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Tricyclic Antidepressants (TCAs)

Tricyclic Antidepressants

Developed in the 1950s, the tricyclic antidepressants have mostly been replaced by newer drugs like selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. The name "tricyclic" comes from the atomic structure of these medications, which consists of three molecular ring shapes. Like all antidepressant medications, these drugs work by changing the amount of specific chemicals in the brain called neurotransmitters. The brain relies on neurotransmitters to send messages back and forth between neurons and regulate mental and physical functions. Some research indicates that depression is related to deficits of certain neurotransmitters. Tricyclic antidepressants increase the amount of serotonin and norepinenphrine in the brain, both of which are involved in mood. Tricyclics also affect other brain chemicals, leading sometimes to undesirable side effects.


Norpramin (desipramine), Aventyl (nortriptyline), Tofranil (imipramine), and Silenor (doxepin) are among the tricyclic drugs approved to treat depression. Research has shown that newer antidepressant medications are no more effective at treating depression than the older tricyclics. However, tricyclics have a much more pronounced and unpredictable side effect profile than the new medications. The potential side effects depend largely on which tricyclic antidepressant a person takes. Drowsiness, dry mouth, and sexual problems are possible with any of these medications. Silenor in particular has been associated with a greater risk of weight gain. Potentially severe side effects of these medications include low blood pressure and seizures. Withdrawal symptoms are also possible when people suddenly stop taking tricyclic antidepressants or miss several doses. Nausea, headache, and dizziness are common symptoms of withdrawal.


Tricyclic antidepressants have received new interest for their potential to alleviate chronic pain conditions. For the treatment of a chronic condition like diabetic neuropathy, doctors usually prescribe a lower dose of these medications. Lower dosages avoid many of the unwanted side effects of tricyclic antidepressants. It is unclear how these medications work to relieve pain, but research into that question is ongoing. In terms of depression treatment, tricyclics are usually only prescribed when other, newer medications have failed.


National Library of Medicine - National Institutes of Health. (n.d.). Antidepressive agents, tricyclic. Retrieved April 25, 2012, from


Mayo Clinic. (n.d.). Depression (major depression). Retrieved April 23, 2012, from


WebMD. (n.d.) Tricyclic antidepressants for pain treatment. Retrieved April 25, 2012, from


Last Update: 06-28-2012


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