Causes, Consequences, and Solutions to Weight Gain in Schizophrenia Treatment
The use of antipsychotics in the treatment of schizophrenia is often associated with the development of overweight and obesity, which poses a risk for the onset of many diseases and increases morbidity and mortality in these patients. Concern about weight gain is also a common reason for non-adherence to antipsychotic treatment. The cause of weight gain may also lie in the symptoms of the disease itself. We, therefore, provide a summary of the causes, consequences, and possible solutions to this undesirable impact of schizophrenia and its treatment.
Causes of Weight Gain in Schizophrenia Patients
Negative symptoms such as apathy or anhedonia, which disrupt the patient's control over food intake and their ability to recognize excessive weight gain, can contribute to weight gain in schizophrenia patients. Some positive symptoms can lead to weight loss, for example, when a patient stops eating because they are "cleansing" or because someone told them to in a hallucination. Weight gain in such patients can indicate symptom relief and improvement in condition.
Some antipsychotics affect food intake regulation, particularly those impacting the serotonergic system, which significantly influences food intake. Down-regulation of 5-HT2 receptors stimulates appetite and reduces satiety, resulting in increased caloric intake and weight gain. Some antipsychotics (clozapine, zotepine) and weak neuroleptics with high affinity for histamine H1 receptors exhibit sedative effects and reduce patient physical activity, leading to weight gain unless caloric intake is restricted.
Antipsychotics with anticholinergic effects can cause dry mouth, inducing a feeling of thirst. These patients often drink large amounts of caloric beverages and gain weight. Clozapine and olanzapine are associated with the highest weight gain among antipsychotics. It has been found that their use is connected with increased leptin levels, a hormone involved in the pathophysiology of obesity. However, this may be a consequence of developing overweight/obesity, as leptin is secreted exclusively by differentiated adipocytes.
Consequences of Weight Gain in Connection with Schizophrenia
In the general population, overweight and obesity are associated with increased risk of hypertension, type 2 diabetes, ischemic heart disease (IHD), osteoarthritis, sleep apnea, and certain malignancies (endometrial, breast, prostate, and colorectal cancer). The increased risk of these diseases and premature death also relates to weight gain within the normal range. Studies show that individuals gaining 5-8 kg after 18 years of age have a 1.9-fold risk of developing type 2 diabetes and a 1.25-fold risk of IHD compared to those maintaining or reducing their weight. Gaining 11 kg in adulthood is associated with a 1.7-2.5-fold increased risk of ischemic stroke (iCMP).
The mere presence of schizophrenia increases somatic morbidity and mortality by 60%. This risk is further exacerbated by overweight or obesity and the common smoking habits of schizophrenia patients. One of the conditions for successful schizophrenia treatment is long-term adherence to the treatment, significantly influenced by the side effect profile of the prescribed medication. The fear of weight gain from antipsychotics (similar to some other medication groups used to treat other diseases) is one of the main factors reducing adherence to this medication.
Consequences of antipsychotic-induced weight gain in schizophrenia patients include:
- Health risks (hypertension, type 2 diabetes, IHD, stroke)
- Stigmatization
- Non-adherence to treatment
- Reduced quality of life
- Social withdrawal
Solutions
The first step in preventing overweight/obesity in schizophrenia patients is to identify individuals prone to weight gain. These patients should be informed about the risk and consequences of increased body weight from the start. All patients should be advised to lead a healthy lifestyle, including a balanced diet and regular physical activity. Before starting schizophrenia therapy, the doctor should identify the presence of risk factors for developing metabolic and cardiovascular diseases and document any smoking and alcohol consumption.
During schizophrenia treatment, it is advisable to regularly monitor patients' body weight and related laboratory parameters, such as blood sugar levels, glycated hemoglobin, and total and LDL cholesterol levels. In terms of pharmacotherapy, it is appropriate to choose antipsychotics with a low potential for increasing patient weight. Other suitable approaches include reducing the dose of antipsychotics with possible adverse effects on body weight, changing antipsychotics when this undesirable side effect occurs, and, in selected cases, administering anti-obesity drugs.
Conclusion
The frequent development of overweight and obesity during schizophrenia therapy has adverse health consequences and needs prevention. Preventive measures include identifying and educating patients prone to weight gain, recommending a healthy diet and regular exercise, monitoring body weight and related laboratory values during treatment, and, last but not least, selecting appropriate medication or adjusting its dose or changing the product.
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Source: Kurzthaler I., Fleischhacker W. W. The clinical implications of weight gain in schizophrenia. J Clin Psychiatry 2001; 62 (Suppl. 7): 32−37.
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