The first antidepressant had a tricyclic chemical structure (imipramine) and was discovered by chance in the 50s of the twentieth century – in the search for drugs for the treatment of schizophrenia. Tricyclic antidepressants (TCAs) were especially popular in the 1970s-1980s.
TCAs increase concentration and facilitate the transfer of both norepinephrine and serotonin between the neurons of the brain. These antidepressants, along with inhibition of seizure of data mediators, also affect other systems (cholinergic, histaminergic, muscarinic, etc.).
Previously, the range of indications for tricyclic antidepressants was quite wide: endogenous, psychogenic, somatogenic depressions, depressions in organic diseases of the central nervous system.
Along with the therapy of depressive phases (seizures), attempts were made to prolong the use of TCAs in the treatment of chronic depressions (dysthymia), and also as a means of preventing recurrent attacks of monopolar depressions.
A number of foreign researchers consider tricyclic antidepressants suitable for the treatment of, first of all, severe depressive states with a high risk of suicide and depressions resistant to other antidepressants.
With the use of clomipramine and amitriptyline in previously untreated patients with endogenous depression, improvement occurs in 65–80% of cases filed by D. Mulrowet al., (2000), the effectiveness of tricyclic antidepressants in the treatment of depression reaches 60% (2000).
It was noted that the effect in the process of treatment with tricyclic antidepressants does not occur immediately (excluding the drug’s hypnotic effect), but after a few weeks. The reason for this phenomenon is currently unknown, and it is not clear in which case which antidepressant will be more effective.
In the course of treatment with antidepressants, the dynamics of improving the patient’s condition are approximately as follows: at the first stage of therapy, sleep is normalized, then the severity of a number of autonomic disorders decreases, anxiety and anxiety disappears, there is an interest in life and the ability to experience a feeling of pleasure, and sorrow.
The common features of tricyclic antidepressants are the inhibitory effect on the reuptake of norepinephrine and serotonin, as well as other effects: anticholinergic, antihistamine, etc.
Side Effects of TCAs
During the treatment of TCA, a sufficiently large number of side effects occur. When taking tricyclic antidepressants, 30% of patients are forced to refuse treatment because of the severity of side effects, whereas in the case of prescription of antidepressants of later generations, only 15% of patients have to interrupt their medication. In elderly patients, TCAs can cause a state of confusion and myoclonic seizures.
The most common consequence of the anticholinergic effect of TCAs is dry mouth, constipation, urinary retention, orthostatic hypotension, drowsiness and lethargy, less frequent palpitations, and in some cases, impaired consciousness. Amitriptyline and clomipramine have the most pronounced side effects.
Antihistamine action is expressed in weight gain, drowsiness, lowering blood pressure (orthostatic collapse is possible).
Effects on alpha adrenergic receptors also cause hypotension and drowsiness. Inhibition of norepinephrine uptake is manifested by tachycardia, muscle twitching, sexual dysfunction: erectile dysfunction, ejaculation.
The result of inhibition of dopamine uptake is motor arousal, exacerbation of psychopathological symptoms.
Inhibition of serotonin uptake is manifested by decreased appetite, nausea, dyspepsia, weakening of erection, ejaculation, deterioration of vision (with contact lenses, the feeling is “sand in the eyes”).
Most of the side effects disappear with time, but in some cases a reduction in the dosage of the drug or its replacement is required.
However, patients themselves can reduce the severity of side effects, for example, when dry mouth sugary sweets, sugar-free, or chewing gum are advised.
It is not recommended to give TCAs to those patients who express suicidal thoughts if the patients at this time point are outside the hospital.
It is well known toxic effects of TCA on the heart, usually manifested in conduction disturbances, accelerating the heart rate rhythm. In violation of the function of the sinus node, the appearance of bradyarrhythmia may occur when taking TCAs. When taking these drugs often develops the phenomenon of increasing the QT interval on the ECG, as a result of the above, the appearance of ventricular tachycardia is possible.
In case of hypersensitivity to these medications, skin disorders, changes in the functionality of the liver and blood are possible. As noted above, the effect on the central nervous system can be manifested by convulsive seizures.
The side effects caused by TCAs often limit the possibility of using adequate doses, and a significant number of patients are forced to receive treatment with insufficient doses. Thus, according to J. McCombs et al. (1990), up to 80% of patients receive treatment with insufficient doses for the effect of drugs. In addition, treatment with low doses creates the danger of the transition of the acute phase to the chronic phase (Bovin R.Ya. et al., 1989).
Abrupt withdrawal of TCAs can lead to anxiety, anxiety, insomnia, severe autonomic disorders, muscle pain, nausea and vomiting (Dilsaver C. et al, 1987).