TCAs vs SSRIs: Key Differences, Uses, and What Works Best

When it comes to treating depression, TCAs, or tricyclic antidepressants, are among the oldest medications still in use today. Also known as tricyclics, they work by boosting levels of serotonin and norepinephrine in the brain, helping to lift mood and reduce anxiety. While newer options have taken center stage, TCAs remain a viable choice—especially when other treatments fail. On the other side, SSRIs, or selective serotonin reuptake inhibitors, are the go-to for most doctors today because they’re easier to tolerate and safer in overdose. SSRIs focus mainly on serotonin, which makes them more targeted and less likely to cause harsh side effects.

So why does this matter? Because the difference isn’t just about chemistry—it’s about your daily life. TCAs often cause dry mouth, blurry vision, weight gain, and drowsiness. Some people can’t handle them, especially older adults, because they also raise the risk of heart rhythm issues. SSRIs? They’re gentler. Common side effects include nausea, sexual dysfunction, or feeling wired at first—but these usually fade after a few weeks. Studies show both types work similarly well for depression, but SSRIs have a much better safety record. That’s why most patients start with an SSRI unless they’ve tried it before and it didn’t work.

There’s also a practical side: cost and access. Generic TCAs like amitriptyline or nortriptyline are dirt cheap—sometimes under $5 a month. SSRIs like sertraline or escitalopram are also affordable, but newer ones can cost more without insurance. If you’ve been on a TCA for years and it works, there’s no reason to switch. But if you’re just starting out, your doctor will almost always suggest an SSRI first. It’s not about which is "better"—it’s about which fits your body, your lifestyle, and your risk profile.

You’ll find posts here that dig into real cases: how people reacted to amitriptyline versus fluoxetine, what happened when someone switched from a TCA to an SSRI, and why some patients still end up on older meds despite the risks. We’ll also cover what to watch for—like serotonin syndrome, withdrawal symptoms, or how these drugs interact with other medications you might be taking. Whether you’re a patient, a caregiver, or just trying to understand your own treatment, this collection gives you the facts without the jargon.