Tricyclic antidepressants (TCAs) are called classical antidepressants because they are the first types of antidepressants that were discovered just a few years after the monoamine oxidase inhibitors (MAOIs) came out in the market. This class of drugs was accidentally discovered when imipramine, the first type of tricyclic antidepressants, was being tested for schizophrenia.
Basically, tricyclic antidepressants inhibit the reuptake of neurotransmitters serotonin and norepinephrine in the synapse after their release. Tricyclic antidepressants also alter neuronal functioning, including, but not limited to, the activity of the receptors, neuronal response to activations, and the synthesis of neurotransmitters during the course of time the drugs were taken; and this alteration may be the reason for the drugs’ effectiveness.
The following are the commonly prescribed tricyclic antidepressants, with their generic names, trade names, dose ranges in milligrams, and half-lives measured in hours:
- Amitryptyline (Elavil): 75-300, 10-46
- Clomipramine (Anafranil): 75-300, 17-37
- Desipramine (Norpramin): 75-300, 12-76
- Doxepin (Sinequan): 75-300, 8-36
- Imipramine (Tofranil): 75-300, 4-34
- Nortriptyline (Aventyl): 40-200, 13-88
- Trimipramine (Surmontil): 75-300, 7-30
Tricyclic antidepressants were developed for the treatment of schizophrenia when it was discovered that its arousing effects can actually be used to treat mood disorders, specifically unipolar mood disorders. In fact, among all the antidepressants that were discovered, TCAs are the most effective in treating major depressive disorder. Around half of the patients with major depression show clinically significant improvement upon treatment with tricyclic antidepressants, which means that severe symptoms are eliminated and only residual symptoms appear; and, half of this half actually comes from a sample that were previously treated with other types of antidepressants but showed no significant improvement in symptom reduction. This highlights the effectiveness of tricyclics compared to other types of antidepressants. TCAs, however, cannot be used to treat bipolar disorders because their arousing effects dangerously precipitate manic episodes. Tricyclic antidepressants can also be used to treat mental disorders besides unipolar mood disorders. These mental disorders include obsessive-compulsive disorder, bulimia, and somatoform pain disorder. One example of tricyclic antidepressants, clomipramine, was shown to be better in treating obsessive-compulsive disorder than major depressive disorder. Around 50 to 70 percent of OCD patients benefit from 25 percent reduction of symptoms, compared to 4 to 5 percent who do better on a placebo. Clomipramine, however, increases OCD symptoms at the first week of administration because its initial effect is to increase serotonin levels in the synapse. Clomipramine thus requires long-term administration (around 6 to 12 weeks) to down-regulate serotonin receptors for OCD symptoms to reduce significantly. Depression is the mental disorder that benefits most with the administration of tricyclic antidepressants, but not all physical or mental problems that comorbid with depression can benefit from them. One good example is that of coronary heart disease with depression. Tricyclic antidepressants appear to be contraindicated with cardiac patients. It is at this particular disease that selective serotonin re-uptake inhibitors (or SSRIs), one of the second-generation antidepressants, appear more superior than TCAs.