Weight gain is a common side effect experienced by individuals taking antipsychotic medications. This increase in weight can lead to various health complications, including a higher risk of developing conditions such as type 2 diabetes and cardiovascular disease. Addressing this issue is important, as the adverse metabolic effects can impact adherence to psychiatric treatment and reduce the quality of life for many patients.
Understanding Antipsychotic-Related Weight Gain
Antipsychotic medications, particularly second-generation or atypical antipsychotics like olanzapine and clozapine, are often associated with substantial weight gain. This occurs due to several physiological changes induced by these drugs. One mechanism involves their interaction with specific receptors in the brain, such as serotonin 2C (5-HT2C) and histamine 1 (H1) receptors, which can lead to increased appetite and food intake. Antagonism of these receptors stimulates central energy intake and overrides satiety signals, encouraging overeating.
Beyond appetite changes, antipsychotics can directly impact metabolic processes. They impair insulin sensitivity, making the body’s cells less responsive to insulin and leading to higher blood glucose levels. Some antipsychotics can also increase the expression of genes involved in fat synthesis and alter the levels of hormones that regulate metabolism, such as leptin and adiponectin. Elevated leptin levels (hyperleptinemia) have been identified as a driver for drug-induced obesity, contributing to insulin resistance and inflammation. These combined effects create an environment conducive to weight accumulation and metabolic disturbances.
How Metformin Helps Manage Weight Gain
Metformin is a medication primarily used to treat type 2 diabetes, but it has shown promise in mitigating antipsychotic-induced weight gain. Its main mechanism involves altering glucose metabolism and improving insulin sensitivity. Metformin reduces the liver’s production of glucose (hepatic gluconeogenesis) and decreases glucose absorption from the intestines. It achieves this by inhibiting the mitochondrial respiratory chain in the liver, which activates an enzyme called AMP-activated protein kinase (AMPK).
Activation of AMPK enhances insulin sensitivity by influencing fat metabolism, leading to reduced fat synthesis and increased fat oxidation. This improved insulin response allows the body’s cells to utilize glucose more effectively. In the context of antipsychotic-induced weight gain, metformin’s effects translate to better glucose control, reduced fat storage, and a potential decrease in appetite. It also increases the secretion of glucagon-like peptide-1 (GLP-1), a hormone that regulates appetite and glucose levels. By addressing metabolic imbalances caused by antipsychotics, metformin counters the tendency for weight gain.
Using Metformin: Expectations and Considerations
Research indicates that metformin can effectively reduce weight gain associated with antipsychotic medications. Studies show that patients taking metformin with antipsychotic treatment experienced an average weight loss of 3 to 3.27 kilograms (6.6 to 7.2 pounds) compared to placebo. The effect on weight reduction may be more pronounced, around 5 kg, in patients receiving antipsychotics for a first episode of psychosis. Metformin also improves related metabolic parameters, such as body mass index (BMI), insulin resistance, and lipid profiles (cholesterol and triglycerides).
Metformin is generally well-tolerated, but common side effects are gastrointestinal, including nausea, vomiting, diarrhea, and abdominal pain. These side effects are usually transient and can be minimized by starting with a low dose, gradually increasing it, and taking the medication with or after food. A typical starting dose for adults might be 500 milligrams once or twice daily, with gradual increases up to a maximum of 1000 to 2000 milligrams per day, often in divided doses.
Medical supervision is necessary when using metformin, as it is a prescription medication. It is not suitable for individuals with severe kidney disease (glomerular filtration rate less than 30 mL/min) or metabolic acidosis due to a small risk of lactic acidosis. Monitoring of kidney function and vitamin B12 levels may be recommended during treatment. Metformin serves as an adjunctive treatment and should be used with lifestyle interventions, such as diet and exercise, for optimal weight management.