A case of musical hallucinations induced by tramadol.

AIM: Although tramadol has been suggested to have a higher risk of producing hallucinations than other opioids, reports of musical hallucinations are extremely rare. CASE PRESENTATION: A 72-year-old woman came to our department complaining of auditory hallucinations. She had been diagnosed with lumbar spinal canal stenosis associated with herniated and slipped disks. Due to persistent back pain, tramadol was started, and the dose was increased to 300 mg/day. The next day, she began to hear nursery rhymes, songs of the Ministry of Education, and folk songs. The musical auditory hallucinations disappeared with the use of antipsychotics and the discontinuation of tramadol. No relapse of musical auditory hallucinations was observed after the discontinuation of antipsychotics. CONCLUSION: Based on the clinical course, we concluded that the auditory hallucinations were musical hallucinations induced by tramadol.

Blood Levels of Ammonia and Carnitine in Patients Treated with Valproic Acid: A Meta-analysis.

Objective: Long-term valproic acid (VPA) administration is associated with adverse metabolic effects, including hyperammonemia and hypocarnitinemia. However, the pathogeneses of these adverse events remain unclear, and not enough reviews have been performed. The aim of this study was to conduct a meta-analysis of studies examining blood levels of ammonia and carnitine in patients treated with VPA. Methods: We conducted database searches (PubMed, Web of Science) to identify studies examining blood levels of ammonia and carnitine in patients treated with VPA. A meta-analysis was performed to conduct pre- and post-VPA treatment comparisons, cross-sectional comparisons between groups with and without VPA use, and estimations of the standardized correlations between blood levels of ammonia, carnitine, and VPA. Results: According to the cross-sectional comparisons, the blood ammonia level in the VPA group was significantly higher than that in the non-VPA group. Compared to that in the non-VPA group, the blood carnitine level in the VPA group was significantly lower. In the meta-analysis of correlation coefficients, the blood VPA level was moderately correlated with blood ammonia and blood free carnitine levels in the random effects model. Furthermore, the blood ammonia level was moderately correlated with the blood free carnitine level. Conclusion: Although the correlation between ammonia and free carnitine levels in blood was significant, the moderate strength of the correlation does not allow clinicians to infer free carnitine levels from the results of ammonia levels. Clinicians should measure both blood ammonia and free carnitine levels, especially in patients receiving high dosages of VPA.

New Insight Concerning Therapeutic Drug Monitoring-The Importance of the Concept of Psychonephrology.

Recently, the concept of psychonephrology was developed and has been recognized as a field of study that focuses on nephrology and mental health fields, such as psychiatry and psychosomatic medicine. Indeed, patients with chronic kidney disease frequently suffer from mental problems as the disease stage progresses. Most psychotropic drugs are hepatically metabolized, but some are unmetabolized and eliminated renally. However, renal disease may affect the pharmacokinetics of many psychotropic drugs, as the decreased renal function not only delays the urinary excretion of the drug and its metabolites but also alters various pharmacokinetic factors, such as protein-binding, enterohepatic circulation, and activity of drug-metabolizing enzymes. Therefore, when prescribing drug therapy for patients with both renal disease and mental issues, we should consider reducing the dosage of psychotropic drugs that are eliminated mainly via the kidney and also carefully monitor the blood drug concentrations of other drugs with a high extrarenal clearance, such as those that are largely metabolized in the liver. Furthermore, we should carefully consider the dialyzability of each psychotropic drug, as the dialyzability impacts the drug clearance in patients with end-stage renal failure undergoing dialysis. Therapeutic drug monitoring (TDM) may be a useful tool for adjusting the dosage of psychotropic drugs appropriately in patients with renal disease. We herein review the pharmacokinetic considerations for psychotropic drugs in patients with renal disease as well as those undergoing dialysis and offer new insight concerning TDM in the field of psychonephrology.

Difficult differentiation of a somatic symptom disorder from anterior cutaneous nerve entrapment syndrome (ACNES): a case report.

BACKGROUND: Somatization is regarded as psychological or emotional distress in the form of physical symptoms that are otherwise medically unexplained. CASE PRESENTATION: We report a case of a patient with a somatic symptom disorder (SSD) and depression who was later diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) when Carnett's test was positive and block anesthesia using trigger point injections dramatically improved the symptom of abdominal pain. CONCLUSION: We concluded that the differentiation of SSDs, such as psychogenic pain, from ACNES is very difficult. Psychiatrists should be aware of this syndrome.

Effects of nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan: A randomized controlled trial.

OBJECTIVE: Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. METHODS: From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Participants were randomly assigned to a standard care (A), doctor's weight loss advice (B), or an individual nutritional education group (C) for 12 months. The prevalence of MetS and body weight were measured at baseline and 12 months. RESULTS: After the 12-month treatment, 189 patients were evaluated, and the prevalence of MetS based on the ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%, respectively. Group C showed increased weight loss (3.2 ± 4.5 kg) over the 12-month study period, and the change in weight differed significantly from that of group A; additionally, 26.2% of the participants in group C lost 7% or more of their initial weight, compared with 8.2% of those in group A. CONCLUSION: Individual nutrition education provided by a dietitian was highly successful in reducing obesity in patients with schizophrenia and could be the first choice to address both weight gain and metabolic abnormalities induced by antipsychotic medications.

The Effect of Yokukansan, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug-Metabolizing Enzyme Activities in Healthy Male Volunteers.

The concomitant use of herb and prescription medications is increasing globally. Herb-drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug-metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7±2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6ß-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug-metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.

Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers.

PURPOSE: We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects. METHODS: In a randomized two phase, open-label crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice. For the uptake studies, oocytes expressing organic anion-transporting polypeptide 2B1 (OATP2B1) were incubated with 100 µM (R)- and (S)-fexofenadine in the presence or absence of 10 % apple juice. RESULTS: One-time ingestion of apple juice significantly decreased the area under the plasma concentration-time curve (AUC0-24) for (R)- and (S)-fexofenadine by 49 and 59 %, respectively, and prolonged the time to reach the maximum plasma concentration (t max) of both enantiomers (P < 0.001). Although apple juice greatly reduced the amount of (R)- and (S)-fexofenadine excretion into urine (Ae0-24) by 54 and 58 %, respectively, the renal clearances of both enantiomers were unchanged between the control and apple juice phases. For in vitro uptake studies, the uptake of both fexofenadine enantiomers into OATP2B1 complementary RNA (cRNA)-injected oocytes was significantly higher than that into water-injected oocytes, and this effect was greater for (R)-fexofenadine. In addition, apple juice significantly decreased the uptake of both enantiomers into OATP2B1 cRNA-injected oocytes. CONCLUSIONS: These results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably inhibits intestinal OATP2B1-mediated transport of both enantiomers. In addition, this study demonstrates that the OATP2B1 inhibition effect does not require repeated ingestion or a large volume of apple juice.

Dietary patterns are associated with obesity in Japanese patients with schizophrenia.

BACKGROUND: Obesity among patients with schizophrenia is a growing concern because being overweight is widely regarded as a major risk factor for cardiovascular disease and premature death. Dietary patterns have been suggested as one modifiable factor that may play a role in development of obesity. The objective of this study was to examine the association between dietary patterns and obesity among patients with schizophrenia in Japan. METHODS: We recruited patients (n = 338) aged 44.0 ± 13.2 (mean ± SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to four psychiatric hospitals using a cross-sectional design. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups were extracted by principal component analysis. RESULTS: A total of 61 subjects (18.0%) were classified as obese. Three dietary patterns were identified: the healthy dietary pattern, the processed food dietary pattern, and the alcohol and accompanying dietary patterns. After adjusting for age and gender, patients within the high tertile of each healthy dietary pattern (OR = 0.29, 95% CI = 0.13 to 0.62) and processed food dietary pattern (OR = 0.44, 95% CI = 0.22 to 0.89) had a significantly lower risk for obesity compared with low tertile of dietary pattern. CONCLUSIONS: Our findings suggest that dietary patterns, including higher intake of protein, fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and vitamins, may be related to a decreased prevalence of obesity within patients with schizophrenia. Future longitudinal research exploring dietary patterns and obesity among patients with schizophrenia is warranted.

The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil.

The effects of ginkgo supplementation on the steady-state plasma concentration of donepezil and the activity of cholinesterase in red blood cells and cognitive function were examined. Fourteen inpatients with Alzheimer's disease received donepezil 5 mg/day, supplemented with extracts of Ginkgo biloba 90 mg/day for 30 days. Blood samples were collected before and during ginkgo supplementation and 30 days after its discontinuation, together with an assessment of cognitive function. Plasma drug concentration was measured using high-performance liquid chromatography (HPLC), and cholinesterase in red blood cells was measured using Ellman methods. Cognitive function was evaluated using the Mini-Mental Scale Examination (MMSE). Plasma concentration of donepezil during ginkgo supplementation (mean +/- SD [95% confidence interval]; 24.4 +/- 12.6 ng/mL [17.1-31.7 ng/mL]) was not significantly different from that before ginkgo supplementation (22.7 +/- 10.3 ng/mL [16.8-28.7 ng/mL]) or that 4 weeks after its discontinuation (25.0 +/- 12.9 ng/mL [17.6-32.4 ng/mL]). There was no significant difference between cholinesterase in red blood cells before ginkgo supplementation (1.75 +/- 0.21 U [1.63-1.87 U]), during ginkgo supplementation (1.91 +/- 0.27 U [1.76-2.07 U]), and 4 weeks after its discontinuation (1.83 +/- 0.29 U [1.66-2.00 U]). Ginkgo supplementation did not alter MMSE scores throughout the study. The present study shows that ginkgo supplementation does not have major impact on the pharmacokinetics and pharmacodynamics of donepezil.