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T Baptista

Publications and source records attributed to T Baptista.

At least 19 recordsLinked to original sources
PubMed2004

Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics.

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.

Animals↗
PubMed2002

Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.

Excessive body weight gain (BWG) is a common side effect of some typical and atypical antipsychotic drugs (APs). Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. BWG may be related to increased appetite that is due to drug interaction with the brain monoaminergic and cholinergic systems and to the metabolic/endocrine effects of hyperprolactinemia. Subjects with schizophrenia and bipolar disorders manifested a significantly high prevalence of diabetes, even before the introduction of atypical APs. However, clozapine and olanzapine appear to display a high propensity to induce glucose dysregulation and dyslipidemia. Sudden BWG, insulin resistance, increased appetite, and related endocrine changes also may be involved in the development of glucose intolerance and dyslipidemia in predisposed individuals. Patients should be informed of these side effects in order to prevent excessive BWG, and their blood glucose and lipids should be monitored before treatment and then at regular intervals. Nutritional advice must be given and regular physical exercise recommended. An appropriate selection of APs ought to be based on drug efficacy for specific patients and assessment of relevant risk factors such as propensity to gain weight; family or personal history of diabetes or hyperlipidemia; and elevated fasting serum glucose, lipid, or insulin levels. At present, there is no standardized pharmacological treatment for AP-induced BWG. Some studies have assessed the effects of agents such as amantadine, orlistat, metformin, nizatidine, and topiramate on AP-induced BWG. Further studies will provide tools to identify patients at high risk for obesity and metabolic abnormalities during AP administration. Excessive body weight gain (BWG), glucose intolerance, and dyslipidemia during treatment with antipsychotic drugs (APs) were reported in the late 1950s [14,101]. However, after 1990, interest in these problems increased noticeably, mainly because of the high propensity of some new atypical APs to induce these side effects (Fig.1). The APs are currently used in diverse mental disorders. Hence, excessive BWG and metabolic dysfunction are not exclusive of subjects with schizophrenia. In the case of bipolar disorders, AP-induced BWG may be additive to that induced by mood stabilizers [14,48,101]. The clinical features [2,14,24,133,139,140] and mechanisms [14,34,68,87,93,101,130] of BWG and metabolic dysfunction have been previously reviewed. In this article, we focus on a unified theory to explain these side effects, based on the interaction of APs with brain neurotransmitters involved in appetite regulation. This review comprises the following sections: 1) the clinical features of AP-induced BWG; 2) the effects of APs on carbohydrate and lipid metabolism in humans and experimental animals; 3) mechanisms involved in BWG, glucose, and lipid dysregulation; 4) strategies for prevention and treatment of these side effects; and 5) research perspectives in the field. The following sources were consulted: MEDLINE, Cochrane database system, and PsychINFO. Numerous articles referred to in leading articles also were consulted. The literature on this subject has increased so rapidly that it was impossible to include all the data recently published. For the first two sections, references that illustrate current controversies in the field were selected.

Animals↗
PubMed2001

Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration.

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Adrenal Glands↗
PubMed2001

Antipsychotic drugs and obesity: is prolactin involved?

OBJECTIVES: To correlate the anthropometric indexes (Body Mass Index [BMI] and Waist-Hip ratio [WHR]) with the serum prolactin levels in a heterogeneous population of patients treated with typical antipsychotic (AP) drugs. METHODS: We evaluated BMI, WHR, and fasting serum prolactin of inpatients (n = 105) and outpatients (n = 122) treated with APs, in outpatients receiving other psychotropic drugs (OPDs) (n = 77), and in drug-free subjects (n = 33). Outpatients had free access to food, whereas the inpatient sample comprised people with a monotonous diet of approximately 2000 Kcal daily. RESULTS: Prolactin correlated positively with the BMI in the whole group of AP-treated outpatient men (P = 0.03) and with the WHR in AP-treated inpatient men (P = 0.053). Regarding treatment duration, prolactin and BMI correlated positively in men consecutively treated for more than 1 year (P = 0.023). By contrast, a trend toward a negative correlation between prolactin and BMI was observed in AP-treated outpatient women (P = 0.08). No significant correlation, or even a trend, was observed in the other groups. CONCLUSIONS: Prolactin may be involved in AP-induced weight gain, particularly in men. Future studies should characterize the period of maximal prolactin impact on body weight during AP treatment. Specific populations particularly sensitive to hyperprolactinemia might be identified as well. The negative correlation between prolactin and BMI detected in AP-treated women resembles the dampened prolactin response observed in severe primary obesity.

Adult↗
PubMed2000

Naltrexone does not prevent the weight gain and hyperphagia induced by the antipsychotic drug sulpiride in rats.

Few pharmacological tools are currently available to counteract the excessive body weight gain often observed during prolonged administration of antipsychotic drugs. Most antipsychotic drugs block dopamine receptors, and both the brain dopaminergic and opioid systems appear to be involved in initiation and maintenance of feeding behavior, respectively. We evaluated whether the opioid antagonist naltrexone (NAL, 0.5-16 mg/kg/ip for 21 days) (a) affects body weight and food intake in gonadally-intact and drug-free female rats, (b) prevents obesity, hyperphagia, hyperprolactinemia and vaginal cycle disruption induced by long-term administration of the antipsychotic drug sulpiride (SUL, 20 mg/kg/ip for 21 days), or (c) reverses the acute hyperphagia induced by SUL (15 microg bilaterally), when directly applied in the perifornical lateral hypothalamus (PFLH). In drug-free rats, only NAL doses above 4 mg/kg, significantly decreased weight gain and food intake. Even though NAL (1 and 8 mg/kg) significantly attenuated SUL-induced hyperphagia and hyperprolactinemia, it did not reverse at any dose the weight gain and permanent diestrous induced by SUL. In addition, local NAL did not prevent the hyperphagia and polidypsia observed after acute intrahypothalamic SUL. Unexpectedly, the cumulative and 24 h food intake in SUL-treated rats was significantly increased by NAL. Collectively, these results do not support a role for endogenous opiates in the neural and endocrine mechanisms involved in weight gain during prolonged antipsychotic drug administration in rats.

Animals↗
PubMed2000

Endocrine effects of lithium carbonate in healthy premenopausal women: relationship with body weight regulation.

The mechanisms involved in Li-induced weight gain remain unclear. The higher frequency of obesity in women than in men under Li treatment, suggests a role for reproductive hormones. The serum levels of the following hormones were evaluated in healthy young women at diverse stages of a control menstrual cycle, and during Li carbonate (900 mg/day) or placebo administration: prolactin, luteinizing hormone, follicle-stimulating hormone, 17-1 estradiol, progesterone, thyroxine, thyrotropin, cortisol, dehidroepiandrosterone sulfate, free testosterone, leptin and an oral glucose tolerance test, in order to measure the areas under the glucose and insulin curve. The body weight was assessed the day before and the last day of treatment. The Li serum levels 15 hours after the last dose were 0.31 +/- 0.1 mEq/L. No significant changes in body weight and in the normal fluctuations of the reproductive hormones along the menstrual cycle were observed during Li administration. An increase in the serum levels of thyrotropic hormone ( p = 0.0001) was the only significant effect of Li, which may predispose to excessive weight gain after prolonged administration of the cation. The remarkable lack of effects of Li on these hormones, question the pertinence of studies conducted in healthy volunteers for the comprehension of the obesity observed in psychiatric patients who may be particularly prone to gain weight under prolonged treatment with high dose of Li.

Adult↗
PubMed2000

Antipsychotic drug-induced obesity in rats: correlation between leptin, insulin and body weight during sulpiride treatment.

Sulpiride (SUL, 20 mg kg-1 day-1) induces weight gain, hyperphagia, hyperprolactinemia, hypogonadism, and perhaps increased insulin sensitivity in rats. Leptin seems to signal the brain about the size of body fat stores and nutrient metabolism. We evaluated the basal serum leptin levels in rats after acute (1 h) or prolonged SUL or vehicle administration (10, 20 and 30 days). At days 10 and 30 leptin was also assessed during a glucose overload test. As the maximal weight gain during SUL administration is observed at days 10-15 of treatment, leptin was measured in a comparison group of insulin-treated rats (5 IU day-1 for 10 days). SUL-treated rats significantly gained weight. However, leptin levels were not significantly increased at any time-point of treatment. SUL did not affect insulin levels either. By contrast, leptin levels were significantly elevated after insulin administration, along with weight gain and hyperinsulinemia. An opposite correlation was also observed at day 10: leptin and insulin correlated negatively in the SUL group and positively in the insulin group. In addition, leptin and the magnitude of weight gain tended to correlate positively after SUL treatment, but negatively after insulin administration. SUL-treated rats, thus, appear to exhibit an unusual type of weight gain, characterized by normal circulating leptin and insulin levels. Such a particular leptin profile may be related to hyperprolactinemia, hypogonadism or lack of hyperinsulinemia. Molecular Psychiatry (2000) 5, 70-76.

Animals↗
PubMed2000

Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones.

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.

Adult↗
PubMed1999

Antipsychotic drugs and reproductive hormones: relationship to body weight regulation.

Excessive body weight gain is an undesirable side effect of prolonged administration of antipsychotic drugs (AP), which affects health and interferes with treatment compliance. It has been suggested that hyperprolactinemia-induced endocrine and metabolic abnormalities, particularly in the gonadal steroids, might be involved in the development of this type of weight gain. To test this hypothesis, reproductive hormones, cortisol, dehydro-epiandrosterone-sulfate (DHEA-S), thyroid hormones, and body weight gain were assessed in 18 patients (9 men, 9 women) with mental disorders receiving AP who had been medication-free for at least 3 months before the study, and in 27 placebo-treated subjects (10 men, 17 women). In women, hormones were evaluated during several phases of the menstrual cycle. A significant weight gain was observed in men but not in women. Under AP administration, women displayed significantly lower serum levels of estradiol and progesterone, whereas in men the levels of free testosterone and DHEA-S were significantly lower than in controls. Hyperprolactinemia was observed in both sexes. The levels of follicle-stimulating hormone in women and luteinizing hormone in men were significantly elevated by treatment, thus suggesting that the functioning of the hypothalamus-pituitary gonads was preserved. In men, such an endocrine profile resembles that observed in subjects with primary obesity. Women under AP administration were found to be relatively hyperandrogenic because of decreased serum estradiol levels, whereas women with primary obesity are known to display actual increased levels of androgens. These endocrine abnormalities may contribute to the excessive weight gain observed after AP treatment, and these could be the target of novel pharmacological treatments.

Adult↗
PubMed1999

Glucose tolerance and serum insulin levels in an animal model of obesity induced by sub-acute or chronic administration of antipsychotic drugs.

1. To assess the role of insulin in the development of the obesity induced by antipsychotic drugs, a glucose tolerance test was conducted in female rats after 0 or 30 days of sulpiride administration. 2. At day 10, the area under the glucose curve did not differ between sulpiride and vehicle-treated rats, however, the area under the insulin curve was significantly decreased by sulpiride. At day, 30 the insulin response was similar in both groups, but the area under the glucose curve was significantly lower in the sulpiride-treated rats. 3. The results suggest that insulin resistance and hyperinsulinemia are not involved in the development and maintenance of the obesity induced by sulpiride. Contrarily, these findings may be related to an increased insulin sensitivity. 4. The absence of hyperinsulinemia and insulin resistance indicates important differences between primary obesity in humans and rodents and this model of drug-induced excessive weight gain.

Animals↗
PubMed1999

Body weight gain induced by antipsychotic drugs: mechanisms and management.

Long-term administration of typical and atypical antipsychotic drugs (AP) induces excessive weight gain which afflicts up to 50% of patients, impairs health and interferes with treatment compliance. Basic and clinical research has shown that AP may affect body weight through diverse mechanisms. Increased appetite is probably related to the interaction of AP with neuronal receptors to dopamine, serotonin and histamine. Additional metabolic-endocrine disruption of weight regulation may be related to the effects of AP-induced hyperprolactinaemia on gonadal-adrenal steroids and insulin sensitivity. In humans, programmed physical activity, dietary restriction, anorectic agents, and drugs that counteract hyperprolactinaemia have been shown to be successful in a limited number of studies. Two novel strategies could expand the available therapeutic options. First, in preclinical experiments in female rats the estradiol antagonist/agonist drug tamoxifen or estradiol itself have been shown to completely prevent the obesity provoked by the AP sulpiride, and to induce an endocrine-metabolic milieu that seems to counteract AP-induced obesity. Secondly, it has also been shown that oral antihyperglycaemic agents such as metformin may decrease body weight and counteract insulin resistance and hyperinsulinaemia which is correlated with several metabolic abnormalities in obese subjects. Lastly, estradiol replacement, tamoxifen and/or antihyperglycaemic agents are not devoid of significant side-effects, and these drugs have not been tested in obese psychiatric patients. Therefore, further research is needed before their clinical use may be recommended.

Animals↗
PubMed1998

Mechanism of the neuroleptic-induced obesity in female rats.

1. Obesity is an undesirable side effect of neuroleptics which affects 50% approximately of patients under a program of chronic administration. 2. An animal model of neuroleptic-induced obesity and hyperphagia has been developed in female rats treated chronically with sulpiride (20 mg/Kg/ip. for 21 days). However, it is unknown whether or not the hyperphagia is essential for the development of this type of obesity. 3. Sulpiride or vehicle was administered in two experimental conditions: in the first one, food was available in an amount which was three times the previous individual daily food intake; in the second one, the daily food provision was maintained at the individual daily average before starting the treatments. This way hyperphagia was prevented in half of the groups. Besides the body weight gain measurement in all the groups, the serum levels of estradiol, prolactin, glucose and lipids were assessed in the groups with unrestricted food intake. 4. Food restriction prevented the sulpiride-induced weight gain, even though the rats displayed a permanent diestrus which suggests an hyperprolactinemia-induced impairment in the balance of the reproductive hormones that may promote weight gain. However, the basal levels of estradiol were not affected by sulpiride. 5. The high density cholesterol was significantly increased by sulpiride, and the serum glucose levels were significantly decreased, however these changes were only detected during the first week of treatment. 6. The decrease in the serum glucose levels may be an early consequence of hyperinsulinemia. 7. Neuroleptic-induced obesity in rats appears to mimic energy intake, endocrine status and carbohydrate metabolism in humans under chronic neuroleptic administration. However, these rodents did not display the typical changes in blood lipids observed in human obesity.

Animals↗
PubMed1998

Congenital neuroblastoma in a boy born to a woman with bipolar disorder treated with carbamazepine during pregnancy.

1. A metastatic neuroblastoma was detected immediately after birth in a boy born to a 26 year old woman with bipolar disorder, who received carbamazepine (400 mg/day) all through her pregnancy. The primary tumor was probably located in the adrenal gland of the right side, and multiple metastatic lesions were detected in the skin. 2. In this report the authors review the literature about the side effects teratogenic and carcinogenic effects of carbamazepine, the epidemiology and evolution of the neuroblastoma, and the current scientific opinion about the pharmacological treatment of the pregnant with mood disorders. 3. A causal relationship between the use of carbamazepine and the neuroblastoma development in the present case can not be established; however, as the carcinogenic and teratogenic effects of the drug have been basically assessed in epileptic women, our aim is to alert the medical community in order to conduct further research in psychiatric patients.

Abnormalities, Drug-Induced↗