Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal adverse effect of neuroleptic, both classic and atypical drugs.

To review the incidence, clinical characteristics, diagnosis and treatment of NMS.

We have described the case of a man of 32 years of age diagnosed with bipolar disorder treated with lithium. He precised high-dose corticosteroids after having tonsillitis. Then, he presented manic decompensation requiring neuroleptic treatment (oral risperidone). After 72 hours, he presented an episode characterized by muscular rigidity, fever, altered mental status and autonomic dysfunction. Life support measures and suspension of neuroleptic treatment were required.

A literature review of the NMS was performed using the PubMed database.

The frequency of NMS ranges from 0.02 to 2.4%. The pathophysiology is not clearly understood but the blockade of dopamine receptors seems to be the central mechanism. Some of the main risk factors described are: being a young adult, the concomitant use of lithium and metabolic causes, among others. NMS occurs most often during the first week of treatment or after increasing the dosage of the neuroleptic medication. Some issues of NMS are those related with diagnosis, treatment and reintroduction of antipsychotic treatment or not.

NMS can be difficult to diagnose due to the variability in the clinical symptoms and presentation. Because of it diagnosis is of exclusion, clinicians should always take it into consideration when a patient is treating with neuroleptic, especially when the dosage has been recently increased. NMS is a clinical emergency.

The authors have not supplied their declaration of competing interest.

Glucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects.

To review the incidence, clinical characteristics, course and treatment of neuropsychiatric effects of glucocorticoids.

We have described the case of a 86-year-old woman. She had no personal and no psychiatric medical history in her family. She presented wrist arthritis requiring high doses of an oral corticoid treatment (prednisona 20 mg/d). After a week, she started with symptoms characterised by persecutory and surveillance delusions. Organicity was ruled out. The patient got a progressive recovery after starting anti-psychotic medication and progressive reduction of the steroid drugs.

We have performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database.

Neuropsychiatric effects of glucocorticoids involve affective, behavioural, and cognitive manifestations. The incidence is variable, between 2 and 60% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although the limited data on this subject, it is a problem that clinicians face on their regular basis. The administration of anti-psychotics or mood stabilizers may be beneficial in the prevention and treatment of this syndrome.

The neuropsychiatric effects of glucocorticoids are unpredictable and non-specific. More controlled trials are needed in order to perform evidence-based clinical guidelines for the treatment with glucocorticoids and for the prevention of neuropsychiatric manifestations.

The authors have not supplied their declaration of competing interest.

In the general practice, psychiatrists widely prescribe antipsychotics for several conditions as schizophrenia, bipolar disorder and behavioral disorders among others.

The aim of this study is to describe the clinical and sociodemographic features of typical patients receiving antipsychotics and their effects after switching to long-acting treatment.

A descriptive analysis of 80 outpatients collected from a mental health clinic in Santander (Spain) was performed. All patients were taking antipsychotics at baseline, both oral and intramuscular, and were switched to a different long-acting antipsychotic drug.

At baseline, 24 patients were taking oral medication and 56 intramuscular. There were 37 females and 43 males. There were no gender differences in the final treatment, but Palmitate Paliperidone (71.3%) was the most prescribed drug, followed by intramuscular risperidone (16.3%) and long-acting aripiprazole (11.3%). We found gender differences regarding cannabis (P = 0.002), alcohol (P = 0.004) and tobacco (P = 0.043) consumption, being their use more common in males. In regard to diagnosis, schizophrenia was predominant in both gender groups, whereas delusional and behavioral disorders were more frequent in females. There were no significant differences in the reason of switching, but the inefficacy was more common in males and the side effects in females. At the switching, females were significantly older than males (P = 0.003). We found significant differences before and after switching regarding the number of admissions, emergency visits and length of stay.

Antipsychotic benefits are individual and unpredictable. When switching, some other different factors should be taking in account, not only regarding medication.

The authors have not supplied their declaration of competing interest.

Patients with psychosis are treated in outpatient community clinics during most of their lifetime. Antipsychotic treatments are commonly used in regular clinical practice. However, the non-adherence is one of the main causes of relapses. Long-acting injectables (LAIs) could be a safe option to guarantee the efficacy.

Our purpose is to evaluate the efficacy of the switch to paliperidone palmitate from other oral or LAI antipsychotics, in terms of hospital and emergency admissions.

We performed a mirror-image study in an outpatient mental health clinic, comparing patients before and after paliperidone palmitate change over 43 months. Fifty-seven patients were included, most of them (n = 47) were diagnosed with psychotic disorders (82.5%) while 4 were bipolar patients (7%), and the remained patients (n = 6; 10.6%) were classified as behavioral disorders. The following variables were studied before and after the switching: number of admissions, days of stay and emergency visits.

From those 57 patients, 44 were previously treated with other LAIs, whereas 13 were taking oral antipsychotics. The median age at switch was 49 years (SD = 12.31). The reasons for switching were: inefficacy (26.3%), non-adherence (19.3%), side effects (38.6%), and non-specified (15.8%). We found significant differences between the three main variables: number of admissions (t = 4.59; P ≤ 0.001), days of stay (t = 2.27; P = 0.027) and emergency visits (t = 3.74; P ≤ 0.001).

Paliperidone palmitate seems to be an effective treatment in order to guarantee the adherence. Our preliminary data show that paliperidone palmitate might reduce the sanitary cost in outpatients.

The authors have not supplied their declaration of competing interest.

There is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Disrupted-in-Schizophrenia 1 (DISC1) gene has been previously associated to the illness and to treatment response in a sample of patients suffering from psychosis. However, there is a lack of studies on the effect of DISC1 on treatment response in samples of first episode psychosis.

The aim of this study was to explore the relation between variations in DISC1 gene and treatment response to antipsychotics in a sample of drug-naïve patients with a first episode of psychosis.

Two hundred and twenty Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys), rs6675281 (Leu607Phe) and rs1000731. Early (6 weeks) response to antipsychotic treatment was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.

We found a significant association between rs1000731 and treatment response. Thus, those patients homozygous for the G allele of rs1000731 were more frequently non-responders, measured with SANS, after 6 weeks of treatment, than those carrying the A allele (X2 = 4.019; P = 0.032). Moreover, when analysing the clinical improvement longitudinally, we observed that those patients carrying the A allele for the rs1000731 presented a greater improvement in positive symptoms dimension (F = 8.905; P = 0.003).

Our results suggest a minor contribution to antipsychotic drug response of genetic alterations in the DISC1 gene.

The authors have not supplied their declaration of competing interest.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.

This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).

Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.

Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Cortical thickness measurement offers an index of brain development processes. In healthy individuals, cortical thickness is reduced with increasing age and is related to cognitive decline. Cortical thinning has been reported in schizophrenia. Whether cortical thickness changes differently over time in patients and its impact on outcome remain unanswered.

Data were examined from 109 patients and 76 healthy controls drawn from the Santander Longitudinal Study of first-episode schizophrenia for whom adequate structural magnetic resonance imaging (MRI) data were available (n = 555 scans). Clinical and cognitive assessments and MRIs were acquired at three regular time points during a 3-year follow-up period. We investigated likely progressive cortical thickness changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The effects of cortical thickness changes on cognitive and clinical variables were also examined along with the impact of potential confounding factors.

There were significant diagnoses × scan time interaction main effects for total cortical thickness (F 1,309.1 = 4.60, p = 0.033) and frontal cortical thickness (F 1,310.6 = 5.30, p = 0.022), reflecting a lesser thinning over time in patients. Clinical and cognitive outcome was not associated with progressive cortical changes during the early years of the illness.

Cortical thickness abnormalities do not unswervingly progress, at least throughout the first years of the illness. Previous studies have suggested that modifiable factors may partly account for cortical thickness abnormalities. Therefore, the importance of implementing practical actions that may modify those factors and improve them over the course of the illness should be highlighted.

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.