Selective serotonin reuptake inhibitors as a class are less likely to affect cardiovascular parameters.Through a combination of anticholinergic activity, direct myocardial depressant activity and an effect on the adrenergic neuron, TCAs can cause a combination of arrhythmias (disturbances in cardiac rhythm or conduction), blood pressure abnormalities (orthostatic hypotension) and congestive heart failure . Both SSRIs and TCAs can cause unwanted weight gain.
The development of the SSRIs, with their selective mode of action, has resulted in a class of antidepressant drugs possessing an improved side-effect profile, while retaining good clinical efficacy.
Tricyclic antidepressants were discovered by chance. The TCAs were the result of an unsuccessful attempt to improve on the antipsychotic effectiveness of phenothiazines (medication used in the treatment of schizophrenia).
Molecular modifications of phenothiazines led to synthesis of imipramine, the first clinically useful tricyclic antidepressant.
Both SSRIs and TCAs work by prolonging the effects of neurotransmitters, but have different mechanism of action.
Tricyclic antidepressants work by raising the levels of neurotransmitters serotonin and norepinephrine in the brain by slowing the rate of reuptake (reabsorption) by nerve cells.
Tricyclic antidepressants are one of the oldest classes of antidepressants and are still widely used.
Before the introduction of Selective Serotonin Reuptake Inhibitors, TCAs were the first-line treatment choice for depression and anxiety disorders.Selective Serotonin Reuptake Inhibitors have replaced TCAs as the drugs of choice in the treatment of depressive disorders, mainly because of their improved tolerability and safety.Prior to the SSRIs, most of psychotropic medications were the result of chance observation.TCAs act as strong inhibitors in the reuptake of both norepinephrine and serotonin.Unfortunately, the TCAs also block histaminic, cholinergic, and alpha1-adrenergic receptor sites, and this lack of selectivity is what accounts for the unwanted side effects such as weight gain, dry mouth, constipation, drowsiness, and dizziness.Antidepressants are the third most-prescribed drugs in the United States.