Risk of weight gain for specific antipsychotic drugs: a meta-analysis

Abstract

People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard ‘as-randomized’ analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0–60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).

Leptin and psychiatric illnesses: does leptin play a role in antipsychotic-induced weight gain?

“…These metabolic side effects are primarily the result of altered energy (food) intake, which mechanisms remain complex [4][5][6]24]. Weight gain induced by SGAs can be responsible for suboptimal medication compliance and high rates of discontinuation, thus leading to the possibility of symptomatic relapse and poor long-term outcomes [7,8,23,24]. Also, AIWG, through cardiovascular risk upswing, can result in reduced life expectancy of patients due to acute complications such as myocardial infarction and stroke, and chronic conditions including heart and kidney failure [4][5][6].…”

“…Also, AIWG, through cardiovascular risk upswing, can result in reduced life expectancy of patients due to acute complications such as myocardial infarction and stroke, and chronic conditions including heart and kidney failure [4][5][6]. Noteworthy, among atypical antipsychotics, clozapine and olanzapine have been proved to more frequently induce metabolic disturbances and weight gain, while demonstrating the highest clinical efficacy regarding psychiatric symptoms [7,24].…”

“…A large number of scientific works have assessed the impact of second-generation antipsychotics on cardiometabolic features with major findings being an increase in morbidity due to QT prolongation with greater risk of sudden cardiac death, increased risk of stroke and coronary heart disease, insulin resistance with a higher risk of developing diabetes [4][5][6]. Antipsychotic-induced weight gain (AIWG), frequently encountered in patients treated with SGAs could be the common denominator despite theories demonstrating direct mechanisms of SGAs on the occurrence of stroke, coronary heart disease and type 2 diabetes [5,7].…”

“…(0.6-5 kg) over the initial 4-12 weeks of therapy [7,8].There are numerous and interconnected underlying mechanisms [7,8] comprising increased appetite, reduced basal metabolism and physical inactivity (probably linked to the sedative effect of antipsychotic drugs), associated with patients specificities such as gender or genetic variants [7,9,10]. Regarding the increase in food intake, it has been shown that atypical antipsychotics can modulate metabolic homeostasis in the hypothalamus, through effects on receptors of neurotransmitters such as serotonin (5-hydroxytryptamine 2c, 1b, 1a, 6), dopamine (D2), histamine (H1 and H3), adrenaline (alpha 2) and acetylcholine (M3) [7,[11][12][13]. Nevertheless, the exact mechanism of weight gain appears to be a more complex association of various neurobiological and metabolic pathways [14].…”

Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

“…Atypical antipsychotics present different profiles on metabolic disturbances. For instance, the dibenzodiazepines clozapine and olanzapine have a greater effect on metabolic processes compared to other atypical drugs, such as the dibenzothiazepine quetiapine or other classes that include risperidone and aripiprazole (Raben et al, 2017;Spertus et al, 2018).…”