Ziv Ezra Cohen, M.D.
How do I decide between each treatment?
How long is the treatment course?
Does insurance cover this treatment?
Ketamine: Insurance will cover a portion of the Ketamine treatment procedures but will not cover the entire infusion.
TMS: TMS is covered under all major private insurance companies including Blue Cross Blue Shield, United Healthcare, Aetna, Cigna, and Oxford. For other questions regarding costs, insurance coverage, and reimbursement, please call our office at 212-335-0236.
In 2008, use of repetitive TMS for the treatment of major depressive disorder was approved by the FDA. The “standard” MDD protocol involves 36 sessions, treating at the left dorsolateral prefrontal cortex daily. What has not been discussed as much is what is known as the “Anxiety Protocol,” which often is used either alone or as an augmentation to the Standard MDD protocol for TMS. Though the Anxiety Protocol has not yet received official FDA approval, it is widely used in the medical community as a treatment for anxiety and OCD symptoms that frequently accompany depression. Furthermore, its efficacy is supported by many clinical studies.
So what has been the literature on the Anxiety Protocol thus far?
Beginning in 1997, Brian Greenberg, M.D., Ph.D. and colleagues found that stimulating any part of the neural circuitry involved in reward processing and salience detection, including cortex, striatum, globus pallidus and thalamus, could produce modulatory effects on symptoms of obsessive-compulsive disorder (OCD). Repetitive TMS at the prefrontal cortex can alter activity in that region of the brain, which can in turn have modulatory effects on the rest of the circuitry. It was also found that a certain protocol of rTMS against the left and right dorsolateral prefrontal cortex (DLPFC) resulted in a statistically significant reduction in obsessive-compulsive-like behavior. The effects were found to have lasted an average of 8 hours, with participant reports of elevated mood for about 30 minutes after stimulation of the right PFC, which is the treatment location for the Anxiety Protocol.
It is thought that the Anxiety Protocol works by activating GABA-releasing interneurons in the prefrontal cortex, which have an inhibitory effect on the rest of the circuitry. The Anxiety Protocol uses a pulse of 1 Hz, which is an inhibitory pulse that activates these GABA-releasing interneurons and in turn can “deactivate” the deeper areas of the brain responsible for inducing that “fight-or-flight” response to stress or perceived threat, most notably the amygdala.
In 2004, researchers showed that repetitive TMS applied over the right dorsolateral prefrontal cortex (DLPFC) led to reduced symptoms of posttraumatic stress disorder (PTSD). Following 30 sessions of TMS over 6 weeks using the Anxiety Protocol, participants suffering from PTSD showed significantly reduced frequency and intensity of symptoms including re-experiencing visual flashbacks, avoidance, and hyperarousal or anxiety. Neuroimaging via PET scans also confirmed lowered metabolic rate in regions of the brain correlated with reduced anxiety symptoms among participants.
What have the clinical outcomes been at Principium Psychiatry?
At Principium Psychiatry, patients will be thoroughly evaluated and an appropriate treatment protocol determined based on individual needs. We prescribe the Standard MDD protocol for treatment of depressive symptoms. We also offer the Anxiety Protocol as an augmentation to the depression treatment, as well as a treatment for symptoms of anxiety comorbid with depression. Clinical outcomes of the Anxiety Protocol have been excellent, with nearly all patients reporting accelerated improvement of both depression and anxiety symptoms since starting the Anxiety Protocol. It is safe and well-tolerated, with no reports of negative outcomes.
Yiling Wang & Estelle Autissier, RN
Ketamine: Ketamine is not currently FDA approved for the treatment of depression (although we predict it will be within the next few years). However, ketamine has been FDA approved as an anesthetic since 1970. It is a safe medication and off-label use of medications is common practice within the medical community.
TMS: Yes, TMS is an FDA-approved treatment for major depressive disorder. The Neurostar Advanced Therapy TMS device was the first to receive FDA approval in October 2008 for use in treatment-resistant depression, and most TMS treatment studies have used the Neurostar. BrainsWay, a Jerusalem-based manufacturer of TMS device, received FDA approval in 2013, and in 2015, MagVenture also received FDA approval for its MagVita TMS Therapy System. At Principium Psychiatry, we use the Neurostar Advanced Therapy device.
An aspiring artist who apprenticed as a barber and then as a cobbler, Santiago Ramón y Cajal went on to become a world-class anatomist. In 1906, Ramón y Cajal won the Nobel Prize in Physiology or Medicine for his drawings of the neuron—spiny, arborous structures that conduct electrical impulses across the brain. Ramón y Cajal is known as the Founding Father of Neuroscience, and rightfully so. His work laid the foundation for the further study of neurons, the physical principles underlying their signal transmission in the brain, and how they give rise to sensory perception, movement, thoughts, and emotions.
Transcranial magnetic stimulation (TMS), a medication-free treatment for depression, builds upon these principles of electrical conduction between neurons. It operates under the notion that cells in the brain relay signals to one another and to muscles in the body via fast-traveling electrochemical gradients down the dendrites of one neuron to synapse upon the receiving axons of another, whereby neurotransmitters have their downstream effects.
This principle of electrophysiology is not new—since 1771, scientists have been able to demonstrate in Frankensteinian fashion that dead animal tissue could be shocked back to life. In 1887, physician Robert Bartholow used an electrode to probe at the exposed brain of his patient, Mary Rafferty, who had been suffering of a large brain tumor that had bore a hole in her skull. By gradually increasing the current applied, Dr. Bartholow induced small muscular contractions, sensations of pain in distal limbs, and eventually seizure and coma in Mary Rafferty. This early study clearly called for a need for ethical monitoring in medical experimentation. However, it also spurred further study on brain stimulation in a new age of neuroscience; it led to a shift in understanding of the brain as an electrical organ that can be modulated with electrical current.
Beginning in the 1930s, electroconvulsive therapy (ECT) introduced the world to the idea of brain stimulation as a therapeutic option for mental illness. However, due to its overuse in the psychiatric arena and the notoriety of its side effects, ECT quickly took on a negative public image. In the second half of the 20th century, deep brain stimulation and spinal cord stimulation using electrodes were found to have pain-relieving effects in cancer patients. Furthermore, it was found that electrically stimulating the peripheral nerves and later, the somatosensory portions of the thalamus, were effective in managing symptoms of chronic pain. Over time, neuromodulation, or the tuning of brain activity via electrical or chemical stimulation, became more and more common in treating patients suffering from nerve damage, stroke, and Parkinson’s disease.
By the late 1970s, clinicians had begun using transcranial (“across the skull”) electrical stimulation as a diagnostic tool to measure motor conduction time in patients with multiple sclerosis. However, due to severe discomfort from the direct electrical stimulation, transcranial magnetic stimulation (TMS) was used instead to deliver single pulses that are safer and much less painful. Thus, the earliest uses of TMS were to measure motor function in patients with multiple sclerosis and Parkinson’s disease.
TMS uses a magnetic coil that produces an electric field via electromagnetic induction, a concept discovered by physicist Michael Faraday in 1831. Depending on the region of the brain being stimulated, TMS may have wide-ranging effects in regulating mood, working memory, attention, and executive functioning.
In 1996, Dr. Alvaro Pascual-Leone and colleagues, through a randomized placebo-controlled study of 17 patients with treatment-resistant depression, found significant reduction of depression symptoms following five consecutive days of repetitive TMS treatment over sham condition. The beneficial effects of the 5-day TMS treatment course lasted approximately 2 weeks with minimal to no side effects. The study by Pascual-Leon et al. (1996) established daily, repetitive TMS as a safe and efficacious treatment option for depression. Subsequent studies in 2007 and 2010 led to FDA approval of the NeuroStar TMS device, replicated earlier study outcomes in terms of alleviation from depression symptoms, and established standardized parameters for the treatment of depression and anxiety.
Ketamine and Transcranial Magnetic Stimulation (TMS) are both cutting-edge treatments being used by psychiatrists and other mental health providers for depression and other mood disorders. At Principium Psychiatry, we are proud to have both of these treatments available to our patients. But what distinguishes these two treatments? Both treat medication-resistant depression, but what are the differences between each treatment, and how do I know which one is best for me? Below are answers to our most frequently asked questions regarding both of these novel therapies.
How long does it take to work?
Can I continue my current medications?
Friday, May 11th, 2018
For those seeking fast-acting relief, Ketamine may be recommended over TMS. On the other hand, TMS may be more suited for those who have certain chronic symptoms of depression such as poor concentration and inability to take pleasure in daily activities.
At Principium Psychiatry, Dr. Cohen will go over both treatments with you during your initial consultation, and will make a recommendation based on his clinical expertise and knowledge of these treatments and what your personal goals are for your mood and symptoms.
Ketamine: The number of infusions needed vary by patient and by depression severity. We recommend an initial treatment with 6-10 infusions over the span of 2-4 weeks. Then, a maintenance phase is recommended with booster infusions every 2-4 weeks to maintain a continued effect on mood.
TMS: The standard TMS treatment course for major depression is 36 sessions, conducted daily on weekdays. Depending on individual patients, additional 10-15 sessions may be recommended to reach full therapeutic effect. Patients have the option to return for maintenance sessions 6-8 weeks following completion of full treatment course on a need basis.
February, April 27th, 2018
@ Principium Psychiatry
How long is each session?
The standard treatment protocol for major depressive disorder (MDD) has the magnetic coil placed against the left dorsolateral prefrontal cortex (DLPFC), an area implicated in mood regulation, working memory, and cognitive control. The left DLPFC is also found to be underactive in patients with MDD. The patient will feel the coil against the top-left side of the head, just above the temple. When the patient is ready to begin treatment, the coil will deliver a rapid train of pulses: 10 Hz (or 10 pulses per second) over 4 consecutive seconds, with 26-second break before the next train of pulses. Though the patient may feel a tapping sensation against the head during the pulses, there is actually nothing physically tapping against the head. The sensation is merely due to nerves of the scalp that are being stimulated by the magnetic pulses.
The mild tapping sensation may feel slightly uncomfortable for the first few sessions until the nerves in the scalp accommodate. Passing headache or mild tenderness in treatment area afterwards is common during the first week. Treatment does not cause drowsiness, though some patients reports feeling tired following initial sessions.
During treatment, the patient is awake, as there is no use of anesthesia. Each session lasts about 37 minutes; treatment time may be shorter or longer depending on the specific protocol determined between doctor and patient. To pass the time, patients may watch television, read books or Kindle, listen to music, or chat with the TMS technician or nurse, who will stay throughout the session to ensure patient’s comfort and safety. Earplugs are provided for hearing protection, though patients are also allowed to use earphones.
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Often likened to a lazy boy chair, the TMS chair is cushioned and reclines such that the patient rests comfortably with his or her head supported by a headrest. The doctor, nurse or TMS technician may ask the patient to remove any metallic jewelry such as earrings, large necklaces, headwear or bracelets prior to starting. This is because, while pulsing, the magnetic coil can interact with metallic devices within 1 foot away, which may cause the metal to heat up and become slightly uncomfortable during treatment. Once the patient is seated, a small cushion is placed against the right temple to hold the head in place. During treatment, the patient is not constricted or held down in the chair in any way.
Ketamine: Most patients find Ketamine infusions to be very relaxing and enjoyable. The most common perceivable effects during infusions are: sleepiness/drowsiness, feelings of relaxation and euphoria, heightened perceptions (colors and sounds are more intense), feeling of mild intoxication, and feelings of “a weight being lifted” or “being reset”.
TMS: Patients sit in a comfortable reclining chair. The patient’s head is secured with light padding and the magnetic coil is placed against the head. The coil then will deliver the treatment pulses twice per minute for the duration of treatment. During TMS sessions, patients are awake and alert, able to carry conversations, watch television, listen to music, or read. No medication is used, and patients are able to drive afterwards.
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Ketamine: The Ketamine dose, calculated for each individual based on his or her weight, is given over 60-75 minutes in one-fourth increments. We encourage patients to stay in our office for an additional 10-15 minutes after the infusion is completed to ensure there are no lingering side effects.
TMS: Each TMS session lasts 25 to 50 minutes depending on the protocol being used. Patients may be prescribed modified treatment protocols depending on individual symptoms.
Ketamine: Although this varies by patient, we usually start seeing the effects of Ketamine on mood after 2 or 3 infusions. However, for a longer lasting effect, patients usually need at least 6 infusions. The response rate for Ketamine is quite high, with 70% of patients showing improvement in depressive symptoms.
TMS: On average, patients report improvement in mood, concentration, and energy levels at around 2-4 weeks of treatment. Timeline of improvement varies from patient to patient, with some noticing changes in mood as early as the 15th session, while others may not notice improvement until closer to the end of the treatment course. Based on scientific literature and data from our practice, about 70% of patients respond to the treatment.
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Depression is a heterogeneous disorder: the combination of symptoms, its etiology, and treatment responses are varied and wide-ranging. Just as each patient’s experience with depression is unique, individual experiences with transcranial magnetic stimulation (TMS) may differ. Through sharing the stories of three patients (whose names and details have been changed to protect their privacy), this post is intended to demonstrate how varied the TMS experience can be.
I. Kaitlin sought TMS treatment as a last resort. Over decades, she had tried several antidepressants to no avail, as she either did not respond to them or was unable to tolerate the side effects. For years, her depression robbed her of her energy and time, such that she would lie slumped on the floor as hours of the day passed. Simple tasks such as brushing her teeth in the morning felt insurmountable. For the first half of TMS, Kaitlin’s mood fluctuated. On some days, she would notice a newfound optimism that allowed her to work, tend to her family, and run errands. On others, she would wake up with the same nauseating sense of dread, one that she likened to a perpetual cloud over her head, weighing her down. Kaitlin felt that one of the most debilitating aspects of depression was the cognitive inflexibility that she experienced. One Monday, at the beginning of her 4th week since starting TMS, Kaitlin noted that she had finally felt able to accomplish a work task that had been on her to-do list for months. For the first time in months, Kaitlin experienced stronger working memory and ability to focus. It was a subtle change, but one that she realized when she compared it to the way that she used to be. Kaitlin believes that TMS allowed her to regain her creativity and joy in her life. Kaitlin has been in remission from major depression for 6 months since the completion of her last TMS treatment course.
II. Michelle was diagnosed with major depressive disorder when she was a teenager. She also struggles with social anxiety. When she came to Principium Psychiatry for TMS treatment, she was in between jobs, and her depression made it extremely challenging for her to seek out new opportunities. As the TMS treatment sessions went on, Michelle noticed she was less irritable and became better able to regulate her emotions. She felt as if she could engage with others without having intrusive thoughts regarding how others perceived her. By the end of the second week of daily TMS treatment, Michelle noticed a difference. She described, “I’m not jumping-off-the-walls happy, but I’m feeling an absence of something…I no longer have that sense of impending doom when I wake up in the morning.” Michelle also likened the change to a “sudden lifting of a weight off my shoulders,” a gradual relief that took place over the course of treatment. She regained energy to go to the gym, she felt more hopeful, and began looking forward to starting the day. It was a feeling that she had not had in years. She also reported being able to more easily disengage the negative, repetitive thoughts. She recognized her own distorted perceptions, particularly when it came to social interactions. Michelle noted feeling more in control of her life, a sense that came with heightened awareness of her own thought patterns that were detrimental or maladaptive. By the end of her TMS treatment course, Michelle felt eager to restart the job search process, a noticeable change from when she was starting out TMS treatment.
III. For years, Robert struggled with work-related anxiety. Pressure to keep up with assignments, learn new skills, and train his assistants left him feeling overwhelmed and depressed. Over nearly the entire course of TMS treatment, Robert did not notice any improvement in depressive symptoms. By the end of the fourth week of daily TMS, Robert had given up hope that TMS would help him at all. It was not until nearly the last couple of sessions in the 36-session treatment course that Robert first began noticing a change. Over the past week, he noticed that the work felt more manageable, and that his improved concentration allowed him to accomplish tasks with greater efficacy and ease than before. He no longer felt sluggish and scattered. He noticed a decrease in ruminations regarding work, as well as decreased stress and anxiety. Robert also noted becoming more cognizant of his own physiological responses to emotions such as hopelessness or anxiety, and was able to reassess them with enhanced clarity of thought.
Responses to transcranial magnetic stimulation (TMS), as with any treatment for depression, manifest in different ways depending on individual circumstance. For further questions or to schedule an initial consultation, please visit our website or give us a call at 212-335-0236
Ketamine: There are few psychiatric medications that interact with Ketamine. During your initial consultation, you will need to disclose what medications (including supplements) you regularly take to ensure there will not be any interactions during treatment.
TMS: Yes, medications are safe to use in combination with TMS. Many patients continue taking their antidepressants when beginning TMS treatment. Over the course of treatment, as the mood improves, medications can be simplified or tapered off. If you are taking benzodiazepines, such as Xanax, Klonopin, Ativan, or Valium, the dose may need to be adjusted prior to starting TMS. Your medications list would be discussed during your initial consultation.
Is the treatment FDA approved?
Transcranial magnetic stimulation (TMS) for treatment of major depression involves placing the coil to target a portion of the brain located just above and behind the left temple, called the dorsolateral prefrontal cortex (DLPFC). This region of the brain is associated with abstract reasoning, attentional control, and working memory. The prefrontal cortex is uniquely developed in humans. It is what allows for meta-cognition, executive function and sophisticated decision-making following conceptual reasoning. The prefrontal cortex is essential in making us who we are: it gives us the ability to evaluate our emotional responses and adapt them according to circumstances.
The left dorsolateral prefrontal cortex (DLPFC) is strongly involved in higher-order perceptual reasoning which can helps regulate mood. Those suffering from major depressive disorder have under-active left DLPFC. Besides mood regulation and executive functioning, however, the DLPFC is also involved in a lesser-known function: working memory. Working memory is described as that temporary storage area that holds sensory memory as it comes in for a brief time, before it is further processed and consolidated into long-term memory. Though it is short-lasting and often limited in “storage space,” working memory is essential in attention. It is the ability to keep in mind one’s to-do list and manipulate it effectively in one’s mind.
For patients with major depression, poorer working memory often accompanies symptoms of low mood, low energy, and blunted affect. This particular manifestation of depression often leads to reduced attention span, difficulty focusing on tasks, and generally what many patients describe as “brain fog.”
There is increasing evidence that TMS has neurocognitive effects, including enhancing working memory and improving speed of perceptual, motor and executive processing. TMS, which uses a pulsing magnet to electrically stimulate neurons in the dorsolateral prefrontal cortex, induces long-term potentiation, or “learning” by the neurons such that with stimulation over time, they eventually “learn” to become more active. In a 2013 study, adolescents with major depressive disorder, who received 30 sessions of daily rTMS, showed not only decrease in severity of depression symptoms, but also showed significant improvement in working memory and delayed verbal recall. Another study found that attention and processing speed were improved following repetitive TMS therapy. In another sham-controlled trial, 20 sessions of TMS in patients with treatment-resistant bipolar depression resulted in significant improvement in language, immediate and long-term verbal memory, attention and processing speed, and working memory at 4-8 weeks after starting TMS.
Further studies on the effects of TMS on working memory are underway. However, from the current literature, there is strong evidence that TMS may have positive neurocognitive effects that accompany the mood regulation in its treatment of major depression and other psychiatric illnesses.
How will I feel during the session?
February, April 20th, 2018
Brain mapping is a procedure used to determine treatment location and energy level of TMS pulses required for optimum effect. Treatment location and energy level are tailored to individual patients, depending on size and shape of the head. Brain mapping takes place only one time, prior to the first treatment session, and it takes about 20-30 minutes to complete.
Though different TMS manufacturers have developed their own methods, the most commonly used brain mapping protocol is the one developed by Neuronetics Inc., which uses the NeuroStar TMS device. With this protocol, the patient is asked to hold up his or her right hand in a relaxed hitchhiker position while the elbow rests against a cushion. The attending physician gently places a magnetic coil against the middle left side of the patient’s head. Patients may hear and feel a light tap against the head—this is a single pulse emanating from the coil. This pulse is, in fact, electrically stimulating a portion of the motor cortex, or a group of neurons in the center top portion of the brain responsible for producing muscle contraction, that corresponds to hand and arm movement. When the pulse goes off, the patient will experience an involuntary twitch of the right hand, which will indicate to the doctor the region of the motor cortex that is being stimulated.
During brain mapping, the doctor and TMS technician or nurse together will observe hand movement corresponding to taps at various locations of the motor cortex. Once treatment location and energy levels are determined, the patient will proceed to the first TMS treatment session.