Alexandre González-Rodríguez

Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia: long-term safety, efficacy, and patient acceptability - a review.

Background and objectives Short-term studies focused on once-monthly paliperidone palmitate (PP) at doses of 25 mg eq, 50 mg eq, 75 mg eq, 100 mg eq, or 150 mg eq have shown its efficacy and tolerability in the treatment of schizophrenia patients. However, few open-label and long-term studies are available regarding this new pharmacological formulation. Thus, our main aim was to review the scientific evidence on efficacy, safety, tolerability, and preference of PP in these populations. Method Electronic searches were conducted by using PubMed and ISI Web of Knowledge databases. All relevant studies published from 2009 until January 2015 were included without any language restriction if patients met diagnostic criteria for schizophrenia, and adequate information on efficacy, safety, and tolerability of once-monthly PP was available. Results Nineteen studies were identified irrespective of the study design and duration of the follow-up period. Randomized, double-blind, placebo-controlled trials found that schizophrenia patients receiving PP showed a significant improvement in psychotic symptoms and similar adverse events compared to placebo and suggested that all doses of PP were efficacious and well tolerated. Other studies demonstrated noninferiority of PP compared to risperidone long-acting injectable in recently diagnosed schizophrenia patients, chronically ill patients, as well as in acute and nonacute symptomatic schizophrenia patients, and a similar proportion of treatment-emergent adverse events between both groups were also noted. Conclusion Several studies have demonstrated that schizophrenia patients treated with PP show higher rates of improvement of psychotic symptoms compared to placebo, and similar efficacy and tolerability outcomes were noted when comparing PP to risperidone long-acting injectable or oral, paliperidone extended release.

Influence of social cognition on daily functioning in schizophrenia: Study of incremental validity and mediational effects

While the role of impaired neurocognition in accounting for functional outcome in schizophrenia is generally established, the influence of social cognition on this relationship is far from clear. This study aims to explore in depth the nature of the relationship between neurocognition, social cognition and daily functioning in people with schizophrenia. Twenty-one individuals diagnosed with schizophrenia and 15 controls completed the assessment of symptom severity, neuropsychological status, social cognition (Theory of Mind and affect processing) and other functional measures. A statistical mediation model based on hierarchical regression analyses was used to establish the mediation path with significant variables. Social cognition played a mediating role between neurocognition and functioning, accounting for significant trends in incremental variance in specific functional indexes (interpersonal behavior and employment/occupation). Consequently, this study adds to the evidence underlining the importance of targeting not only social cognitive or neurocognitive functions but to combine both interventions to reveal the best daily functioning results in schizophrenia patients.

Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.

Background The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia. Methods Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response. Results Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms. Discussion Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.

Suicidal Ideation and Suicidal Behaviour in Delusional Disorder: A Clinical Overview

Background. Most of the existing studies suggest that suicide is one of the leading causes of premature death in patients with chronic psychotic disorders. However, very few studies have specifically investigated suicidal behaviour in patients with delusional disorder. Thus, our objective was to review the literature regarding the percentage of lifetime ideation and suicidal behaviour in delusional disorder in order to provide suggestions for clinical practice. Methods. MEDLINE and PsycINFO were searched from January 1980 to September 2012 using the following keywords: delusional disorder, paranoia, suicidal ideation, and suicidal behaviour. Results. A total of 10 studies were identified and included in the review. The percentage of suicidal behaviour in delusional disorder was established between 8 and 21%, which is similar to schizophrenia. Suicidal ideation and suicide attempts were more frequent in patients showing persecutory and somatic delusions in the reviewed studies. Conclusions. To the best of our knowledge this is the first attempt to specifically review the suicide phenomenon in patients with delusional disorder. Interestingly, our results support the notion that percentages of both suicidal ideation and behaviour in delusional disorder are similar to patients with schizophrenia.

Effectiveness of long-acting injectable antipsychotics in delusional disorders with nonprominent hallucinations and without hallucinations.

The presence of nonprominent hallucinations in delusional disorder (DD) has been accepted by the current Diagnostic and Statistical Manual of Mental Disorders, 5th ed. A recent meta-analysis revealed that patients with schizophrenia treated with long-acting atypical antipsychotics showed a significant improvement in psychotic symptoms. However, little research has been conducted on DD. Our goal was to investigate demographic and clinical differences between two subgroups of DD patients, those with nonprominent hallucinations and those without hallucinations, and to determine treatment effectiveness of long-acting antipsychotics in these patients. We conducted a longitudinal observational study with a 6-month follow-up period in a clinical group of 45 DD outpatients. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale, and Hamilton Rating Scale for Depression-17 (HRSD-17) were used for assessment. Age at onset of DD, scores in baseline assessment scales, and drug compliance were included in the analysis as potential confounders. When uncorrected for influencing factors, patients treated with long-acting antipsychotics showed lower scores in PANSS positive and negative subscales. There were no statistically significant clinical subgroup×treatment group interactions for any of the scores in assessment scales at 6 months. After adjustment, patients treated with long-acting antipsychotics showed lower scores in the PANSS negative subscale and a tendency toward improvement in scores in the PANSS positive subscale. Our study suggests that risperidone long-acting injection and paliperidone palmitate long-acting injection may be useful in the treatment of DD patients, specifically those with nonprominent hallucinations.

Delusional disorder: no gender differences in age at onset, suicidal ideation, or suicidal behavior

OBJECTIVE To investigate gender differences in age at onset, psychopathology, and suicidal behavior rates in delusional disorder (DD). METHODS We conducted a prospective longitudinal study of 97 patients with DD. Demographic and clinical data at baseline were recorded. Gender differences were investigated by applying analysis of covariance, using age at onset and age at first psychiatric consultation as dependent variables, comorbid depression and gender as between-subject factors, and employment status, social support, and DD types as covariates. RESULTS Seventy-six percent of the patients were women. The average age at onset was 48.76 ± 12.67 years, mean age at first psychiatric consultation was 54.13 ± 13.67 years, and men were more likely to be employed than women (p = 0.041). Despite the earlier age at onset and at first psychiatric consultation in men, these differences tended to disappear when adjusted for potential confounders. There were no significant gender differences in depressive comorbidity, presence of suicidal ideation and behavior, or compliance rates at follow-up. CONCLUSIONS Our findings could not confirm that male and female DD patients differ in age at onset, age at first psychiatric consultation, or suicidal ideation and behavior, even after controlling for potential confounders.

The search for new biomarkers for cognition in schizophrenia

The search for biomarkers in cognition has been the focus of a large part of the research on patients suffering from schizophrenia. The scientific literature is heterogeneous, and few studies establishing an integrative model of pathogenesis and therapeutic response are available in this field. In this review, we aimed to summarize three essential aspects correlated with cognitive performance: 1) the relationship between inflammation and cognition in schizophrenia, 2) the role of prolactin in cognition, and 3) the association between cognition and neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF). Several studies support the association of inflammatory markers with cognitive status in schizophrenia. In recent decades, the development of effective therapies for cognitive impairment in schizophrenia has focused on the search for anti-inflammatory and immunomodulatory medications. Conversely, the implications of prolactin and its functions in cognition, the transition to psychosis and the diagnosis and prognosis of schizophrenia have been established independent of antipsychotic treatment. With regard to neurotrophic factors, a recent study has correlated BDNF levels with cognitive recovery in schizophrenic patients treated with cognitive remediation. We conclude that although there is a diversity of biomarkers focused on cognitive function in schizophrenia, BDNF is the biomarker that has accumulated the vast majority of evidence in the current literature.

Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and critical review

AIM To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia. METHODS A systematic, computerised literature search was conducted in the PubMed/Medline and PsychInfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [(“cogniti*” and “remediation” or “training” or “enhancement”) and (“fMRI” or “MRI” or “PET” or “SPECT”) and (schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included. RESULTS A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimaging studies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless, great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of whole-brain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive, functional and structural improvements tended to be positively correlated. CONCLUSION Neuroimaging studies of cognitive remediation in patients with schizophrenia suggest a positive effect on brain functioning in terms of the functional reorganisation of neural networks.

Delusional disorder: an overview of affective symptoms and antidepressant use

Background and Objectives: In clinical practice, the coexistence of delusions and affective symptoms is often observed. The current Diagnostic and Statistical Manual of Mental Disorders, fourth edition- Text Revision (DSM-IV-TR) accepts the existence of mood disturbances in delusional disorder. Little research has been done regarding this field and prevalence rates are unclear. Our purpose was to review the frequency of affective symptoms in delusional disorder patients and to identify the proportion of these patients that are reported to be treated with antidepressants. Methods: Three electronic databases were searched from 1980 to July 2012: MEDLINE, PsycINFO and PubMed, using the following keywords: delusional disorder, depression, affective illness, antidepressants and paranoia. Results: A high frequency of affective disturbances was found in this population (21- 55.8%). In contrast, a low antidepressants prescription rate was shown. When focusing on delusional disorder somatic subtype, a particularly high mood disorder comorbidity rate was described and a good efficacy of antidepressant drugs was reported, in monotherapy or in combination with antipsychotics. Conclusions: A high frequency of comorbid depression in delusional disorder and a low antidepressants prescription rate could be concluded. Further studies are needed to better clarify the role of mood symptoms in clinical practice among delusional disorder patients.

Delusional Disorder over the Reproductive Life Span: The Potential Influence of Menopause on the Clinical Course.

Background and Objectives. Recent evidence supports an association between estrogen levels and severity of psychopathology in schizophrenia women. Our main goal was to investigate whether delusional disorder (DD) women with premenopausal onset and those with postmenopausal onset differ in demographic and clinical features. Methods. Psychopathological symptoms were assessed in 80 DD women (DSM-IV-TR), at baseline and after six and 24 months. Scores in the PANSS, PSP for functionality, HRSD 17 items, C-SSRS for suicide, and the SUMD were considered outcome variables. For comparison purposes, t- and χ 2-tests were performed and nonparametric tests when necessary. Analysis of Covariance (ANCOVA) was conducted for multivariate comparisons. Results. 57 out of 80 DD women completed the study. When unadjusted, DD with premenopausal onset had a longer DUP, higher educational level, and a tendency toward higher rates of gynaecological disorders. Erotomanic type was most frequent in DD women premenopausal onset, and somatic and jealous types were most frequent in those with postmenopausal onset. After 24 months, DD women with premenopausal onset showed higher depressive symptoms and a tendency toward higher rates of psychotic relapses. Conclusions. Our results support that some aspects of psychopathology and insight may differ according to the onset of DD and the reproductive status.