Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease.

PURPOSE: Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). METHODS: Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. RESULTS: The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. CONCLUSIONS: The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.

Mental and somatic symptoms related to suicidal ideation in patients visiting a psychosomatic clinic in Japan.

Patients with suicidal ideation (SI) have various mental or somatic symptoms. A questionnaire-based interview elicited details concerning mental and somatic symptoms in patients visiting a psychosomatic clinic in Japan. Univariate logistic regression analyses followed by multiple regression models using a stepwise method were selected for identifying the candidate symptoms. Overall, symptoms related to depression were associated with SI in both sexes. Although women showed more various somatic symptoms associated with SI than men, many of those associations were diminished once severity of the depression was controlled. The current results suggest that a variety of self-reported symptoms, mainly related to depression, might reveal suicidal risk in outpatients with an urban hospital clinical setting.

Gender differences in psychiatric symptoms related to suicidal ideation in Japanese patients with depression.

Recent figures show that more than 30,000 people suicide each year in Japan, and that many of them are considered to suffer from depression. In addition, the suicide rate among Japanese women has been shown to be higher than in other countries. However, it is not clear whether the psychiatric symptoms leading to suicide differ by gender. The authors examined gender differences in psychiatric symptoms related to suicidal ideation (SI) in Japanese patients with depression. Study subjects were 199 new patients (66 men and 133 women) who were diagnosed with a major depressive disorder. SI and psychiatric symptoms were assessed by several psychological tests using questionnaires. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (CI) with an adjustment for all relevant factors simultaneously. The stepwise method was also used for selecting variables. In univariate analysis, several psychosocial factors such as self-reproach, derealization, depressive moods, depersonalization, and anxiety traits were statistically significantly associated with SI in both men and women. However, multivariate analysis using the stepwise method distinguished gender differences. Low social/family support and depersonalization were statistically significantly associated with SI in men, while depressive moods and an anxiety state were significantly associated with SI in women. The relation between derealization and SI was statistically significant in women but not significant in men.

Somatic symptoms most often associated with depression in an urban hospital medical setting in Japan.

Somatic symptoms are known to be a prominent characteristic in patients with depression. The aim of the present study was to investigate the major somatic and psychiatric symptoms associated with depression in each sex. Patients with a DSM-IV diagnosis of depressive disorders (n=335) and comparison patients without depression (n=423) among new outpatients in an urban hospital medical setting were eligible for study. The relationship between the the most distressing subjective symptoms at first visit, confirmed by the patient's description on a health questionnaire and the admitting physician's interview, and depression was investigated in each sex. Most (73.5%) of the complaints in patients with depression were somatic. In a simple logistic regression analysis, diarrhea, excessive sweating and psychomotor retardation in men and headache, depressed mood and grief in women were associated with depression. In multiple logistic regression analysis, diarrhea, excessive sweating and weight loss in men, and headache, dysesthesia and grief in women, as well as sleep disturbance, loss of appetite, general fatigue loss on interest and agitation in both sexes, were significantly associated with depression. Fever in men was also associated with depression by Fisher's exact test.

Somatic symptoms most often associated with depression in an urban hospital medical setting in Japan.

Somatic symptoms are known to be the major manifestation in patients with depression. The aim of the present study was to investigate the major somatic and psychiatric symptoms associated with depression in each sex. Patients with a DSM-IV diagnosis of depressive disorders (n=335) and comparison patients without depression (n=425) among new outpatients in an urban hospital medical setting were eligible for study. The relationship between the three most distressing subjective symptoms at the first visit, confirmed by the patient's description on a health questionnaire and the admitting physician's interview, and depression was investigated in each sex. Most (77.4%) of the complaints in patients with depression were somatic. In a simple logistic regression analysis, diarrhea, excessive sweating and psychomotor retardation in men, and headache, depressed mood and grief in women were associated with depression. In multiple logistic regression analysis, diarrhea, excessive sweating and weight loss in men, and headache, dysesthesia and grief in women, as well as sleep disturbance, loss of appetite, general fatigue, loss of interest and agitation in both sexes, were statistically significantly associated with depression. Fever in men was also associated with depression by Fisher's exact test.

Brain blood perfusion hypothesis for migraine, anger, and epileptic attacks.

The common physiological rationale for migraine, anger, and epileptic attacks is discussed. The potential importance of homeostatic reactions in brain blood perfusion is described. The author speculates that these attacks are induced to meet some urgent biological needs. Each attack of migraine, anger, and epilepsy results in increased regional cerebral blood flow, with hypoperfusion being shown in inter-icteric states. This hypoperfusion may also be related to cerebral ischemic disease, organic change, some critical condition, or vasoconstriction due to sympathetic hyperactivity. Migraine attack is a subacute local vasomotor response. In contrast, anger and epileptic attacks are different manifestations of acute solemn general neuropsychiatric vasomotor reflexes. The newer paradigm of the etiological integration of these three kinds of attacks based on cerebral hemodynamic change does not only explain the mechanism of seizure-producing treatments such as electroconvulsive therapy, but also indicates the significance of cerebral vasodilative demands for the particular treatment of migraine, aggressive behavior, and epileptic seizures.

Nightmares and panic disorder associated with carvedilol overdose.

OBJECTIVE: To report a case of nightmares and sleep disorder associated with improper use of carvedilol, an alpha/beta-blocker, and to model the time course of receptor occupancy in this patient. CASE SUMMARY: A 41-year-old man with panic disorder had been treated with alprazolam 1.2 mg/d (3 times daily), carvedilol 10 mg/d (once in the morning), and etizolam 0.5 mg (for anxiety attack). Although the physical and psychological symptoms gradually improved, he reported nightmares and panic attacks. An interview revealed that he had been taking carvedilol 5 mg twice a day after lunch and dinner on his own initiative, in addition to the prescribed dosage. The patient was asked to take carvedilol 10 mg only after breakfast, as had been advised. Consequently, the sleep disorder and nightmares disappeared. METHODS: We calculated the time courses of beta(2)-adrenoceptor binding occupancy in the central nervous system after oral administration of carvedilol with the ordinary and improper regimens by using pharmacokinetic/pharmacodynamic parameters obtained from the literature. RESULTS: Compared with the ordinary dose of carvedilol 10 mg once a day, the improper regimen (10 mg after breakfast followed by 5 mg after lunch and dinner) increases the beta(2)-adrenoceptor binding occupancy at night (2300) to as high as the mean beta(2)-adrenoceptor binding occupancy after an ordinary dose of propranolol. CONCLUSIONS: The sleep disorder and nightmares experienced by this patient had been induced by elevation of central beta(2)-adrenoceptor binding occupancy at night as the result of improper use of carvedilol.