Treatment-Resistant Depression Treatment in Los Angeles

When “Try Another Antidepressant” Is No Longer a Real Answer

You’ve done what you were supposed to do. You saw a doctor. You tried the medications. You gave them time. Maybe you tried more than one. Maybe you tried five. Maybe you’ve been on and off antidepressants for years — experiencing side effects that made daily life harder, or feeling nothing at all, or feeling better for a while only to slide back.

If this is your experience, you may have been told you have treatment-resistant depression, or TRD. That diagnosis carries a particular kind of weight — not just the continued suffering, but the implication that medicine doesn’t have much left to offer you.

That is not true. And Julian Macias, PMHNP-BC, has spent his career focused on exactly this population.

What Treatment-Resistant Depression Actually Is

Treatment-resistant depression (TRD) has a specific clinical definition: depression that has not responded adequately to at least two different antidepressant medications, each tried at an appropriate dose for an appropriate length of time.

By that definition, TRD is more common than most people realize. Approximately one-third of people with major depressive disorder do not achieve adequate relief from standard antidepressant treatments. That represents millions of people in the United States alone — people who are not treatment failures, but people whose depression operates through pathways that standard treatments don’t reach.

TRD is not about a lack of effort or willpower. It is a biological reality: for a significant subset of people, depression is driven by mechanisms other than serotonin dysregulation, and treating those patients with serotonin-targeting medications is, at best, an incomplete solution.

The Biology: Why SSRIs Don’t Work for Everyone

Most antidepressants — SSRIs, SNRIs, and many others — work by modulating serotonin and norepinephrine. This approach helps many people. It does not help everyone.

For patients with TRD, the biological picture is often more complex. Emerging research points to dysfunction in the glutamate system — the brain’s primary excitatory neurotransmitter pathway — as a key driver of TRD. Glutamate dysregulation affects synaptic plasticity: the brain’s ability to form and strengthen the neural connections that underlie mood regulation, motivation, and emotional resilience.

In simple terms: some people’s brains have lost the ability to build the connections that healthy mood regulation requires. SSRIs don’t fix that. Treatments that act directly on the glutamate system — like ketamine — do. TMS works through a complementary mechanism: directly stimulating underactive brain regions through targeted magnetic pulses, promoting neuroplasticity and reactivating circuits that have gone quiet under the weight of depression.

Julian’s Combined Approach to TRD

Julian does not offer a single protocol for every patient with TRD. He offers a comprehensive evaluation followed by a treatment plan that may include:

• IV ketamine infusion therapy for rapid symptom relief and neuroplasticity induction — particularly for patients with severe or acutely impairing depression
• TMS therapy for sustained, non-medication stimulation of the prefrontal cortex — particularly for patients who prefer to avoid medication or who want to build on ketamine’s effects over a longer arc
• The 12-Week Integration Program to ensure that the neuroplasticity gains from ketamine translate into durable neural and behavioral change
• Medication management where appropriate, including evaluation of whether any current medications may be interfering with treatment response

For many patients with TRD, the most effective approach is a combination of ketamine and TMS — using ketamine’s rapid neuroplasticity induction to prime the brain, then using TMS to sustain and deepen the changes over a longer period. Julian is one of very few providers in Los Angeles trained and certified to offer both.

Who This Is For

If you are reading this page, you may recognize yourself in one or more of these descriptions:

• You have tried SSRIs, SNRIs, or other antidepressants and found limited or no benefit
• You have experienced side effects from antidepressants that significantly impacted your quality of life
• You have tried mood stabilizers, augmentation strategies, or combinations of multiple medications
• You have been through ECT (electroconvulsive therapy) or are currently considering it
• You are in therapy and doing the work, but the biological weight of depression is still preventing meaningful progress
• You are exhausted — not just from depression, but from the years of trying and not finding relief

You are not out of options. You have arrived at a different category of treatment — interventional psychiatry — that exists specifically because standard treatments don’t work for everyone. This is where that road has always been leading.

What the Evidence Shows

The clinical evidence for ketamine in treatment-resistant depression is substantial and growing. A landmark study published in JAMA Psychiatry found response rates of approximately 70% in patients with TRD treated with ketamine — a remarkable figure for a population that had previously failed multiple treatment trials. The speed of response — often within hours to days — is unlike anything available through traditional antidepressants.

TMS has demonstrated consistent efficacy in multiple large randomized controlled trials for major depressive disorder, with approximately 50–60% of patients showing meaningful response and roughly 30–35% achieving full remission. For patients with TRD, these numbers represent something that standard antidepressant trials have not offered: a realistic, evidence-based path to relief.