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Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis.
Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse.
Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical−striatal−thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse.
MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.
Paliperidone 3-monthly (PP3M) long-acting injection has proven efficacy and effectiveness in schizophrenia. Little is known of its effectiveness in other diagnoses.
All patients starting PP3M were followed up for 2 years. Main outcome measures were relapse and discontinuation from PP3M. Post hoc we examined outcomes in those switched back to one monthly paliperidone (PP1M) long-acting injection.
Overall, 186 patients were followed-up. At the 2-year end point, 110 patients (59%) were still receiving PP3M, and 129 (70%) were receiving some form of paliperidone long-acting injection. Discontinuation from paliperidone long-acting injections (PPLAIs) was more likely with a nonschizophrenia diagnosis (hazard ratio [HR] for continuation 0.429 [95% confidence intervals (CI) – 0.21, 0.87 p = 0.018)), and prior clozapine use [in PP3M patients; HR for discontinuation 1.87 [95% CI – 1.05, 3.30 p = 0.032]). Relapse occurred in 20 (11%) of those receiving PP3M. Relapse on PP3M and PPLAIs was more likely in nonschizophrenia diagnosis (HR 0.17 for remaining relapse-free [95% CI – 0.06, 0.50; p = 0.001]; HR 0.21 [95% CI – 0.08, 0.58 p = 0.002], respectively), polypharmacy in PP3M patients (HR for relapse 7.91 [95% CI – 3.73, 22.9; p < 0.001]) and PPLAI patients (HR for relapse 6.45 [95% CI – 2.49, 16.5; p < 0.001]), and prior clozapine use in PP3M patients (HR for relapse 6.11 [95% CI – 1.82, 20.5; p = 0.003]) and PPLAI patients (HR for relapse 4.52 (95% CI – 1.51, 13.5; p = 0.007).
Outcomes with PP3M are excellent in practice, even when used outside its formal license. PP3M was relatively more effective in those with an F20 schizophrenia diagnosis and in those never before considered for or prescribed clozapine.
Protracted abstinence syndrome represent group of attenuated psyc that lead to a persistant sense of discomfort among misuse patients after detoxification and may last for some months.Poor sleep in terms of duration and quality is one of the major symptoms of protracted abstinence syndrome
To assess polysomnography parameters as potential risk for relapse over six months
60 male patients with heroin misuse according to DSM V have been recruited immediately after detoxification phase, they were not receiving other psychactive substances or medications, polysomnography was done in the second week after detoxification to allow washout of medications used during detoxification and then a monthly sleep assessment through sleep diary and daytime sleepiness using visual analogue scale. Relapse was prooved through urine test.
Sample contained 60 male patients with heroin misuse disorder, detoxified successfully with a mean age 35.47±7.32 and addiction severity index total score 3.21±0.22, polysomnography was done to all sample patients one week after detoxification, 20% relapsed by the third month, rising to 30% by the six month. NREM stages I and II, both limb movement and arousal indices showed significant differnce between relapsed and non-relapsed patients.
Sleep disturbance is common among detoxified heroin misuse patients. Polysomnographic parameters such as percentage of NREM I and I, arousal index and limb mouvement index can potentially predict future relpase over six month follow up period.
Relapse prevention is a key objetive for patients with a First Episode Psychosis (FEP) and the low adherence to antipsychotic (AP) treatment is the main reason for relapse after a FEP.
There are no clear recommendations about the early use of long-acting injectables (LAIs) in FEP. We review the impact on hospitalization rates of the early use (earlier than 1 year after the inclusion in our Early Intervention Service “Lehenak”) of LAI paliperidone in a FEP sample.
We evaluated in a naturalistic study a sample (N=384) of patients with a FEP. We carried out a mirror-design study to compare the numer of hospitalizations before and after the introduction of LAI paliperidone (1 and 3 monthly) in early users (<1 year) vs late users (>1 year).
A total of 384 FEP patients with LAI paliperidone were assessed.
Early Paliperidone LAI (n=201)
Late Paliperidone LAI (n=173)
Within groups comparisons t (p)
Hospitalizations pre-LAI mirror period (media, standard deviation)
Days in hospital pre-LAI mirror period
Hospitalizations post-LAI mirror period
Days in hospital post-LAI mirror period
There was no difference between the early and late introduction of LAI Paliperidone in the number of hospitalizations after treatament. There was a trend to present more previous hospitalizations and days in hospital in late users. This could support an earlier use of paliperidone LAI to prevent an excess of hospitalizations due to late introduction.
The presenting author has received honouraria for lectures or advisory boards from Janssen, Otsuka, Lundbeck and Angelini in the last five years.
Insomnia has been related to a more severe substance use disorder presentation (1). There are few longitudinal studies in outpatients center for SUD treatment that evaluate how insomnia impacts on relapses.
To analyze how insomnia impacts on the time of the first substance relapse in SUD outpatients after the onset of addiction treatment.
This is a one-year follow-up study performed on 116 patients (73.3% males; mean age 43.4±14.3) for whom we had information from baseline insomnia and the time for the first relapse. A Kaplan-Meier survival analysis was performed. This is part of a greater research on Alexithymia in SUD in a longitudinal study.
The initial sample consisted of 116 patients, information on relapses was available for 113 patients. The main substances used at baseline were alcohol (62.1%), cocaine (56.0%), cannabis (42.2%), and opiates (30.2%).
It is important to evaluate insomnia at the onset of addiction treatment because insomnia may be related to earlier relapses. Furthermore, it should be analyzed further on how insomnia treatment impact on substance relapses. REFERENCES 1. Miller MB, Donahue ML, Carey KB, Scott-Sheldon LAJ. Insomnia treatment in the context of alcohol use disorder: A systematic review and meta-analysis. Drug Alcohol Depend. 2017;181:200-207. doi:10.1016/j.drugalcdep.2017.09.029
Patients are often treated with high doses or combinations of antipsychotics, which may hamper recovery. Dose-reduction (DR) or discontinuation of antipsychotic medication in chronic patients carries the risk of psychotic relapse.
To identify risk factors of psychotic relapse after DR or discontinuation, we (i) determined the rate of relapse after DR or discontinuation in patients with chronic schizophrenia, and (ii) assessed risk factors for psychotic relapse.
From studies on dose-reduction from January 1950 through June 2019 we calculated event rates per person-years including 95% confidence intervals. We extracted: (1) patient characteristics (age, percentage of male subjects, setting, duration of illness), (2) dose-reduction/discontinuation characteristics (start-dose, end-dose, dose-reduction in milligrams and percentage of start-dose, time-period of dose-reduction), (3) follow-up characteristics (time after dose-reduction), and (4) study characteristics (blinding, publication-year and relapse definition).
46 unique cohorts, presenting 1677 patients in which doses were reduced/discontinued were included in meta-analysis. We found an overall event rate per person-years on psychotic relapse of 0.55 (CI95% 0.46-0.65;p<0.0001;I2 =79). Most robust event rates for psychotic relapse were seen for discontinuing antipsychotics, and if not discontinuing, dose-reduction till under 5mg haloperidol equivalents daily (HE). Abrupt reduction yielded higher rates than gradual reduction. During short follow-up time more relapses occurred than in studies with long follow-up time.
In patients with chronic schizophrenia discontinuing, and to a lesser extent DR till end-dose<5mgHE, patients who reduce doses abrupt, inpatients, and patients with a short duration of illness carry highest relapse risk. Most relapses occur during the first half year after DR.
The present study aimed to determine the 3-month incidence of relapse and associated factors among children who recovered under the Optimising treatment for acute MAlnutrition (OptiMA) strategy, a MUAC-based protocol. A prospective cohort of children successfully treated for acute malnutrition was monitored between April 2017 and February 2018. Children were seen at home by community health workers (CHWs) every 2 weeks for 3 months. Relapse was defined as a child who had met OptiMA recovery criteria (MUAC ≥ 125 mm for two consecutive weeks) but subsequently had a MUAC < 125 mm at any home visit. Cumulative incidence and incidence rates per 100 child-months were estimated. Multivariable survival analysis was conducted using a shared frailty model with a random effect on health facilities to identify associated factors. Of the 640 children included, the overall 3-month cumulative incidence of relapse was 6⋅8 % (95 % CI 5⋅2, 8⋅8). Globally, the incidence rate of relapse was 2⋅5 (95 % CI 1⋅9, 3⋅3) per 100 child-months and 3⋅7 (95 % CI 1⋅9, 6⋅8) per 100 child-months among children admitted with a MUAC < 115 mm. Most (88⋅6 %) relapses were detected early when MUAC was between 120 and 124 mm. Relapse was positively associated with hospitalisation, with an adjusted hazard ratio (aHR) of 2⋅06 (95 % CI 1⋅01, 4⋅26) for children who had an inpatient stay at any point during treatment compared with children who did not. The incidence of relapse following recovery under OptiMA was relatively low in this context, but the lack of a standard relapse definition does not allow for comparison across settings Closer follow-up with caretakers whose children are admitted with MUAC < 115 mm or required hospitalisation during treatment should be considered in managing groups at high risk of relapse. Training caretakers to screen their children for relapse at home using MUAC could be more effective at detecting early relapse, and less costly, than home visits by CHWs.
Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes.
The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF).
We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09–0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37–0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06–0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies.
Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation.
Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression.
Two hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse.
Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups.
PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.
Symptoms may be more useful prognostic markers for mental illness than diagnoses. We sought to investigate symptom domains in women with pre-existing severe mental illness (SMI; psychotic and bipolar disorder) as predictors of relapse risk during the perinatal period.
Data were obtained from electronic health records of 399 pregnant women with SMI diagnoses from a large south London mental healthcare provider. Symptoms within six domains characteristically associated with SMI (positive, negative, disorganization, mania, depression, and catatonia) recorded in clinical notes 2 years before pregnancy were identified with natural language processing algorithms to extract data from text, and associations investigated with hospitalization during pregnancy and 3 months postpartum.
Seventy-six women (19%) relapsed during pregnancy and 107 (27%) relapsed postpartum. After adjusting for covariates, disorganization symptoms showed a positive association at borderline significance with relapse during pregnancy (adjusted odds ratio [aOR] = 1.36; 95% confidence interval [CI] = 0.99–1.87 per unit increase in number of symptoms) and depressive symptoms negatively with relapse postpartum (0.78; 0.62–0.98). Restricting the sample to women with at least one recorded symptom in any given domain, higher disorganization (1.84; 1.22–2.76), positive (1.50; 1.07–2.11), and manic (1.48; 1.03–2.11) symptoms were associated with relapse during pregnancy, and disorganization (1.54; 1.08–2.20) symptom domains were associated with relapse postpartum.
Positive, disorganization, and manic symptoms recorded in the 2 years before pregnancy were associated with increased risk of relapse during pregnancy and postpartum. The characterization of routine health records from text fields is relatively transferrable and could help inform predictive risk modelling.
The aim of this case report is to describe the clinical presentation and imaging features of a patient with optic nerve leukaemic infiltration as the first site of relapse after complete response to systemic treatment.
Materials and methods:
We report the case of a 23-year-old man with history of acute lymphoblastic leukaemia (ALL) in complete remission. Six months later, the ocular examination revealed decreased visual acuity. Fundus examination showed a pale optic disk with blurred margins and multiple flame-shaped and dot and blot retinal haemorrhages in his left eye. A diagnosis of leukaemic infiltration to the optic nerve was made by magnetic resonance imaging (MRI). Cytological analysis of the cerebrospinal fluid did not show any abnormal cells or blasts.
A course of oral corticosteroid therapy was prescribed and 20 Gy of radiation was administered to the whole brain including the left orbit. Vision was improved dramatically in the left eye. Isolated optic nerve relapse of leukaemic infiltration is of paramount importance to early diagnosis, as vision can be saved if treatment with orbital radiotherapy is initiated promptly.
Outcomes with long-acting injections (LAIs) are generally better than with oral antipsychotic therapy. However, the use of LAIs does not assure compliance with treatment and in clinical practice patients often miss injections or receive their injections later than intended.
We conducted a case–control study to identify demographic and treatment associations with relapse (cases) on paliperidone 1-monthly injection (PP1M) compared with age-, gender-, and ethnicity-matched controls.
We identified 16 cases and matched 43 controls. Baseline variables did not differ except that cases had received significantly more antipsychotic drugs before initiation with PP1M (3.94 vs. 2.12; p < 0.001). Cases had fewer PP1M injections administered compared with the control group (9.69 vs. 11.37; p < 0.001) and this group had a longer interval between injections than the control group (37 vs. 33 days; p < 0.001).
Relapse on PP1M is associated with reduced frequency of injection and a longer interval between doses.
Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains.
Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included.
Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22–7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36–3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16–4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15–0.85)]. None of the moderators included significantly change the results.
These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.
Predicting and preventing relapse presents a crucial opportunity and first step to improve outcomes and reduce the care gap for persons living with schizophrenia. Using commercially available smartphones and smartwatches, technology now affords opportunities to capture real-time and longitudinal profiles of patients’ symptoms, cognition, physiology and social patterns. This novel data makes it possible to explore relationships between behaviours, physiology and symptoms, which may yield personalised relapse signals.
Smartphone Health Assessment for Relapse Prevention (SHARP), an international mental health research study supported by the Wellcome Trust, will inform the development of a scalable and sharable digital health solution to monitor personal risk of relapse. The resulting technology will be studied toward predicting and preventing relapse among individuals diagnosed with serious mental illness.
SHARP is a two-phase study with research sites in Boston, Massachusetts, and Bangalore and Bhopal, India. During phase 1, focus groups will be conducted at each study site to collect feedback on the design and features available on mindLAMP, a digital health platform. Individuals with serious mental illness will use mindLAMP for the duration of a year during phase 2.
The results of the research outlined in this protocol will guide the development of technology and digital tools to help address pervasive challenges in global mental health.
The digital tools developed as a result of this study, and participants’ experiences using them, may offer insight into opportunities to expand digital mental health resources and optimize their utilisation around the world.
Prolonged remission of dystonia occurs rarely; however, well-documented cases are lacking. We report the clinical characteristics and course of four patients with botulinum toxin (BoNT)-associated prolonged remission of idiopathic cervical dystonia. Mean age at onset was 40 years. All had a relatively short duration of symptoms (mean 10.3 months), and with remission occurring after ≤ 3 treatments with BoNT. At last examination, the remission duration was 2–5 years. In the two cases that subsequently relapsed after 4–5 years, there was an altered phenomenology and worsened severity than at the onset. Recognizing this rare phenomenon has valuable clinical implications.
Relapse rates among individuals with psychotic disorders are high. In addition to the financial burden placed on clinical services, relapse is associated with worse long-term prognosis and poorer quality of life. Robust evidence indicates that stressful life events commonly precede the onset of the first psychotic episode; however, the extent to which they are associated with relapse remains unclear. The aim of this systematic review is to summarize available research investigating the association between recent stressful life events and psychotic relapse or relapse of bipolar disorder if the diagnosis included psychotic symptoms. PsycINFO, Medline and EMBASE were searched for cross-sectional, retrospective and prospective studies published between 01/01/1970 and 08/01/2020 that investigated the association between adult stressful life events and relapse of psychosis. Study quality was assessed using the Effective Public Health Practice Project guidelines. Twenty-three studies met eligibility criteria (prospective studies: 14; retrospective studies: 6; cross-sectional: 3) providing data on 2046 participants in total (sample size range: 14–240 participants). Relapse was defined as a return of psychotic symptoms (n = 20), a return of symptoms requiring hospitalization (n = 2) and a return of symptoms or hospitalization (n = 1). Adult stressful life events were defined as life events occurring after the onset of psychosis. Stressful life events included but were not limited to adult trauma, bereavement, financial problems and conflict. Eighteen studies found a significant positive association between adult stressful life events and psychotic relapse and five studies found a non-significant association. We conclude that adult stressful life events, occurring after psychosis onset, appear to be associated with psychotic relapse.
Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates.
Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale.
Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed.
Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.
This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.