Discovered by accident in the 1950s when scientists were researching antihistamines and antipsychotic drugs, tricyclic antidepressants, together with monoamine oxidase inhibitors (MAOIs), were the first drugs to successfully treat depression. While effective in up to 70% of patients, tricyclic antidepressants need careful management and can cause uncomfortable side effects.
What Are Tricyclic Antidepressants (TCAs)?
TCA drugs are so named because of their chemical structure, which includes three rings of atoms and a chain. These three rings influence how the drugs interact with the brain by influencing neurotransmitter pathways. In particular, the rings slow down the reuptake of neurotransmitters, including serotonin and norepinephrine, in the brain.
There are two broad types of TCA: tertiary and secondary amines. They differ in that TCAs with secondary amines primarily inhibit norepinephrine reuptake, while tertiary amines affect the reuptake of both serotonin and norepinephrine. Tertiary amine TCAs are regarded as slightly more effective than secondary amines, but they have more severe side effects.
TCA medication is considered a first-generation antidepressant and, while still in use, has largely been superseded by newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
How TCAs Work in the Brain
The neurotransmitters in the brain are chemical messengers that carry signals between neurons. They’re part of the body’s nervous system, controlling all bodily functions and your mood. Once a neurotransmitter delivers its message, it’s usually reabsorbed into the transmitting nerve cell.
Two neurotransmitters, serotonin and norepinephrine, play a vital role in regulating mood. Serotonin is primarily responsible for feelings of happiness, emotion, appetite and sleep. Norepinephrine affects energy levels, cognitive ability and level of concentration.
People with depression have low levels of serotonin and norepinephrine in their brains. Tricyclic antidepressants work by inhibiting the reabsorption (reuptake) of these neurotransmitters into nerve cells. Consequently, the levels of serotonin and norepinephrine increase, helping alleviate symptoms of depression and anxiety.
Common TCAs and What They’re Prescribed For
The FDA has approved the use of tricyclic antidepressants for treating depression. Additionally, doctors have found these drugs useful for the off-label treatment of various conditions, including anxiety, fibromyalgia and chronic pain.
Tertiary amine tricyclic antidepressants for off-label treatment include:
- Amitriptyline. Sold as Elavil and Vanatrip (brand names), amitriptyline is used for the off-label treatment of anxiety, insomnia, post-traumatic stress disorder (PTSD), chronic pain, migraines and irritable bowel syndrome (IBS).
- Clomipramine. Available under the brand name Anafranil, clomipramine is FDA-approved for treating obsessive-compulsive disorder (OCD). Its off-label uses include treatment for panic disorders, anxiety, treatment-resistant depression, insomnia and chronic pain.
- Doxepin. Offered as a generic and under the brand names of Silenor and Sinequan, this drug is used for neuropathic pain (caused by damage to the nervous system), headaches and fibromyalgia.
- Imipramine. Obtainable as Tofranil, imipramine is used off-label for neuropathic pain, attention deficit hyperactivity disorder (ADHD), PTSD and panic disorders.
Secondary amine TCA antidepressants generally have fewer side effects than tertiary amine TCAs when used for treating depression. Secondary amine TCAs include:
- Despiramine. Retailed under the brand name of Norpramin, desipramine is used off-label for treating IBS, ADHD, bulimia nervosa and neuropathic pain.
- Maprotiline. Sold under the brand name Ludiomil, maprotiline isn’t currently available and was mainly used to treat bipolar disorders.
- Nortriptyline. Available as Aventyl and Pamelor, nortriptyline is used to treat major depressive disorder (MDD) and off-label for IBS, neuralgia, chronic and myofascial pain.
Benefits and Side Effects to Know
Although now largely replaced by SSRIs for treating depression, tricyclic antidepressants continue to be used in certain circumstances.
Specific benefits of TCAs include:
- Best alternative to SSRIs. Not every patient responds well to SSRI treatment, and in these instances, TCAs remain the best choice.
- Good for comorbid disorders. TCAs work well when used for treating comorbid disorders, such as OCD, anxiety, chronic pain and panic disorders.
- Effective for associated symptoms. Tricyclic antidepressants are effective for treating depression-related symptoms such as muscle pain and headaches.
- Longer lasting. These drugs have a long-lasting effect, which can be beneficial for long-term depression treatment.
Unfortunately, tricyclic antidepressant use has notable side effects, such as:
- Overdose toxicity. Inadvertent or deliberate overdose of TCAs can be fatal.
- Sedative effect. When starting treatment, many patients experience severe drowsiness that may affect their ability to function.
- Dizziness. These drugs tend to lower blood pressure, leading to dizziness.
- Blurred vision. Some patients experience blurred vision.
- Dry mouth. TCA affects saliva production, leading to a dry mouth and possible mouth infections.
- Confusion. Some patients, especially seniors, may become confused and experience memory problems.
- Loss of interest in sex. Tricyclic antidepressants reduce sexual desire and may cause erectile dysfunction.
- Tremors. Some people experience shakiness.
- Weight gain. When used for an extended period, changes in appetite and metabolism may lead to weight gain.
- Urination. The sedative effects of TCAs extend to the bladder muscle, making it more difficult to urinate.
TCAs vs. SSRIs: What’s the Difference?
SSRIs are currently the preferred drugs for treating depression. The main difference between tricyclic antidepressants and selective serotonin reuptake inhibitors is that SSRIs only block serotonin reuptake. Selective serotonin reuptake inhibitors have fewer side effects than tricyclic antidepressants, and they’re less debilitating. SSRIs don’t cause drowsiness to the same extent as TCAs, and this condition reduces as the body adjusts to the medicine. Other differences are less confusion and problems with blurred vision. The risk of a fatal overdose with SSRIs is lower as well.
From a treatment perspective, SSRIs act more quickly, with patients experiencing an improvement in their symptoms within 1 to 2 weeks, compared to 4 weeks for TCAs. While SSRI side effects are similar to those of TCAs, they’re often less debilitating.
When TCAs Might Be the Right Option
There are certain instances where tricyclic antidepressants may be preferable to SSRIs. Some patients with depression don’t respond positively to SSRI treatment, and in these instances, doctors may switch them to a TCA. If patients have had previous episodes of serious depression, it’s often recommended to treat them using TCAs. Other indications for prescribing TCAs are a history of insomnia or gastrointestinal problems. TCAs may also be better for treating people who have chronic pain, such as fibromyalgia or migraines.
Finding Treatment for Depression
If you or someone you care about is struggling with depression that never seems to lift, treatment can help. At FHE Health, we treat all types of depression using a combination of talk therapy and medication. We also treat underlying conditions that may be contributing to depression. Contact us now for a confidential discussion and to schedule an appointment.
