When Depression Medications Don't Work

Sequenced Treatment Alternatives for the Relief of Depression (STAR*D), the most extensive study of the efficacy of antidepressants, found that only one in three patients reached remission with their first antidepressant attempt.

Although that conclusion may be, well, depressing, we see it as an affirmation of all we have learned about depression over the years. Dr. Karen Giles and our Breakthru Psychiatric Solutions team understand the challenges related to depression treatment and have helped patients in the greater Atlanta, Georgia, area find help and hope in evidence-based therapies.

We don’t view these findings as a roadblock, but rather as a call to explore the alternatives in depression management.

What the STAR*D study reveals about depression treatment

The STAR*D study underlines the challenging nature of major depressive disorder and the limitations of conventional treatment pathways.

This landmark research revealed disheartening statistics; as patients embarked on a successive line of medications, the likelihood of achieving remission diminished. By the third antidepressant failure, there was only a 7% chance that a person’s depression would improve. Worse still, the tolerability and side-effect profile of these medications often compounded an already burdensome experience.

The good news is that these findings inspired a pivot toward innovative interventions and new hope for those battling treatment-resistant depression. If your depression has not improved with multiple antidepressants, it does not mean that your depression is untreatable. It means that it is time to shift to interventional treatments. Consider these evidence-based solutions.

Transcranial magnetic stimulation (TMS)

TMS, a painless procedure that uses magnetic fields to stimulate nerve cells, has garnered acclaim for its efficacy in cases that don’t respond well to medication. Cleared by the FDA in 2008, TMS has undeniable benefits.

Noninvasive and safe
Minimal side effects: You may have a temporary mild headache during the initial sessions
Effective in treatment-resistant depression
Boosts cognitive function, including memory and concentration
Quickly noticeable results, within a week for some

At Breakthru, our 2023 response rate for TMS for depression was 87.5% and response for TMS treatment of anxiety was 79%. Our remission rates for depression and anxiety were 38% and 42%, respectively.

Dr. Giles also offers accelerated TMS, an advanced version of traditional TMS therapy, distinguished primarily by its condensed treatment schedule. Though standard TMS typically involves six weeks of once-daily sessions that taper off over the next three weeks, accelerated TMS compresses this timeframe significantly so you experience the results faster.

Esketamine (Spravato®)

The introduction of esketamine — marketed as Spravato and FDA-approved in 2019 for treatment-resistant depression in adults — ushered in a new era of hope for depression sufferers.

Classified as the S-enantiomer of ketamine, a substance traditionally known for its anesthetic utilities, esketamine taps into an innovative mechanism of action distinct from other antidepressants. By targeting the brain's N-methyl-D-aspartate (NMDA) receptors, glutamatergic signaling pathways are modulated, which are instrumental in mood regulation and cognitive functions.

Spravato is a nasal spray, and Dr. Giles administers it in our office to monitor your reaction. Its rapid onset of effects provides a unique advantage, potentially offering symptomatic relief within hours to days, contrasting significantly with the weeks traditionally required by conventional antidepressants to manifest benefits.

This swift action, coupled with a novel approach to affecting brain chemistry, positions Spravato as a vital option in the toolkit for treating major depressive disorder.

At Breakthru, our 2023 response rates for Spravato for depression and anxiety was 85% and 83%, respectively. Our remission rate for depression treatment was 38% and for anxiety treatment it was 33%.

Intravenous ketamine

IV ketamine, with origins in anesthetic practice, has been reborn in the mental health arena. Administered intravenously, it breaks the mold of traditional slow-release pharmaceuticals, providing rapid relief to those in the throes of depression.

Intravenous ketamine operates on a principle fundamentally different from that of conventional antidepressants. At its core, ketamine is an NMDA receptor antagonist, which, when administered intravenously, directly influences your brain’s neurotransmitter system.

Unlike traditional treatments that target the monoaminergic system (serotonin, norepinephrine, and dopamine), ketamine swiftly crosses the blood-brain barrier to modulate the glutamate pathway. Glutamate is the brain’s most abundant excitatory neurotransmitter.

By inhibiting NMDA receptors, ketamine induces a rapid increase in glutamate levels. This surge leads to the activation of AMPA receptors, fostering neuroplasticity and the growth of new synaptic connections. Researchers believe this process contributes to its rapid antidepressant effects, which can occur within hours of administration.

Ketamine’s ability to circumvent the brain’s slow and often insufficient response to conventional antidepressants makes it a revolutionary approach for those suffering from severe, treatment-resistant depression. Its quick mechanism of action offers immediate relief, restoring a sense of possibility to those who have endured the relentless grip of depression without effective reprieve.

At Breakthru, our 2023 response rates for IV Ketamine for depression and anxiety were 70% and 73%, respectively. Our remission rate for IV Ketamine for depression was 40% and 27% for anxiety.

*Remission rates include patients who shifted from severe to mild symptoms (at least 75% clinical improvement) and/or those who experienced complete cessation of symptoms with a full course of treatment.

Bridging disciplines for better outcomes

A collaborative approach is central to our philosophy of care. We, as mental health advocates, don’t replace the competent care of your primary psychiatrist, who manages the medication side of your treatment. Instead, we stand shoulder to shoulder to extend the care spectrum. Collaboration strengthens these alternative pathways, ensuring a continuum of care that’s both integrative and individualized.

We offer next-level treatments when the pharmaceutical approach doesn’t serve you well.

We encourage you to view the STAR*D findings not as a pronouncement of defeat but as an incitement to venture toward alternatives that, though once on the periphery, are edging into the center stage of depression care.

Learn more about these innovative treatments by calling Breakthru Psychiatric Solutions in Sandy Springs, Georgia, or requesting an appointment online.