Tricyclic antidepressants (TCAs) are non-selective pharmacological agents belonging to a primary class of antidepressants. Their main function is the non-selective inhibition of monoamine reuptake in synaptic clefts.
Latent period2–3 weeks of continuous administration
PrototypesAmitriptyline, imipramine
Main mechanismNon-selective monoamine reuptake inhibition
ContraindicationCombination with non-selective MAO inhibitors
Mechanism of Action at the Synaptic Level
The pharmacological effect of tricyclic compounds is realized through several successive stages at the synaptic level:
Competitive blockade: The active substance binds to specialized transporter proteins located on the presynaptic membrane.
Mediator accumulation: Substances such as norepinephrine, serotonin, and dopamine remain in the synaptic cleft longer than usual.
Receptor stimulation: The increased concentration of neurotransmitters actively stimulates postsynaptic receptors.
Adaptation: After two to three weeks of regular use, an adaptive reaction develops, manifesting as a decrease in the density and sensitivity of central adrenoceptors (down-regulation).
Pharmacodynamics and Psychotropic Spectrum
The intrinsic antidepressant effect of TCAs does not appear immediately: due to the time required for receptor remodeling, there is a latent period lasting 2–3 weeks.
Sedative effect: Develops significantly earlier than the antidepressant effect.
Alpha-adrenoceptor blocking activity: Leads to a drop in blood pressure and the development of hypotension.
Drug Interactions
When prescribing therapy, it is essential to strictly follow drug combination rules:
Absolute contraindication: It is strictly prohibited to combine TCAs with non-selective monoamine oxidase inhibitors.
"Washout" period: An interval of at least 2 weeks must be maintained between the discontinuation of MAO inhibitors and the initiation of tricyclic antidepressants.
Mnemonic
TCAs — Tri-cyclic Central Amines (block reuptake of norepinephrine and serotonin, requiring 2–3 weeks to see clinical effects).
Frequently asked questions
What other drugs belong to the TCA group besides amitriptyline and imipramine?
In addition to amitriptyline and imipramine, tricyclic antidepressants (non-selective monoamine reuptake inhibitors) include the following medications:
Clomipramine — used, among other things, as a second-line drug for tension headaches.
Doxepin — a classic representative of non-selective inhibitors.
Pipofezine — used in treatment regimens to combat pathological craving for psychoactive substances.
What are the contraindications for TCA use besides MAO inhibitors?
Besides taking MAO inhibitors, absolute contraindications for prescribing tricyclic antidepressants include the following somatic conditions:
Heart disease
Glaucoma
Prostatic hyperplasia
Chronic constipation
Additionally, drugs of this group are strictly contraindicated in the treatment of psychoses caused by antituberculosis drug poisoning. Furthermore, TCAs are not recommended in patients with multiple system atrophy due to the high risk of exacerbating respiratory dysfunction and autonomic failure (orthostatic hypotension, urinary retention).
What other receptors do TCAs block besides muscarinic and alpha-adrenoceptors?
In addition to muscarinic and alpha-adrenoceptors, tricyclic antidepressants are also capable of blocking histamine receptors.
Non-selective monoamine reuptake inhibitors have a broad receptor profile, which accounts for their numerous side effects. Histamine receptor blockade is one of the causes of adverse reactions during therapy with these drugs. Unlike TCAs, selective serotonin reuptake inhibitors (SSRIs) have only a minor effect on these receptors.
What are the symptoms of acute tricyclic antidepressant overdose?
Symptoms of acute tricyclic antidepressant overdose: the clinical picture resembles phenothiazine poisoning. Coma is preceded by a period of agitation, and sometimes seizures.
In the comatose stage, the following are observed:
Cardiac disturbances: tachycardia, atrial fibrillation, atrioventricular or intraventricular block.
Psychotic episodes with delirium-like hallucinations.
Intestinal and urinary bladder atony.
Why does the antidepressant effect of TCAs take 2–3 weeks to develop?
This is due to the mechanism of central adrenoceptor adaptation (so-called down-regulation), where 2–3 weeks of continuous administration leads to a decrease in their density and sensitivity.
What is the main contraindication for tricyclic antidepressants?
An absolute contraindication is the combination of TCAs with non-selective monoamine oxidase inhibitors. The interval between their administration must be at least 2 weeks.
What are the key prototype drugs in the TCA group?
The key representatives of non-selective tricyclic antidepressants are amitriptyline and imipramine.
Go deeper
General classification of antidepressants and the place of TCAs in section 15.2.1
Non-selective (nialamide) and selective (moclobemide) monoamine oxidase inhibitors
Antidepressants from other groups (tianeptine, mirtazapine)
Differences in the spectrum of psychotropic activity between amitriptyline and imipramine
Clinical manifestations of anticholinergic and alpha-adrenoceptor blocking actions