purpose of this study was to evaluate the predictive validity and temporal link of early signs to this.
A study sample of 60 out-patients with schizophrenia was examined every second week over a period of six months. The study design included self-reporting (Early Signs Scale) and objective assessment (General Psychopathology of Positive and Negative Symptom Scale) of behavioural and phenomenological changes (early signs). Criterion cut-off points were based on a comparison to the subjects' individual baseline scores.
Twenty-seven subjects (45%) experienced a relapse. Composite increased score (> or = 10 points) of self-reported/objectively assessed early signs predicted the relapse with a sensitivity of 81% and a specificity of 79%. Thus the predictive validity of early signs of relapse was considerable, particularly self-reporting of early signs of relapse: sensitivity 74% and specificity 79%. The inclusion of objective assessment added only marginally to the prediction. Early signs were detected most often (70%) within the four weeks immediately before the individuals' relapse.
Psychotic relapse is most often preceded by early signs. Clinical practice should integrate this knowledge by an ongoing monitoring including self-reporting.
The objective of this study was to determine the association between the patterns of change in the dopaminergic metabolite plasma homovanillic acid (HVA), the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and psychosis following haloperidol withdrawal in schizophrenic patients. Weekly plasma measurements were obtained in 107 subjects with schizophrenia or schizoaffective disorder. Random regression was used to control for individual variance while modeling metabolite changes over time and relationships with psychosis. Changes in plasma MHPG were not significantly associated with relapse or psychosis, while increased plasma HVA was found to be associated with relapse. Psychosis was correlated negatively with plasma HVA levels. The current analysis, controlling for individual variance, indicates that there is evidence for pharmacological effects on plasma HVA, but not plasma MHPG. In addition, these metabolites do not appear to be direct markers of psychosis, but may be associated with a compensatory response by the system to return to the steady state.
In spite of advances in neuroleptic treatment, relapse of positive symptoms continues to punctuate the course of schizophrenia. In this paper the conceptual and empirical basis for early intervention in the process of psychotic relapse as a preventative manoeuvre is evaluated. The predictive efficacy of early, 'prodromal' signs, their nature, and the utility of early detection and intervention strategies are reviewed. There is strong evidence that relapse is preceded by early signs, but the classical (medical) concept of prodrome is inadequate to explain the findings. The early detection and treatment of early signs appears to confer protection from relapse, but the active ingredients of the pharmacological and psychological based treatment studies are as yet unclear and suggest important avenues for future research.
Insomnia is a common feature in schizophrenia. However, it seldom is the predominant complaint. Nevertheless, severe insomnia is often seen during exacerbations of schizophrenia, and may actually precede the appearance of other symptoms of relapse. The sleep disturbances of either never-medicated or previously treated schizophrenia patients are characterized by a sleep-onset and maintenance insomnia. In addition, stage 4 sleep, slow wave sleep (stages 3 and 4), non-REM (NREM) sleep in minutes and REM latency are decreased. The atypical antipsychotics olanzapine, risperidone, and clozapine significantly increase total sleep time and stage 2 sleep. Moreover, olanzapine and risperidone enhance slow wave sleep. On the other hand, the typical antipsychotics haloperidol, thiothixene, and flupentixol significantly reduce stage 2 sleep latency and increase sleep efficiency. Future research should address: (1) the sleep patterns in subtypes of schizophrenia patients; (2) the role of neurotransmitters other than dopamine in the disruption of sleep in schizophrenia; (3) the functional alterations in CNS areas related to the pathophysiology of schizophrenia during NREM sleep and REM sleep (brain imaging studies); (4) the short-term, intermediate-term, and long-term effects of atypical antisychotics on sleep variables.
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