Metacognition in schizophrenia: A practical overview of psychometric metacognition assessment tools for researchers and clinicians

Metacognition refers to the cognitive ability to control, monitor and modulate cognitive processes thus guiding and orienting behavior: a continuum of mental activities that ranges from more discrete ones, such as the awareness of the accuracy of others’ judgment, to more integrated activities, such as the knowledge of cognitive processes. Metacognition impairment in schizophrenia, which is considered a core feature of the illness, has become a growing research field focusing on a wide range of processes including reasoning, autobiographical memory, memory biases, cognitive beliefs and clinical insight. There is a well-established relationship between metacognition and schizophrenia symptoms severity, as well as between impaired metacognitive functioning and specific symptomatic sub-domains, such as positive symptoms, negative symptoms, or disorganization. The development of specific cognitive-derived psychotherapies for metacognitive deficits in schizophrenia has been ongoing in the last years. Although sharing a metacognitive feature, these treatments focus on different aspects: false or unhelpful beliefs for metacognitive therapy; cognitive biases for metacognitive training; schematic dysfunctional beliefs for cognitive behavioral therapy (CBT) for psychoses; metacognitive knowledge and sense of identity for MERIT; interpersonal ideas or events triggering delusional thinking for MIT-P. This article reviews the instruments designed to assess metacognitive domains and functions in individuals with schizophrenia, providing mental health professionals with an overview of the heterogeneous current scenario ranging from self-administered scales to semi-structured interviews, which are supported by a variety of theoretical frameworks. Future directions may address the need for more specific and refined tools, also able to follow-up psychotherapeutic-induced improvements

A Systematic Review on the Effectiveness of Antipsychotic Drugs on the Quality of Life of Patients with Schizophrenia

Pharmacological antipsychotic drug interventions represent the cornerstone of the management of patients with schizophrenia and other psychotic spectrum disorders. The choice of the “best” treatment should be made on the basis of several clinical domains. However, despite available treatments, the quality of life reported by patients with schizophrenia taking antipsychotics is still very poor, and this outcome is rarely taken into account in trials assessing the efficacy and effectiveness of antipsychotic treatments. Therefore, we performed a systematic review in order to assess the impact of antipsychotic treatment on patients’ quality of life. In particular, we aimed to identify any differences in the improvement in quality of life according to the (a) type of formulation of antipsychotic drugs (i.e., oral vs. depot vs. long-acting injectable); (b) type of the drug (first vs. second vs. third generation); and (c) patients’ clinical characteristics. One hundred and eleven papers were included in the review. The main findings were as follows: (1) quality of life is usually considered a secondary outcome in trials on the efficacy and effectiveness of drugs; (2) second-generation antipsychotics have a more positive effect on quality of life; and (3) long-acting injectable antipsychotics are associated with a more stable improvement in quality of life and with a good safety and tolerability profile. Our systematic review confirms that quality of life represents a central element for selecting the appropriate treatment for people with schizophrenia. In particular, the availability of new treatments with a better tolerability profile, a proven effectiveness on patients’ cognitive and social functioning, and with a more stable blood concentration might represent the appropriate strategy for improving the quality of life of people with schizophrenia

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group

Introduction: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still unclear. Objectives: To evaluate the efficacy and tolerability of ESK-NS in older subjects with TRD. Methods: This is a post-hoc analysis of the REAL-ESK study, a multicenter, retrospective, observational study. Participants here selected were 65 years or older at baseline. The Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms, respectively. Data were collected at three-time points: baseline, 1 month after the start of treatment (T1), and 3 months after treatment (T2). Results: The sample included older adults with TRD (n = 30). MADRS and HAM-A values decreased significantly at T1 (T0 versus T1: pholm <0.001, Cohen's d = 0.840) and T2 follow-ups (T0 versus T2: pholm <0.001, Cohen's d = 1.419). At T2, 53.3% of subjects were responders (MADRS score reduced ≥50%), while 33.33% were in remission (MADRS<10). ESK-NS-related adverse effects were in order of frequency dizziness (50%), followed by dissociation (33.3%), sedation (30%), and hypertension (13.33%). Six out of 30 participants (20%) discontinued treatment. Conclusions: Our findings provide preliminary evidence of ESK-NS effectiveness in older adults with TRD, a highly debilitating depressive presentation. Furthermore, we observe high levels of treatment-emergent adverse events, which, in the majority of instances, did not require treatment suspension

The effect of paliperidone palmitate long-acting injectable (PP-LAI) on "non-core" symptoms of schizophrenia. a retrospective, collaborative, multicenter study in the "real world" everyday clinical practice

Background. Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. Aim. The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. Results. Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. Discussion. The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. Conclusions. PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings

Real-world experience of esketamine use to manage treatment-resistant depression: a multicentric study on safety and effectiveness (REAL-ESK study)

Background: Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings.Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services.Methods: REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups.Results: A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities.Limitations: The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale.Conclusions: Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings

Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study)

Background: Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings.Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services.Methods: REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups.Results: A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities.Limitations: The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale.Conclusions: Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings

Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa.

The endocannabinoid system, consisting of two cannabinoid receptors (CB1 and CB2) and the endogenous ligands anandamide (arachidonoylethanolamide (AEA)) and 2-arachidonoylglycerol (2-AG), has been shown to control food intake in both animals and humans, modulating either rewarding or quantitative aspects of the eating behavior. Moreover, hypothalamic endocannabinoids seem to be part of neural circuitry involved in the modulating effects of leptin on energy homeostasis. Therefore, alterations of the endocannabinoid system could be involved in the pathophysiology of eating disorders, where a deranged leptin signalling has been also reported. In order to verify this hypothesis, we measured plasma levels of AEA, 2-AG, and leptin in 15 women with anorexia nervosa (AN), 12 women with bulimia nervosa (BN), 11 women with binge-eating disorder (BED), and 15 healthy women. Plasma levels of AEA resulted significantly enhanced in both anorexic and BED women, but not in bulimic patients. No significant change occurred in the plasma levels of 2-AG in all the patients' groups. Moreover, circulating AEA levels were significantly and inversely correlated with plasma leptin concentrations in both healthy controls and anorexic women. These findings show for the first time a derangement in the production of the endogenous cannabinoid AEA in drug-free symptomatic women with AN or with BED. Although the pathophysiological significance of this alteration awaits further studies to be clarified, it suggests a possible involvement of AEA in the mediation of the rewarding aspects of the aberrant eating behaviors occurring in AN and BED