Ketamine or SSRIs? What the Research Tells Us About Rapid Relief in Depression Treatment

For anyone struggling with depression, especially when traditional treatments haven’t helped, the question becomes urgent: What else is out there?

SSRIs have long been the go-to prescription. But in recent years, ketamine has emerged as a promising—and faster-acting—alternative. So how do they compare? And how do you decide which one is right for you?

Let’s break it down.

SSRIs vs. Ketamine: What’s the Difference?

SSRIs (Selective Serotonin Reuptake Inhibitors) are a class of antidepressants that include medications like Prozac, Zoloft, Lexapro, and Paxil; they’re taken daily in pill form. They work by increasing serotonin levels in the brain—a chemical associated with mood regulation. They’re designed to slowly improve mood, energy, and outlook.

But here’s the catch: they take time. It can take 4–6 weeks (or more) to see if they’re effective. And for many people, they’re not. 

According to the STAR*D trial—the largest study of its kind—only about 1 in 3 people find relief with the first antidepressant they try.

Ketamine, on the other hand, works on a completely different brain pathway: the glutamate system. It promotes neuroplasticity—your brain’s ability to form new connections—and can provide relief in hours or days, not weeks. Sustained maintenance treatments can truly change your life.

The Role of Time in Mental Health Recovery

Let’s be honest: when you’re in the depths of depression, waiting six weeks just to find out if a treatment might work is a big ask.

That’s why a recent clinical trial, published in Psychiatry Research, is so important. It looked at patients with treatment-resistant depression (TRD)—people who had already tried SSRIs with no success—and gave them six ketamine infusions over two weeks.

Here’s what happened:

• After just two treatments, about 50% of patients saw significant relief. 
• After six treatments, that number climbed to over 67%. 
• One month later, many were still doing well without needing to start new medications.

The speed of this response is almost unheard of in mental health care. And when time feels like the enemy, that matters.

What the Research Really Tells Us

The 2024 study showed that a short series of treatments can provide meaningful, lasting change, even for people who have been struggling for years.

That doesn’t mean SSRIs are useless. They’ve helped millions of people. But the difference in onset time is clear, and for many patients that speed can be life-changing.

And here’s an important note: ketamine isn’t just a chemical fix. It creates a window of neuroplasticity, which means your brain becomes more open to change. That’s why we combine it with Ketamine-Assisted Psychotherapy (KAP) here at New Pathways—so you can actually make use of that window and work through the underlying causes of depression.

Let’s take a quick look at how both medications addressed suicidal thoughts in patients. SSRIs can take weeks to address suicidal ideation—and in rare cases, might briefly worsen it in early phases. Ketamine has been shown to reduce suicidal thoughts within hours, a critical benefit for patients in crisis.

 

According to the study, “No suicide attempts or behaviors were reported across 135 patients during months of maintenance ketamine care.” That’s a big deal.

Safety, Side Effects, and What Patients Should Know

SSRIs come with side effects like weight gain, sexual dysfunction, and emotional numbing. Some people tolerate them well; others don’t.

Ketamine, too, has side effects—most commonly mild nausea or dissociation during the treatment window—but they’re short-lived and typically resolve within an hour or so. There’s no long-term “build-up” in your body. And ketamine is non-habit forming when administered in a controlled medical setting like ours.

In fact, ketamine has an FDA-approved cousin—Spravato (esketamine)—which we also offer at New Pathways. It’s approved for TRD and is covered by many insurance plans.

Why Ketamine Isn’t Replacing SSRIs, But It Might Be the Right First Step for You

This isn’t an either-or situation.

SSRIs are still useful. Some patients benefit from them. But for people who’ve tried one or more antidepressants without relief—or who need help now, not two months from now—ketamine can be a powerful first step.

For others, it may be part of a broader toolkit. In fact, many patients use ketamine to stabilize quickly, then work with their provider to determine whether an SSRI is still needed for maintenance.

We don’t believe in a one-size-fits-all model. We believe in what works for you.

SSRIs may be a first-line option for mild to moderate depression or anxiety, especially if patients respond well to medication and aren’t in immediate distress.

Ketamine may be more appropriate for:

• People who haven’t responded to 2+ medications (TRD) 
• Those experiencing suicidal ideation 
• Patients seeking fast relief after long periods of stagnation

How New Pathways Helps You Choose

Choosing between ketamine and SSRIs isn’t something you should do alone. At New Pathways, we’ll walk with you through every step:

• Comprehensive evaluation by a licensed medical provider 
• Detailed treatment planning, including medication history and current symptoms 
• Access to ketamine, Spravato, and psychotherapy under one roof 
• Ongoing monitoring of your progress and mood

We’re here to help you weigh the options, understand the science, and make the best decision for your mental health—not just the easiest or most familiar one.

The Bottom Line

If SSRIs haven’t helped—or if the idea of waiting another month to feel better feels impossible—you’re not out of options.

Ketamine is fast. It’s well-studied. And when paired with therapy, it can open the door to real change.

Let’s find your path forward.