What To Do When Depression Symptoms Linger

Sometimes depression doesn’t go away, even when you’ve done everything you’re supposed to. You’ve tried medication, therapy, exercise, maybe even changed your routine and still, the heaviness sticks around. It can feel confusing, frustrating, and honestly, pretty lonely.

This experience is more common than most people realize. When symptoms don’t fully respond to standard treatments, it’s called treatment-resistant depression. It doesn’t mean you’ve failed or that recovery isn’t possible, it just means your brain and body may need a different approach.

Treatment-resistant depression (TRD) is a type of major depression that typically doesn't respond to two or more treatments.  It’s not uncommon, and it can feel frustrating, discouraging, and overwhelming. But most importantly, it is not hopeless.

What Does Treatment-Resistant Depression Really Mean?

Treatment-resistant depression is a term doctors use when someone has tried at least two different antidepressants, each for an adequate amount of time and at the right dose, but hasn’t seen enough improvement. It doesn’t mean you’re beyond help. It simply means your brain may need a different approach. Depression affects people differently, and one-size-fits-all treatment rarely works for everyone.

Why Doesn’t Standard Treatment Always Work?

There are a number of reasons why someone might not respond to typical antidepressants. Brain chemistry is complex, and no two people have exactly the same neurobiology. In some cases, underlying factors like anxiety disorders, bipolar disorder, trauma, or chronic illness can also play a role in how depression shows up and how it responds to treatment. Sometimes, even daily stress, poor sleep, or lack of social support can make it harder for medications to take effect. And for some people, their depression is rooted in a deeper neurochemical imbalance that traditional medications just don’t address well.

The Emotional Weight of TRD

If you’re dealing with TRD, you might know the cycle well. You try a new medication or therapy. You wait. You hope. And then nothing changes—or maybe you feel a bit better at first, only to crash again later. Over time, this can take a real emotional toll. You might start to wonder if anything will ever work. You might even stop hoping altogether.

But even when it feels like nothing is working, new options continue to emerge. And many people who once felt hopeless are now finding relief thanks to advances in mental health care.

Emerging Treatments Offer New Hope

When typical antidepressants don’t help, other treatment options may still bring relief. Ketamine is one example. Originally developed as an anesthetic, ketamine is now being used to treat depression in a whole new way. Unlike traditional antidepressants that affect serotonin or norepinephrine, ketamine works on a different neurotransmitter—glutamate. This unique action seems to “reboot” certain brain pathways and provide quick relief for some people.

At Palo Alto Mind Body, we offer two types of ketamine-based treatment:

• IV Ketamine Infusion: Delivered intravenously under medical supervision, this form of ketamine has helped many people experience noticeable relief—sometimes within hours or days.
• SPRAVATO® (Esketamine Nasal Spray): This is an FDA-approved option that’s used alongside an oral antidepressant. It’s administered in a clinical setting and monitored closely to ensure safety and effectiveness.

These therapies won’t work for everyone, but for many people with TRD, they represent a turning point after months or years of disappointment.

More Than Just Medication

Living with treatment-resistant depression is about more than finding the right medication. It’s also about surrounding yourself with support, compassion, and care. Therapy can be incredibly helpful in learning to manage symptoms, process trauma, or rebuild after long periods of struggle. Support groups can connect you with others who understand what you’re going through. And lifestyle tools like sleep, movement, and mindfulness—while not cures—can help you build resilience and strength along the way.

You Deserve to Feel Better

If you’ve been stuck in a place where nothing seems to help, know that there are still options. Your pain is real, and so is your strength. New treatments like ketamine offer hope to those who’ve tried everything and still feel trapped by depression.

We're With You Every Step of the Way

At Palo Alto Mind Body, we understand how hard the journey can be. Our team specializes in caring for people who feel like they’ve run out of options. We offer advanced treatments like IV ketamine and SPRAVATO® in a safe, supportive setting where your comfort and well-being come first. Every person is different, and we work closely with you to create a treatment plan that fits your needs, values, and goals.

Whether you’ve just begun to explore new options or you’ve been searching for relief for years, we’re here to help you take the next step. You are not alone, and you don’t have to navigate this on your own.

Let’s talk. Let’s find what works for you.