Lurasidone Augmentation of Clozapine in Refractory Schizophrenia: A Case Series.

PURPOSE: Clozapine represents the criterion standard therapy for patients with treatment-resistant schizophrenia. Unfortunately, a significant percentage of such patients are also partial responders to clozapine. Consequently, several augmentation strategies have been proposed with various and sometimes controversial efficacy. Among these add-on treatments, lurasidone has been recently introduced and could represent a potential option, especially for the additional positive effect on cognitive symptoms. METHODS: This case series aims to determine possible advantages of lurasidone augmentation in four patients treated with clozapine, who were diagnosed with treatment-resistant schizophrenia. Positive and Negative Syndrome Scales were used to evaluate psychopathology, the Udvalg for Kliniske Undersøgelser scale for tolerability and safety. FINDING: All patients achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported. IMPLICATIONS: Our observation suggests that lurasidone can lead to clinically significant improvements in psychopathology with a good tolerability profile when added to clozapine.

Understanding source monitoring subtypes and their relation to psychosis: a systematic review and meta-analysis.

AIMS: Source monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy controls classifying SM subtypes by source discrimination (internal/external/reality monitoring) and stimulus modality (visual/auditory/imagined/performed). METHODS: This systematic review adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Meta-analyses Of Observational Studies in Epidemiology and Population, Intervention, Comparison and Outcomes guidelines. Core demographical and clinical parameters were extracted. Newcastle-Ottawa Scale was used as quality check. SM differences between (i) psychosis patients versus healthy controls and (ii) patients with versus without hallucinations were investigated via random-effect model meta-analysis. The primary effect size measure was standardized mean difference (SMD) in each SM subtype performance (error or accuracy). Heterogeneity, publication biases and meta-regressions were assessed. RESULTS: Five thousand two hundred and fifty-six records were screened to finally include 44 studies (1566 patients, 1175 controls). Mean Newcastle-Ottawa score was 7.41 out of 9. Few studies measured SM associations with cognition (n = 9) and symptoms (n = 19), with heterogeneous findings. SM performance across all measures was reduced in psychosis versus healthy controls (SMD = 0.458). Internal SM (SMD: errors = 0.513; accuracy = 0.733) and imagined stimuli (SMD: errors = 0.688; accuracy = 0.978) were specifically impaired. Patients with versus without hallucinations showed SM deficits only for externalizing (SMD = 0.410) and imagined/auditory (SMD = 0.498/0.277) errors. CONCLUSION: The proposed classifications highlight specific SM deficits for internal/imagined stimuli in psychosis, providing evidence-based indications to design and interpret future studies.

Cognitive Effects of Lurasidone and Cariprazine: A Mini Systematic Review.

Cognitive deficits are associated with schizophrenia and show a progressive worsening, often being unresponsive to treatment. New antipsychotic molecules acting as antagonist at the serotoninergic 5-hydroxytryptamine receptor 7 (e.g. lurasidone) or partial agonists at dopamine D3 receptor (e.g. cariprazine) could have an impact on cognition in this patient group. The aim of the systematic review is to explore the efficacy of lurasidone and cariprazine in improving cognition in both animal models and human studies. The following terms: (lurasidone AND cognit*) OR (cariprazine AND cognit*) were searched in Web of Science from inception to December 2021. We included all studies that assessed changes in cognitive function after treatment with cariprazine or lurasidone. Of 201 selected articles, 36 were included. Twenty-four articles used animal models (rats, mice and marmosets), five evaluating the effects of cariprazine and 19 the effects of lurasidone. Twelve articles were clinical studies (cariprazine n = 2; lurasidone n = 10). In both animal and human studies lurasidone showed a greater efficacy on cognitive performance compared to placebo, quetiapine, ziprasidone or treatmentas- usual. Cariprazine was superior to other antipsychotics in improving cognitive functions in both animal and human studies. The cognitive effect of lurasidone could be explained by its potent antagonism at the 5-HT7 receptors combined with partial agonism at 5-HT1A receptors. The pro-cognitive effect of cariprazine is probably explained by its very high affinity for D3 receptors. Head-to-head studies comparing lurasidone and cariprazine are needed to establish the "first-choice" treatment for cognitive dysfunction associated with schizophrenia.

Use of intranasal esketamine in a girl with treatment-resistant depression and autism spectrum disorders: a case report.

Major depression is a common comorbidity in autism spectrum disorder (ASD), often difficult to identify and to treat. Autistic subjects are more at risk for suicidal thoughts and behaviors compared to typically developing peers. Unfortunately, ASD individuals are more frequently treatment-resistant and often show side-effects which reduce efficacy. Intranasal esketamine has been recently approved as an add-on medication for treatment-resistant depression (TRD), but it has never been used in ASD with comorbid major depression. Of note, a pilot study of intranasal ketamine has shown no effect on social withdrawal in ASD without depression. The present case report describes the first girl with ASD and comorbid TRD treated with intranasal esketamine.

Two Faces of a Coin? A Systematic Review of Source Monitoring and Its Relationship with Memory in Autism.

The ability to discriminate the origin of stimuli, known as source monitoring, is crucial for self-other distinction and the integration of internally generated and externally generated experiences. Despite its valence, evidence on source monitoring in autism is yet scarce and unclear. We systematically reviewed literature concerning source monitoring in autism and its relationship with other constructs, such as memory type, encoding effects, social cognition, general intelligence, and clinical factors. Source-monitoring performance (operationalized as error or accuracy) was reduced in autistic participants in 9 of the 15 studies that met the inclusion criteria. When explicitly investigated, free-recall memory impairments in autism were shown to influence source monitoring deficits. General intelligence was another important factor linked to source-monitoring performance. Conversely, other memory types or encoding effects were not impaired in autism, and no univocal association could be found with source monitoring. Social cognition and clinical symptoms were rarely assessed in spite of their possible involvement in source monitoring. The heterogeneity of the task design, outcome measures and demographical factors limited study comparability. As a research framework on source monitoring as a construct of primary interest in autism is still lacking, we propose preliminary indications for future investigations based on the collected findings.