Functional single nucleotide polymorphisms in dopaminergic receptors D2 predict clinical response to Cariprazine.

Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of -2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment.

Effectiveness of crisis resolution home treatment for the management of acute psychiatric crises in Southern Switzerland: a natural experiment based on geography.

BACKGROUND: Crisis Resolution Home Treatment (CRHT) is an alternative to inpatient treatment for acute psychiatric crises management. However, evidence on CRHT effectiveness is still limited. In the Canton of Ticino (Southern Switzerland), in 2016 the regional public psychiatric hospital replaced one acute ward with a CRHT. The current study was designed within this evaluation setting to assess the effectiveness of CRHT compared to standard inpatient treatment. METHODS: CRHT was offered to patients aged 18 to 65 with an acute psychiatric crisis that would have required hospitalization. We used a natural experiment based on geography, where intervention and control groups were formed according to the place of residence. Primary endpoints were reduction of psychiatric symptoms at discharge measured using the Health of the Nation Outcome Scales, treatment duration in days, and rate and length of readmissions during a two-year follow-up period after discharge. Safety during the treatment period was measured with the number of serious adverse events (suicide/suicide attempts, major self-harm episodes, acute alcohol/drug intoxications, aggressions to caregivers or family members). We used linear, log-linear and logistic regression models with propensity scores for the main analysis. RESULTS: We enrolled 321 patients; 67 were excluded because the treatment period was too short and 17 because they were transferred before the end of the treatment. Two hundred thirty-seven patients were available for data analysis, 93 in the intervention group and 144 in the control group. No serious adverse event was observed during the treatment period in both groups. Reduction of psychiatric symptoms at discharge (p-value = 0.359), readmission rates (p-value = 0.563) and length of readmissions (p-value = 0.770) during the two-year follow-up period did not differ significantly between the two groups. Treatment duration was significantly higher in the treatment group (+ 29.6% on average, p-value = 0.002). CONCLUSIONS: CRHT was comparable to standard hospitalization in terms of psychiatric symptoms reduction, readmission rates and length of readmissions, but it was also characterized by a longer first treatment period. However, observational evidence following the study indicated that CRHT duration constantly lowered over time since its introduction in 2016 and became comparable to hospitalization, showing therefore to be an effective alternative also in terms of treatment length. TRIAL REGISTRATION: ISRCTN38472626 (17/11/2020, retrospectively registered).

Case Report: Long-Acting Oral Cariprazine.

Introduction: Cariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1-2 days and 2-3 weeks, respectively. Case Report: Here we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72-96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing. Discussion: Reported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a "oral long-acting" seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.

Home Treatment for Acute Mental Health Care: Protocol for the Financial Outputs, Risks, Efficacy, Satisfaction Index and Gatekeeping of Home Treatment (FORESIGHT) Study.

BACKGROUND: Crisis Resolution and Home Treatment (CRHT) teams represent a community-based mental health service offering a valid alternative to hospitalization. CRHT teams have been widely implemented in various mental health systems worldwide, and their goal is to provide care for people with severe acute mental disorders who would be considered for admission to acute psychiatric wards. The evaluation of several home-treatment experiences shows promising results; however, it remains unclear which specific elements and characteristics of CRHT are more effective and acceptable. OBJECTIVE: This study aims to assess the acceptability, effectiveness, and cost-effectiveness of a new CRHT intervention in Ticino, Southern Switzerland. METHODS: This study includes an interventional, nonrandomized, quasi-experimental study combined with a qualitative study and an economic evaluation to be conducted over a 48-month period. The quasi-experimental evaluation involves two groups: patients in the northern area of the region who were offered the CRHT service (ie, intervention group) and patients in the southern area of the region who received care as usual (ie, control group). Individual interviews will be conducted with patients receiving the home treatment intervention and their family members. CRHT members will also be asked to participate in a focus group. The economic evaluation will include a cost-effectiveness analysis. RESULTS: The project is funded by the Swiss National Science Foundation as part of the National Research Program NRP74 for a period of 48 months starting from January 2017. As of October 2021, data for the nonrandomized, quasi-experimental study and the qualitative study have been collected, and the results are expected to be published by the end of the year. Data are currently being collected for the economic evaluation. CONCLUSIONS: Compared to other Swiss CRHT experiences, the CRHT intervention in Ticino represents a unique case, as the introduction of the service is backed by the closing of one of its acute wards. The proposed study will address several areas where there are evidence gaps or contradictory findings relating to the home treatment of acute mental crisis. Findings from this study will allow local services to improve their effectiveness in a challenging domain of public health and contribute to improving access to more effective care for people with severe mental disorders. TRIAL REGISTRATION: ISRCTN registry ISRCTN38472626; https://www.isrctn.com/ISRCTN38472626. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28191.

Are Schizophrenic disorders with or without early cannabis use neurobiologically distinct disease entities? A meta-analysis of magnetic resonance imaging studies.

Cannabis use is considered an important risk factor for the development of psychotic illness and is associated with worse outcomes of the disorder. This study aimed to determine through a meta-analytic approach whether patients at the onset of schizophrenia with comorbid cannabis use (SCH CU+) show a different pattern of brain abnormalities as compared to patients with no comorbid cannabis use (SCH CU-). Ten Magnetic Resonance Imaging (MRI) studies were identified as suitable for analysis leading to the inclusion of n= 465 patients with schizophrenia (n= 227 SCH CU+ and n= 238 SCH CU-) and n= 366 healthy controls. Compared to healthy controls, both SCH CU+ and SCH CU- patients showed reduction of whole brain, total grey matter and hippocampal volumes. The direct comparison of SCH CU+ and SCH CU- patients, including up to 5 independent studies, did not demonstrate significant differences of brain volumes between the two groups even though total and regional grey matter volume deficits were more prominent in SCH CU+ patients. The available literature data indicate that, essentially, there is an overlap of brain abnormalities in SCH CU+ and SCH CU- patients at the onset of schizophrenia. The common vs specific trajectories of brain pathomorphology in SCH CU+ and SCH CU- patients are discussed.

Typologies of psychiatric admissions and length of inpatient stay in Italy.

OBJECTIVE: To describe admissions to an inpatient psychiatric unit in Italy over a two-year period and explore the influence of demographics, clinical variables and organisational and context-related factors on length of stay. METHODS: Data were obtained from clinical records and recorded by a psychiatrist through a proper checklist. RESULTS: Shorter admissions involved patients with personality disorders and substance use disorders. Greater illness severity and difficulties in setting a post-discharge programme were associated with longer admissions. CONCLUSIONS: Clinical, organisational and context-related factors all had significant effects on length of stay.

Association between CYP1A2 polymorphisms and clozapine-induced adverse reactions in patients with schizophrenia.

We investigated the relationships between common polymorphisms in CYP1A2 (CYP1A2(⁎)1C and (⁎)1F), CYP1A2-mRNA levels in circulating lymphocytes and clozapine(CLZ)-induced adverse drug reactions (ADRs) in 34 patients. Patients with ADRs had a higher frequency of CYP1A2 low activity allele combinations (8/12; 67%) and lower CYP1A2-mRNA levels than patients without ADRs (6/22; 27%, P=0.019).

Migrant pathways to community mental health centres in Italy.

BACKGROUND: Many studies indicate that migrants in western countries have limited access to and low utilization of community mental health centres (CMHCs) despite the high prevalence of mental disorders. AIMS: We aimed to compare migrant pathways to care across four CMHCs located in different Italian provinces and to identify pathway to care predictors. METHODS: Migrants attending the four CMHCs between 1 July 1999 and 31 December 2007 were included in the study. Data were gathered retrospectively from clinical data sets and chart review. RESULTS: Five hundred and eleven (511) migrants attended the four CMHCs, 61% were referred by GPs or other health services and 39% followed non-medical pathways to care (self-referral or through social and voluntary organizations), with important site variations. Younger age and being married were predictors of medical pathways to care; lacking a residence permit and having a diagnosis of substance abuse were related to non-medical pathways. CONCLUSIONS: Pathways to CMHCs are complex and influenced by many factors. Non-medical pathways to care seem to be frequent among migrants in Italy. More attention should be paid to developing psychiatric consultation liaison models that also encompass the social services and voluntary organizations.

Gluten encephalopathy with psychiatric onset: case report.

Many cases of coeliac disease, a gastrointestinal autoimmune disorder caused by sensitivity to gluten, can remain in a subclinical stage or undiagnosed. In a significant proportion of cases (10-15%) gluten intolerance can be associated with central or peripheral nervous system and psychiatric disorders.A 38-year-old man was admitted as to our department an inpatient for worsening anxiety symptoms and behavioural alterations. After the addition of second generation antipsychotic to the therapeutic regimen, the patient presented neuromotor impairment with high fever, sopor, leukocytosis, raised rhabdomyolysis-related indicators. Neuroleptic malignant syndrome was strongly suspected. After worsening of his neuropsychiatric conditions, with the onset of a frontal cognitive deficit, bradykinesia and difficulty walking, dysphagia, anorexia and hypoferraemic anaemia, SPET revealed a reduction of cerebral perfusion and ENeG results were compatible with a mainly motor polyneuropathy. Extensive laboratory investigations gave positive results for anti-gliadin antibodies, and an appropriate diet led to a progressive remission of the encephalopathy.