For decades, traditional antidepressants like SSRIs and SNRIs have been the foundation of treatment for depression and anxiety disorders. They’ve helped millions of people manage symptoms, regain balance, and live healthier lives. Yet for some, those medications simply don’t go far enough — or work at all.
That’s where ketamine therapy comes in. Once known primarily as an anesthetic, ketamine is gaining recognition as a safe, fast-acting option for people who haven’t found relief through standard medications. While both approaches can be effective, they work in very different ways. Understanding those differences can help patients and providers make the right choice for each individual.
How Traditional Antidepressants Work
Traditional antidepressants, including SSRIs (such as Prozac® and Zoloft®) and SNRIs (such as Effexor® and Cymbalta®), primarily target the brain’s serotonin and norepinephrine systems. These neurotransmitters influence mood, energy, sleep, and emotional regulation. By increasing their availability, antidepressants gradually help stabilize mood and reduce symptoms of depression.
The process, however, takes time. It can take 4-6 weeks or longer for patients to feel meaningful improvement, and even then, results can vary. Studies suggest that up to one-third of people with depression experience only partial relief or no response to first-line antidepressants. For those living with severe or treatment-resistant depression, waiting weeks for change can feel discouraging and even unsafe.
How Ketamine Works Differently
Ketamine acts through a completely different mechanism. Rather than targeting serotonin, ketamine interacts with the brain’s glutamate system, specifically the NMDA receptor. This interaction triggers a surge of brain-derived neurotrophic factor (BDNF), which supports the growth of new neural connections. This process is known as neuroplasticity.
In simpler terms, ketamine helps the brain “reboot” and form new communication pathways, interrupting rigid patterns of depressive thinking. Many patients describe the results as feeling like a mental reset: mood, motivation, and clarity can improve within hours or days, rather than weeks.
Because of its fast action, ketamine therapy can be particularly beneficial for people struggling with suicidal thoughts or deep emotional stagnation. By helping the brain reconnect to more adaptive thought patterns, it often restores the sense of possibility that chronic depression erodes.
Rapid Relief for Treatment-Resistant Depression
For individuals who have tried multiple antidepressants without success, ketamine therapy can be transformative. Intravenous (IV) ketamine and intranasal esketamine (Spravato®) have both shown significant reductions in depressive symptoms, even among patients who haven’t responded to other treatments.
This rapid relief can be life-changing. Instead of waiting weeks to feel better, many patients report improvement within the first few sessions. That early progress often gives them the energy and focus to engage more fully in psychotherapy, self-care, and lifestyle changes that reinforce long-term recovery.
Safety, Side Effects, and Monitoring
Ketamine therapy is administered in a controlled medical environment, with continuous monitoring from trained professionals. Treatments typically last about 45-60 minutes, followed by a short recovery period before going home.
Some patients experience mild, temporary side effects such as dizziness, lightheadedness, or a sense of floating or detachment (known as dissociation). These sensations generally subside within an hour and are part of the therapeutic process for many.
In contrast, traditional antidepressants are taken daily and can cause side effects like nausea, sleep disturbance, sexual dysfunction, or emotional “blunting.” They can also interact with other medications or lose effectiveness over time, requiring dosage adjustments or medication changes.
Neither approach is inherently “better.” They simply differ in how they act on the brain and how quickly results are felt.
The Right Choice Depends on the Individual
While ketamine therapy offers a new path forward, it isn’t a replacement for all antidepressants. For patients whose symptoms are well-managed with SSRIs or SNRIs, continuing those medications under a clinician’s guidance remains a proven, effective approach.
However, for those who haven’t responded to traditional medications — or who need rapid stabilization during a severe depressive episode — ketamine provides a promising alternative. It bridges neuroscience and mental health innovation, helping patients regain hope and healing when conventional treatments fall short for them.
Some patients even benefit from a combined approach, using ketamine to achieve fast symptom relief while continuing traditional antidepressants for long-term maintenance under medical supervision.
A New Frontier in Mental Health Care
What makes ketamine therapy truly different isn’t just its speed, it’s the ability to help the brain reconnect and heal. By promoting neuroplasticity and calming overactive brain networks, ketamine supports the kind of deep emotional reset that can make therapy and self-growth possible again.
It doesn’t erase depression overnight, but it can open a crucial window for change to begin.
If you’d like to learn more about ketamine treatment and how it might help you, contact Psychiatry Unplugged today. For patients who have felt stuck, that renewed sense of clarity and possibility can mark the start of something powerful: a life no longer defined by depression, but by recovery, resilience, and hope.
Sources:
boldhealthinc.com/ketamine-therapy-vs-traditional-antidepressants/