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1.
Eur Neuropsychopharmacol ; 56: 92-99, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648886

ABSTRACT

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this.


Subject(s)
Antipsychotic Agents , COVID-19 , Clozapine , Psychotic Disorders , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Critical Care , Hospitalization , Humans , Pandemics , Psychotic Disorders/drug therapy , Psychotic Disorders/epidemiology , SARS-CoV-2
3.
J Psychiatr Pract ; 28(1): 62-66, 2022 01 06.
Article in English | MEDLINE | ID: covidwho-1603948

ABSTRACT

Clozapine is the antipsychotic of choice in treatment-resistant schizophrenia. Serum clozapine concentration testing is essential to monitor adherence, adjust dosing, and ensure treatment safety. However, patients who are acutely unwell are frequently reluctant to undergo blood testing requiring venipuncture. Also, conventional laboratory-based measurement of clozapine plasma levels can take days, thus contributing to the suboptimal use of clozapine when it is most needed. We pioneered clozapine whole-blood point of care (POC) testing in the acute inpatient setting in the treatment of a group of actively psychotic patients receiving clozapine during the outbreak of the COVID-19 pandemic. POC clozapine testing using automated homogenous immunoassay requires only finger prick blood sampling and is more acceptable to patients. As it produces results in minutes, clozapine POC testing serves to promptly ascertain adherence with treatment and inform therapeutic dosing. POC testing offered a more practical, less invasive, and quicker alternative to conventional methods of monitoring clozapine levels. Near immediate availability of clozapine levels expedited clinical decisions and helped ensure safe clozapine prescribing to our severely psychotic patients in a time of crisis. By facilitating patients' early safe discharge from the hospital, clozapine POC testing also reduced length of hospitalization.


Subject(s)
Antipsychotic Agents , COVID-19 , Clozapine , Psychiatry , Antipsychotic Agents/therapeutic use , Clozapine/adverse effects , Humans , Inpatients , Pandemics , Point-of-Care Testing , SARS-CoV-2
6.
Int J Environ Res Public Health ; 18(21)2021 10 27.
Article in English | MEDLINE | ID: covidwho-1488556

ABSTRACT

Despite its severe adverse effects, such as agranulocytosis, clozapine is the primary treatment for treatment-resistant schizophrenia. The established clozapine monitoring system has contributed to reducing agranulocytosis incidence and mortality rates. However, the pandemic coronavirus disease 2019 (COVID-19) has caused changes in the monitoring system. This review aimed to assess the current evidence on the neutrophil changes in the patient on clozapine treatment and infected with COVID-19. Individual cases reported various absolute neutrophil count (ANC) levels, normal, reduced, or elevated. No agranulocytosis case was reported. One case had a borderline moderate-severe ANC level, but the patient was in the 18-week period of clozapine treatment. A cumulative analysis of case the series initially reported inconclusive results. However, a more recent study with a larger sample size reported a significant reduction in the ANC during COVID-19 infection. Nevertheless, this effect is transient as no significant difference was found between the baseline and the post-infection period in ANC levels. In conclusion, COVID-19 is associated with a temporary reduction in ANC levels. The results supported the recommendation to reduce the frequency of clozapine monitoring in the eligible candidates. However, more data are required to confirm the current findings given the limitations, including study design, sample size, and statistical analysis.


Subject(s)
Antipsychotic Agents , COVID-19 , Clozapine , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Humans , Leukocyte Count , Neutrophils , SARS-CoV-2
7.
Acta Psychiatr Scand ; 145(1): 79-85, 2022 01.
Article in English | MEDLINE | ID: covidwho-1480084

ABSTRACT

OBJECTIVE: To investigate whether patients with clozapine treatment are at an increased risk of a more severe COVID-19 infection as compared with patients on other antipsychotic drugs. METHODS: In this register-based cohort study, all residents (age 18 or older) in the Stockholm Region with a psychotic disorder diagnosis and antipsychotic treatment were included (N = 8 233) and followed from 1 March 2020 to 14 January 2021. The exposure was defined as clozapine treatment and the outcome measures (indicating a more severe COVID-19 infection) were: inpatient care, care within intensive care unit or death due to COVID-19 infection. Differences in outcome rates between exposed (n = 966) and unexposed (other antipsychotics; n = 7 267) were examined using Cox proportional hazards models and expressed as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: No statistically significant differences in outcome rates were found between the two groups of patients after adjusting for age, sex and residence in retirement homes. The adjusted HR for the exposed compared to the unexposed was 0.96 (95% CI: 0.54, 1.70) for inpatient care; 1.69 (0.48, 5.93) for care in intensive care unit (ICU); and 0.86 (0.26, 2.80) for death. Regarding inpatient care, additional adjusting for country of birth, living in socioeconomically vulnerable areas, number of care visits during the previous year, and comorbid medical illnesses did not alter the results. CONCLUSIONS: Our results may add support to the present guidelines, recommending sustained clozapine treatment during the current COVID-19 pandemic with careful monitoring and readiness to alter drug doses as needed.


Subject(s)
COVID-19 , Clozapine , Adolescent , Clozapine/adverse effects , Cohort Studies , Humans , Pandemics , SARS-CoV-2
8.
J Clin Psychiatry ; 82(5)2021 09 07.
Article in English | MEDLINE | ID: covidwho-1399456

ABSTRACT

Treatment-resistant schizophrenia (TRS) represents a major clinical challenge. The broad definition of TRS requires nonresponse to at least 2 sequential antipsychotic trials of sufficient dose, duration, and adherence. Several demographic, clinical, and neurologic predictors are associated with TRS. Primary (or early) TRS is present from the beginning of therapy, while patients with secondary (or later-onset) TRS initially respond to antipsychotics but become resistant over time, often after relapses. Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers. Importantly, studies indicate that response rates are higher when clozapine is initiated earlier in the treatment course. Side effects are common with clozapine, particularly in the first few weeks, but can mostly be managed without discontinuation; they do require proactive assessment, intervention, and reassurance for patients. Furthermore, plasma leucocyte and granulocyte levels must be monitored weekly during the first 18-26 weeks of treatment, and regularly thereafter, according to country regulations. Therapeutic drug monitoring of clozapine trough plasma levels is helpful to guide dosing, with greatest efficacy at plasma clozapine levels ≥350 µg/L, although this level is not universal. Notably, plasma clozapine levels are generally greater at lower doses in nonsmokers, patients with heavy caffeine consumption, in women, in obese people, in those with inflammation (including COVID-19 infection), and in older individuals. Earlier and broader use of clozapine in patients with TRS is an important measure to improve outcomes of patients with this most severe form of the illness.


Subject(s)
Antipsychotic Agents/administration & dosage , Clozapine/administration & dosage , Schizophrenia/drug therapy , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Drug Resistance/drug effects , Drug Tolerance , Female , Humans , Male
14.
J Psychiatr Pract ; 27(2): 137-144, 2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1292182

ABSTRACT

The widespread prevalence of coronavirus disease 2019 (COVID-19) means that inpatient psychiatric units will necessarily manage patients who have COVID-19 that is comorbid with acute psychiatric symptoms. We report a case of recurrence of respiratory symptoms and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) testing in a patient on an inpatient psychiatric unit occurring 42 days after the initial positive SARS-CoV-2 RT-PCR test, 38 days after initial symptom resolution, and 30 days after the first of 3 negative SARS-CoV-2 RT-PCR tests. Over the course of the admission, the patient was safely initiated on clozapine. Recent literature on COVID-19's potential recurrence and neuropsychiatric effects is reviewed and implications for the management of COVID-19 on inpatient psychiatric units are discussed. In the era of COVID-19 and our still-developing understanding of this illness, psychiatrists' role as advocates and collaborators in our patients' physical health care has become even more critical.


Subject(s)
Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , COVID-19/complications , Depressive Disorder, Major/complications , Depressive Disorder, Major/drug therapy , Psychotic Disorders/complications , Psychotic Disorders/drug therapy , Adult , Alcoholism/complications , Alcoholism/diagnosis , COVID-19/diagnosis , COVID-19/psychology , COVID-19 Nucleic Acid Testing , Clozapine , Depressive Disorder, Major/diagnosis , Hospitals, Psychiatric , Humans , Inpatients/psychology , Male , Mirtazapine/therapeutic use , Psychotic Disorders/diagnosis , Recurrence , SARS-CoV-2 , Sertraline/therapeutic use , Suicide, Attempted
16.
Br J Psychiatry ; 219(1): 368-374, 2021 07.
Article in English | MEDLINE | ID: covidwho-1282279

ABSTRACT

BACKGROUND: Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia. AIMS: To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK. METHOD: Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use. RESULTS: Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73-3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14-2.72). CONCLUSIONS: These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.


Subject(s)
COVID-19 , Clozapine , Clozapine/adverse effects , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
17.
Br J Psychiatry ; 219(1): 357-358, 2021 07.
Article in English | MEDLINE | ID: covidwho-1282281

ABSTRACT

Clozapine is under-used in the UK, and Casetta et al's recent paper in the BJPsych adds to a growing number of small studies that support the use of intramuscular clozapine to initiate and maintain treatment with oral clozapine. However, intramuscular clozapine remains unlicensed and, because of the risks associated with its administration, it should be used only cautiously before it can be adopted more widely into mainstream clinical practice.


Subject(s)
Antipsychotic Agents , Clozapine , Psychotic Disorders , Schizophrenia , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Humans , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy
18.
Ann Palliat Med ; 10(5): 5010-5016, 2021 May.
Article in English | MEDLINE | ID: covidwho-1200421

ABSTRACT

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.


Subject(s)
Antipsychotic Agents , COVID-19 , Clozapine , Schizophrenia , Antipsychotic Agents/therapeutic use , Benzodiazepines/therapeutic use , Body Weight , China , Clozapine/therapeutic use , Humans , Olanzapine/therapeutic use , Pandemics , Retrospective Studies , Risperidone/therapeutic use , SARS-CoV-2 , Schizophrenia/drug therapy
20.
Ir J Psychol Med ; 38(4): 249-257, 2021 12.
Article in English | MEDLINE | ID: covidwho-1169339

ABSTRACT

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.


Subject(s)
COVID-19 , Clozapine , Clozapine/therapeutic use , Humans , Pandemics , Quality of Life , SARS-CoV-2
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