A 29-year-old man was admitted to our hospital with severe nausea and hyperglycemia due to diabetic ketoacidosis (DKA). He had started receiving olanzapine (2.5 mg/day) from another hospital for clinical depression 3 months before presentation. His olanzapine plasma level on the second day (before the administration of insulin) was 1.887 ng/mL. (The therapeutic blood level is 9.3 ng/ml after 24 hours in the acute phase). By checking both the plasma level of olanzapine and the U-CPR every few days, we tried to verify impaired glucose tolerance during treatment with olanzapine. Our findings suggest that even young adults who are judged to not be at any risk of diabetes can develop DKA at low plasma concentrations of olanzapine (even in low-dose olanzapine therapy), and can recover from impaired glucose tolerance. In addition, HbA1c levels go down as insulin secretory ability improves.
The patient was a 67-year-old man. After the patient received a diagnosis of schizophrenia, various antipsychotics were prescribed but did not improve symptoms. However, 18 mg/day aripiprazole (APZ) was found to be highly effective and enabled the patient to continue treatment on an outpatient basis. Two weeks after prescribing clarithromycin for fever and cough, he was readmitted to our psychiatric ward because of anuresis and deterioration of bradykinesia and salivation. Biochemical analysis revealed elevated serum creatine phosphokinase (26060 U/I) and creatinine (2.2 mg/dL). On admission, the patient had a high blood concentration of APZ and its metabolite(s). APZ was therefore discontinued, but the concentration remained elevated until day 8. Hemodialysis was started on day 4 to treat persistent renal dysfunction. The patient's CYP2D6 genotype was CYP2D6*10/CYP2D6*10. The elevated APZ levels may have resulted from the inhibitory action of clarithromycin on CYP3A4 combined with the lower inherent CYP2D6 enzymatic activity of the CYP2D6*10/CYP2D6*10 genotype.
Purpose: Antidepressants possessing a wide range of pharmacological properties are available for the daily treatment of major depressive disorders (MDD). However, MDD patients with a partial response or a resistance to standard antidepressant therapy need to be treated with adjunctive psychotropic drugs such as mood stabilizers or atypical antipsychotics in order to achieve full remission. Investigation of combination pharmacotherapy in actual clinical practice could provide an insight into the features of adjunctive medications. Methods: The subjects of the study were MDD inpatients who were admitted from April 2010 to March 2013. The demographic and clinical data and prescription profiles for the psychotropic drugs at discharge were obtained from the medical charts of the patients. A statistical analysis of the data was conducted to clarify the difference between a single episode and recurrent episodes of MDD. Results: The adjunctive medication prescription rate for patients with recurrent episodes was significantly higher for antipsychotics, mood stabilizers and hypnotic drugs than that for patients with a single episode, even though no statistically significant differences were found between the two types of patients in their background characteristics. In addition, the proportion of patients who received prescriptions for both adjunctive antipsychotics and adjunctive mood stabilizers was understandably higher for recurrent MDD patients. Discussion: The present cross-sectional study demonstrated that there is a general tendency toward the prescription of multiple psychotropic drugs for the treatment of MDD inpatients, and that this tendency was more prominent in patients with recurrent episodes. Therefore, a well-designed treatment protocol that is supported by evidence from clinical trials is indispensable for the treatment of MDD in clinical practice.
Purpose: We administered olanzapine to 24 outpatients with bipolar disorder who had experienced a depressive or mixed episode as their most recent episode to evaluate the efficacy and safety of olanzapine in clinical practice. Methods: The duration of study treatment was 8 weeks. Symptoms in each subject were assessed using the Montgomery Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity of Illness, Bipolar Version (CGI-BP) at the start of treatment with olanzapine and at Week 4 and Week 8 of treatment. Results: A total of 17 subjects underwent the assessments at Week 4, and 13 subjects completed the 8-week treatment regimen and the assessments at Week 8. The mean total score and each individual item score of the MADRS were significantly improved at Week 4 and Week 8 compared to those at the start of treatment. The mean CGI-BP Depression and CGI-BP Overall scores were significantly improved at Week 4 and Week 8, while the mean CGI-BP Mania score was not significantly different at Week 4 or Week 8 compared to that at the start of treatment. Adverse drug reactions were reported in 3 subjects during the study: hyperphagia in 2 subjects and light-headed feeling in 1 subject. No manic switches were observed. Discussion: The results of this study confirmed the efficacy and safety of olanzapine in outpatients with bipolar depression in clinical practice.
A 54-year-old Japanese man who had received a diagnosis of schizophrenia and been treated with olanzapine for nearly 16 months consulted our department because of severe hyperglycemia (535 mg/dL). The use of antipsychotics, switching the patient from olanzapine to aripiprazole, and 7 weeks of insulin therapy resulted in a decrease in the patient's postprandial blood glucose levels and an increase in his postprandial C-peptide levels (442 mg/dL to 106 mg/dL and 1.72 ng/mL to 4.94 ng/mL, respectively) as well as an improvement in his pre-prandial levels (250 mg/dL to 85 mg/dL and 1.00 ng/mL to 1.69 ng/mL, respectively) with almost no change in the 24- hour urinary excretion of C-peptide. These results suggested that an insufficiency of insulin secretion, not insulin resistance, was associated with the patient's severe hyperglycemia, and that olanzapine-induced pancreatic β-cell impairment might be reversible if the hyperglycemia is diagnosed and treated sufficiently early. When prescribing second-generation antipsychotics such as olanzapine, clinicians should take the level of insulin into account in addition to monitoring serum glucose levels.