Psychotic patients are a vulnerable population from a social and health point of view. The SARS Cov-2 pandemic affected millions of people around the world, however, its effects on psychotic patients in Avilés Spain, have not been analized.

The objective of this study was to determine and compare the mortality of patients with psychosis due to SARS Cov-2 in Avilés, Spain with others regions and countries in the European Union. Determine the influence of social condition and antipsychotic treatment on the condition of these patients.

This is a descriptive, observational study, in which patients diagnosed with psychosis in the period 2020-2021 who contracted SARS Cov-2 infection in Avilés, Spain, were studied to determine those who died from this cause. The influence of social status and antipsychotic medication, as well as sociodemographic factors (age, sex, marital status) were analyzed and compared with other regions and countries of the European Union.

Despite the high mortality rate in patients with psychosis, during the years of the pandemic SARS Cov-2 played an important role given the vulnerability of these patients.

The negative effects and deaths during the COVID-19 pandemic were at the time a major problem for public health worldwide. This study concluded that the morbidity and mortality of psychotic patients who contracted COVID-19 was lower than the rest of the population.

None Declared

Pregabalin is indicated for the treatment of GAD in adults in Europe. The efficacy and safety of pregabalin for the treatment of adults and elderly patients with GAD has been demonstrated in 6 of 7 short-term clinical trials of 4 to 8 weeks.

To characterise the long-term efficacy and safety of pregabalin in subjects with GAD.

Subjects were randomised to double-blind treatment with either high-dose pregabalin (450-600 mg/d), low-dose pregabalin (150-300 mg/d), or lorazepam (3-4 mg/d) for 3 months. Treatment was extended with drug or blinded placebo for a further 3 months.

At 3 months, mean change from baseline Hamilton Anxiety Rating Scale (HAM-A) for pregabalin high- and low-dose, and for lorazepam ranged from -16.0 to -17.4. Mean change from baseline Clinical Global Impression-Severity (CGI-S) scores ranged from -2.1 to -2.3 and mean CGI-Improvement (CGI-I) scores were 1.9 for each active treatment group. At 6 months, improvement was retained for all 3 active drug groups, even when switched to placebo. HAM-A and CGI-S change from baseline scores ranged from -14.9 to -19.0 and -2.0 to -2.5, respectively. Mean CGI-I scores ranged from 1.5 to 2.3. The most frequently reported adverse events were insomnia, fatigue, dizziness, headache, and somnolence.

Efficacy was observed at 3 months, with maintained improvement in anxiety symptoms over 6 months of treatment. These results are consistent with previously reported efficacy and safety trials of shorter duration with pregabalin and lorazepam in subjects with GAD.

This study was funded by Pfizer Inc.

Pregabalin is indicated for the treatment of generalised anxiety disorder (GAD) in adults in Europe. When pregabalin is discontinued, a 1-week (minimum) taper is recommended to prevent potential discontinuation symptoms.

To evaluate whether a 1-week pregabalin taper, after 3 or 6 months of treatment, is associated with the development of discontinuation symptoms (including rebound anxiety) in subjects with GAD.

Subjects were randomised to double-blind treatment with low- (150-300 mg/d) or high-dose pregabalin (450-600 mg/d) or lorazepam (3-4 mg/d) for 3 months. After 3 months ~25% of subjects in each group (per the original randomisation) underwent a double-blind, 1-week taper, with substitution of placebo. The remaining subjects continued on active treatment for another 3 months and underwent the 1-week taper at 6 months.

Discontinuation after 3 months was associated with low mean changes in Physician Withdrawal Checklist (PWC) scores (range: +1.4 to +2.3) and Hamilton Anxiety Rating Scale (HAM A) scores (range: +0.9 to +2.3) for each pregabalin dose and lorazepam. Discontinuation after 6 months was associated with low mean changes in PWC scores (range: -1.0 to +3.0) and HAM A scores (range: -0.8 to +3.0) for all active drugs and placebo. Incidence of rebound anxiety during pregabalin taper was low and did not appear related to treatment dose or duration.

A 1-week taper following 3 or 6 months of pregabalin treatment was not associated with clinically meaningful discontinuation symptoms as evaluated by changes in the PWC and HAM A rating scales.

This study was funded by Pfizer Inc.

The use of second-generation antipsychotic (SGA) treatments in psychosis has been associated with metabolic changes. However, there are differences in metabolic profile between SGAs. In a previous study conducted in our sample of first episode psychosis patients, we observed that the ziprasidone had a more benign metabolic profile compare to aripiprazole and quetiapine, at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.

The aim of this study was to investigate if the differentiated metabolic profile of aripiprazole, ziprasidone and quetiapine observed at short-term is maintained after 1 year of treatment in a sample of drug-naïve patients with a first episode of psychosis.

One hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to receive quetiapine, ziprasidone or aripiprazole. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.

No significant differences between antipsychotic groups (all F < 2.61; P > 0.05) were found in any of the metabolic parameters studied after one year of treatment.

Despite the metabolic profile differences observed at short-term in our previous studies, we did not find significant differences in the metabolic and weight parameters studied between treatment groups after one year of treatment, concluding that they present similar metabolic profiles at long-term. Other clinical individual interventions (e.g.: diet, exercise), not here controlled, may have influenced possible differences in long-term metabolic outcomes.

The authors have not supplied their declaration of competing interest.

There is growing evidence indicating that the use of second-generation antipsychotic (SGA) treatments in psychosis is related to potential metabolic side effects. Previous studies have shown clear metabolic side effects at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.

The aim of this study was to investigate the effect of aripiprazole, ziprasidone and quetiapine on metabolic measures in medication-naïve first episode psychosis patients after 1 year of treatment.

One hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to quetiapine, ziprasidone or aripiprazole treatment lines. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.

Weight (t = −10.85; P < 0.001), BMI (t = −11.38; P < 0.001), total cholesterol (t = −5.37; P < 0.001), LDL-cholesterol (t = −5.21; P < 0.001), triglycerides (t = −5.18; P < 0.001) and the triglyceride/HDL insulin resistance index (t = −4.09; P < 0.001), showed statistically significant increments after 1 year of treatment.

Moreover, on comparing the percentage of patients with pathological levels before and 1 year after the antipsychotic treatment, we detected higher percentages of patients with obesity (5.1% vs. 15.3%; P < 0.001), hypercholesterolemia (23.2% vs. 39.6%; P < 0.001) and hypertriglyceridemia (5.8% vs. 14.2%; P = 0.021) after 1 year of treatment.

The primary exposure to SGAs during the first year of psychosis was associated with significant increments in weight and metabolic parameters leading to a significant increment in the proportion of obesity, hypertriglyceridemia and hypercholesterolemia in our sample.

The authors have not supplied their declaration of competing interest.

Although mild to moderate major depressive disorder (MDD) is one of the main reasons for consulting a general practitioner (GP), there is still no international consensus on the most appropriate therapeutic approach.

The aim of this study is to evaluate the clinical effectiveness of watchful waiting (WW) compared with the use of antidepressants (ADs) for the treatment of mild to moderate depressive symptoms in 263 primary care (PC) usual-practice patients in a 12-month pragmatic non-randomised controlled trial. Both longitudinal and per-protocol analyses were performed, through a multilevel longitudinal analysis and a sensitivity analysis.

We observed a statistically significant time x treatment interaction in the severity of depression (Patient Health Questionnaire, PHQ-9) and disability (World Health Organization Disability Assessment Schedule, WHODAS) in favour of the AD group at 6 months but not at 12 months. The effect size of this difference was small. No statistically significant differences were observed between groups in severity of anxiety (Beck Anxiety Inventory, BAI) or health-related quality-of-life (EuroQol-5D, EQ-5D). Sensitivity analysis and per-protocol analysis showed no differences between the two groups in any of the evaluated scales.

Superiority of either treatment (WW and AD) was not demonstrated in patients treated for depression in PC after one year of follow-up.

Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.

This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.

Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.

Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features.

We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated.

Patients showed a significant total cortical thinning (F=17.55, d=−0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=−0.24, p=0.021) and parietal cortical thickness (r=−0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls.

Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.

It has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables.

A total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method.

Sustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery.

The limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.

Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders.

One hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset.

No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers.

Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?