TCAs vs SSRIs: What You Need to Know About These Depression Medications

When it comes to treating depression, two classes of medications have shaped decades of care: tricyclic antidepressants, a first-generation class of antidepressants developed in the 1950s that work by increasing serotonin and norepinephrine in the brain. Also known as TCAs, they were the go-to option before newer drugs came along. Today, SSRIs, a modern class of antidepressants that selectively boost serotonin levels with fewer side effects than older drugs. Also known as selective serotonin reuptake inhibitors, they’ve become the most commonly prescribed antidepressants in the U.S. and Canada. But even with SSRIs dominating prescriptions, TCAs still have a place—especially when SSRIs don’t work or when patients have certain symptoms like chronic pain or severe insomnia.

So what’s the real difference? TCAs hit multiple brain chemicals at once—serotonin, norepinephrine, and even histamine and acetylcholine—which is why they’re effective but also cause more side effects: dry mouth, constipation, dizziness, weight gain, and sometimes dangerous heart rhythm changes. SSRIs, by contrast, mostly target serotonin alone. That makes them cleaner, safer for most people, and easier to tolerate. But they’re not magic. Many people still struggle with nausea, sexual side effects, or feeling emotionally flat on SSRIs. And for some, especially those with treatment-resistant depression or nerve pain, TCAs deliver results SSRIs simply can’t match.

Doctors don’t pick one over the other based on trends—they look at your history. If you’ve tried an SSRI and it didn’t help, or if you have depression along with chronic back pain or nighttime anxiety, a TCA might be worth considering. If you’re older or have heart issues, SSRIs are usually safer. If you’re young and just starting treatment, your doctor will likely start with an SSRI because the risk profile is lower. But neither is perfect. Both take weeks to work. Both need careful monitoring. And both can be stopped only under medical supervision.

You’ll find posts here that dig into real-world use cases: how people manage side effects, why some switch from SSRIs to TCAs after years, and what blood tests or heart checks are needed when using either. You’ll see how these drugs interact with other medications like blood thinners or painkillers. And you’ll get clear, no-fluff advice from people who’ve lived with these treatments—not just textbook summaries.