ISSN ONLINE: 2558-815X
ISSN PRINT: 1584-9244
ISSN-L: 1584-9244

The link between psychotropic drugs and metabolic syndrome


Cardiovascular diseases (CVD), cancers, and mental disorders currently represent the greatest global burden in terms of morbidity, mortality, and costs to public health systems1. Studies in recent years have reported a close, bidirectional correlation between psychological factors and CVD. Thus, mental disorders can precede CVD, or, on the contrary, they can be secondary (for example, anxiety or depression caused by the global burden of CVD)2. According to a retrospective study that examined data from 52 countries, the risk of acute myocardial infarction is elevated by long-term stress, even after accounting for dietary habits or refraining from certain harmful behaviors3. Considerable evidence indicates that depression increases CVD risk through both behavioral and direct pathophysiological effects4. In terms of behavioral factors, depression is linked to vices including smoking, poor eating habits, and low self-esteem4. Hypercortisolemia, changes in platelet function (including higher platelet reactivity and release of platelet products such as platelet factor 4 and beta-thromboglobulin), diminished regulation of the vagus nerve, and reduced heart rate variability are the direct pathophysiological effects4.
Metabolic syndrome is a group of conditions that are related to resistance to insulin5. The components of the metabolic syndrome are hypertension, dyslipidemia, central obesity, and impaired glucose tolerance/diabetes5. Many of the currently used psychotropic drugs have a negative impact on metabolic syndrome components, which are risk factors for CVD5,6. The three main categories of medications that are frequently prescribed for the treatment of various psychiatric disorders and have the potential to cause adverse effects on the cardiovascular and metabolic processes are antidepressants, mood stabilizers, and antipsychotics5.
Psychotropic drugs may induce weight gain through a variety of mechanisms5, such as the antagonism of histamine H1 receptors, serotoninergic receptors (5-HT2A, 5-HT2C), or α1-adrenergic receptors6-8. Increased central and secondary appetite, as well as increased food ingestion, are linked to the antagonism of serotonin and histamine receptors5. Furthermore, the inhibition of H1 receptors results in an increase in appetite and carbohydrate consumption6. Consequently, monoamine oxidase inhibitors and tricyclic antidepressants result in a greater weight gain than other antidepressants because of their more potent antagonism of H1 receptors7. The regulation of signaling pathways mediated by leptin and adiponectin can also be disrupted by psychotropic substances5.
The precise mechanisms by which psychotropic drugs alter the lipid profile are not completely understood. To date, the following pathogenic hypotheses have been proposed: association between dyslipidemia and weight gain caused by psychotropic drugs, enhancement of lipid biosynthesis through the upregulation of genes that encode specific enzymes essential for lipid metabolism10.
A significant association exists between the utilization of psychotropic medications and occurrence of insulin resistance, exacerbation of insulin resistance, or diabetes mellitus onset5. Therefore, there is a 2.5-fold increase in the prevalence of diabetes among patients who are taking antipsychotic medications or valproic acid derivatives in comparison to the general population5.
While most second-generation antipsychotics act as antagonists on serotonergic 5HT2A receptors, aripiprazole acts as a partial agonist5. Activation of 5HT2A receptors results in the contraction of smooth muscles in blood vessels, leading to an increase in vascular resistance and blood pressure5. Furthermore, tricyclic antidepressants and first-generation antipsychotics have anticholinergic properties that can potentially cause high blood pressure5. Weight gain associated with the use of psychotropic drugs may also mediate increased blood pressure values5. Psychostimulants, including amphetamines, directly release norepinephrine, dopamine, and serotonin at the synaptic level, resulting in an increase in blood pressure through central dopaminergic and peripheral adrenergic effects5. Valproate functions by elevating the levels of gamma-aminobutyric acid (GABA) in the bloodstream, blocking sodium channels, and inhibiting the glutamate/N-methyl-D-aspartate (NMDA) receptor5.
In conclusion, treatment with psychotropic drugs requires a careful monitoring to allow for the early detection of adverse effects and establishment of appropriate management. Psychotropic medications’ side effects, particularly weight gain, may reduce adherence to this treatment. Therefore, it is necessary to monitor body weight throughout psychotropic treatment and carefully select drugs for overweight or obese patients. To address weight gain that occurs because of treatment, it may be advisable to reduce medication doses, transition to a new class of drug, or maybe stop the use of psychiatric medication7. It is also recommended to encourage lifestyle changes, with regular physical activity and a balanced diet. However, the presence of cardiovascular disease (CVD) should not be a reason to avoid antipsychotic treatment, as many of these medications have been found to have a favorable cardiovascular safety profile.

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Camelia C. DIACONU


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Diaconu CC. The link between psychotropic drugs and metabolic syndrome. Arch Balk Med Union. 2024;59(2):139-141.