Antipsychotic Augmentation With N-Acetylcysteine for Patients With Schizophrenia.

N-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

BACKGROUND: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition. METHODS: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated. RESULTS: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (ß =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found. CONCLUSIONS: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.

The impact of COVID-19 on a cohort of patients treated with clozapine.

OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic and its associated restrictions on a cohort of patients with severe and enduring mental illness treated with clozapine. METHODS: Semi-structured interviews were conducted with 63 individuals attending a clozapine clinic within the Galway-Roscommon Mental Health Services to determine the impact of COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life, by utilising Likert scale data. The Beck Anxiety Inventory (BAI) and Hamilton Anxiety Rating Scale (HAM-A) were additionally utilised to measure anxiety symptoms cross-sectionally. RESULTS: Anxiety symptoms were low with a median BAI score of 4.0 and HAM-A score of 4.0. Likert scale measurements recorded only a modest adverse impact of COVID-19 restrictions on anxiety and depressive symptoms, quality of life and occupational and social functioning. Free-text comments from patients (n = 55), were grouped into five themes: neutral impact (n = 22), negative psychological impact (n = 13), negative social impact (n = 11), positive psychological impact (n = 5) and media coverage inducing anxiety (n = 4). CONCLUSIONS: Three months into the COVID-19 pandemic and its restrictions, the impact on individuals with treatment-resistant psychotic disorders attending a clozapine clinic has been modest, with preliminary evidence demonstrating minimal increases in subjective symptoms of anxiety and reduced social functioning. Reduced social engagements and supports attainable both within the community and from mental health services were noted by some participants.

COVID-19 infection causes a reduction in neutrophil counts in patients taking clozapine.

Background: Monitoring of white cell counts during clozapine treatment leads to cessation of therapy if levels fall below predetermined values. Reductions in white cell counts, driven by lower levels of lymphocytes, have been observed with coronavirus disease 2019 (COVID-19). Neutropenia during COVID-19 has not been reported. We present data for 56 patients who were taking clozapine and had COVID-19. Methods: We included patients who were taking clozapine at the time they tested positive for COVID-19. We compared absolute neutrophil counts, lymphocyte counts and white cell counts between baseline and the first week of infection, and baseline and the second week of infection. Results: We observed reductions in absolute neutrophil counts (p = 0.005), lymphocyte counts (p = 0.003) and white cell counts (p < 0.001) between baseline and the first 7 days of COVID-19. All cell counts had returned to baseline levels by days 8 to 14. Six patients experienced neutropenia (absolute neutrophil counts < 2.0 × 109/L) and of those, 4 underwent mandatory cessation of clozapine. For 3 patients, clozapine treatment had been established for more than 6 months with no previous neutropenia, neutrophil levels returned to baseline within 2 weeks and no further neutropenia was observed on restarting treatment. Limitations: This was a retrospective chart review; larger cohorts are required. Clozapine plasma levels were largely not measured by clinicians. Conclusion: These data strongly suggest that mild neutropenia in the acute phase of COVID-19 in patients who are well established on clozapine is more likely to be a consequence of the virus than of clozapine treatment.

Non-convulsive status epilepticus: COVID-19 or clozapine induced?

We present a case of non-convulsive status epilepticus in a 57-year-old woman with a schizoaffective disorder, without an antecedent seizure history, with two possible aetiologies including SARS-CoV-2 infection and clozapine uptitration. We discuss the presentation, investigations, differential diagnosis and management. In particular, we focus on the electroencephalogram (EEG) findings seen in this case and the electroclinical response to antiepileptic medication. We review the literature and discuss the relevance of this case to the SARS-CoV-2 global pandemic. We emphasise the importance of considering possible neurological manifestations of SARS-CoV-2 infection and highlight seizure disorder as one of the possible presentations. In addition, we discuss the possible effects of clozapine on the electroclinical presentation by way of possible seizure induction as well as discuss the possible EEG changes and we highlight that this needs to be kept in mind especially during rapid titration.

[Recommendations about the Use of Psychotropic Medications during the COVID-19 Pandemic]. / Recomendações sobre a Utilização de Fármacos Psicotrópicos durante a Pandemia COVID-19.

INTRODUCTION: The COVID-19 pandemic is a particularly relevant threat to mentally ill patients, and it constitutes a new challenge for health care providers. To the best of our knowledge, there is not any embracing published review about the use of psychotropic drugs during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic literature review. A search in the PubMed database was performed, with the terms 'psychotropic drugs', 'COVID-19', 'psychiatry' and 'pandemic'. Consensus and clinical guidelines about psychotropic drugs and COVID-19 approach, published by scientific societies, governmental entities and drug regulatory agencies were included. RESULTS AND DISCUSSION: We present the recommendations about the use of psychotropic drugs during the COVID-19 pandemic, in the outpatient and inpatient settings. The treatment of affective bipolar disorder and schizophrenia have now added increased difficulties. Some psychotropic drugs interfere with the pathophysiology of the novel coronavirus infection and they could interact with the drugs used in the treatment of COVID-19. Some patients will need pharmacological interventions due to the presence of delirium. Smoking cessation changes the serum levels of some psychotropic drugs and may influence their use. CONCLUSION: The COVID-19 pandemic has created new challenges in clinical practice. Psychiatric patients are a vulnerable population and often a careful clinical, laboratorial and electrocardiographic evaluation may be needed, particularly in those diagnosed with COVID-19. The regular treatment of mentally ill patients with COVID-19 presents increased complexity.

Introdução: A pandemia de COVID-19 constitui uma ameaça particularmente relevante para os portadores de doença mental e um novo desafio para os profissionais que os acompanham. Até à data, tanto quanto sabemos, não existe qualquer revisão abrangente publicada relativamente à utilização de fármacos psicotrópicos durante a pandemia COVID-19. Material e Métodos: Revisão não sistemática da literatura. A pesquisa na PubMed foi realizada com os termos 'psychotropic drugs', 'COVID-19', 'psychiatry' e 'pandemic'. Foram incluídos os consensos e as normas publicadas pelas sociedades científicas, entidades governamentais e agências regulamentares de medicamentos. Resultados e Discussão: Apresentam-se recomendações relativamente à utilização de psicofármacos durante a pandemia COVID-19, em contexto de ambulatório e de internamento. O tratamento da perturbação afetiva bipolar e da esquizofrenia tem agora dificuldades acrescidas. Alguns psicofármacos interferem com os mecanismos fisiopatológicos envolvidos na infeção pelo novo coronavírus e têm interações com os fármacos utilizados no tratamento da COVID-19. Em doentes com COVID-19 e com delirium, a utilização de psicofármacos poderá ser necessária. A cessação tabágica altera os níveis séricos de alguns psicofármacos e pode condicionar a sua utilização. Conclusão: A pandemia de COVID-19 coloca novos desafios na prática clínica. Os doentes psiquiátricos constituem uma população vulnerável, sendo frequentemente necessária uma avaliação clínica, laboratorial e eletrocardiográfica cuidadosa, naqueles com o diagnóstico de COVID-19. Os doentes mentais com COVID-19 apresentam uma complexidade acrescida na gestão da sua terapêutica habitual.