A guide from Washington Interventional Psychiatry
Depression remains one of the most common and challenging mental health conditions. For many people, traditional antidepressants such as SSRIs and SNRIs provide meaningful relief. For others, symptoms persist despite multiple medication trials and therapy.
Understanding the differences between traditional antidepressants and ketamine therapy—and how they can work together—can help patients and families make informed, safe decisions about care.
Treating depression, whether with traditional medications or advanced interventions like ketamine, requires specialized medical training in psychopharmacology, diagnosis, and comprehensive mental health care. Psychiatrists are physicians uniquely trained to evaluate complex symptoms, manage medication interactions, monitor for medical complications, and integrate biological, psychological, and social factors into treatment. This expertise is essential for safe, effective outcomes.
How Traditional Antidepressants Work and When They’re Used
Traditional antidepressants regulate neurotransmitters such as serotonin, norepinephrine, and dopamine to support long-term mood stability. Psychiatrists are the medical specialists trained to prescribe and manage these medications, carefully selecting from dozens of options based on symptom profiles, medical history, and potential drug interactions. They are often considered first-line treatments and are commonly prescribed for:
- Major depressive disorder
- Generalized anxiety disorder and related conditions
These medications typically take 4–8 weeks to show benefit. They are widely effective, but some individuals experience only partial relief or side effects such as decreased libido, sleep changes, or emotional blunting.
For those who respond well, antidepressants can serve as a safe and steady foundation for recovery. However, when symptoms remain despite multiple trials, or when side effects make ongoing use difficult, psychiatrists may consider other approaches, including augmentation strategies like ketamine therapy.
How Ketamine Therapy Works and Why Psychiatric Expertise Is Essential
Ketamine acts on the brain’s glutamate system, enhancing synaptic plasticity and restoring communication between neural networks that can become disrupted in depression and trauma. This mechanism is fundamentally different from antidepressants and can rapidly reverse the neurobiological rigidity that often accompanies severe mood and stress disorders.
Unlike traditional antidepressants, ketamine’s effects are often felt within hours to days. This speed of action can be critical for patients experiencing suicidal thoughts or rapid decline; situations where waiting weeks for a medication response is not feasible.
Because ketamine affects the brain differently than traditional psychiatric medications and can have dissociative effects, psychiatric oversight is not optional, it is medically necessary. Psychiatrists are trained to evaluate whether patients are appropriate candidates, monitor for contraindications, adjust dosing based on response, and manage any psychiatric side effects or complications that may emerge.
Ketamine therapy is typically considered when:
- Multiple antidepressants have not provided adequate relief
- Symptoms are severe or long-standing
- Rapid improvement is needed due to suicidal thoughts or functional decline
When provided under psychiatric supervision, ketamine can also serve as an augmentation strategy. It’s used alongside traditional antidepressants to accelerate improvement or bridge the time needed for other medications to take effect.
Ketamine, Trauma, and the Healing Process
In addition to treating depression, ketamine has shown promise in the treatment of trauma and post-traumatic stress disorder (PTSD). During the dissociative or “journey” period of treatment, patients often experience a temporary softening of psychological defenses.
This can:
- Enhance neuroplasticity, allowing the brain to form new connections around painful memories
- Reduce defense mechanisms such as avoidance or emotional numbing
- Increase cognitive flexibility, helping patients process trauma in a new and less distressing way
These effects are significantly different from traditional antidepressants, which primarily regulate mood but do not directly alter the brain’s capacity to reprocess traumatic experiences. Under psychiatric guidance, and when integrated with therapy, ketamine can open a unique window for emotional healing and insight.
Effectiveness, Onset, and Side-Effect Differences
The table below compares Ketamine Therapy vs. Traditional Antidepressants for Depression, highlighting key differences in effectiveness, onset, and potential side effects to help you understand which treatment may be right for you.
| Feature | Traditional Antidepressants | Ketamine Therapy |
| Onset of benefit | 4–8 weeks | Hours to days |
| Mechanism | Serotonin, norepinephrine, dopamine modulation | Glutamate modulation, neuroplasticity, and synaptic repair |
| Ideal patient | Mild–moderate depression, first-time treatment | Treatment-resistant depression, severe symptoms, trauma, or suicidal thoughts |
| Administration | Oral medication, daily | IV or intranasal dosing, typically 1–2 times per week (short-term) |
Both treatments can be safe and effective when used thoughtfully and monitored by qualified psychiatrists.
Who Might Benefit Most from Each Approach
When it comes to which treatment is more effective, traditional antidepressants or ketamine therapy, it really depends on the individual. Let’s break down who might benefit most from each approach:
Traditional antidepressants may be best for:
- First-time treatment of depression
- Individuals who prefer gradual, long-term medication support
Ketamine therapy may be most appropriate for:
- Individuals not responding to antidepressants
- Patients who experience intolerable side effects from standard medications
- Those needing rapid relief from suicidal thoughts or severe depressive symptoms
- People with trauma-related symptoms or PTSD who may benefit from increased neuroplasticity and emotional processing
In many cases, these treatments are complementary rather than competing. Psychiatrists often use ketamine alongside traditional antidepressants to help patients regain stability while continuing to refine their medication plan.
Comprehensive Depression and Trauma Care in Washington, D.C.
If you’re exploring treatment options for depression or trauma, working with a clinic experienced in both traditional and interventional psychiatry ensures you receive personalized, evidence-based care.
At Washington Interventional Psychiatry, our board-certified psychiatrists trained at Yale, Cornell, Mount Sinai, and Georgetown provide physician-led care for complex mood and trauma disorders. We offer:
- Ketamine infusions and Spravato® (esketamine)
- TMS for treatment-resistant depression
- Stellate Ganglion Block (SGB) for trauma
- Medication management and therapy integration
Our clinicians tailor each treatment plan to the individual, ensuring continuity of care before, during, and after ketamine therapy. For those that are interested in Ketamine Therapy, we encourage you to schedule a consultation to find out if it’s the right treatment for you. We currently service residents of Washington, D.C., Maryland, and Virginia.
