By: Dr. W. Scott West, Chief Medical Officer, Nashville Neurocare Therapy
Many people seek help for depression expecting medication to bring meaningful relief. For some, symptoms improve. For many others, depression lingers—sometimes for months or even years. When depression does not improve with medication alone, it can feel confusing, discouraging, and isolating.
The truth is that this experience is more common than many people realize. Depression is a complex brain-based condition, and effective treatment often requires more than one approach. Fortunately, there are evidence-based treatments available today that go beyond traditional antidepressants.
You are not out of options. With the right approach, meaningful recovery is possible.
What Is Depression?
Depression is a medical condition that affects mood, energy, motivation, thinking, and daily functioning. It is more than sadness or a temporary emotional downturn.
Clinically, depression can include:
- Major Depressive Disorder (MDD)
- Persistent depressive symptoms that last for long periods
- Depression that does not respond adequately to standard treatments
When medication alone does not lead to improvement, it does not mean depression is untreatable. It simply means the brain may respond better to additional or different evidence-based therapies.
Signs Your Antidepressant Isn’t Working
It can be difficult to know whether symptoms are related to medication, dosage, or an underlying form of depression that requires a different treatment strategy. Common signs that an antidepressant may not be effective include:
- Persistent low mood or emotional numbness
- Difficulty functioning day-to-day
- Little to no improvement in sleep, appetite, or energy
- Increased irritability or anxiety
- Feeling disconnected or unable to enjoy activities
- Symptoms that worsen or return quickly after changes
Recognizing when something is not working is an important step toward finding a treatment that will.
The Best Evidence-Based Treatments for Depression
Modern mental health care offers several effective treatments that can be used alone or alongside medication. These approaches are backed by research and are often helpful for individuals who have not found sufficient relief with antidepressants alone.
1. Transcranial Magnetic Stimulation (TMS)
TMS is a non-invasive, FDA-cleared therapy that uses magnetic pulses to stimulate underactive areas of the brain involved in mood regulation. In depression, these areas often show reduced activity. TMS helps increase activity in these regions and supports neuroplasticity, the brain’s ability to form and strengthen new connections.
By improving brain communication and flexibility, TMS can lead to meaningful improvements in mood, clarity, motivation, and daily functioning.
Key advantages of TMS include:
- Non-invasive and drug-free
- Minimal side effects
- No downtime
- Can be used while continuing antidepressant medications
- Particularly helpful when oral medications have not provided enough relief
Advanced systems, such as Apollo TMS, offer precise targeting and a more comfortable treatment experience.
2. Spravato (Esketamine)
Spravato works differently than traditional antidepressants. Instead of targeting serotonin pathways, it acts on the NMDA receptor system, which plays a key role in learning, memory, and brain adaptability. This mechanism helps increase neuroplasticity, allowing the brain to form new, healthier connections.
For many individuals, this leads to improvements in depressive symptoms when other treatments have fallen short.
Benefits of Spravato include:
- FDA-cleared for individuals who have not improved with oral antidepressants
- May provide faster symptom relief for some patients
- Administered in a monitored clinical environment for safety
- Works well alongside psychotherapy and medication management
3. Medication Management
Sometimes improvement comes from refining—not replacing—medication treatment. A thoughtful medication management approach may include:
- Adjusting dosage levels
- Switching medication classes
- Combining medications safely
- Monitoring side effects and making timely adjustments
Guided medication management helps ensure treatment is tailored to each individual’s needs.
4. Psychotherapy (Talk Therapy)
Psychotherapy is a core component of effective depression treatment and is often most beneficial when combined with medical therapies.
Common psychotherapy approaches include:
- Cognitive Behavioral Therapy (CBT) to address unhelpful thought patterns
- Behavioral activation to rebuild healthy routines and reduce avoidance
- Trauma-informed therapy when past experiences affect current symptoms
Psychotherapy helps patients develop coping skills, improve emotional regulation, and build long-term resilience. It also enhances outcomes when paired with TMS, Spravato, or medication.
TMS vs. Spravato: Which Is Right for You?
Both treatments are effective but work in different ways. The best option depends on symptoms, treatment history, and personal preferences.
TMS may be recommended if:
- You prefer a non-medication treatment
- You want to avoid systemic side effects
- Medications have not provided enough relief
Spravato may be recommended if:
- You need faster symptom improvement
- Multiple antidepressants have not been effective
- You tolerate medication but need a different mechanism of action
Some individuals benefit from a combination of treatments over time. A comprehensive evaluation helps determine the most appropriate plan.
Insurance Coverage for Depression Treatments
Insurance coverage is often better than people expect. In many cases:
- TMS is covered after trying antidepressant medications
- Spravato is covered for eligible patients
- Medicare and Tricare also provide coverage
- Clinics typically assist with benefits verification and prior authorizations
Understanding coverage options can help patients move forward with confidence.
What to Expect During Treatment
Treatment usually begins with a consultation to understand symptoms, history, and goals. A personalized treatment plan is then created.
During TMS:
- Sessions are brief and comfortable
- Patients remain awake and alert
- Normal activities can be resumed immediately
During Spravato:
- Sessions are monitored in a calm clinical setting
- Patients rest while the medication takes effect
- A safe ride home is required afterward
Over time, many individuals notice improvements in mood, sleep, clarity, and motivation.
Real Patient Stories of Improvement
Many people who struggled with ongoing depression for years have found meaningful relief through TMS, Spravato, psychotherapy, medication management, or a combination of these treatments. Patients often report renewed energy, improved daily functioning, and a stronger sense of hope.
When to Seek Help: A Quick Checklist
Consider exploring additional treatment options if:
- You have tried multiple antidepressants and/or therapy
- Symptoms remain the same or worsen
- Daily functioning is affected
- You feel emotionally stuck or exhausted
- You are ready for a more advanced treatment approach
Seeking help is a proactive and hopeful step forward.
A Closing Message of Hope
Depression that does not improve with medication and/or psychotherapy can feel overwhelming, but it is not a dead end. TMS, Spravato, psychotherapy, and guided medication management offer additional pathways to recovery. Many individuals begin feeling better after years of frustration simply because they found a treatment that works differently.
With compassionate care and evidence-based options, relief is possible.
References & Sources
American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder.
National Institute of Mental Health (NIMH). Depression Overview and Treatment Options.
U.S. Food & Drug Administration (FDA).
- FDA clearance for Transcranial Magnetic Stimulation (TMS) for Major Depressive Disorder
- FDA clearance for Spravato (esketamine) nasal spray
Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: Potential therapeutic targets. Science.
George, M. S., et al. (2010). Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder. Archives of General Psychiatry.
Zarate, C. A., et al. (2006). A randomized trial of an NMDA antagonist in treatment-resistant major depression. Archives of General Psychiatry.
Cuijpers, P., et al. (2013). The efficacy of psychotherapy and pharmacotherapy in treating depressive disorders. World Psychiatry.