What Is Treatment-Resistant Depression and How Is It Treated?

For some people, depression doesn’t lift even after trying several antidepressants. The sadness lingers, motivation fades, and every new medication feels like another dead end. What many don’t realize is that these symptoms have a name: treatment-resistant depression (TRD).

While living with TRD can be discouraging, it’s important to remember that it is treatable. Here’s what you need to know.

The Definition of Treatment-Resistant Depression

Treatment-resistant depression is a major depressive disorder that doesn’t respond to at least two first-line antidepressant medications within a sufficient time frame. First-line antidepressants usually include either:

• SSRIs (Selective Serotonin Reuptake Inhibitors)
• SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors)

While these medications can be effective, many patients don’t experience meaningful or lasting relief after taking them.

Why Traditional Antidepressants Don’t Always Work

There are several reasons why traditional first-line antidepressants may not bring relief to those with TRD. A few common ones include:

• Biology. The person’s brain or body may not be able to process certain drugs. In some cases, it could even worsen symptoms instead of relieving them.
• Incorrect Diagnosis. Depression shares symptoms with other conditions like bipolar disorder, anxiety disorders, or thyroid disorders. A misdiagnosis could lead to treatments that don’t address the root cause.
• Underlying Conditions. Other conditions like chronic pain, substance use disorders, or sleep disorders can affect how well antidepressants work. For example, someone with treatment-resistant bipolar depression and a sleep disorder would struggle with challenges like lower resilience to stress and irritability. Addressing the sleep disorder reduces barriers to treating their bipolar depression.
• Drug Interactions. In some cases, other drugs or herbal supplements could suppress or negatively affect antidepressants. For example, St. John's wort can interact with sertraline (Zoloft) and potentially increase serotonin to dangerous levels.
• Inadequate Dose or Duration. Sometimes, someone may need a higher dosage or a longer treatment period for the results to take effect. Adjusting one or both can bring positive results.
• Psychological and Social Factors. Thoughts and beliefs brought on by trauma, isolation, culture, or lack of support can worsen depression and reduce the benefits of medication alone.

Once these factors are identified, treatment can be refined—and that’s often when real progress begins.

Exploring Other Options for Treatment-Resistant Depression

If you’ve tried conventional antidepressants without success, there are options for treatment-resistant depression that can make a real difference.

At SD Wellness Group, we take an integrated approach, combining medical expertise, advanced therapies, and compassionate care to support lasting recovery.

• Medication Adjustment or Combination Therapy: Your psychiatrist may increase your dosage, switch to a different antidepressant, or combine medications that target multiple neurotransmitters. These adjustments are often the first step when initial treatments aren’t effective.
• Addressing Underlying Conditions: Conditions like thyroid imbalance, anxiety, or treatment-resistant bipolar depression can all influence how antidepressants work. Treating these issues alongside depression can significantly improve results.
• Behavioral Health Therapy: Therapy can play a crucial role in managing TRD. Approaches like Cognitive Behavioral Therapy (CBT) help reframe thought patterns, build coping skills, and address challenges such as motivation, self-worth, and chronic symptoms.
• Transcranial Magnetic Stimulation (TMS): TMS is a safe, non-invasive treatment that uses magnetic pulses to stimulate brain regions involved in mood regulation. It’s FDA-cleared for depression and often helps patients who haven’t responded to medication.
• Ketamine and Esketamine (SPRAVATO®) Therapy: Among the most promising new options for treatment-resistant depression are ketamine and esketamine therapies. These treatments act on the brain’s glutamate system (rather than serotonin), helping restore healthy neural connections and improve mood within hours or days.

SD Wellness Group: Care Built Around You

Living with treatment-resistant depression can feel discouraging, but you don’t have to navigate it alone. At SD Wellness Group, we combine advanced options for treatment-resistant depression with personalized care designed around your needs.

Let us help you build a treatment plan that finally works for you. Contact us today!