Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid.

Introduction: Valproic acid (VPA) and its various formulations can be given in conjunction with clozapine for seizure prophylaxis or for augmentation in schizophrenia. There is conflicting literature on how VPA affects clozapine metabolism and the incidence of clozapine-related side effects. The purpose of this study is to compare the effects of VPA when given concurrently with clozapine to patients on clozapine monotherapy. Methods: A retrospective medical record review was completed to identify patients admitted to the inpatient psychiatry unit at an academic medical center with an order for clozapine with and without concurrent VPA from August 7, 2010 to August 7, 2020. The primary outcome was the difference in clozapine doses in patients on clozapine as monotherapy versus dual therapy with VPA. Secondary outcomes include the difference in incidence of adverse effects in monotherapy versus dual therapy, as well as clozapine and norclozapine concentrations in both treatment groups. Results: During the study period, 73 patients were included in the monotherapy group and 35 patients were included in the dual therapy group. The average clozapine dose in the dual therapy group was 250 mg (95% CI = 194.7, 305.4) which was significantly higher than the average monotherapy dose of 175.9 mg (95% CI = 134.0, 208.7; P = .016). However, there was no significant difference in the average clozapine concentration between the dual therapy group (392.5 ng/mL; 95% CI = 252.8, 532.2) and monotherapy group (365.9 ng/mL; 95% CI = 260.5, 471.3; P = .756). There were higher rates of tachycardia (45.7% vs 17.8%; P = .002), sedation (51.4% vs 8.2%; P < .001), and constipation (42.8% vs 9.5%; P < .001) in the dual therapy group compared to the monotherapy group, respectively. Discussion: Patients on concurrent clozapine and VPA received higher doses of clozapine and experienced a higher incidence of tachycardia, sedation, and constipation.

Major depressive disorder in children and adolescents.

Major depressive disorder (MDD) is one of the most common psychiatric disorders of childhood and adolescence, but because of symptom variation from the adult criteria, it is often unrecognized and untreated. Symptom severity predicts the initial mode of treatment ranging from psychotherapy to medications to combination treatment. Several studies have assessed the efficacy of treatment in children and adolescents, and others have evaluated the risk of developing adverse effects and/or new or worsening suicidal thoughts and behaviors. Optimal treatment often includes a combination of therapy and antidepressant medication. The most studied combination includes fluoxetine with cognitive behavioral therapy. Once symptom remission is obtained, treatment should be continued for 6 to 12 months before a slow taper is initiated. Although most children and adolescents recover from their first depressive episode, a large number will continue to present with MDD in adulthood. Untreated depression in children and adolescents may increase the risk of substance abuse; poor work, academic, and social functioning; and risk of suicidal behaviors.

A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization.

OBJECTIVES: Clozapine is the drug of choice for treatment-resistant schizophrenia. While pediatric clozapine use is not contraindicated, the literature describing its clinical application is limited. The primary objective of this study was to assess the use of clozapine in a child and adolescent population by characterizing the documented safety and clinical benefits of the medication. METHODS: A multicenter retrospective study at sites in the United States and Australia included children and adolescents admitted to a psychiatric unit who were administered at least one dose of clozapine. Information related to demographics, patient history, past treatments, clozapine, and adverse events was collected. RESULTS: Eighty-two patients from eight sites were included in this study. Patients were predominantly clozapine naive (76.8%), and most had a discharge diagnosis of a primary psychotic disorder (61%) or bipolar disorder (25.6%). Four clozapine discontinuations occurred during hospitalization due to severe neutropenia, ileus, need for diagnostic clarification, and significant psychomotor retardation. The remainder (n = 78) were discharged on a mean clozapine dose of 218.1 ± 142.2 mg. Sedation (26.8%) and sialorrhea (17.1%) were the most common documented adverse events. The mean number of previously trialed antipsychotics before clozapine was 3.5 ± 1.4 (range 1-10). Improvement with clozapine was documented as significant (31.7%), moderate (32.9%), minimal (12.2%), no improvement (2.4%), and not described (20.7%). CONCLUSIONS: In this cohort, 95% of pediatric patients admitted with or started on clozapine during an acute psychiatric hospitalization were discharged on the medication. The high incidence of adverse events should reinforce to clinicians the need for vigilant monitoring. Pediatric guidelines recommend clozapine for refractory schizophrenia but stress the critical need to ensure an accurate diagnosis. Limited data exist for the use of clozapine in pediatric patients with other diagnoses.

Psychiatric admission in adolescent transgender patients: A case series.

Gender dysphoria is defined as a marked incongruence between one's natal gender and gender identity that causes significant distress. It may be present in children but often fades prior to puberty. Gender dysphoria is more likely to persist into adulthood when present in adolescents. Due to the common occurrence of psychiatric comorbidities, gender dysphoria is a contributing factor leading to outpatient and inpatient psychiatric care in children and adolescents. There is currently limited available literature on psychiatric hospitalization and management in transgender adolescents. A PubMed search revealed no case reports regarding psychiatric admission for transgender adolescents with comorbid anxiety, depression, or suicidal ideation. Due to the lack of literature related to psychiatric management of transgender adolescent patients, this case series briefly describes the past medical history, pharmacotherapy, and discharge diagnoses of 5 transgender adolescents admitted to an inpatient psychiatry unit. In this case series, 4 of the 5 patients identified as female to male and ages ranged from 13 to 17 years. All patients had a history of depressive symptoms with suicidal ideation as the key factor prompting admission. All patients were managed on psychotropic pharmacotherapy, and 3 of the 5 patients were on pharmacotherapy related to gender transition. Anxiety, depression, and suicidal ideation were common comorbidities leading to psychiatric hospitalization of adolescent transgender patients in various stages of gender transitioning in this case series.