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Ketamine and Treatment Resistant Depression

Ketamine and Treatment Resistant Depression

Ketamine and Treatment Resistant Depression

A Look at Treatment-Resistant Depression and New Hope with Ketamine

“Antidepressants aren’t helping my depression” is one of the most common things we hear from people when they contact us at KureIV, an IV ketamine clinic in Houston, TX. Despite seeing a psychiatrist and trying numerous medications, many find little to no relief from their depressive symptoms. Often, these individuals are dealing with something called Treatment-Resistant Depression (TRD).

Understanding Treatment Resistant Depression

In the realm of mental health, depression stands as a common and debilitating condition affecting one in ten adults in any given year. While many benefit from conventional treatments like psychotherapy and medication, not everyone experiences relief.

This group of patients, with what is known as treatment resistant depression (TRD),  have been a challenge to medical providers and researchers alike. TRD not only prolongs suffering but also poses a considerable burden on healthcare systems and society at large, but with new treatments there is hope to alleviate those who have long-suffered from depression.

What Defines Treatment Resistant Depression?

The actual criteria of what Treatment Resistant Depression (TRD) varies among doctors and researchers. While some say that it is when a person tries two different first-line antidepressants,other doctors diagnose patients with Treatment Resistant Depression after the use of four different antidepressants with-in at least two different types of antidepressants.

In order for it to be considered unsuccessful a patient must take the antidepressant at the proper dose for 6-8 weeks without at least a 50% reduction in depressive symptoms, which can be calculated via the Hamilton Depression Rating Scale (HAM-D)

What is a first-line antidepressant?

A first-line antidepressant is a medication commonly prescribed as the initial treatment for depression. These medications are selected based on their efficacy, safety, and tolerability, and are supported by clinical evidence and guidelines. Here are some common classes of first-line antidepressants:

SSRIsSelective Serotonin Reuptake Inhibitors

SSRIs are the most commonly prescribed antidepressants. They work by increasing the levels of serotonin in the brain, a neurotransmitter associated with mood regulation. Examples include: Fluoxetine (Prozac), Sertraline (Zoloft), Citalopram (Celexa), Escitalopram (Lexapro), and Paroxetine (Paxi

SNRIs – Serotonin-Norepinephrine Reuptake Inhibitors

SNRIs increase levels of both serotonin and norepinephrine, another neurotransmitter that influences mood and anxiety. Examples include: Venlafaxine (Effexor), Duloxetine (Cymbalta), and Desvenlafaxine (Pristiq)

NDRIs – Norepinephrine-Dopamine Reuptake Inhibitors

NDRIs, such as bupropion, work by inhibiting the reuptake of norepinephrine and dopamine, neurotransmitters involved in mood regulation. The most common NDRI is Bupropion.

Atypical Antidepressants

These medications work differently from other antidepressants. Mirtazapine, for example, increases the release of norepinephrine and serotonin.

Who has TRD?


If you are wondering if you could possibly have Treatment Resistant Depression a simple way is to  ask yourself some basic questions.

  “Is your treatment making you feel better?

  “Do you feel like your old self?”

  “Are the side effects severe enough to affect you?”

If you find that you aren’t feeling better, like your old self, or that the side effects are outweighing the benefits, it might be time to consult a medical professional about Treatment Resistant Depression. 

Alternative Treatments for Treatment Resistant Depression

Despite its name, there are treatments that can be effective for those with TRD. These include:

Transcranial Magnetic Stimulation (TMS)

Transcranial Magnetic Stimulation is a non-invasive therapy that uses magnetic pulses to stimulate specific brain regions, promoting neuroplasticity and balancing neurotransmitters associated with mood regulation, like serotonin and dopamine. Side effects are generally mild, such as scalp discomfort or headaches during treatment sessions.

Transcranial magnetic stimulation TMS non invasive field obsessive compulsive disorder PTSD treat

Electroconvulsive Therapy (ECT)

Electroconvulsive therapy (ECT) is more invasive than TMS and involves inducing controlled seizures through electrical currents under general anesthesia. It can significantly improve mood and functioning, especially in severe TRD cases. Short-term side effects like memory loss and confusion usually ease over time, making the benefits outweigh the risks for many.

Electroconvulsive therapy, ECT, a treatment involving the use of electrical currents to stimulate the brain, 3D illustration


Ketamine for TRD 

Intravenous (IV) ketamine therapy has emerged as a promising treatment for depression, particularly in cases of treatment-resistant depression (TRD). Ketamine, originally developed as an anesthetic agent, has garnered attention for its rapid and great antidepressant effects seen in individuals who have not responded to conventional treatments. Unlike traditional antidepressants that primarily target neurotransmitters, ketamine has a unique pharmacological profile, which has sparked considerable interest in exploring ketamine as a potential breakthrough in the treatment of depression.

Mature doctor adjusting saline IV drip for patient in hospital ward

Historical Context and Development as a Treatment for Depression: 

The use of ketamine for depression started in the late 20th century when clinicians noted significant improvements in mood among patients receiving ketamine for anesthesia. This led to controlled clinical trials for depression. While ketamine’s use for treatment-resistant depression is considered off-label, its efficacy in TRD has been increasingly recognized, prompting interest from researchers, clinicians, and patients alike. 

Efficacy of IV Ketamine Therapy in TRD:

One of the most striking features of IV ketamine therapy is its rapid onset of action, with many patients experiencing significant symptom relief within hours of administration. This rapid antidepressant effect stands in stark contrast to the delayed onset typically associated with conventional antidepressants, providing a valuable treatment option for individuals in acute distress or at imminent risk of self-harm.

Clinical Trials and Studies Evaluating Ketamine for TRD: 

Numerous clinical trials and studies have demonstrated the efficacy of IV ketamine therapy in TRD, providing compelling evidence of its antidepressant effects. These trials have typically employed randomized, double-blind, placebo-controlled designs to rigorously evaluate ketamine’s efficacy and safety. 

Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series 

Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression 

Use of Ketamine in Elderly Patients with Treatment-Resistant Depression

Intravenous Ketamine for Adults with Treatment-Resistant Depression or Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines

Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)

Safety Considerations: 

Despite its therapeutic potential, with IV ketamine therapy there must be consideration of certain health conditions and safety concerns. Ketamine is associated with psychotomimetic effects, including dissociation, perceptual disturbances, and transient increases in blood pressure and heart rate. These acute effects are typically well-tolerated and transient, but caution is warranted, particularly in individuals with a history of psychosis or cardiovascular complications. 


For individuals with TRD, treatments like IV ketamine offer new hope. Ketamine provides an  alternative when traditional medications fail, offering rapid and sustained relief from depressive symptoms. If you or someone you know is struggling with TRD, exploring alternative treatment options with a healthcare provider could be the key to finding effective treatment and improving quality of life.

If you are interested in learning if IV Ketamine therapy is an option for you please contact us here or call us at (832) 598-5100.


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KureIV provides safe, monitored ketamine infusion therapy for people who suffer from major depression, bipolar disorder, severe anxiety, PTSD, OCD, and chronic pain in a friendly, professional environment.