Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

Abstract

Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine. Weight increases rapidly in the initial period after starting antipsychotics. Patients continue to gain weight in the long term. Children appear to be particularly vulnerable to antipsychotic-induced weight gain. Tailoring antipsychotics according to the needs of the individual and close monitoring of weight and other metabolic parameters are the best preventive strategies at the outset. Switching to an agent with lesser tendency to cause weight gain is an option, but carries the risk of relapse of the illness. Nonpharmacologic interventions of dietary counseling, exercise programs and cognitive and behavioral strategies appear to be equally effective in individual and group therapy formats. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Multiple compounds have been investigated as add-on medications to cause weight loss. Metformin has the best evidence in this respect. Burden of side effects needs to be considered when prescribing weight loss medications. There is no strong evidence to recommend routine prescription of add-on medication for weight reduction. Heterogeneity of study methodologies and other confounders such as lifestyle, genetic and illness factors make interpretation of data difficult.

Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

“…Therefore, a relatively low risk of prolactin elevation would be an important factor in selecting antipsychotics. Weight gain is generally induced with most SGAs, but the risk is lower in blonanserin. The excitability increase in blonanserin group was likely due to low affinity to adrenaline α 1 and histamine H 1 , resulting in blonanserin not being likely to cause excessive sedation.…”

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

“…This includes the inhibitory effect on melanocortin receptor 4 (MC4R4), as well as on histamine receptor 1 (H1R), some serotonin receptors (5-HT2c and 5-HT1b) and dopamine receptor 2 (D2), and the stimulatory effect on muscarinic receptors (M3) as well as on some serotonin receptors (5-HT1a and 5-HT6) and adrenergic ones (α2) [11][12][13][14]. Apart from direct action on food intake through various brain neurotransmitters, several other hypotheses have been aroused to explain metabolic disturbances, particularly weight gain, induced by SGAs [10,27,28]. We so have several observations showing decreased energy expenditure linked to the sedative effect of SGAs [10,27].…”

“…Apart from direct action on food intake through various brain neurotransmitters, several other hypotheses have been aroused to explain metabolic disturbances, particularly weight gain, induced by SGAs [10,27,28]. We so have several observations showing decreased energy expenditure linked to the sedative effect of SGAs [10,27]. Indeed, for this last, a recent systematic review investigating the role of the gut microbiome on metabolic alterations pertaining to SGAs concluded that AAPs' related microbiome alterations potentially result in body weight gain [28].…”

“…The degree of weight gained from SGAs is often greatest early in treatment and a meta-analysis showed that mean weight increases from 1.4 to 11 lb. (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].…”

Pharmacotherapeutic interventions for bipolar disorder type II: addressing multiple symptoms and approaches with a particular emphasis on strategies in lower and middle-income countries

“…Consequently, any treatment prescribed to overweight or diabetic patients with BD must include lifestyle changes tailored to the specific population [9]. In addition, prescribers must be cognizant of the weight gain potential with antipsychotic medicines such as olanzapine versus for instance risperidone and quetiapine (moderate weight gain potential) and aripiprazole (low weight gain potential) [153]. Co-morbidities are a particular issue in patients with BD as adherence to therapies is already a concern [125,139].…”