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Biomedical subjects

Jose de Leon

Publications and source records attributed to Jose de Leon.

At least 55 records · Page 3Linked to original sources
PubMed2004

Possible individual and gender differences in the small increases in plasma prolactin levels seen during clozapine treatment.

In vitro, animal studies and acute short-term clinical studies suggest clozapine releases prolactin but the effect is much smaller than that of typical antipsychotics. Repeated early morning trough measures of plasma clozapine and prolactin levels on each subject were studied during the course of a double-blind dose-response clozapine study. After a 4-week 10 mg/day haloperidol trial and a one-week washout, treatment- refractory schizophrenics were successively randomized to 100, 300,or 600 mg/day of clozapine for a 16- week treatment. The statistical analyses included 35 subjects (19 females and 16 males). The within-subject correlation of prolactin levels was 0.32 with clozapine levels and 0.75 with haloperidol levels. An increment of 100 ng/ml in clozapine level yielded an average increment of 0.45 ng/ml of prolactin levels in females and of 0.15 ng/ml in males. An increment of 1 ng/ml in haloperidol level yielded an average increment of 2.6 ng/ml of prolactin levels in females and of 1.5 ng/ml in males. At least one fourth of patients demonstrated a significant and strong (r > 0.6) correlation between clozapine and prolactin levels. This study suggests that clozapine has effects on prolactin levels but effects are small and may be more evident in some individuals, particularly females.

Adult↗
PubMed2004

Premenstrual symptoms and luteal suicide attempts.

OBJECTIVE: If premenstrual symptoms (PMS) are temporally and specifically associated with suicidal attempts, suicide attempts in women with PMS should occur more frequently in the luteal phase. METHOD: In a general hospital, 125 fertile female suicide attempters (and 83 blood donors as controls) with regular menstrual cycles were prospectively studied. A retrospective DSM-IV diagnosis of Premenstrual Dysphoric Disorder (PMDD) was made. RESULTS: Attempts during the luteal phase were not more frequent in females with PMDD (34%,23/68) than in those without PMDD (35%, 20/57). The sample had enough power to detect medium and large effect sizes. As expected, there was a significantly higher frequency of PMDD in suicide attempters than in the controls (54% vs 6%; Fisher's exact test, p < or = 0.001). CONCLUSION: This study was limited by the use of retrospective PMDD diagnosis but suggests that PMDD may not be associated with suicidal acts during the luteal phase,when PMS are present.

Adult↗
PubMed2004

Lack of association between polymorphic variations in the alpha 3 subunit GABA receptor gene (GABRA3) and suicide attempts.

This is the first case-control study exploring the association between suicide attempts and the polymorphic variations of the alpha 3 subunit gamma-aminobutyric acid (GABA) receptor gene (GABRA3) located in chromosome X. In a Spanish general hospital, 184 suicide attempters (127 women and 57 men) and 275 control blood donors (109 women and 166 men) were recruited. The four frequent variants (A1, A2, A3 and A4) of GABRA3 were studied. There were no significant differences in the total or by-gender frequencies of the four alleles. In females, there were no significant differences in the genotypes. This study can rule out even small size effects in the total sample and suggests a lack of association between GABRA3 polymorphism and suicide attempt, in the Spanish population.

Adult↗
PubMed2004

Caffeine intake in outpatients with schizophrenia.

Several studies suggest that caffeine intake is high in patients with schizophrenia and a few of them suggest that caffeine may contribute to schizophrenia symptomatology. None of these studies control for the effect of tobacco smoking, which is associated with induction of caffeine metabolism. Therefore, the high amount of caffeine intake among patients with schizophrenia may be due to their high prevalence of smoking. This is the first large study to explore whether caffeine intake in patients with schizophrenia is related to tobacco (or alcohol) use or to the severity of schizophrenia symptomatology. The sample included 250 consecutive consenting outpatients with a diagnosis of DSM-IV schizophrenia from Granada, Spain. Fifty-nine percent (147/250) of patients consumed caffeine. Current caffeine intake was associated with current smoking and alcohol use. As none of the females used alcohol, the association with alcohol was only present in males with schizophrenia. Among caffeine consumers, smoking was associated with the amount of caffeine intake. Cross-sectional schizophrenia symptomatology was not associated with caffeine intake.

Antipsychotic Agents↗
PubMed2004

Haloperidol half-life after chronic dosing.

In normal subjects after a single oral dose, haloperidol half-life has been reported to range 14.5-36.7 hours (or up to 1.5 days). After chronic administration, half-lives of up to 21 days have been reported. The objective of this study was to evaluate specific factors that might account for differences in haloperidol half-life in patients taking haloperidol chronically, including gender, age, weight, race, CYP2D6 and CYP3A5 genotypes, comedication, and smoking.Thirty-one patients were administered haloperidol for 4 weeks followed by a 1-week washout before administration of clozapine. Haloperidol plasma levels were measured weekly for at least 2 months after discontinuation. The geometric mean for haloperidol half-life and detectable levels duration were 3.9 and 13.8 days, respectively. Within 31 subjects, 58% (18/31) had half-lives <3 days (1.2-2.3 days) and 42% (13/31) had half-lives > or =3 days. Two of 3 patients with half-lives longer than 30 days (720 hours) and levels detectable >2 months had received haloperidol decanoate. Five patients who received haloperidol decanoate in the prior year were excluded from a comparison between patients with long haloperidol half-lives (> or =3 days, n = 10) and patients with short half-lives (<3 days, n = 16). The only significant difference between the two groups was that African-Americans (n = 4) were all found to have a long haloperidol half-life (P = 0.014). CYP3A5 genotype did not appear to influence haloperidol half-life but the two CYP2D6 poor metabolizer had half-lives > or =3 days. This study suggests that haloperidol half-life following repeated drug administration is substantially more prolonged than what has been observed after acute haloperidol administration.

Adult↗
PubMed2004

Variables associated with hospitalization decisions by emergency psychiatrists after a patient's suicide attempt.

OBJECTIVE: This study explored the factors psychiatrists considered in deciding on hospitalization for a large sample of suicide attempters in the emergency department of a general hospital in Madrid, Spain, between 1996 and 1998. METHODS: Psychiatrists assessed 509 patients who had attempted suicide; 196 of these (39 percent) were hospitalized in the psychiatric unit, and 313 (61 percent) were discharged from the emergency department. The assessment included Beck's Suicidal Intent Scale (SIS) and a checklist of 47 clinical variables. RESULTS: Of the 32 clinical variables significantly associated with hospitalization that were introduced in a logistic regression model, 11 remained significant. Six variables were associated with an increased odds of hospitalization: intention to repeat the attempt, plan to use a lethal method, low psychosocial functioning before the suicide attempt, previous psychiatric hospitalization, a suicide attempt in the past year, and planning that nobody would try to save their life after they had attempted suicide. Five variables decreased the odds: a realistic perspective on the future after the attempt, relief that the attempt was not effective, availability of a method to kill oneself (that was not used), belief that the attempt would influence others, and family support. Models based on the SIS total score and individual SIS items had lower specificity and sensitivity. CONCLUSIONS: Psychiatrists appear to rely on patients' self-report in deciding on hospitalization rather than focus on demographic, diagnostic, or psychosocial issues. If the findings of this study were replicated in other hospital settings, the implication would be that the guidelines for assessing suicide attempts need to encourage thorough and detailed assessment of the attempt and the future plans.

Adolescent↗
PubMed2004

Variables associated with high olanzapine dosing in a state hospital.

BACKGROUND: Olanzapine has a U.S. Food and Drug Administration-approved dosing range of 10 to 20 mg/day but is often used at doses exceeding this range. Olanzapine is largely metabolized by cytochrome P450 (CYP) 1A2. Smoking, which induces CYP1A2, is expected to increase clearance of olanzapine by 40%; however, dosage adjustment in smokers is not currently recommended. Additionally, female gender is expected to reduce clearance by 30%. Many institutions target high-dose olanzapine prescribers in an effort to reduce unnecessary drug costs. However, factors such as smoking or gender may necessitate increased doses. METHOD: A retrospective review of all patients receiving olanzapine during an inpatient stay at a state psychiatric hospital in Kentucky during 2001 was conducted. Demographic information and smoking status were collected for all patients. Olanzapine doses of > 20 mg/day were considered high doses. RESULTS: Nine percent (48/522) of olanzapine patients were prescribed high doses. The percentages were similar in women and men (10% vs. 9%, p =.69) and in smokers and nonsmokers (9% vs. 9%, p =.82). Moreover, the mean maximum olanzapine dose was also similar in men and women (15.4 +/- 7.2 vs. 14.9 +/- 7.3 mg/day, p =.51). The odds of receiving a high dose of olanzapine were increased 2.1 for patients with a schizophrenia spectrum diagnosis (DSM-IV schizophrenia or other psychotic disorder). The odds of receiving a high dose of olanzapine were increased with each incremental increase in length of stay (intermediate length of stay [8-60 days], OR = 5.6; long-term length of stay [> 60 days], OR = 12.0, relative to acute length of stay [< 8 days]). CONCLUSIONS: Neither gender nor smoking status was associated with receiving a high dose of olanzapine. The association of increased length of stay with high dose suggests that treatment resistance may be an important factor in receiving high daily doses of olanzapine.

Adult↗
PubMed2003

Schizophrenia and tobacco smoking in a Spanish psychiatric hospital.

This study in a Spanish hospital replicated two US studies suggesting that schizophrenia is associated with smoking when compared with other severe mental illnesses. Neither antipsychotics nor institutionalism could explain this relationship. Seventy of the 100 schizophrenic and 53 of the 100 non-schizophrenic inpatients were current smokers. After correcting for confounding factors, schizophrenia increased the risk of smoking by 2- to 3-fold. Heavy smoking was not associated with schizophrenia.

Catchment Area, Health↗
PubMed2003

Polydipsia--a study in a long-term psychiatric unit.

This is a retrospective review of the author's experience with polydipsia in a long-term unit for treatment refractory patients at a US psychiatric state hospital during a 5-year period [1996-2000]. Sixty-one patients were admitted to this long-term unit, comprising approximately 1 % of the hospital admissions. Polydipsic patients were followed with diurnal weight changes and other biological measures. This longitudinal study of 61 chronic inpatients suggests that polydipsia is no doubt present in at least 20 % of chronic psychiatric inpatients and hyponatremia in more than 10 %. Two polydipsic patients worsened when switched from clozapine to other atypical antipsychotics. Polydipsia in severe mentally ill patients continues to be a neglected subject and a challenge for psychiatrists. Polydipsic patients should not be switched to other atypical antipsychotics, unless new prospective studies prove that they are as effective as clozapine for polydipsia.

Adult↗
PubMed2003

A pilot study on a gene-hormone interaction in female suicide attempts.

This one-year naturalistic study included all suicide attempters in a catchment area. In the first published set of analyses, an association between menses and suicide attempts was replicated. According to the polymorphism of the serotonin transporter promoter area, the subjects can be classified as S individuals (s/s or s/l) or L individuals (l/l). In the second published set of analyses, L females appeared protected from suicide attempts since they were underrepresented among female (and not male) attempters. This new, unpublished third set of analyses tested for an interaction between the same polymorphism and low hormonal activity (during menses and menopause). In fertile female attempters, the proportion of L women in the menses (41%, 7/17) was significantly higher than expected in the population (15.5 %) and almost significantly higher than in S female attempters (22%,19/87). L females were also overrepresented in postmenopausal attempters. Despite sample size limitations, this gene-hormone interaction needs to be further investigated in female suicide attempters.

Carrier Proteins↗
PubMed2003

A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers.

Even though 85% of adults drink caffeinated beverages daily, very limited studies on plasma caffeine concentration in the US population have been published. Smoking induces cytochrome P450 1A2 (CYP1A2), which is the main enzyme involved in caffeine metabolism. The current naturalistic pilot study explores plasma caffeine concentrations in a US sample, and presents a mathematical model of the relationship between caffeine intake and plasma concentrations for smokers and nonsmokers. Caffeine intake and average plasma caffeine concentrations from morning (7:30-9:30 a.m.) and afternoon (2:00-4:00 p.m.) samples were studied in 69 volunteers (21 smokers and 48 nonsmokers). The mean caffeine intake obtained from caffeinated beverages was 3.02 mg/kg/day, which is similar to the intake in the US population. Almost all subjects in the present sample (99%; 95% confidence interval [CI]: 96-100) had detectable plasma caffeine concentrations. Smokers had significantly higher caffeine intake than nonsmokers. The ratio of concentration/dose of caffeine from caffeinated beverages was approximately four-fold higher in nonsmokers (1.33 kgxday/l) than in smokers (0.29 kgxday/l). According to the model, the median plasma caffeine concentration was two- to three-fold higher in nonsmokers for each level of caffeine intake. Our model improves our understanding of the interactions between caffeine and smoking. Additional studies are needed to replicate the model. This model may help epidemiologists to correct for the effects of smoking on caffeine intake and pharmacologists to screen for the activity of CYP1A2.

Adult↗