The blood test for tricyclic antidepressants (TCAs) measures the level of these medications in the blood to ensure they are effective and prevent toxicity. TCAs are a type of psychotropic drug mainly used to treat major depressive disorder, anxiety, and certain chronic pain conditions. Because they have a narrow therapeutic range and their metabolism varies, monitoring blood levels is crucial for achieving optimal clinical results and minimizing serious side effects. The test is typically ordered when steady-state levels are required, symptoms of toxicity are present, or if treatment resistance or non-adherence is suspected.
Tricyclic antidepressants work by blocking the reuptake of neurotransmitters, such as norepinephrine and serotonin, at the synaptic cleft, thereby increasing their levels in the central nervous system. In addition, TCAs have antagonistic effects on various receptors, including muscarinic, histaminergic, and adrenergic receptors, contributing to their wide range of effects and side effects. They are mainly metabolized in the liver through cytochrome P450 enzymes. As a result, there is significant variability among individuals in how they absorb, distribute, metabolize, and eliminate these medications. Factors such as age, genetic differences, liver health, and other medications can influence these processes.
Elevated blood levels of tricyclic antidepressants can cause toxic effects such as confusion, seizures, cardiac arrhythmias, low blood pressure, and anticholinergic symptoms like dry mouth, urinary retention, and blurred vision. Severe toxicity often shows up as QRS complex widening on electrocardiograms and may need urgent treatment. High levels may result from overdose, drug interactions, liver problems, or decreased drug clearance. In patients with altered drug metabolism—due to genetic differences or liver enzyme inhibition—even usual doses can lead to buildup and toxicity.
Conversely, low blood levels of TCAs may indicate subtherapeutic dosing, poor adherence, rapid metabolism, or drug interactions that increase clearance. In such cases, the desired antidepressant or analgesic effect might not be achieved, requiring dose adjustments or investigation of pharmacokinetic factors. Some individuals metabolize TCAs into active or inactive metabolites at different rates, which can affect their overall drug response and side effect profiles.
