Two Patients with Schizophrenia Treated with Clozapine Developed Neutropenia After Receiving a COVID-19 Vaccine.

BACKGROUND: We observed two cases of patients with schizophrenia who were treated with clozapine (250mg/day and 275mg/day, respectively) and showed neutropenia after receiving a COVID-19 vaccine (BNT162b2). CASE PRESENTATION: Case 1 is a twenty-two year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2017 and had been taking clozapine for 4 years. She received two doses of a COVID-19 vaccine and developed neutropenia (1850/mm3 (37.9% of white blood cell 4880/mm3)) 6 days after the second vaccination, but her neutropenia self-resolved naturally. Case 2 is a twenty year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2020 and had been taking clozapine for 10 months. She received two doses of a COVID-19 vaccine and white blood cell and neutrocyte counts were below (3730/mm3 and 1440/mm3 (38.6%), respectively) the lower limits 3 days after the second vaccination. She had to discontinue clozapine according to the withdrawal definition (her neutrocyte count was <1500/mm3), and her neutropenia self-resolved naturally. CONCLUSION: Physicians need to have a strict follow-up protocol in place for patients after vaccination for COVID-19.

Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study.

BACKGROUND: Antidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. METHODS: We evaluated 25 consecutive outpatients with depression who discontinued their use of escitalopram. The presence of ADS was evaluated according to the Antidepressants Discontinuation Syndrome checklist. RESULTS: Antidepressant discontinuation syndrome was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). The treatment doses and plasma concentrations of escitalopram were significantly higher in patients with ADS than in patients without ADS. No group differences were observed regarding age, sex, or duration of escitalopram treatment before the discontinuation. CONCLUSIONS: These findings suggest that a higher dose and lower clearance of escitalopram lead to a higher risk of ADS. Very slow tapering is recommended for all patients.

Parental bonding and attitudes toward suicide among medical college students in Japan.

BACKGROUND: Suicide is a grave public health issue that is responsible for a high mortality rate among individuals aged 15-44 years. Attitudes toward suicide among medical staff members have been associated with appropriate therapeutic responses to suicidal individuals. The aim of this study was to examine the effects of parental rearing on attitudes toward suicide among Japanese medical college students. METHODS: We examined the association between parental bonding and attitudes toward suicide in 160 medical college students in Japan. The Parental Bonding Instrument was used to assess the attitudes and behaviors of parents. The attitudes toward suicide were evaluated using the Japanese version of the Attitudes Toward Suicide questionnaire. RESULTS: The mean age of the subjects was 25.2±4.0 years old. The majority of the participants in our study agreed that anyone could commit suicide (88.8%) and that suicide is preventable (86.3%). After adjusting for age and sex, multivariate regression analysis revealed that maternal care approached a statistically significant association with the "right to suicide" attitude. Under the same conditions, maternal care was shown to be significantly associated with the "common occurrence" attitude. No other significant relationships were observed between parental bonding and attitudes toward suicide. CONCLUSION: This study suggests that a higher level of maternal care ensures that children think that suicide occurs less commonly. The promotion of best practices for suicide prevention among medical students is needed. Child rearing support might be associated with suicide prevention.

The effects of additional treatment with terguride, a partial dopamine agonist, on hyperprolactinemia induced by antipsychotics in schizophrenia patients: a preliminary study.

Hyperprolactinemia is a frequent consequence of treatment with antipsychotics. Earlier studies have indicated that terguride, which is a partial dopamine agonist, reduces the prolactin levels that are induced by prolactinemia. Thus, we examined the dose effects of adjunctive treatment with terguride on the plasma concentrations of prolactin in patients with elevated prolactin levels resulting from antipsychotic treatment. Terguride was concomitantly administered to 20 schizophrenic patients (10 males and 10 females) receiving paliperidone and risperidone. The dose of terguride was 1.0 mg/day. Sample collections for prolactin were conducted before terguride (baseline) and 2-4 weeks after administration. The samples were obtained after the morning dose of terguride. The average (± standard deviation) plasma prolactin concentration during terguride coadministration was significantly lower than the baseline concentration in females (82.3±37.1 ng/mL versus 56.5±28.5 ng/mL, P<0.01) but not in males (28.8±18.0 ng/mL versus 26.2±13.1 ng/mL, not significant). Additionally, a significant correlation between the ratio of prolactin reduction and the baseline prolactin concentration was identified in males (r s=-0.638, P<0.05) but not in females (r s=-0.152, not significant). Many patients complained of various adverse events following terguride administration, such as insomnia, agitation, and/or the aggravation of hallucinations. This study suggests that additional treatment with terguride decreases the prolactin concentrations in females experiencing high prolactin levels as a result of antipsychotic treatment. However, its utility for schizophrenia may be diminished because of its low tolerability.

Comorbidity of Stevens-Johnson syndrome and neutropenia associated with lamotrigine: a case report.

A 19-year-old woman with a medical history of depressive mood arrived and was treated with lamotrigine at 25 mg/day. On day 10, a high fever of 39.3 °C and a diffuse, erythematous, pruritic full-body rash involving the palms of her hands and the soles of her feet developed, and she was diagnosed with Stevens-Johnson syndrome (SJS). On day 17, white blood cell count (WBC) result was 1,240/µl with 54.1% neutrophils (670/µl), and the WBC decreased to 840/µl with 60.7% neutrophils (510/µl) on day 18. The trend toward improvement included skin symptoms after steroid pulse therapy using 1000 mg/day. Based on the clinical course, we concluded that the SJS and leukopenia and/or neutropenia are associated with lamotrigine. Monitoring of WBC should be kept in mind when administering lamotrigine.

Neuroleptic malignant syndrome induced by lamotrigine.

This case report describes a 54-year-old man with bipolar I disorder who was treated with aripiprazole (ARP) and lithium. The patient was admitted to our hospital because of aggravation of depressive symptoms, and treatment with lamotrigine (LTG) was initiated. Two weeks after admission, we discontinued administration of ARP after the appearance of a tremor. Three weeks after discontinuing ARP, the patient developed a high fever, rigidity of the arms, diarrhea, dysphagia, and diaphoresis. We suspected these symptoms were consistent with neuroleptic malignant syndrome and therefore removed the application of LTG. After 2 days, most of the patient's symptoms and blood results had improved, leading us to conclude that the LTG treatment had induced neuroleptic malignant syndrome. Thus, the purpose of this case report was to warn psychiatrists against therapy with LTG, as it may be conducive to neuroleptic malignant syndrome.

Interaction between paliperidone extended release and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative, in a schizophrenic patient.

Until now there has been no information available on drug interaction between paliperidone and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative. The patient in the case presented here was a 39-year-old man with a 15-year history of schizophrenia. The patient's usual treatment of 2 mg/day of risperidone was changed to 3 mg/day of paliperidone extended release. He experienced worsening psychotic symptoms after switching from risperidone to paliperidone while he was also receiving TS-1. Retrospective analyses showed plasma concentration of paliperidone was consistently lower during the treatment with TS-1 than without TS-1. This case suggests there is drug interaction between paliperidone extended-release tablets and TS-1.

No association between hormonal abnormality and sexual dysfunction in Japanese schizophrenia patients treated with antipsychotics.

OBJECTIVE: Although sexual dysfunction is believed to be caused by hormonal abnormalities, few reports have studied sexual dysfunction and its association with hormonal abnormalities in Asian populations with schizophrenia. METHODS: We employed a cross-sectional, case-control survey design to collect data from 191 (108 men) Japanese schizophrenia outpatients treated with antipsychotics and 182 (49 men) healthy subjects. Sexual dysfunction was evaluated using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. We measured plasma concentrations of prolactin in both genders and testosterone in men and estradiol in women. RESULTS: Multiple regression analyses revealed the following findings: the number of antipsychotics correlated with diminished sexual desire (standardized beta = 0.241, p < 0.05); the dose of antipsychotics correlated with gynecomastia (standardized beta = 0.277, p < 0.01), increased sexual desire (standardized beta = 0.229, p < 0.05), and ejaculatory dysfunction (standardized beta = 0.248, p < 0.05); and the dose of antipsychotics correlated with menorrhagia in women (standardized beta = 0.284, p < 0.05). However, neither plasma concentrations of prolactin, testosterone nor estradiol correlated with sexual dysfunction. CONCLUSIONS: The present study demonstrated that an association between sex hormone abnormalities and sexual dysfunction is unlikely but that the dose or number of antipsychotics is associated with some sexual dysfunction.