Blood Cell Count Ratios at Baseline are Associated with Initial Clinical Response to Clozapine in Treatment-Resistant, Clozapine-Naïve, Schizophrenia-Spectrum Disorder.

BACKGROUND: Clozapine is the recommended treatment for managing treatment-resistant schizophrenia (TRS), and immunological mechanisms may be involved in its unique antipsychotic efficacy. This study investigated whether baseline immune abnormalities measured with blood cell count ratios can predict the clinical response after initiating treatment with clozapine in patients with clozapine naïve TRS. METHODS: A longitudinal design was developed, involving 32 patients diagnosed with treatment-resistant, clozapine-naïve schizophrenia-spectrum disorder. Patients were evaluated at baseline before clozapine starting and 8 weeks of follow-up. Psychopathological status and immune abnormalities (blood cell count ratios: neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], platelet-lymphocyte ratio [PLR] and basophil-lymphocyte ratio [BLR]) were evaluated in each visit. RESULTS: Baseline NLR (b=- 0.364; p=0.041) and MLR (b =- 0.400; p=0.023) predicted the change in positive symptoms over the 8-week period. Patients who exhibited a clinical response showed higher baseline NLR (2.38±0.96 vs. 1.75±0.83; p=0.040) and MLR (0.21±0.06 vs. 0.17±0.02; p=0.044) compared to non-responders. In the ROC analysis, the threshold points to distinguish between responders and non-responders were approximately 1.62 for NLR and 0.144 for MLR, yielding AUC values of 0.714 and 0.712, respectively. No statistically significant differences were observed in the blood cell count ratios from baseline to the 8-week follow-up. CONCLUSION: Our study emphasizes the potential clinical significance of baseline NLR and MLR levels as predictors of initial clozapine treatment response in patients with TRS. Future studies with larger sample sizes and longer follow-up periods should replicate our findings.

Nurse-led lifestyle intervention in a cohort of schizophrenia patients treated with clozapine.

Patients diagnosed with schizophrenia are characterized by early mortality compared to the general population. The main cause of this premature death reflects medical complications linked to metabolic syndrome (MetS). The use of antipsychotics such as clozapine is associated with weight gain and metabolic disturbances in certain predisposed individuals. Non-pharmacological interventions for weight control have become a key element for secondary prevention in the health of patients diagnosed with schizophrenia. Here, we aim to evaluate the physical health effects of a nurse-led non-pharmacological intervention program in patients with a diagnosis of schizophrenia treated with clozapine. Thirty-one outpatients from the outpatient clinical facility of Hospital Clinic in Barcelona, Spain diagnosed with schizophrenia and other psychotic disorders receiving clozapine treatment were enrolled in a prospective interventional study, comprising an 8-week group program of therapeutic education in a healthy lifestyle. MetS factors, physical activity, diet, and lifestyle were evaluated at baseline, post-intervention (8 weeks), and 3 months after the program. Weight, body mass index, high-density lipoprotein cholesterol, and diet patterns displayed significant differences post-intervention and after 3 months, while only waist, hip perimeter, and lifestyle improved post-intervention. Our results suggest the effectiveness of the lifestyle intervention in patients under clozapine treatment despite its long-time differential effect. Strategies to prevent weight gain and metabolic decline will help prevent premature cardiometabolic disease in this vulnerable population.

Antipsychotic-Associated Weight Gain and Clinical Improvement Under Clozapine Treatment.

BACKGROUND: Antipsychotic-associated weight gain is a common adverse effect with several negative outcomes in the clinical evolution of patients, which might also affect patients' self-identity from physical appearance and imply treatment discontinuation. However, recent research has drawn attention to an unexpected clinical improvement associated with weight gain, mostly in patients under treatment with clozapine or olanzapine. METHODS: Twenty-three treatment-resistant psychosis patients initiating clozapine were evaluated. Longitudinal psychopathological assessment through the Positive and Negative Syndrome Scale (PANSS) and anthropometric evaluation were performed at baseline, week 8, and 18. RESULTS: Body mass index (BMI) change during clozapine treatment was associated with clinical improvement measured with PANSS total score at week 8 (P = 0.021) while showed a trend at week 18 (P = 0.058). The PANSS general score was also associated with weight gain at week 8 (P = 0.022), whereas negative subscale score showed a trend at week 8 (P = 0.088) and was associated between week 8 and 18 (P = 0.018). Sex differences applied at week 8 for PANSS total score, where clinical improvement was significantly associated with BMI in male subjects (P = 0.024). We also stratified for time to initiate clozapine, finding significant associations in negative symptom at week 8 (P = 0.023) and week 18 (P = 0.003) for subjects, which started clozapine after 3 years of illness. CONCLUSIONS: Our results suggest that in subjects initiating clozapine, clinical improvement is associated with BMI increase, mostly in negative symptom and in patients after 3 years of antipsychotic use. Our findings were already described in the preantipsychotic era, suggesting some pathophysiological mechanism underlying both conditions.

Food craving and consumption evolution in patients starting treatment with clozapine.

BACKGROUND: Antipsychotic-induced weight gain has been especially related to clozapine and olanzapine. Underlying mechanisms in relation to food preferences with an increased food craving and consumption of specific nutrients have not been extensively studied in patients with serious mental illness (SMI). We aim to describe specific food preferences (craving) and subsequent food consumption in SMI patients starting clozapine, as well as their possible relation to weight and body mass index (BMI). METHODS: An observational prospective follow-up study (18 weeks) was conducted in a cohort of 34 SMI patients who started clozapine due to resistant-psychotic symptoms. Anthropometric measures, Food Craving Inventory (FCI), and a food consumption frequency questionnaire were evaluated at baseline, weeks 8 and 18 of treatment. Statistical analysis included generalized estimating equations models with adjustment for potential confounding factors. RESULTS: No longitudinal changes over time were found across the different food craving scores after 18 weeks of treatment. However, adjusted models according to BMI status showed that the normal weight (NW) group presented an increased score for the "complex carbohydrates/proteins" food cravings (- 0.67; 95% CI [- 1.15, - 0.19]; P = 0.010), while baseline scores for "fast-food fats" cravings were significantly higher in the overweight/obese (OWO) group in comparison with NW patients (NW, 2.05; 95% CI [1.60, 2.49]; OWO, 2.81, 95% CI [2.37, 3.25]; P = 0.016). When considering if food craving could predict weight gain, only increments in "fast-food fats" cravings were associated (ß = - 5.35 ± 1.67; 95% CI [- 8.64, - 2.06]; P = 0.001). CONCLUSIONS: No longitudinal differences were found for any of the food craving scores evaluated; however, in the NW group, food craving for "complex carbohydrates/proteins" changed. Thus, changes in "fast-food fats" cravings predicted weight increase in this sample. Interventions targeting food preferences may help to mitigate weight gain in patients starting treatment with clozapine.

Antipsychotic-induced weight gain and birth weight in psychosis: A fetal programming model.

Antipsychotic induced weight gain is a frequent reason for treatment discontinuation in psychosis, subsequently increasing the risk of relapse and negatively affecting patient well-being. The metabolic effect of weight gain and the subsequent risk of obesity constitute a major medical problem on the long term. Despite its consequences, to date few risk factors have been identified (age, gender, body mass index at baseline), with some authors suggesting the implication of early life stressful events, such as perinatal conditions. We aim to describe if a surrogate marker of intrauterine environment (birth weight) might predict weight gain in a cohort of 23 antipsychotic naïve patients at the onset of the psychotic disease evaluated during 16 weeks with olanzapine treatment and in another cohort of 24 psychosis-resistant patients initiating clozapine assessed for 18 weeks. Two independent linear mixed model analyses were performed in each cohort of patients, with prospective weight gain as the dependent variable, age, gender, body mass index, duration of treatment and time as independent variables. Only in naïve patients, weight gain due to antipsychotics was significantly associated with birth weight, while male gender and body mass index at baseline were associated in both cohorts of patients. Treatment-resistant psychotic patients under clozapine were older, had previous antipsychotic treatment and more years of disease, confounders that might have influence a non significant association. Our results suggest that early environmental events might be playing a role in weight evolution in naïve patients treated with antipsychotics.