Association Between the Serum Carnitine Level and Ammonia and Valproic Acid Levels in Patients with Bipolar Disorder.

PURPOSE: Valproic acid (VPA) is not only an antiepileptic drug but also a mood stabilizer for patients with bipolar disorder. Long-term VPA therapy can cause carnitine deficiency, which may result in an increase in the blood ammonia level, in patients with epilepsy. However, information about this effect in patients with bipolar disorder is limited. The aim of this study was to investigate the associations between the serum VPA level and the carnitine and ammonia levels in psychiatric adult patients with epilepsy. METHODS: The subjects were 182 consecutive Japanese adult patients (mean age 54.3 ± 19.5 years) diagnosed with bipolar disorder and treated with VPA. The serum VPA level, carnitine fraction, and plasma ammonia level were measured. Furthermore, the free carnitine and acylcarnitine fractions were measured using an enzyme cycling method. RESULTS: Sixty-nine patients (38%) had a low free carnitine level. There were significant differences in sex, height, VPA dose, serum VPA level, total carnitine level, acylcarnitine level, and acylcarnitine/free carnitine ratio between patients with a low free carnitine level and those with a normal range of free carnitine. The simple and multiple regression analyses revealed that the VPA dose and the serum VPA level were inversely and significantly correlated with the free carnitine level. The plasma ammonia level was correlated with the VPA dose, serum VPA level, and acylcarnitine level but not with the free carnitine level. CONCLUSIONS: These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder.

Differences in etiological beliefs about schizophrenia among patients, family, and medical staff.

OBJECTIVES: To determine whether etiological beliefs are different among schizophrenia patients, their family, and medical staff. PATIENTS AND METHODS: A cross-sectional study was performed at five hospitals and one mental clinic and included 212 patients, 144 family members, and 347 medical staff other than psychiatrists. A questionnaire about the possible etiological causes of schizophrenia was used. RESULTS: There were significant differences in response scores among the three groups on using Angermeyer's and Goulding's classifications. Factor analyses revealed the following four subscales: Psychosocial, Biological, Environmental, and Cultural connotations. The structure varied among patients, family, and medical staff. CONCLUSION: The perspectives of schizophrenia etiology were different among patients, family, and medical staff.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

BACKGROUND: Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. METHODS: A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. RESULTS: The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. LIMITATIONS: Patients were asked about possible participation in placebo-controlled clinical trials. CONCLUSIONS: Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial.

Successful treatment with tacrolimus of refractory pyoderma gangrenosum with pouchitis after restorative proctocolectomy for ulcerative colitis.

We describe herein a case of severe relapsed pyoderma gangrenosum (PG) concomitantly with severe pouchitis treated by tacrolimus. A 25-year-old woman had undergone proctocolectomy with construction of ileo-anal pouch surgery for refractory ulcerative colitis (UC). She first developed PG with refractory pouchitis, and infliximab (IFX) was administered to induce remission due to resistance to glucocorticoid therapy. After achieving remission, IFX was stopped. Five years later, severe skin ulcers concomitantly with severe pouchitis recurred and treatment with 30 mg oral prednisolone (PSL) combined with topical tacrolimus showed partial improvement. When PSL was tapered to 15 mg, the skin ulcers and diarrhea aggravated. Endoscopy revealed multiple ulcers in the ileal pouch. Treatment with oral tacrolimus was initiated for severe pouchitis and refractory PG. Forty days later, all skin ulcers became scars and multiple ulcers in the ileal pouch were also improved. Our case suggests that oral tacrolimus treatment could be a valuable treatment option for UC patients with refractory PG and pouchitis.

Delirium in hemodialysis predicts mortality: a single-center, long-term observational study.

OBJECTIVES: Delirium signifies underlying brain dysfunction; however, its clinical significance in hemodialysis remains unclear. In this study, we sought to determine whether the occurrence of delirium during hemodialysis was associated with higher mortality. PATIENTS AND METHODS: This was a retrospective, 10-year cohort study. This study was performed at the urology department located within a hospital in Oyokyo, Hirosaki. We analyzed 338 of 751 patients who underwent hemodialysis. Psychiatrists diagnosed patients with delirium according to the corresponding DSM-IV-TR criteria. Cox proportional hazard regression, which was adjusted for patient age at the time of hemodialysis initiation, sex, and the presence of diabetes mellitus, was performed. Hazard ratios (HRs) and their 95% CIs were also reported. RESULTS: In total, 286 patients without psychiatric diseases and 52 patients with delirium were evaluated. Eighty percent of patients with delirium died within 1 year of hemodialysis initiation, while only 22% of patients without delirium died within the same time period (P<0.01). Kaplan-Meier plots demonstrated the existence of associations between delirium and all-cause mortality (global log-rank P<0.001), cardiovascular disease-related mortality (global log-rank P<0.001), and infection-related mortality (global log-rank P<0.001). Moreover, Cox proportional hazard regression showed that delirium was associated with all-cause mortality (HR=1.96, 95% CI: 1.32-2.90), cardiovascular disease-related mortality (HR=2.65, 95% CI: 1.31-5.35), and infection-related mortality (HR=3.30, 95% CI: 1.34-8.10). CONCLUSION: Delirium is an independent predictor of death in patients undergoing hemodialysis.

Levodopa-responsive depression associated with corticobasal degeneration: a case report.

A 60-year-old female was treated for depression with the antidepressant paroxetine for 13 years. The patient had experienced clumsiness and mild rigidity in the left hand, and had agraphia and mild subjective memory complaints for 3 years prior to admission in our hospital. She experienced exacerbated depression that included worsened depressive mood, lowered motivation, and suicidal ideation without precipitating stressful life events for 2 years prior to admission, and although she had continued taking the antidepressant, these symptoms were not ameliorated by increasing the dose of paroxetine. Following the development of myoclonus and pain in her left arm, we performed magnetic resonance imaging of her head, that revealed diffuse atrophy and right parietal lobe atrophy. The patient was ultimately diagnosed with corticobasal degeneration (CBD). Her left arm myoclonus and depression improved following levodopa administration. Therefore, we concluded that the recurrent depression may have been induced by CBD.