Exposure to antiepileptic drugs during pregnancy increases the risk of congenital malformations and delayed cognitive development in offspring. This population-based study was performed to determine whether prenatal exposure to valproate led to an increased risk of autism in the children. Data were extracted from Danish national registers for children born in 1996 to 2006 and for those exposed to valproate during pregnancy and subsequently diagnosed with autism spectrum disorders (ASDs), including childhood autism, Asperger syndrome, atypical autism, and other/unspecified pervasive developmental disorders. The estimated daily antiepileptic drug dose was divided into high (>750 mg/d) and low (≥750 mg/d) levels. The primary outcome was the hazard ratio of ASD and childhood autism after exposure to valproate during pregnancy, as determined by Cox regression. The secondary outcome was the risk of autism following valproate exposure after accounting for maternal epilepsy before birth. Of 655,615 births, 5437 children had a diagnosis of ASD, including 2067 with childhood autism. The mean age of the children at the end of follow-up was 8.84 years. Of 2644 children exposed to antiepileptic drugs during pregnancy, 508 were exposed to valproate. In all children, the absolute risks for ASD and childhood autism were 1.53% (95% confidence interval [CI], 1.47%–1.58%) and 0.48% (95% CI, 0.46%–0.51%), respectively. Valproate use during pregnancy was associated with absolute risks of 4.42% (95% CI, 2.59%–7.46%) for ASD and 2.50% (95% CI, 1.30%–4.81%) for childhood autism. The adjusted hazard ratio (aHR) for ASD was 2.9 (95% CI, 1.7–4.9), and for childhood autism it was 5.2 (95% CI, 2.7–10.0). Risks were similar for children of women who used high valproate doses (aHR 2.5; 95%CI, 1.03–6.1 for ASD; 4.3; 95%CI, 1.4–13.4 for childhood autism) compared with those for children of women who used low doses (aHR, 3.2; 95% CI, 1.7–6.2 and 5.4; 95% CI, 2.4–12.1, respectively). For other antiepileptic drugs, no increased risk of ASD or childhood autism was found. For women of childbearing age who use antiepileptic drugs, these findings must be considered against the benefits for those who need valproate to control epilepsy. The less than 5% absolute risk of ASD should be considered when counseling patients about use of valproate during pregnancy.

Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20385

The current conceptualization of negative symptoms in schizophrenia.

The role of a reduced N100 (or N1) component of the auditory event related potential as a potential trait marker of schizophrenia is critically discussed in this review. We suggest that the extent of the N100 amplitude reduction in schizophrenia depends on experimental and subject factors, as well as on clinical variables: N100 is more consistently reduced in studies using interstimulus intervals (ISIs) > 1 s than in studies using shorter ISIs. An increase of the N100 amplitude by allocation of attention is often lacking in schizophrenia patients. A reduction of the N100 amplitude is nevertheless also observed when such an allocation is not required, proposing that both endogenous and exogenous constituents of the N100 are affected by schizophrenia. N100 is more consistently reduced in medicated than unmedicated patients, but a reduction of the N100 amplitude as a consequence of antipsychotic medication was shown in only two of seven studies. In line with that, the association between the N100 reduction and degree of psychopathology of patients appears to be weak overall. A reduced N100 amplitude is found in first degree relatives of schizophrenia patients, but the risk of developing schizophrenia is not reflected in the N100 amplitude reduction.

Reduced auditory evoked potential component N100 in schizophrenia — A critical review

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2051-5545.2008.tb00181.x

Deficit schizophrenia: an update

Negative symptoms refer to the weakening or lack of normal thoughts, emotions or behaviour in schizophrenia patients. Their prevalence in first-episode psychosis is high, 50-90%, and 20-40% of schizophrenia patients have persisting negative symptoms. Severe negative symptoms during the early stages of treatment predict poor prognosis. The aim of the study was to review the current literature on the negative symptoms of schizophrenia. In June 2007, the following databases were searched: Web of Science, PubMed, PsycINFO, Medline (Ovid) and Scopus. The search included articles written in English and no time limit was determined. The studies were manually screened by one of the authors according to the title and abstract. About one in three schizophrenia patients suffer from significant negative symptoms. In these patients, negative symptoms constitute a key element of overall symptoms, weakening their ability to cope with everyday activities, affecting their quality of life and their ability to manage without significant outside help. About one in three schizophrenia patients suffer from significant negative symptoms. Attention should be focused on negative symptoms during the early phase of treatment, because they cause significant impairment to patients' quality of life. So far, no treatment appears to substantially improve negative symptoms narrowly defined. However, according to clinical experience, when treating negative symptoms, the best effect is achieved by optimizing the dose of medication and by complementing it with psychosocial therapies.

Negative symptoms in schizophrenia—A review

Efficacy of low vs. high doses of levosulpiride on negative symptoms of schizophrenia.

Objective Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs). Methods This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. Results In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. Discussion The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process. Conclusions In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority.

https://www.rivistadipsichiatria.it/r.php?v=2304&a=24792&l=326936&f=allegati/02304_2016_03/fulltext/03.Prisco (96-103).pdf

[Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

Drug safety warnings in psychiatry: Adverse drug reactions’ signaling from 2002 to 2014

Double dissociation of N1 and P3 abnormalities in deficit and nondeficit schizophrenia.

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Efficacy of low vs. high doses of levosulpiride on negative symptoms of schizophrenia.

[Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

Drug safety warnings in psychiatry: Adverse drug reactions’ signaling from 2002 to 2014

Double dissociation of N1 and P3 abnormalities in deficit and nondeficit schizophrenia.