Lipids are of concern mainly due to their association with atherosclerosis and increased risk of cardiovascular events. Lipids such as cholesterol and TGs are transported by lipoproteins to various tissues. In addition to HDL and LDL, other lipoproteins include chylomicrons, very low-density lipoprotein (VLDL) , and intermediate-density lipoprotein (IDL). They each carry varying degrees of cholesterol and TGs, with LDL-C carrying the majority of cholesterol and VLDL and chylomicrons carrying the majority of TGs.

A standard serum lipid profile measures TC , HDL-C , and TGs; LDL-C is generally calculated though it can be measured directly. The LDL-C calculation is affected by the amount of triglycerides in the blood, which is higher in the nonfasting state. TC and HDL-C , which are directly measured, do not differ significantly in the nonfasting state.

Cholesterol levels are directly related to cardiovascular risk by accelerating atherosclerosis. TGs are also associated with elevated cardiovascular risk but it is not clear if the relationship is causal.

HDL-C removes cholesterol from cells of arterial walls and is associated with decreased atherosclerosis. Hence, higher levels are associated with lower cardiovascular risk.

Disorders in lipid metabolism can occur from genetic mutations that affect either production or clearance of lipoproteins resulting in elevated TGs and cholesterol. But secondary causes are more common reasons for dyslipidemia. Common secondary etiologies are sedentary lifestyle, excess dietary intake of cholesterol, and obesity . Other secondary etiologies are diabetes mellitus, chronic kidney disease, hypothyroidism, cholestatic liver disease, and certain medications.

Antipsychotics with increased propensity for metabolic syndrome also increase risk for developing lipid disorders. The mechanism is mainly via increased weight and resulting insulin resistance. There may also be adiposity-independent effects on glucose and lipid metabolism [1] though no receptor targets have been identified as causative. Increases in TGs and TC have been seen as early as 4 months after antipsychotic initiation [2]. Similar to metabolic syndrome, clozapine and olanzapine carry the highest risk of dyslipidemia while ziprasidone and aripiprazole carry the least risk.

Olanzapine and other antipsychotics are also associated with severe hypertriglyceridemia that is independent of and occurs before weight gain is established. The mechanism is hypothesized to be due to a direct effect on triglyceride metabolism and indirect effect on inflammation and insulin resistance [3]. As with obesity and other metabolic side effects, propensity to cause hypertriglyceridemia is highest with olanzapine and clozapine. Extreme elevations of triglycerides can cause pancreatitis and hypertriglyceridemia may be the mechanism in at least some cases of pancreatitis induced by clozapine and olanzapine.

Statins and other agents that are effective in improving lipid profile in the general population are also effective in people on antipsychotics. When the offending medication is stopped, the lipid abnormalities may reverse if weight reduces. Acute elevation in triglycerides has been documented to improve when the medication is stopped.

Antidepressants also may adversely affect lipid profile and the mechanism is thought to be predominantly due to weight increase from medications that promote weight gain [4]. Among mood stabilizers, carbamazepine may increase lipids while valproate and lithium do not [5].

Hyperlipidemia is generally asymptomatic until it causes complications like coronary artery disease or stroke or triglyceride pancreatitis. But high levels can cause xanthomas that are firm and nontender skin deposits of cholesterol-rich cells in tendons, joint surfaces, hands, and feet.