What is a Tricyclic Antidepressant?

Tricyclic antidepressants (TcAs) are one of the most commonly used drugs in the treatment of depression. Its core structure consists of a seven-membered heterocyclic ring connected to both sides by a benzene ring. Among them, imipramine is the earliest found compound with antidepressant effect. At present, clomipramine, amitriptyline and docepine are commonly used drugs. TCAs are mainly metabolized in the liver, and the metabolic enzymes involved are CYP1A2, CYP2D6, CYP3A4 and so on. The main metabolism is tricyclic nuclear oxidation, such as hydroxylation of carbon atoms at 2 or 10 (CYP2D6 catalysis), oxidation of fatty side chains, demethylation of nitrogen atoms (catalyzed by CYP3A4). Because the activity of CYP is affected by many factors, the ratio of the concentration of active metabolites in plasma to the concentration of the original drug has obvious individual differences.

Basic Information

Drug Name

Tricyclic antidepressants

Foreign name

Tricyclic Antidepressive Agents

Main indications

Endogenous depression, adverse mood disorders, reactive depression, etc.

Adverse reactions

Dry mouth, constipation, low mood, orthostatic hypotension, tachycardia

Main medication contraindications

Severe heart, liver and kidney diseases, granulocytopenia, glaucoma, etc.

Pharmacological effects of tricyclic antidepressants

TCAs block the reuptake of NA and 5-HT by norepinephrine (NA) energy and serotonin (5-HT) energy nerve endings, and increase the concentration of monoamine transmitters in the synaptic cleft. Improvement of depressive symptoms. Current research has found that the inhibitory effect of antidepressants on transmitter reuptake occurs immediately, and long-term use can reduce the sensitivity of the receptor (down-regulation), which is lagging with the clinical effect of antidepressants (medication 2 Effective after 3 weeks) are closely related. The blockade of NA reuptake increases the endogenous NA concentration in the synaptic cleft, which can reduce the sensitivity of the presynaptic membrane 2 receptors. Long-term use may also reduce the number of central 2 receptors. Inhibition of 5-HT reuptake firstly increases the endogenous 5-HT concentration in the synaptic cleft of the somatic site. By down-regulating the 5-HT _1A receptor on the presynaptic somatic membrane, it increases the release of 5-HT from the periphery and finally achieves antidepressant effects . TCAs also have a strong blocking effect on 5-HT _2A receptors.

Application of tricyclic antidepressants

It is suitable for the treatment of various types of mental disorders with depressive symptoms, such as internal cause depression, adverse mood disorders, reactive depression and organic depression. It can also be used to treat generalized anxiety, panic attacks and phobias. Low-dose imipramine can be used to treat enuresis in children, and clomipramine is often used to treat obsessive-compulsive disorder. For patients with schizophrenia, the symptoms of depression should be treated with caution. TCAs may exacerbate or make psychotic symptoms worse.

Tricyclic antidepressants have been the first choice of antidepressants, but because of their large anticholinergic and cardiovascular adverse reactions, there are more contraindications and drug interactions, and the narrower safety range makes them clinically affected. limit. TCAs are fatal when taken more than 10 times a day, and arrhythmias are the most common cause of death.

Adverse effects of tricyclic antidepressants

Anticholinergic adverse reaction

Common adverse drug reactions of tricyclic antidepressants include dry mouth, constipation, blurred vision, urinary retention, drowsiness, and weight gain. These are the results of their anticholinergic and antihistamine effects, which are related to blood drug concentrations. It can appear within the therapeutic concentration range, and there are large individual differences, not the manifestation of poisoning. Mild anticholinergic drugs generally do not require special treatment, and a small amount of pseudocholine drugs can be added if necessary.

2. Central nervous system toxicity

Central nervous system toxic reactions caused by TCAs include decreased mood, inattention, abnormal social behavior, tremors, dyskinesias, seizures, thinking disorders, hallucinations, disorientation, anxiety, delirium, confusion, and coma.

3. Cardiovascular system toxicity

Cardiotoxicity caused by TCAs includes orthostatic hypotension, tachycardia, conduction block, arrhythmia, and cardiac arrest. Orthostatic hypotension caused by TCAs is mainly related to the sensitivity of the receptor, which can occur at lower blood concentrations, and is more common in the elderly and patients with congestive heart failure.

Precautions for tricyclic antidepressants

Patients with severe heart, liver, and kidney disease, as well as patients with agranulocytopenia, glaucoma, and enlarged prostate are contraindicated. It is contraindicated in the first 3 months of pregnancy. Use with caution in patients with epilepsy and the elderly.

(Note: The above content is only for introduction, the drug use must be carried out by a regular hospital under the guidance of a doctor.)