Motivations for and Experiences With Antipsychotic Tapering Among Patients With Schizophrenia Seeking Guided Dose Reduction.

Objective: Over time, most patients with schizophrenia wish to reduce or discontinue their antipsychotic medication treatment. In Denmark, a specialized government-funded outpatient clinic was established to offer guided antipsychotic dose reduction. This study aimed to provide data on motivations for and previous experiences with antipsychotic tapering among patients attending the clinic.

Deprescribing antipsychotics in patients with schizophrenia: findings from a specialized clinic.

Background: While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic.

The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta-analysis.

Background: Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic-induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.

Method: A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness.

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Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse prevention. However, the pharmacokinetic properties of LAI greatly differ from oral antipsychotics. This necessitates an increased knowledge about LAI among clinicians, especially when commencing treatment, changing doses and discontinuing treatment.

Functional Connectivity Between Auditory and Medial Temporal Lobe Networks in Antipsychotic-Naïve Patients With First-Episode Schizophrenia Predicts the Effects of Dopamine Antagonism on Auditory Verbal Hallucinations.

Background: Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVHs) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response.

Methods: This case-control study included examinations at baseline and at follow-up after 6 weeks. Initially, antipsychotic-naïve patients with first-episode schizophrenia who were experiencing AVHs were recruited together with healthy control participants.

Clinical response to treatment with a partial dopamine agonist is related to changes in reward processing.

Aberrant neuronal coding of reward processing has been linked to psychosis. It remains unresolved how treatment with a partial dopamine agonist affects reward processing, and whether treatment affects reward processing differently in patients responding and not responding to treatment. Here, 33 antipsychotic-naïve psychosis patients and 33 matched healthy controls underwent functional magnetic resonance imaging before and after patients received aripiprazole monotherapy for six weeks.

Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels.

Background: Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation.

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry).

Introduction: Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity.

Reward Processing as an Indicator of Vulnerability or Compensatory Resilience in Psychoses? Results From a Twin Study.

Background: Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where 1 twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this.

Methods: We used Danish registries to identify twin pairs with at least 1 twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex, and zygosity.

Dopamine Synthesis Capacity and GABA and Glutamate Levels Separate Antipsychotic-Naïve Patients With First-Episode Psychosis From Healthy Control Subjects in a Multimodal Prediction Model.

Background: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects.

Methods: We included 23 patients (mean age 22.

Differential Effects of Aripiprazole and Amisulpride on Negative and Cognitive Symptoms in Patients With First-Episode Psychoses.

Introduction: Aripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses.

Dopaminergic Activity in Antipsychotic-Naïve Patients Assessed With Positron Emission Tomography Before and After Partial Dopamine D Receptor Agonist Treatment: Association With Psychotic Symptoms and Treatment Response.

Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of F-DOPA to F-dopamine (k) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D receptor agonist (aripiprazole) on k and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method.

Associations Between Cognitive Function and Levels of Glutamatergic Metabolites and Gamma-Aminobutyric Acid in Antipsychotic-Naïve Patients With Schizophrenia or Psychosis.

Background: Abnormal glutamate and GABA (gamma-aminobutyric acid) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naïve patients.

Methods: In total, 56 antipsychotic-naïve patients with schizophrenia or psychotic disorder and 51 healthy control subjects underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (Glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and Glx levels in left thalamus.

Associations of neural processing of reward with posttraumatic stress disorder and secondary psychotic symptoms in trauma-affected refugees.

: Psychological traumatic experiences can lead to posttraumatic stress disorder (PTSD). Secondary psychotic symptoms are not common but may occur. : Since psychotic symptoms of schizophrenia have been related to aberrant reward processing in the striatum, using the same paradigm we investigate whether the same finding extends to psychotic and anhedonic symptoms in PTSD.

Differential effects of age at illness onset on verbal memory functions in antipsychotic-naïve schizophrenia patients aged 12-43 years.

Background: The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition.

Methods: The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset.

Increased use of coercive procedures and prolonged hospitalization in compulsory admitted psychotic patients, who refuse antipsychotic medication.

Current Danish legislation imposes that compulsory admitted psychotic patients have the right to refuse antipsychotic medication, which markedly delays pertinent medical treatment. In a retrospective, observational cohort study, we analyzed data from a 1-year period on 34 consecutively admitted patients with schizophrenia, who had been compulsory admitted due to need of treatment, or because they were judged to constitute an acute danger to themselves or others. We compared the use of other coercive procedures and hospitalization time.

Validation of the Danish version of the brief negative symptom scale.

: The Brief Negative Symptom Scale (BNSS) is an instrument for evaluating negative symptoms (NS) in schizophrenia based on the 2005 consensus statement by the National Institute of Mental Health. This study examines the validity and reliability of the Danish version of BNSS. : Acutely and chronically affected patients with schizophrenia or schizoaffective disorder were assessed with BNSS along with other psychopathological scales and clinical measures.

The relation between dopamine D receptor blockade and the brain reward system: a longitudinal study of first-episode schizophrenia patients.

Background: Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.

Associations between cortical thickness and auditory verbal hallucinations in patients with schizophrenia: A systematic review.

Auditory verbal hallucinations are common symptoms in schizophrenia patients, and recent magnetic resonance imaging studies have suggested associations between cortical thickness and auditory verbal hallucinations. This article summarises the associations between cortical thickness reduction and auditory verbal hallucinations, conceptualising the findings based on the Research Domain Criteria framework. Six studies identified in a systematic literature search were included in the review.

Alterations of Intrinsic Connectivity Networks in Antipsychotic-Naïve First-Episode Schizophrenia.

Background: The investigation of large-scale intrinsic connectivity networks in antipsychotic-naïve first-episode schizophrenia increases our understanding of system-level cerebral dysfunction in schizophrenia while enabling control of confounding effects of medication and disease progression. Reports on functional connectivity in antipsychotic-naïve patients have been mixed and the relation between network alterations, psychopathology and cognition is unclear.

Methods: A total number of 47 patients with first-episode schizophrenia who had never received antipsychotic medication and 47 healthy controls were scanned with functional magnetic resonance imaging under resting conditions.

Negative Symptoms and Reward Disturbances in Schizophrenia Before and After Antipsychotic Monotherapy.

Background: Negative symptoms (NS) are a central part of the symptomatology of schizophrenia, which is highly correlated to the functional outcome. Disturbances of the brain reward system are suggested to be central in the pathogenesis of NS by decreasing motivation and hedonic experiences. In this study, we compared reward-related brain activity in patients improving and not improving in NS after treatment with amisulpride.

Striatal D(2/3) Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome.

One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being.