Why Antidepressants Don’t Work For Everyone

Summary: SSRIs are a common treatment for depression and anxiety, but they don’t work for everyone. For those with chronic stress, trauma, or neurodivergence, medication alone may not be enough. True healing goes beyond neurotransmitters—reshaping brain pathways and exploring alternative treatments like ketamine therapy.

SSRIs (Selective Serotonin Reuptake Inhibitors) are often the first treatment option for depression and anxiety. While they can help some people feel more stable, many find the relief is partial—or temporary. At first, symptoms improve, but over time, the brain adjusts, and old patterns return.

This isn’t a failure of the medication—it’s the brain’s natural tendency to maintain balance. The common assumption is that if depression is linked to low serotonin (a neurotransmitter), increasing serotonin should fix the problem. But the brain is far more complex.

While boosting serotonin can improve mood, it doesn’t necessarily shift deeply ingrained emotional responses, heal past trauma, or rewire thought patterns. For those who have spent years in a state of chronic stress or hypervigilance, even feeling “better” can feel unfamiliar or even unsafe.

The mind may instinctively reestablish a baseline that still carries the weight of unresolved trauma, habitual self-criticism, or deeply ingrained emotional patterns. When this happens, it can feel as though SSRIs have “stopped working”—but the medication itself isn’t necessarily failing. This is why treatment needs to go beyond neurotransmitters.

Traditional antidepressants shift brain chemistry, but they don’t address the internal landscape—the beliefs, emotions, and survival mechanisms that keep someone stuck. True healing involves reshaping the brain’s pathways, teaching it that safety, connection, and self-worth aren’t fleeting states but stable foundations. For some, this means incorporating therapy, trauma processing, or nervous system regulation. Others explore alternative treatments like ketamine therapy, which works differently from SSRIs—helping to break rigid thought patterns and support neuroplasticity in ways traditional antidepressants often cannot.

So why don’t SSRIs work for everyone? And how does ketamine provide another path to healing?

SSRIs are a type of antidepressant designed to increase serotonin levels in the brain. Serotonin, often called the "feel-good chemical," helps regulate mood, sleep, and emotions.

These medications are commonly prescribed for:

For many, SSRIs can be helpful, particularly in the first few weeks of treatment, as serotonin stabilizes mood and improves the brain’s ability to regulate stress.

However, not everyone experiences lasting relief. People with conditions like CPTSD, PTSD, or neurodivergence often find that SSRIs either don’t work at all or only offer temporary improvement before symptoms return. This is because increasing serotonin doesn’t necessarily resolve trauma-driven emotional patterns or deeply ingrained ways of thinking.

For individuals with neurodivergence—such as ADHD or autism—SSRIs may not address the root causes of their struggles. Many neurodivergent people have spent years adapting to a world that wasn’t designed for them, relying on coping mechanisms like dissociation or hypervigilance. These survival strategies can contribute to anxiety and depression, but they aren’t caused by a simple serotonin imbalance.

SSRIs might provide a temporary mood lift, but the neurodivergent brain often resists these changes, returning to its baseline of self-protection. A more effective approach acknowledges the deeper neurobiological differences and provides treatments that support emotional regulation and resilience.

For those with PTSD or CPTSD, the challenges run even deeper. Trauma physically alters the brain, keeping it locked in a hypervigilant state driven by the fight-or-flight response.

Key changes include:

SSRIs can help in some cases, but they don’t address the core problem: the way trauma rewires the brain. Many people with CPTSD feel emotions more intensely and struggle with self-regulation, making generalized treatments like SSRIs less effective. True healing requires approaches that target trauma’s impact on brain function—not just serotonin levels.

Unlike SSRIs, which focus on serotonin, ketamine takes an entirely different approach. It works on the glutamatergic system, targeting N-methyl-D-aspartate (NMDA) receptors to promote neuroplasticity—the brain’s ability to rewire itself.

For neurodivergent individuals, ketamine can help:

Ketamine’s ability to create new neural pathways is particularly valuable for people with PTSD and CPTSD.

It:

This is why some people turn to ketamine, psychedelic integration, or deeper therapeutic work when SSRIs don’t provide the full relief they need. These approaches don’t just increase neurotransmitters—they disrupt rigid thought patterns and allow for new emotional processing. The key is creating conditions where the mind and body can learn a new way of being. SSRIs may help stabilize, but real healing comes from untangling the deeper knots that keep the system stuck.

Mental health care is more than just balancing brain chemistry—it’s about understanding the brain’s complex needs. Neurobiology and pharmacology work together, shaping how we experience emotions, process stress, and respond to treatment. That’s why a one-size-fits-all approach, like standard antidepressants, doesn’t always work.

If you’re curious about ketamine therapy and whether it could be right for you, consider speaking with a provider who understands both the science and the lived experience of neurodivergent and trauma-affected individuals. Unlike some treatment models that focus solely on administering ketamine without deeper therapeutic support, a comprehensive approach integrates ketamine with intentional mental health care. This ensures that treatment fosters true, lasting healing.