Cognitive Effects of Reducing First-Generation Antipsychotic Dose Compared to Switching to Ziprasidone in Long-Stay Patients with Schizophrenia.

Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone.

Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring: Can the regulations be relaxed?

After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at which clozapine must be discontinued definitively. The fear of agranulocytosis and the need for intensive blood monitoring is the single most important barrier for prescribers and patients alike and leads to underprescription of the only effective and approved medication for treatment-resistant schizophrenia.

Feasibility and Effect of Increasing Clozapine Plasma Levels in Long-Stay Patients With Treatment-Resistant Schizophrenia.

Background: It is unknown whether increasing the clozapine plasma level to 400, 750, or even 1000 ng/mL is a feasible and effective strategy in patients with treatment-resistant schizophrenia (TRS). We investigated this in long-stay patients with TRS.

Methods: In long-stay TRS patients, doses of clozapine were increased gradually to reach target plasma levels of 400, 750, or 1000 ng/mL, depending on the clinical response and tolerability.

Risk Factors for Psychotic Relapse After Dose Reduction or Discontinuation of Antipsychotics in Patients With Chronic Schizophrenia. A Meta-Analysis of Randomized Controlled Trials.

Background And Hypothesis: Although maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced.

Clozapine and COVID-19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study.

Objective: To investigate the safety of COVID-19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.

Methods: We conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 μg/L increase compared to baseline) and clozapine alert levels (>1000 μg/L).

COVID-19: Risks, Complications, and Monitoring in Patients on Clozapine.

The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection for patients on clozapine and we give advice on measures to be taken, especially in regard to the monitoring of clozapine plasma levels, WBC count and differentiation during COVID-19 and after vaccination. We present an overview of relevant editorials, observational studies, and case studies, in which COVID-19 was reported in patients on clozapine.

Differences between physicians' and nurse practitioners' viewpoints on reasons for clozapine underprescription.

Introduction: Clozapine (CLZ) is the only proven effective therapy for treatment-resistant schizophrenia, but it is underutilized across the globe. Previous findings suggest a lack of experience with CLZ prescription and concerns about CLZ's pharmacological characteristics are the prime reasons for CLZ underutilization. To our knowledge, it is currently unknown whether the reasons for underutilization and suggested solutions differ between physicians and nurse practitioners.

Dose reduction of high-dose first-generation antipsychotics or switch to ziprasidone in long-stay patients with schizophrenia: A 1-year double-blind randomized clinical trial.

Long-stay patients with severe schizophrenia are frequently treated with high doses of first-generation antipsychotics (FGA). Dose reduction or switching to ziprasidone may reduce the severity of negative symptoms and side effects. We investigated in a randomized double-blind trial whether a dose-reduction strategy to achieve an adequate dose of a FGA (5 mg/day haloperidol equivalents, n = 24) or switching to ziprasidone (160 mg/day, n = 24) in treatment resistant patients would decrease negative symptoms after 1 year of treatment.

Low levels of vitamin D poorly responsive to daylight exposure in patients with therapy-resistant schizophrenia.

Background: Low vitamin D levels are associated with schizophrenia, but the possible association between vitamin D levels and illness severity or duration of exposure to daylight has barely been investigated.

Aims: To compare vitamin D levels in therapy-refractory severely ill schizophrenia patients and members of staff. To investigate the influence of daylight exposure on vitamin D levels in patients.

Capillary compared to venous blood sampling in clozapine treatment: patients׳ and healthcare practitioners׳ experiences with a point-of-care device.

Underuse of the antipsychotic clozapine for schizophrenia is an impediment to improving outcomes for patients. Because of its possible severe side effects, including granulocytopenia or even agranulocytosis, clozapine treatment entails regular WBC monitoring, which can be a major drawback for patients and practitioners. The HemoCue WBC DIFF system is a point-of-care device using capillary blood sampling which provides WBC counts with differentials, including granulocytes.

Add-on filgrastim during clozapine rechallenge unsuccessful in preventing agranulocytosis.

Granulocyte colony-stimulating factor agents such as filgrastim can be administered in order to reduce the duration of clozapine-induced agranulocytosis. Successful long-term combination treatment with filgrastim and clozapine in patients with previous clozapine-induced agranulocytosis has been described in several cases. We describe a patient with schizophrenia who developed agranulocytosis during treatment with clozapine and who did not respond to other antipsychotics.

Beyond white blood cell monitoring: screening in the initial phase of clozapine therapy.

Objective: Clozapine is the preferred option for treatment-resistant schizophrenia. However, since 1975, clozapine has been known to cause agranulocytosis. In the clozapine screening guidelines, white blood cell count is mandatory.

Interaction of St John's wort (Hypericum perforatum) with clozapine.

St John's wort (Hypericum perforatum) is notorious for its ability to induce the enzymes of the P450 system. Especially, it induces CYP1A2 and CYP3A4, enzymes that are closely involved in the metabolism of clozapine. We present a patient with schizophrenia, who was stable on a fixed dose with stable plasma level of clozapine, and who deteriorated after she started self-medicating with St John's wort.