Reduction Of Psychotic Symptoms Research Articles

APPS-Study 2020 - On outpatient psychotherapeutic care for people with psychotic disorders

Although patients with psychotic disorders (PPS) are indicated for outpatient psychotherapy at any stage of their illness, they are rarely treated in this way. For this purpose, structural conditions, the experience of competence of therapists, as well as content-related aspects of training and further education of psychotherapists are analyzed. Based on a qualitative preliminary study, an online survey was conducted among 487 psychological psychotherapists. Half of the respondents indicated a high willingness to treat PPS. In the acute phase of the disease only 20% are willing to do so. In the studies as well as in the theoretical part of the education and further education, there is hardly any preparation for a corresponding treatment. In contrast, practical experience in psychiatric clinics is considered very important. With regard to structural framework conditions, low hourly quotas and inflexible billing modalities are criticized. With regard to patients, in addition to sufficient motivation for treatment, low reliability, low cognitive ability, low insight into the illness, and frequent discontinuation of therapy are stated. Contrary to some prejudices, patients are characterized as "peaceful" in their interactions. The reduction of psychotic relapses, social integration and reduction of comorbid symptoms are mainly mentioned as achievable outcomes. The reduction of psychotic symptoms is rated less optimistically. Psychotherapists from psychiatric outpatient clinics (PIA) differ from other outpatient psychotherapists by better competence experience and correspondingly more frequent work with PPS, also in the acute stage. Although every second therapist does not feel well trained, the willingness to treat PPS seems to be higher than the pure supply figures suggest. There is potential for optimization in education and training as well as in networking with other professional groups/relatives. This could be responsible for the fact that in the acute psychotic stage there are fears of contact and competence concerns. Psychotherapists in PIAs, where there is closer networking with other professional groups for structural reasons, experience corresponding deficits to a lesser extent. With regard to other structural barriers, the question arises as to whether these represent disorder-specific or rather general problems in psychotherapy.

The Influence of Electroconvulsive Therapy (ECT) on Brain-Derived Neurotrophic Factor (BDNF) Plasma Level in Patients with Schizophrenia-A Systematic Review and Meta-Analysis.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = -0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.

Mindfulness for psychosis: Current evidence, unanswered questions and future directions.

Mindfulness for psychosis research has grown exponentially over the last 15 years. In this paper, a brief overview of mindfulness for psychosis is provided followed by a summary of the findings from a systematic search of meta-analyses dated up to February 2023. Current issues in the field are discussed and a future research agenda is presented. Ten meta-analyses published between 2013 and 2023 were identified. Reported effect sizes on reductions in psychotic symptoms ranged from small-large across reviews. Four key issues in the field are identified and discussed - (1) is mindfulness for psychosis safe? (2) is home practice essential and related to clinical outcomes? (3) what is the impact of mindfulness practice versus metacognitive insights derived from practice, on clinical outcomes? (4) do the benefits translate into routine clinical practice? Mindfulness is a promising intervention that is emerging as being both safe and effective for people with psychosis. Future research focused on evaluating mechanisms of change and implementation in routine clinical practice should be prioritised.

Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial.

Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications. Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial. The participants were treated with amisulpride for 4 weeks. Levels of complement and coagulation proteins at baseline were measured using both data-dependent and data-independent mass spectrometry approaches. The primary outcome was remission status at 4 weeks and the secondary outcomes included change in psychotic and functional symptoms over the period of treatment. In addition, immunoassays were performed at baseline for complement C1R, as well as for activation markers C4a and sC5b-9. The plasma level of complement variant C4A was significantly associated with remission at 4 weeks. Moreover, higher levels of several complement and coagulation pathway proteins were associated with a reduction in psychotic symptoms and an improvement in functioning. Immunoassays showed an association of baseline levels of C1R and C4a as well as complement activation marker sC5b-9 levels with treatment response. The results demonstrated that the response to antipsychotic treatment might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is consistent with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these results inform the development of novel therapeutic approaches that target the complement system for psychosis.

Neuropsychiatric consequences of Covid 19- CASE REPORT

IntroductionSARS-CoV-2 is a virus with a multisystem effect, and it can cause numerous neuropsychiatric disorders, both in the acute phase of infection and in the period after the disease has passed. According to Nalbandian et al. (2021), post-acute COVID-19 syndrome is a condition of persistent symptoms and/or delayed long-term complications caused by SARS-CoV-2 infection lasting longer than four weeks after the onset of symptoms.ObjectivesTo indicate the possible role of the SARS-COV 2 virus in the development of long-term neuropsychiatric and cognitive consequences of COVID-19.MethodsWe undertook a search of the available medical literature in the period after 2020 with the keywords COVID 19 and neuropsychiatric complicationsResults: Case report: Female patient, 40 years old, unemployed, married, mother of two children. She was admitted for the first hospital treatment at the Psychiatry Clinic of the UCC of Niš due to psychological disturbances in the form of experiencing her own body changes and changes in the environment, moodiness, anxiety, the conviction that she is suffering from incurable diseases, the experience of being centered and existentially threatened, insomnia. In 2020, one month after the recovery from COVID-19, she was treated at the Neurology Clinic of the UCC of Niš for a crisis of consciousness, diagnosis at discharge: encephalitis, encephalopathy. At the end of the treatment, cognitive-mnestic deficits remain. In April 2021, after reinfection with the SARS-COV2 virus, a depressive-interpretive syndrome developed, which is the reason for the current hospitalization. Depersonalization and derealization phenomena, time disorientation, hypochondrial delusions, ideas of self-accusation, cenesthetic hallucinations, impaired volitional-instinctual dynamism and deficits in cognitive-mnestic functioning are observed during hospitalization. NMR of the endocranium with contrast shows changes in the form of encephalomalacia, porencephaly, which indicates a condition after a cerebrovascular insult. She was treated with low doses of haloperidol (2 mg pd), antidementia and vasoactive therapy, which led to a reduction of psychotic symptoms as well as an initial improvement in cognitive-mnestic functioning.ConclusionsThis case report confirms the neurotoxicity of the SARS-CoV-2 virus and it is in accordance with the available literature. The neuropsychiatric and cognitive complications that accompany COVID-19 are different and have a significant impact on the health of people who recovered from COVID-19. It is necessary for the health system to recognize this problem in time and provide organized neuropsychiatric and cognitive monitoring to patients suffering from COVID-19.Disclosure of InterestNone Declared

COVID-19-Associated Schizophrenia-Like Psychosis

Background: COVID-19-associated psychoses are psychotic disorders that have developed during a new coronavirus infection. Criteria of these psychoses are the manifestation of psychosis simultaneously with infection with the SARS-CoV-2 virus and the presence of documented COVID-19 disease. Information about these diseases appears as brief reports of mental services or with rare clusters. The need to study COVID-19-associated psychoses is due to the relatively high risk of their development, reaching 2.8%. The aim of study was to analyse the identified cases of COVID-19-associated psychosis in comparison with the results presented in the scientific literature. Patients and methods: 50 cases of COVID-19-associated psychosis were analyzed using a clinical method, taking into account the results of physical examination from April 2020 to September 2021. Results: 27 women and 23 men aged 20 to 57 were examined. Common symptoms were revealed: simultaneously or immediately after infection and identification of the virus against the background of growing anxiety and dissomnia, delusional ideas were formed, which quickly turned into fantastic delusion with disturbing agitation and hallucinations and subsequent marked disorganization of behavior with possible confusion of consciousness at the peak of psychosis. Perceptual deceptions were the most common, auditory hallucinations were the most prevalent, and catatonia was relatively common. The cupping therapy led to reduction of psychotic symptoms, and returned patients to a pre-morbid level of functioning. In most cases, there was a critical resolution of the attack, which probably indicates a favorable outcome of the disorder. Such dynamics is consistent with scientific literature data. Conclusion: the question of the primary or secondary nature of COVID-19-associated psychoses remains unresolved. It is necessary to continue the study of COVID-19-associated psychosis with the identification of risk factors for the development of psychosis, manifestation features, psychopathological picture, outcome options to determine the optimal rehabilitation program.

A randomized controlled trial of a peer-facilitated self-management program for people with recent-onset psychosis

Early patient-centered interventions can improve mental health and prevent psychotic relapse in people with recent-onset psychosis (ROP). However, limited effective peer-facilitated early interventions are found worldwide. We aimed to test the effects of a four-month peer-facilitated self-management intervention (PFSMI) for Chinese patients with ROP compared with a psychoeducation group (PEG) and treatment-as-usual (TAU) group. A randomized controlled trial was conducted at six Integrated Community Centers for Mental Wellness in Hong Kong. The primary outcome was level of recovery. Secondary outcomes were improvement of problem-solving ability, insight into illness/treatment, and functioning, and reducing psychotic symptoms and re-hospitalization rates. Overall, 180 ROP patients were randomly selected, and after collecting baseline data, randomly assigned to the PFSMI, PEG or TAU (60 per group). Their outcomes were measured at 1-week and 6-month post-intervention. One hundred and sixty-one patients (89.4 %) completed their interventions, with an overall attrition rate of 7.8 % (n = 14). Based on intention-to-treat principle, results of generalized estimating equation test indicated that the PFSMI group reported significantly greater improvements in levels of recovery, functioning and insight into illness/treatment and reductions in psychotic symptoms and duration of re-hospitalizations (p = 0.0007–0.02, with moderate to large effect sizes) than the TAU group at 1-week post-intervention, and both the TAU and PEG at 6-month post-intervention. Significantly fewer PFSMI participants were hospitalized than the TAU and PEG over 6-month follow-up (p = 0.003). The findings support that PFSMI can produce medium-term positive effects on the mental health and functioning of patients with ROP.

Aripiprazole: examining the clinical implications of D2 affinity.

Schizophrenia is a prevalent psychiatric illness, which causes significant financial and social burden on the population overall. The development of second generation antipsychotics, such as Aripiprazole, Risperidone, and Paliperidone, has changed treatment practice for many psychiatrists. Aripiprazole has extremely high binding affinity for the dopamine D2 receptor, which is the receptor thought to be responsible for the antipsychotic effect, although Aripiprazole is not the most potent of the second generation antipsychotics. In theory, Aripiprazole could displace or outcompete other, more potent antipsychotics, prompting decreased antipsychotic effect. We describe a proposed case of this phenomenon, Ms. A. We describe how Aripiprazole may have caused a worsening of psychiatric symptoms by blocking the antipsychotic effects of Paliperidone due to its strong binding affinity for the D2 receptor. Aripiprazole has a high affinity for the D2 receptor, but may have a lesser reduction of psychotic symptoms compared to other antipsychotics. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of Aripiprazole to avoid this phenomenon.

A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p < 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p = 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES.

Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistantschizophrenia.

RationaleThough numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ’s efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ’s unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning.ObjectiveIn a cohort of 22 individuals with TRS, we examined response to CLZ in relation to the following: (1) change in corticostriatal functional connectivity; and (2) change in a magnetic resonance-based measure of striatal tissue iron (R2’), which demonstrates utility as a proxy measure for elements of DA functioning.MethodsParticipants underwent scanning while starting CLZ and after 12 weeks of CLZ treatment. We used both cortical and striatal regions of interest to examine changes in corticostriatal interactions and striatal R2’ in relation to CLZ response (% reduction of psychotic symptoms).ResultsWe first found that response to CLZ was associated with an increase in corticostriatal connectivity between the dorsal caudate and regions of the frontoparietal network (P < 0.05, corrected). Secondly, we observed no significant changes in striatal R2’ across CLZ treatment.ConclusionOverall, these results indicate that changes in corticostriatal networks without gross shifts in striatal DA functioning underlies CLZ response. Our results provide novel mechanistic insight into response to CLZ treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00213-022-06138-0.

Associations of CYP2D6, ABCB1 2677G&gt;T/A and 3435C&gt;T with effectiveness and safety of pharmacotherapy for acute psychotic episodes in adolescents over 28 days

Introduction. Pharmacokinetic genetic factors are prognostically relevant when prescribing antipsychotics to adult patients. Currently, there is a dearth of research on adolescents with an acute psychotic episode. Aim. To identify possible associations of CYP2D6, CYP3A4/5 and ABCB1 gene polymorphic variants with the efficacy and safety of pharmacotherapy in adolescents with an acute psychotic episode within 28 days. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD- 10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms CYP3A4*22 (rs2740574), CYP3A5*3 (6986A&gt;G, rs776746), CYP2D6*4, *9, *10 (rs3892097, rs4986774, rs1065852), ABCB1 1236C&gt;T (rs1128503), 2677G&gt;T/A (rs2032582), 3435C&gt;T (rs1045642) by real-time PCR. Results. Carriers of ABCB1 2677G&gt;T/A significantly less frequently demonstrated response to pharmacotherapy according to PANSS scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014). Carriers of the ABCB1 3435C&gt;T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037). Patients with «intermediate» CYP2D6 metabolism were more likely to have reduced sleep duration (13.6 % vs. 0 %; p=0.031). ABCB1 2677G&gt;T/A (51 % vs. 15.8 %; p=0.012) and 3435C&gt;T (46.6 % vs. 10 %; p=0.039) were more frequently associated with dry mouth. ABCB1 3435C&gt;T carriers were also more likely to have orthostatic vertigo (34.5 % vs. 0 %; p=0.028). Conclusion. Carriage of the ABCB1 3435C&gt;T was associated with greater efficacy of pharmacotherapy for acute psychotic episode in adolescents after 28 days, but also increases the risk of adverse reactions in the first 2 weeks of treatment. The ABCB1 2677G&gt;T/A was associated with an increased risk of adverse reactions as well as less reduction of psychotic symptoms on day 14 of pharmacotherapy.

Cognitive Remediation Therapy for People With Schizophrenia Spectrum Disorder: A Rapid Qualitative Review

&#x0D; This rapid qualitative review analyzed 8 studies describing the perspectives of people living with schizophrenia spectrum disorder (SSD) who use cognitive remediation therapy (CRT), and their caregivers and clinicians.&#x0D; People living with SSD reported notable improvements in their attention, memory, and problem solving; improvement in their lives when they applied the cognitive strategies acquired from CRT into daily life activities; improvement in communication skills, social engagement, motivation, independence; and a reduction in psychotic symptoms.&#x0D; This review found a common preference among people living with SSD and caregivers to provide personalized delivery and treatment of CRT.&#x0D; People living with SSD cited several ways to introduce personalized CRT: cognitive trainer or clinician’s support and guidance; the content, design, and implementation of CRT; using technology; and group environment and interacting with peers. The constant presence of a polite, friendly, empathetic, and encouraging clinician contributed to beneficial views of CRT.&#x0D; People living with SSD enjoyed the structure of sessions and cognitive tasks, specifically working on tasks at their own pace with gradual increases in difficulty that gave them a sense of accomplishment and mastery. They also enjoyed using technology and playing games to complete tasks; however, some found accessing a computer and a high-quality internet connection difficult.&#x0D; While people living with SSD reported several social benefits to group-based CRT, others found group-based CRT to be unconducive for their learning, especially when the group environment was not supportive or encouraging.&#x0D; Caregivers and clinicians recognized the importance of matching the type of cognitive exercises and structure of sessions to the cognitive needs of people living with SSD.&#x0D;

Immune-inflammatory markers in remission after a first-episode psychosis in young patients

To study clinical, psychopathological and immunological features of remission after first-episode psychosis in young patients to determine the patterns of this stage and the possibility of using the results for monitoring, prognosis and optimization of therapy. Fifty patients, aged 15-25 years, mean age 20.8±2.2 years, experiencing first-episode psychosis (F20, F25) and 45 healthy age-matched young men (mean age 19.2±3.2 years) were examined. The average age of psychosis manifestation was 19.8±2.5 months. Clinical, psychopathological, psychometric (PANSS and HDRS) and immunological («Neuro-immuno-test» technology) examinations were carried out at the psychotic state, during period of psychopathological symptoms reduction and further for 1-2 years until complete/significant reduction of psychotic symptoms. Three stages of remission are revealed: I - the stage of reduction and modification of leading psychotic symptoms, II - the stage of stabilization of mental functions, III - the stage of reintegration of mental functions. It has been shown that each stage corresponds to different features of clinical symptoms and also certain spectra of immune markers (activity of leukocyte elastase, α1-proteinase inhibitor and level of autoantibodies to S100-B and OBM proteins) in blood serum of patients. The differences in the spectra of immune parameters at the second stage of remission in patients with affective (depressive) disorders define various patterns of post-psychotic development of disease. The most representative are immunological features of the third stage of remission. The dynamics of immune markers in the course of remission can be considered as a biological criterion for assessment of the outcome of the first first-episode psychosis and the completeness of remission.

Systematic review of the methods of health economic models assessing antipsychotic medication for schizophrenia.

BackgroundNumerous economic models have assessed the cost-effectiveness of antipsychotic medications in schizophrenia. It is important to understand what key impacts of antipsychotic medications were considered in the existing models and limitations of existing models in order to inform the development of future models.ObjectivesThis systematic review aims to identify which clinical benefits, clinical harms, costs and cost savings of antipsychotic medication have been considered by existing models, to assess quality of existing models and to suggest good practice recommendations for future economic models of antipsychotic medications.MethodsAn electronic search was performed on multiple databases (MEDLINE, EMBASE, PsycInfo, Cochrane database of systematic reviews, The NHS Economic Evaluation Database and Health Technology Assessment database) to identify economic models of schizophrenia published between 2005–2020. Two independent reviewers selected studies for inclusion. Study quality was assessed using the National Institute for Health and Care Excellence (NICE) checklist and the Cooper hierarchy. Key impacts of antipsychotic medications considered by exiting models were descriptively summarised.ResultsSixty models were included. Existing models varied greatly in key impacts of antipsychotic medication included in the model, especially in clinical outcomes used for assessing reduction in psychotic symptoms and types of adverse events considered in the model. Quality of existing models was generally low due to failure to capture the health and cost impact of adverse events of antipsychotic medications and input data not obtained from best available source. Good practices for modelling antipsychotic medications are suggested.DiscussionsThis review highlights inconsistency in key impacts considered by different models, and limitations of the existing models. Recommendations on future research are provided.

Identification of a Serotonin 2A Receptor Subtype of Schizophrenia Spectrum Disorders With Pimavanserin: The Sub-Sero Proof-of-Concept Trial Protocol.

BackgroundAll current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naïve patients will respond to serotonin 2A receptor (2AR) blockade.AimsThis investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin.Materials and EquipmentForty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses.Outcome MeasuresThe primary clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary clinical endpoints comprise multiple clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response.Anticipated ResultsClinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored.PerspectivesSub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a “serotonergic subtype” of schizophrenia spectrum patients, thereby promoting development of precision medicine in clinical psychiatry.Clinical Trial RegistrationClinicalTrials, identifier NCT03994965.

Interrelation of clinical-anamnestic, medical-biological and neurocognitive characteristics of maladaptation in remission as a component of pathopersonological transformations in patients with schizoaffective disorder

The aim of the study was to study the interrelation between clinical, medical, biological and neurocognitive characteristics of maladaptation (as a component of pathopersonological transformations) in patients with schizoaffective disorder in remission. On the basis of the Regional Clinical Psychiatric Hospital (Zaporizhzhia, Ukraine) 102 persons with the established diagnosis of “schizoaffective disorder” were examined. Diagnosis was per formed according to the International ICD-10. The mandatory criteria for inclusion in the study were the presence of a condition of clinical remission with reduction of psychotic symptoms and the absence of severe somatic and neurological pathology, abuse of psychoactive substances. The main methods of the study were clinical psychopathological, psychodiagnostical, clinical-anamnestic and clinical-cathamnestic as well as medi cal and statistical analysis. The study established the presence and regularities of conjugation of clinical, medical, biological, and neurocognitive characteristics of maladaptation (as a component of pathopersonological transformations) in patients with schizoaffective disorder in remission. The structure of neurocognitive deficits in schizoaffective disorder in remission is related to the clinical type of the disease, the sex, the duration of the pathological process, and the characteristics of psychopharmacological treatment. The established regularities emphasize the importance of neurocognitive disorders in the structure of pathopersonological transformations and can be used in the formation of the system of diagnostic and treatment and rehabilitation measures to improve the quality of differential diagnosis and to carry out preventive and therapeutic rehabilitation measures to reduce the level of social maladaptation of patients with schizoaffective disorder. Keywords: schizoaffective disorder, clinic, neurocognition, social maladaptation, pathopersonalogical transformations

“MANAGING THE MENAGERIE IN MY HOME”, SUCCESSFUL CLOZAPINE TITRATION FOR “PIMAVANSERIN-RESISTANT” PARKINSON'S DISEASE PSYCHOSIS

Introduction The umbrella term “synucleinopathies” includes Parkinson's disease (PD), Dementia with Lewy bodies (DLB), Parkinson's disease-dementia (PDD), and Multiple System Atrophy (MSA), all of which share a similar pathogenesis, clinical presentation, and treatment plan. The shared clinical features include neurocognitive decline, autonomic dysfunction, parkinsonian motor features, and neuropsychiatric symptoms including depression, anxiety, and psychosis. Parkinson's Disease Psychosis (PDPsy) is best characterized by visual hallucinations. These psychotic symptoms can lead to impairments in activities of daily living, earlier nursing home placement, and caregiver burnout. The initial treatment plan for PDPsy usually involves a dose reduction of dopaminergic agents. If an acceptable reduction of psychotic symptoms is not achieved with this strategy, the use of an antipsychotic medication is often considered – usually clozapine, quetiapine, and now pimavanserin (a novel 5-HT2A inverse agonist). All of these agents share a minimal propensity to worsen parkinsonian motor symptoms. At present, there are no trials directly comparing clozapine and pimavanserin (the two agents with the best evidence base for PDPsy), making the choice of antipsychotic somewhat arbitrary. Methods Presented here is a case of PDPsy, wherein the patient's psychosis improved after a cross-titration from a dual-antipsychotic regimen of pimavanserin and quetiapine to a monotherapy regimen of clozapine. A review of the literature was gathered through October 2019 MEDLINE, EMBASE, and PsycINFO. Further studies found through this process were reviewed to identify additional reports. Results Mrs. KJ is a 62-year-old, married female with a medical history limited to idiopathic PD diagnosed in 2011. When first diagnosed, she developed an acute adjustment disorder and was treated with escitalopram. In January 2019, she was referred to our clinic for management of PDPsy that had begun in 2016. She described her psychosis as a “circus-menagerie” of animals living in her house as well as significant delusions of marital infidelity. Prior to our involvement, carbidopa-levodopa and ropinirole had been decreased, quetiapine had been initiated, and pimavanserin had been added, all with minimal resolution of psychosis. After discontinuing escitalopram and increasing the dose of quetiapine without benefit, a decision had to be made whether to abandon pimavanserin and try clozapine. The barriers to starting clozapine, including side effects, were weighed against its unknown comparative efficacy to pimavanserin. An eventual decision was made to initiate clozapine followed by the discontinuation of quetiapine and then pimavanserin. The “circus of animals” greatly decreased, and she gained insight into her delusions. The accompanying review resulted in 16 articles from MEDLINE, 29 from EMBASE and 4 from PsycINFO. While the literature supports clozapine's efficacy, there are frequent references to barriers to its initiation, including the need for frequent blood draws and the high potential side effect burden (though one of these potentially problematic side effects – its anticholinergic properties, may result in a reduced need for dopaminergic agents). There are no trials (open-label or otherwise) or case reports directly comparing clozapine to pimavanserin for PDPsy. Conclusions This is the first report of a successful titration from pimavanserin to clozapine for PDPsy. As access to pimavanserin increases, its use will expectedly increase, and it may become a first-line treatment for PSDsy. This case describes a potentially useful treatment strategy for the “pimavanserin-resistant” patient by demonstrating that a trial of clozapine after sub-optimal response to pimavanserin can lead to further symptom improvement. The decision to use antipsychotics for PDPsy should take a shared, patient-centered approach. For clozapine, this includes a discussion of its potential life-threatening side effects, the need for enrollment in a national REMS program, and its blood monitoring requirements. To date, there have been no head-to-head comparisons of clozapine with pimavanserin making the step-wise plan of when to initiate and/or abandon quetiapine, clozapine, or pimavanserin for PDPsy an unknown. This case adds to the shared decision-making process by providing evidence of the potential benefits of switching to clozapine when psychosis persists. Additional, large scale studies are needed to compare pimavanserin with other atypical antipsychotics, particularly clozapine. This research was funded by: Not applicable

Monitoring the Clinical Evolution of A Psychotic Patient Presenting A First-Schizophrenic Episode Thanks to Bimodal Oddball-P300 Event-Related Potentials: First Evidence from A Single-Case Study

Objective: Previous studies showed that a bimodal oddball design allows to increase the sensitivity of the P300 in subjects with anxious-depressive tendencies and patients presenting an adjustment disorder. In this case report we illustrate the increased sensitivity of a bimodal oddball task in the clinical follow-up of a patient presenting a psychosis in the context of a first onset schizophrenia. Method: The patient was instructed to detect deviant stimuli in three separate oddball tasks by hitting a button. Tasks comprised an auditory, a visual and a synchronized and congruent audio-visual block of stimuli. The peak-latency and the amplitude of the P300 evoked response were compared and confronted to scores of the clinical assessment. Results: Only the bimodal task mirrored the clinical evolution of the patient, as the reduction of psychotic symptoms was accompanied by an increase of the bimodal P300 amplitude. However, this was not true for both unimodal tasks (auditory and visual). Conclusions: A bimodal oddball design combined with unimodal ones could be necessary to monitor the joined clinical/neurophysiological evolution of a patient presenting a first onset psychosis. Significance: Further longitudinal studies applying the bimodal P300 paradigm should be designed in order to verify whether the oddball-bimodal P300 component could be used as “state” and/ or “trait” biological marker of the disease.

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics

BackgroundThe aims of this study were to explore the relationship between early reduction in psychotic symptoms and the ultimate response in patients with schizophrenia treated by atypical antipsychotics, and to determine the best time to switch or maitain the regimen. We also explore the possible predictors for the clinical response.MethodsOne hundred eleven inpatients with acutely exacerbated schizophrenia were randomized to give optimal therapy of olanzapine, risperidone, and paliperidone in one-week run-in period and 12 weeks’ intervention. All participants were assessed using Positive and Negative Syndrome Scale (PANSS). Early Response, defined as reduction of 25% in PANSS score, was examined at weeks 1, 2, 3, 4 and 8, and these ratings were used to predict ultimate response (25% PANSS reduction) at week 12. We hypothesized that early treatment response at Week 1 or 2 could predict Week 12’s treatment outcome.ResultsThe early treatment response at Week 2 had a greater negative prediction value (NPV, 93.6%) than did the response at Week 1 (NPV, 69.7%), Week 3 (NPV, 91.5%), Week 4 (NPV, 90.7%) and Week 8 (NPV, 87.2%). The positive predictive value became more acceptable (65%) until Week 4. There was no any other potential predictors, including types of antipsychotics medication and treatment dosage, were associated with ultimate response in this study.ConclusionThe treatment non-response at Week 2 optimally predicted the ultimate (Week 12) non-response, in terms of negative predictive value (NPV). These finding suggests that the revision of treatment strategy should be considered t if patients with schizophrenia was not responsive to them after 2 weeks’ treatment, and for those who are responders at Week 2, another two weeks are needed to further evaluate whether they will be continuously responsive.Trial registrationNCT03730857 at ClinicalTrial.gov. Date of registration: 30/Oct/2018.

Combination of Electroconvulsive Therapy and Clozapine in Treatment-Resistant Schizophrenia

ObjectiveThis study aimed to investigate the effectiveness and tolerability of the combination of electroconvulsive therapy (ECT) in patients with clozapine-treated schizophrenia. MethodsPatients with clozapine-treated schizophrenia during five years of pre-determined period were recruited from Electronic Medical Record. Clinical effects of acute ECT on psychotic symptoms were investigated. We also tried to identify predictive variables requiring maintenance treatment of ECT. ResultsFourteen patients received ECT and clozapine and sixteen were treated with clozapine alone. In the ECT group, which could be refined as clozapine-resistance, PANSS total score was significantly reduced by 19.0±9.9 points, corresponding to a reduction rate of 18.5±8.3%. The clinical remission defined as 20% PANSS reduction criteria was achieved at 42.9%. The subscale factors were significantly reduced, among which the negative symptom was the least. There was no difference in demographic and clinical information between patients receiving and not receiving maintenance ECT, and not all patients seemed to need maintenance ECT if clozapine is continued. ConclusionCombination of ECT and clozapine in patients with clozapine-resistant schizophrenia resulted in a rapid and substantial reduction of psychotic symptoms. Further studies are needed to improve the effectiveness and tolerability of ECT.