flupenthixol-decanoate and Weight-Gain

Chronic interference with dopamine (DA) transmission has been found to facilitate opiate reward and opiate-induced behavioral activation derived from the nucleus accumbens. This study was aimed at determining the extent to which these effects are generalizable to opiate-induced feeding. Rats were tested for their feeding response to morphine following chronic interference with DAergic transmission with the long-acting neuroleptic, flupenthixol decanoate (FLU). It was found that FLU-treated animals showed an enhanced feeding response to morphine following three and four weeks of DA blockade, but not on weeks 1 and 2. Neither morphine treatment in FLU-control animals nor chronic FLU treatment alone produced any such time-dependent facilitation in feeding. The results indicate that the increased sensitivity to the rewarding effects of opiates following chronic DA blockade is generalizable to opiate-induced feeding.

Topics: Animals; Body Weight; Dopamine; Dopamine Antagonists; Drug Synergism; Eating; Flupenthixol; Male; Morphine; Rats; Rats, Wistar; Weight Gain

Treatment-emergent weight gain is associated with antipsychotic efficacy in schizophrenia patients treated with clozapine and olanzapine. However, few studies have investigated this relationship in first-episode patients treated with other antipsychotics, in particular those with a lower obesogenic potential. Aim To investigate the relationships between weight gain and associated metabolic changes with psychopathology improvement in relation to age, sex, ethnicity, substance use, treatment duration and antipsychotic dose in first-episode schizophrenia spectrum disorder patients.. This single site cohort study included 106 minimally treated or antipsychotic-naive patients treated with flupenthixol decanoate over 12 months. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) and BMI, fasting blood lipids and glucose were assessed at regular intervals. Linear regression models were constructed to determine the effects of socio-demographic, clinical and metabolic factors as predictors of change in total PANSS score and factor-derived domains.. BMI change scores were inversely correlated with change in PANSS total (R = -0.25; p = 0.011), positive (R = -0.23; p = 0.019), depressive anxiety (R = -0.21; p = 0.031) and disorganized symptoms (R = -0.32; p < 0.001). Linear regression analysis showed that increased BMI and treatment duration both predicted improvement in global psychopathology and disorganized symptoms independent of age, sex, ethnicity, substance use, co-medication with antidepressants and/or anticholinergics, as well as the dose and duration of antipsychotic exposure.. Our findings suggest that the relationship between treatment-emergent weight gain and psychopathology improvement is not limited to patients treated with antipsychotics most associated with weight gain, and is not confounded by treatment duration and dose.

Topics: Adult; Body Mass Index; Dopamine Antagonists; Female; Flupenthixol; Humans; Longitudinal Studies; Male; Outcome Assessment, Health Care; Schizophrenia; Severity of Illness Index; Weight Gain; Young Adult

To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects.. We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months.. Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P<.0001), waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P=.008). The only significant predictor of BMI increase was non-substance abuse (P=.002).. The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.

Topics: Adult; Antipsychotic Agents; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol; Cohort Studies; Female; Flupenthixol; Humans; Male; Metabolic Syndrome; Metabolome; Schizophrenia; South Africa; Triglycerides; Weight Gain