Medication strategies in first episode psychosis patients:A survey among psychiatrists

Aim There is an ongoing debate regarding the optimal timing of discontinuation of antipsychotic drugs for patients with first episode psychosis. Although most guidelines recommend maintenance therapy for at least 1 or 2 years after reaching remission, study results indicate that early discontinuation may be beneficial for at least a subsample of patients. To date, little is known about which medication strategies are applied in patients recovering from a first psychotic episode. In this study, we examined the beliefs and practices of clinicians on medication discontinuation. Methods We performed a survey among 50 experienced Dutch psychiatrists to assess how often specific treatment strategies have been applied in the past 12 months, as well as their knowledge and expectations with respect to medication discontinuation. Results Psychiatrists estimated that, after remission, they continued medication at the same dose for at least 12 months in 51.2% of cases, continued in a reduced dose in 33.8% of cases and discontinued medication in 9.1% of cases after 4.4 months of remission on average. Although the medication is discontinued in only a relatively small proportion of patients, almost half of all clinicians (45.9%) used this strategy at least once in the past 12 months. Conclusions There is substantial practice variation in antipsychotic medication strategies after remission from a first psychotic episode. Future research on long-term effects of early medication discontinuation can guide clinicians in making evidence-based decisions when treating first-episode patients

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 J

Exercise Improves Clinical Symptoms, Quality of Life, Global Functioning, and Depression in Schizophrenia : A Systematic Review and Meta-analysis

BACKGROUND: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. METHODS: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges' g. RESULTS: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges' g = .39, P < .001), positive (k = 15, n = 715: Hedges' g = .32, P < .01), negative (k = 18, n = 854: Hedges' g = .49, P < .001), and general (k = 10, n = 475: Hedges' g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges' g = .55, P < .001), global functioning (k = 5, n = 342: Hedges' g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges' g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges' g = .32, P < .05), while exercise in general or in any other form had no effect on cognition. CONCLUSION: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga

Exercise improves clinical symptoms, quality of life, global functioning, and depression in schizophrenia: A systematic review and meta-analysis

Background: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. Methods: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges' g. Results: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges' g =. 39, P <. 001), positive (k = 15, n = 715: Hedges' g =. 32, P <. 01), negative (k = 18, n = 854: Hedges' g =. 49, P <. 001), and general (k = 10, n = 475: Hedges' g =. 27, P <. 05) symptoms, quality of life (k = 11, n = 770: Hedges' g =. 55, P <. 001), global functioning (k = 5, n = 342: Hedges' g =. 32, P <. 01), and depressive symptoms (k = 7, n = 337: Hedges' g =. 71, P <. 001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges' g =. 32, P <. 05), while exercise in general or in any other form had no effect on cognition. Conclusion: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga

Sex hormones and oxytocin augmentation strategies in schizophrenia : A quantitative review

INTRODUCTION: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in the treatment of schizophrenia is summarized. METHODS: Double-blind, placebo-controlled, randomized studies were included, examining augmentation with estrogens, selective estrogen receptor modulators (SERMs), testosterone, dehydroepiandrosterone (DHEA), pregnenolone, and oxytocin. Outcome measures were total symptom severity, positive and negative symptom subscores, and cognition. In meta-analyses, combined weighted effect sizes (Hedges' g) per hormone were calculated. RESULTS: Twenty-four studies were included, examining 1149 patients. Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001). Subgroup analyses yielded significant results for estrogens in premenopausal women (k=6) for total, positive, and negative symptoms, and for the SERM raloxifene in postmenopausal women (k=3) for total and negative, but not positive symptoms. Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027). No overall effects were found for DHEA (k=4), pregnenolone (k=4), and oxytocin (k=6). Results for cognition (k=12) were too diverse for meta-analyses, and inspection of these data showed no consistent benefit. CONCLUSIONS: Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account. Future trials are needed to study long-term effects and effects on cognition

The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis

Background: Computerized methods for improving cognitive functioning in schizophrenia have gained popularity during the past decades. Therefore, this study evaluates the available evidence for the efficacy of computerized cognitive drill and practice training for patients with schizophrenia-spectrum disorders. Methods: A systematic search was carried out using PubMed, Embase, Cochrane Database of Systematic Reviews, and PsycINFO. A meta-analysis was performed to compare cognitive drill and practice training in patients with a schizophrenia-spectrum disorder with non-cognitively oriented control conditions. The primary outcome was cognitive functioning. Secondary outcome measures included psychotic symptoms, depressive symptoms, and functional outcomes. Effect sizes (ES) for all included studies were calculated as Hedges' g. Results: 24 studies were included with 1262 patients in total. Compared to a control condition, patients receiving computerized cognitive drill and practice training showed significantly more improvement on attention (ES = 0.31, p = 0.001), working memory (ES = 0.38, p <0.001), positive symptoms (ES = 0.31, p = 0.003), and depressive symptoms (ES = 0.37, p= 0.002). Small, marginally significant effect sizes were found for processing speed, verbal and visual learning and memory, and verbal fluency. However, significant effects on functional outcomes and social cognition were absent. Discussion: The current study showed evidence for the efficacy of computerized cognitive drill and practice training in patients with schizophrenia-spectrum disorders. However, the absence of effects on social cognition and functional outcomes questions the generalization of treatment effects. Together, these results stimulate further development of computerized training programs for schizophrenia that not only improve cognitive functioning, but also generalize cognitive improvement to functional outcomes. (C) 2018 Elsevier B.V. All rights reserved

The influence of stimulus detection on activation patterns during auditory hallucinations

AbstractIntroductionNeuroimaging studies investigating auditory verbal hallucinations (AVH) have revealed involvement of several cortical structures. These findings may however be biased by brain activity related to stimulus detection and motor processes associated with the task to indicate the presence of AVH. Disentangling brain activation specifically related to AVH and to additional cognitive processes may help focus on the true neuronal substrates of AVH and strengthen the development of new focal treatment strategies.MethodsBrain activation during AVH as indicated by button press was compared to brain activation during auditory stimulus detection indicated by button press. We performed two neuroimaging meta-analyses, assessing 10 AVH and 11 auditory stimulus detection studies. A random-effects activation likelihood estimation was performed using GingerALE to assess commonalities and differences across AVH and stimulus detection studies.ResultsActivity in the claustrum, pulvinar area, medial geniculum body, pyramis, culmen, putamen, insula, and parahippocampal, medial frontal, precentral, postcentral, superior temporal and right inferior frontal gyri was found to be specifically related to AVH. The pars opercularis of the left inferior frontal gyrus and the left transverse temporal gyrus were activated to a similar extent during AVH and auditory stimulus detection.DiscussionDevelopment of new focal treatment strategies for AVH may focus on the areas uniquely activated in the AVH analysis. The pars opercularis and the transverse temporal gyrus may not be directly involved in the experience of AVH itself, but rather in auditory stimulus detection