Tricyclic Antidepressants: What They Are, How They Work, and Alternatives

When it comes to treating depression, tricyclic antidepressants, a class of prescription medications first developed in the 1950s that work by balancing brain chemicals like serotonin and norepinephrine. Also known as TCAs, they were the go-to option before SSRIs became popular—but they’re still used today, especially when newer drugs don’t work or for certain types of chronic pain. Unlike newer antidepressants, tricyclics affect more than one neurotransmitter, which can make them more effective for some people—but also more likely to cause side effects like dry mouth, drowsiness, or dizziness.

These drugs are amitriptyline, one of the most commonly prescribed TCAs, often used for depression and nerve pain, nortriptyline, a metabolite of amitriptyline with fewer side effects, and imipramine, one of the first TCAs ever made, still used for bedwetting in kids and depression in adults. They’re not just for sadness—doctors sometimes prescribe them for migraines, fibromyalgia, or anxiety disorders because they calm overactive nerve signals. But they’re not for everyone. People with heart conditions, glaucoma, or a history of seizures often avoid them. And unlike SSRIs, stopping TCAs suddenly can cause withdrawal symptoms like nausea, headaches, or mood swings.

If you’ve tried an SSRI like sertraline or escitalopram and it didn’t help, your doctor might suggest a TCA. But they’re not the only option left. Drugs like mirtazapine or SNRIs like venlafaxine can offer similar benefits with fewer side effects. Even non-drug approaches—like therapy, exercise, or supplements—can play a role in managing symptoms. The key is finding what fits your body, your lifestyle, and your goals.

Below, you’ll find real-world comparisons and insights from people who’ve used these medications—whether they worked, what side effects showed up, and how they stacked up against other treatments. No fluff. Just clear, practical info to help you understand where tricyclic antidepressants still fit in modern care.