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Top Solutions for Treatment Resistant Depression

by Dr Nima Fahimian(more info)

listed in depression, originally published in issue 282 - November 2022


Depression is one of the most common mental conditions in the United States, affecting and challenging the lives of over 40 million adults. As is generally accepted in the psychiatric community, talk therapy combined with medication and building healthy habits are the best initial treatment choices for individuals struggling with depression. However, depression is a very complex and variable disease, and invariably some people with depression may need additional help. Often, the most effective path to lasting wellness is finding the right combination of treatments for the individual and maintaining the most promising approaches as discerned by the individual and the professional(s) they’re working with.

Despite the diversity found in discussions of depression treatment, we can’t ignore the fact that when people think of treatment for depression, they usually think of antidepressants – SSRIs would be a good example of a commonly-used antidepressant. Medications such as SSRIs remain the front-line treatments prescribed, but statistics show that they often do not provide full relief and sometimes have intolerable side effects. About one-third of individuals with depression don't see a significant change in symptoms with their first antidepressant; each subsequent medication trial may not be more effective and increase the period of time for recovery while patients experience significant functional impairment. When depression does not respond to multiple medication options and additions, it can be considered treatment-resistant depression, which can entail different therapeutic approaches.

For individuals with treatment-resistant depression, numerous options are available. Clinicians, such as ours at TMS & Brain Health, work with patients to create personalized mental health treatment plans that are comprehensive and unique to the individual's needs, often combining various forms of treatment as components of a relatively holistic strategy. Plans often combine different forms of therapy and alternative treatments to standard medication to promote the individuals’ own capacity to heal. Transcranial magnetic stimulation therapy (TMS), ketamine therapy, and neurofeedback are some of the safest and most effective alternatives to traditional antidepressant medication, especially when combined with other mental health programs such as therapy:

Transcranial Magnetic Stimulation for Depression


1.  TMS

TMS, short for transcranial magnetic stimulation, is a non-invasive procedure that is FDA-approved to treat treatment-resistant depression. TMS has been used in the clinical field since the 1980s as a tool to measure neural activity.  Since the 1990s, it has been researched as a depression treatment. By 2008 it had earned its FDA approval. TMS involves using a small machine to send magnetic pulses into the brain to stimulate neural activity. Specific areas of the brain can be targeted; for depression, a cortical region that regulates limbic centers responsible for emotion regulation is often targeted.

Numerous studies, as well as the results found in clinical settings, attest to the efficacy and viability of TMS. Over 60% of individuals with treatment-resistant depression find significant relief from TMS treatment. There are no mainstream antidepressants with efficacy rates that high. The leading antidepressant, Zoloft, has an efficacy rate of about 40%, and Prozac follows with 30%. With TMS, around 40% of individuals experience full remission, or complete symptom relief, after a treatment course. A standard course consists of 5 TMS sessions per week for 6 weeks, totalling 30 sessions; however each individual’s needs are assessed independently and alterations to the program are not uncommon. What makes TMS (and the other treatments listed here) unique is that it delivers lasting results. Patients often experience relief from depression symptoms for months to years before considering follow-up sessions.

Ultimately, TMS is effective and promising, but the concept of magnetic waves being sent through the brain can be a little intimidating, and many people are concerned with its safety; so, is TMS safe? The evidence available to us now points to a resounding “yes”, especially when compared to standard medication treatment. Very few adverse health effects have been observed throughout TMS clinical trials. The greatest health risk posed is the risk of seizure, which is less than 0.1%. Additionally, individuals with a predisposed risk of seizure such as epilepsy may not be approved for treatment. Individuals with metal implants of any kind are also not approved for TMS due to the possible interactions with the magnetic device.

As for common side effects, patients typically report a mild headache or lightheadedness that subsides after the session. While the device is on, it is common to feel a sensitivity on the scalp or knocking sensation, but most patients find these tolerable. Additionally, it is common for side effects to lessen in intensity as the treatment course progresses.

Ketamine Treatment for Depression


2.  Ketamine

Ketamine is another unique alternative option for treatment-resistant depression. Used in the medical field for anesthetic purposes for over 50 years, research on ketamine as a depression treatment began in the early 2000s. In 2019, one type of ketamine became FDA-approved, the nasal spray known as Spravato. The approval process for Spravato was actually expedited due to the surprising results from clinical trials in order to make the medication more accessible to the public. As such, we can probably expect to see FDA indication for other forms of ketamine coming in the near future.

An important distinction to be made about clinical ketamine for treatment resistant depression concerns its dosage. In therapeutic contexts for depression, ketamine is administered at sub-anesthetic doses which drastically reduces some of the side effects and risks commonly associated with the use and abuse of ketamine in non-clinical settings. When it comes to ketamine for depression, very small doses are facilitated in specialized clinical settings over multiple sessions, allowing maximum healing with relatively minimal drug use.

Although ketamine is a medication, it works differently from other antidepressants. Standard antidepressants alter levels of neurotransmitters in your brain, while  taking the pills daily. With ketamine, the brain has a chemical reaction almost immediately after the first dose. Ketamine regulates glutamate activity in the brain which can impact regulation of other neurotransmitter systems implicated in depression.  Studies also have shown that ketamine stimulates factors in the brain that stimulate neuronal pathways. This leads to learning, restoration, and strengthening of healthy neuronal circuits. This unique mechanism of action is thought to contribute to ketamine's immediate and lasting results as a depression treatment.

Ketamine can be administered in a number of ways with the two most common being an intravenous infusion and a nasal spray (Spravato). A standard ketamine treatment course consists of six total sessions over the course of 2-3 weeks. Ketamine is always administered in a clinic with a trained care physician to monitor the patient's reaction. The most commonly reported side effects include lightheadedness, floating sensations or mild hallucinations. These usually subside shortly after treatment. It is also common to feel drowsy after ketamine sessions, so patients are advised to have someone else drive them home from sessions.

TMS & Brain Health Neurofeedback Program


3.  Neurofeedback

Neurofeedback is another non-invasive process that doesn't involve medications of any kind. During neurofeedback, brain waves are measured in real time, and feedback on neural activity is provided during therapy.

The goal of neurofeedback is to help the patient achieve voluntary control over mental functions. By receiving feedback on brain activity and help from a medical professional, the individual can learn how to control certain neural functions or their reactions to different stimuli. When neurofeedback is successful, patients reach a state of relaxation, similar to meditation, and have more control over their thoughts and emotions.

The best depression treatment is different for each individual, but these three treatment options offer extremely promising results compared to traditional antidepressants. They are all well researched, known to be exceptionally safe and effective and may reduce daily medication burden. These treatments can often be covered by insurance depending on the plan and mental health history. For individuals with treatment-resistant depression, there is hope, so any person struggling it should feel confident that they have access to a variety of potential solutions and programs.


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About Dr Nima Fahimian

Dr Nima Fahimian MD, Medical Director is double board-certified in both Integrative Medicine and Addiction Medicine and is the Medical Director for TMS & Brain Health in Los Angeles, California. Dr Fahimian is well known for advancing the field of psychiatry with his expertise in psychopharmacology, biofeedback, and Personalized TMS. He was trained at the UCLA David Geffen School of Medicine, where he was appointed to be the Chief Resident during his psychiatry residency. Dr Fahimian has held faculty appointments at UC Davis, UC Irvine, and is currently an Associate Professor of Clinical Psychiatry at UC Riverside. He may be contacted on Tel: +1 833 248-7221;

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