Association between Serum Lipids and Antipsychotic Response in Schizophrenia

Abstract

Metabolic abnormalities are serious health problems in individuals with schizophrenia. Paradoxically, studies have noted an association where individuals who gained body weight or who have increased their serum lipids demonstrated a better antipsychotic response. As serum lipids serve as more specific physiological markers than body weight, the objective of this study was to review studies that examined the association between changes in serum lipids and changes in symptoms during antipsychotic treatment in individuals with schizophrenia. A Medline® literature search was performed. Fourteen studies were included and analyzed. Evidence suggests that increases in serum lipids may be associated with decreases in symptoms during antipsychotic treatment. This inverse association may be independent of confounding variables, such as weight gain, and may be most evident during treatment with clozapine. Also, according to recent randomized controlled trials, lipid-lowering agents do not appear to worsen symptoms although this needs to be further investigated in clozapine-treated patients. Future studies should investigate the association in question in a larger population and identify underlying mechanisms.

A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models

“…The second generation drugs are largely preferred to their predecessors due to their lower incidence of neurological side-effects, which include extrapyramidal symptoms and tardive dyskinesia [5]. However, after several decades of use, it is well established that the second generation drugs have their own side-effects, which predominantly include metabolic dysregulation, characterized by weight gain, hyperglycemia, hyperinsulinemia and hyperlipidemia [6][7][8][9][10][11][12]. These side-effects can ultimately lead to an increased risk of developing cardiometabolic disorders such as Type 2 diabetes mellitus (DM) [13,14].…”

Differential Effects of Acute Treatment With Antipsychotic Drugs on Peripheral Catecholamines

“…The second generation drugs, however, have been linked to their own serious side-effects as well. These most commonly include cardiometabolic side-effects, which significantly increase the risk of developing cardiometabolic disorders such as Type 2 diabetes mellitus (DM) and cardiovascular disease (11)(12)(13)(14)(15)(16)(17)(18)(19). Typically, Type 2 DM is preceded by the onset of the metabolic syndrome, which is characterized by weight gain, hypertension, hyperlipidemia, hyperglycemia, glucose intolerance, and insulin resistance (20)(21)(22).…”

A Focused Review of the Metabolic Side-Effects of Clozapine

“…The causal association between clozapine treatment and hyperlipidemia is further confirmed in discontinuation studies, when increased triglyceride levels in clozapine-treated patients resolve follow switching to another antipsychotic (116). Of interest, elevated triglycerides in clozapine-treated patients are associated with improved outcome in patients with schizophrenia, as measured by decreased Positive and Negative Syndrome Scale (PANSS) scores (113,117) and this is independent of weight gain (34). This raises the possibility of serum lipids influencing the pharmacokinetics and efficacy of clozapine (118), warranting further research, although it is unlikely clozapine causes changes in brain lipid levels (119,120) which have been associated with clinical improvement.…”

“…Numerous studies have reported clozapine significantly raises serum triglyceride levels in patients (34,35,41,112,113).…”

“…Serious adverse effects include neutropenia/agranulocytosis (28), myocarditis/ cardiomyopathy and tachycardia (29)(30)(31), and obsessivecompulsive symptoms (32,33). However, the most common issues associated with clozapine use are the metabolic side-effects (34,35), which occur in a majority of patients. These span a range of metabolic substrates, including glucose, insulin, lipids and body fat, which are collectively referred to as the "metabolic syndrome" (36).…”