Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration–time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose–response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0–14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose–response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = −0.5; 95% CI: −1.1 to 0.1; per protocol set: P = 0.012, mean difference = −0.8; 95% CI: −1.3 to −0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose–response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.
We treated a patient with neurosarcoidosis, which caused the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in whom diagnosis was performed using neuroendoscopy. The patient was a 56-year-old female who was hospitalized for hyponatremia and diagnosed with SIADH based on a detailed examination. During the course, she developed impaired consciousness due to acute hydrocephalus, which improved after ventricular drainage. Head magnetic resonance imaging (MRI) confirmed nodular lesions at the floor of the third ventricle and the cerebral aqueduct. Neuroendoscopic biopsy led to the diagnosis of neurosarcoidosis. Her hyponatremia improved after steroid therapy. Neurosarcoidosis can cause SIADH, and complication of hydrocephalus may lead to a poor prognosis. Neuroendoscopy appears to be effective for the diagnosis of neurosarcoidosis with hydrocephalus and helps in deciding the treatment modality.
BackgroundPatients with psychiatric disorders have a high rate of suicide. The present study investigated factors influencing hospital stays for Japanese patients with psychiatric disorders attempting suicide by jumping.MethodsWe diagnosed all suicide attempts (n = 113) by jumping based on the International Classification of Diseases 10th Revision (ICD-10) and investigated the mean hospital stays of patients with each diagnosis based on the ICD-10 code. We then analyzed differences in the demographic and clinical characteristics between the diagnostic groups to identify factors influencing the duration of hospital stay.ResultsPatients diagnosed with schizophrenia (F2 code) were the most frequent (32.7%) of all diagnoses; therefore, we divided the diagnostic groups into schizophrenia group (n = 37) and other psychiatric diagnoses group (n = 76). The patients with schizophrenia showed a significantly longer hospital stay (125.7 ± 63.9 days) compared with the patients with other psychiatric diagnoses (83.6 ± 63.2) (β ± SE = 42.1 ± 12.7, p = 0.0013), whereas there was no difference in the jump height between the two groups (the average was the 3rd to 4th floor; p > 0.05). The number of injured parts, particularly lower-limb fractures, was significantly higher (p = 0.017) in patients with schizophrenia than in patients with other psychiatric diagnoses. The duration of psychiatric treatment in patients with schizophrenia were significantly longer (z = 3.4, p = 0.001) than in patients with other psychiatric diagnoses.ConclusionOur findings indicate that the number of injuries and the body parts injured in patients with schizophrenia are associated with a longer duration of hospital stay following a suicide attempt by jumping. The current use of antipsychotics and a longer duration of taking antipsychotics might contribute to the risk of bone fracture via hyperprolactinemia. Further cognitive impairment in patients with schizophrenia might prevent rehabilitation for the management of lower-limb fractures. From these results, we suggest that clinicians should monitor the level of prolactin and cognitive function in patients with schizophrenia in future studies on managing of lower-limb fractures.
We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose metabolism.
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