Developed in the 1950s, tricyclic antidepressants, or TCAs, have a strong history of anxiety and depression treatment. The name "tricyclic" comes from the atomic structure of these medications, which consists of three molecular ring shapes. TCAs were first developed when scientists began working on a series of compounds to improve antihistamines, sedatives, analgesics, and anti-Parkinson’s drugs. Imipramine, the first tricyclic antidepressant developed in the late ‘50s, showed positive effects when it was first tested on a group of participants diagnosed with depressive psychosis. Modifications to TCA formulas led to the discovery of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).
Until 1988, TCAs were commonly prescribed by physicians. However, with the discovery of many SSRIs, TCAs lost their significance due to a harsher profile of side effects. Today, many TCAs are used when other prescription antidepressant medications fail to produce positive treatment results. The TCAs most commonly prescribed today include:
TCAs may be used in the treatment of a variety of conditions including, but not limited to:
Norpramin (desipramine), Aventyl (nortriptyline), Tofranil (imipramine), and Silenor (doxepin) are among the tricyclic drugs approved to treat depression. Research shows that newer antidepressant medications are no more effective at treating depression than the older tricyclics. However, tricyclics have much more pronounced and unpredictable side effects than many newer medications.
Tricyclic antidepressants have received new interest by some physicians for their potential to alleviate conditions involving chronic pain. For the treatment of a chronic condition, such as diabetic neuropathy, doctors usually prescribe a lower dose of these medications. Lower dosages help prevent many of the unwanted side effects of tricyclic antidepressants.
TCAs increase the quantity of neurotransmitters, such as serotonin and norepinephrine, in the central nervous system. They block specific serotonin (SERT or 5-HTT) and norepinephrine transporters (NET). When affected, these transporters cannot play their part in the reuptake of neurotransmitters, which increases the concentration and ultimately has an effect on mood. Some TCAs bind with SERT and some bind with NET. Clomipramine, for example, is a potent binder of SERT, but it is a weak binder of NET. Desipramine, on the other hand, is a strong binder of NET.
Additionally, it should be noted that antidepressant medications, when used for anxiety, depression, or other mental health issues, tend to be more effective when combined with some type of therapy. Medication can help treat symptoms of mental health conditions, but pills do not address the underlying emotions, behaviors, and root causes of mental health issues. If you are prescribed an antidepressant or other psychotropic medication, consider finding a qualified therapist to better understand and help treat your condition.
The potential side effects of these medications 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. Other effects can include:
It is important to discuss with your doctor any additional medications you are taking prior to starting treatment with a tricyclic drug. TCAs may have dangerous interactions with certain medications, drugs, or substances.
The FDA urges that the lowest dose should be used to start the treatment. Monitoring of the person in treatment is necessary and dose should be adjusted based on the results.
Withdrawal symptoms are possible when people suddenly stop taking tricyclic antidepressants or miss several doses. Nausea, headache, depression, anxiety, insomnia, and dizziness are common symptoms of withdrawal. Consult your doctor if you experience unwanted withdrawal symptoms.
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Page content reviewed by James Pendleton, ND.