Real-life effectiveness of transitioning from paliperidone palmitate 1-monthly to paliperidone palmitate 3-monthly long-acting injectable formulation.

Background: Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. Objectives: The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. Methods: This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Results: Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. Conclusion: These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.

Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings.

BACKGROUND: Highly prevalent in schizophrenia, tobacco smoking substantially increases the risk of cardiac-related death. Compared to the general population, tobacco smoking cessation rates are lower in schizophrenia. Unfortunately, the reasons for these low cessation rates remain poorly understood. Recently, it has been shown that tobacco cravings are increased in schizophrenia smokers compared to smokers with no comorbid psychiatric disorder. In view of these results, we sought to examine - for the first time - the neurophysiologic responses elicited by cigarette cues in schizophrenia smokers. We hypothesized that cigarettes cues would elicit increased activations in brain regions involved in drug cravings in schizophrenia smokers relative to control smokers. METHODS: Smokers with (n=18) and without (n=24) schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging (fMRI) while viewing appetitive cigarette images. RESULTS: Schizophrenia smokers and smokers with no psychiatric comorbidity did not differ in subjective cravings in response to appetitive smoking cues. However, in schizophrenia smokers relative to control smokers, we found that appetitive cigarette cues triggered increased activations of the bilateral ventro-medial prefrontal cortex, a core region of the brain reward system. Moreover, a negative correlation was observed between cigarette cravings and activations of the right ventro-medial prefrontal cortex in schizophrenia smokers. DISCUSSION: The current results highlight a key role of the brain reward system in cigarette craving in schizophrenia, and suggest that the neurophysiologic mechanisms involved in the regulation of cue-induced cigarette craving are impaired in this population.

Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits.

OBJECTIVE: Although new atypical antipsychotic agents have been found to improve overall cognitive function in patients with schizophrenia (SZ), some aspects of memory, attention and executive functions still remain impaired. Acetylcholinesterase (AChE) inhibitors, such as rivastigmine, have been shown to improve cognition in other disorders, particularly Alzheimer's disease. Dysfunctions in cholinergic systems, especially in the prefrontal cortex, have been identified in SZ, suggesting that cholinesterase inhibitors may be effective in treating cognitive deficits in this disease. RESEARCH DESIGN AND METHODS: Using a randomized crossover design, we assessed SZ patients with stable symptoms and poor cognitive functioning. Fifty-eight patients with memory deficits, according to subjective complaints or based on clinicians' observations, were assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Only 24 of these subjects met the inclusion criteria. Twenty patients took part in the study (four dropped out). All subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for SZ were maintained on their current antipsychotic medication (18 atypicals and two typicals) and were randomly assigned to treatment with rivastigmine. Dosage was a function of tolerability, beginning at 3 mg/day and progressively increasing to 9 mg/day. Subjects were given the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and 3 and 6 months. RESULTS: The results revealed no significant improvement in any of the cognitive variables investigated following rivastigmine treatment and symptom severity scores remained unchanged over all recorded time periods. CONCLUSION: Rivastigmine treatment did not appear to enhance cognition in SZ patients with important cognitive impairments. This finding needs to be interpreted with care and requires substantiation with larger sample size studies with patients treated with cognitive enhancer for longer periods.