From the Editor
He’s had two antidepressant trials, yet he still can’t get out of bed. What’s the next step for my patient with depression? With so many antidepressant options available, the simplest answer is another med. But what could be an alternative? These questions are highly practical – consider that roughly 700 000 Canadians struggle with treatment-refractory depression.
Iris Dalhuisen (of Radboud University) and her co-authors attempt to shed light on the issue. In a newly published American Journal of Psychiatry study, they describe a randomized comparison involving 89 people with treatment-refractory depression who received either rTMS or another antidepressant. “In a sample of patients with moderately treatment-resistant depression, rTMS was more effective in reducing depressive symptoms than a switch of antidepressant medication.” We analyze the study, the Editorial that accompanies it, and the implications for practice.
In this week’s other selection, Jonathan N. Stea (of the University of Calgary) writes about the wellness industry in an essay for The Globe and Mail. He bemoans the snake-oil salesmen and their big promises. “As a clinical psychologist, I have encountered many patients who received pseudoscientific assessments and treatments for their mental-health concerns. The tidal wave of pseudoscientific mental-health practices originates both within and outside of the mental-health professions.”
DG
Selection 1: “rTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches”
Iris Dalhuisen, Iris van Oostrom, Jan Spijker, et al.
The American Journal of Psychiatry, 7 August 2024
With nearly 300 million people affected worldwide, major depressive disorder (MDD) is one of the most common psychiatric disorders. Although pharmacotherapy and psychotherapy offer effective treatment options for MDD, one-third of patients experience inadequate response to these treatments. Remission rates drop drastically from approximately 35% for the first two trials of antidepressants to less than 15% for a third or fourth trial, while intolerance to pharmacotherapy increases substantially. Up to 35% of patients fail to respond to first-line treatments and suffer from treatment-resistant depression (TRD)…
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation treatment that is increasingly and successfully used to treat MDD, most commonly in patients with TRD. The exact positioning of rTMS within depression treatment algorithms remains unresolved. Within these algorithms, the biological treatment options often follow a stepped-care approach, starting with multiple, sequential psychopharmacological steps and ending with ECT. Research on the comparative efficacy of rTMS and other biological steps is lacking. For the treating physician, it is difficult to decide when rTMS should be considered as a viable treatment option for the patient…
Here’s what they did:
- They conducted a “pragmatic randomized controlled trial comparing treatment with rTMS combined with psychotherapy and continued antidepressant medication (if present) to treatment consisting of a switch from the current antidepressant medication in combination with psychotherapy.”
- Patients had unipolar nonpsychotic depression with an inadequate response to at least two treatment trials.
- The rTMS consisted of 25 high-frequency sessions to the left dorsolateral prefrontal cortex.
- Alternatively, participants were switched in their antidepressant medication following the Dutch treatment algorithm.
- The primary outcome: change in depression severity based on the Hamilton Depression Rating Scale (HAM-D).
Here’s what they found:
- 90 patients were included; one of whom dropped out after giving informed consent. 89 patients were in the intention-to-treat sample (48 in the rTMS group and 41 in the medications group).
- Demographics and illness experience. The mean age was 43.6 years and most participants were female (66.3%). The mean HAM-D was 21.4. Most participants had four or fewer depressive episodes and had failed one to four antidepressant trials.
- Depressive symptoms. “rTMS resulted in a significantly larger reduction in depressive symptoms than medication, which was also reflected in higher response (37.5% vs. 14.6%) and remission (27.1% vs. 4.9%) rates.”
- Secondary outcomes. “A larger decrease in symptoms of anxiety and anhedonia was observed after rTMS compared with a switch in antidepressants, and no difference from the medication group was seen for symptom reductions in rumination…”
- Tolerability. One patient in the rTMS group and two patients in the medication group dropped out because of intolerability.
A few thoughts:
1. This is a good study on a relevant topic, published in a major journal.
2. The main finding in two sentences: “We assessed the effectiveness of both treatments in reducing depressive symptoms and in achieving response and remission. Across all these outcome measures, rTMS was the superior treatment.”
3. Wow.
4. Perspective is needed. The sample was 89 participants and they were unevenly distributed between the interventions.
5. Still, if we are trying to do better than simply offering the next antidepressant, this study helps show a possible way forward.
6. In an accompanying Editorial titled “Positioning rTMS Within a Sequential Treatment Algorithm of Depression,” Drs. Tyler S. Kaster and Daniel M. Blumberger (both of the University of Toronto) comment that the study “provides important knowledge.”
They put depression management in a larger context, noting the advances of the past two decades: “we have emerged from an era of stagnation with no new treatments for depression to an era of rapid progress of new and meaningful interventions for the clinical care of patients with TRD.” They continue: “Advancements in the treatment of TRD since STAR*D include atypical antipsychotic augmentation, the approval of intranasal esketamine, the growing use of intravenous ketamine at subanesthetic doses, the explosion of interest in the use of psychedelic interventions such as psilocybin, and… the use of rTMS. Individually, each of these interventions now plays an important role in the care of patients, while collectively, these approaches represent a fundamental shift in the delivery of care for patients with TRD.” Well said.
And they focus on one treatment in particular. “rTMS is an intervention that encompasses a broad parameter space that includes different patterns and locations of stimulation. It is a noninvasive approach that delivers repetitive magnetic field pulses to modulate neural firing in local and distant brain circuits. The treatment was approved by the FDA in 2008 for TRD and has repeatedly been demonstrated to be safe, tolerable, and effective. Side effects are generally minimal and consist of local scalp discomfort and headache. The worst side effect of seizure is exceedingly rare and less common than seizures associated with pharmacotherapy. While some have questioned its effectiveness, rTMS has repeatedly been shown to be superior to sham or placebo procedures and cost-effective compared to pharmacotherapy. The FDA clearance in 2018 of a more efficient form of rTMS, called intermittent theta burst stimulation (iTBS), using a comparative effectiveness clinical trial design has greatly increased the scale and availability of this treatment.”
The AJP editorial can be found here:
https://psychiatryonline.org/doi/full/10.1176/appi.ajp.20240604
The full AJP study can be found here:
https://psychiatryonline.org/doi/10.1176/appi.ajp.20230556
Selection 2: “In the wellness industry, your mental health is for sale”
Jonathan N. Stea
The Globe and Mail, 31 August 2024
In 2018, millions of subscribers to Goop – Gwyneth Paltrow’s wildly successful natural lifestyle company – were introduced to a new promoted product: the Implant O’Rama, a do-it-yourself coffee-enema device. The product’s website claimed that coffee enemas ‘can mean relief from depression, confusion, general nervous tension, many allergy related symptoms, and most importantly, relief from severe pain.’ The company told its consumers: ‘Ask not what your colon can do for you, but rather, what you can do for your colon.’ Coffee enemas were even endorsed on Goop by seemingly respectable physicians: namely, a cardiologist, Alejandro Junger, identified as an ‘adrenal fatigue expert,’ and ‘holistic psychiatrist’ Kelly Brogan in her New York Times bestseller…
What’s the problem? Well, it turns out that shooting coffee up your bum will not help with depression or any other health concern. Coffee enemas have a long history in the alternative-medicine community despite their lack of credible evidence.
So begins an essay by Stea.
Of course, he notes that “there is no medical theory or body of research supporting the use of coffee enemas, and in fact they can be quite dangerous and result in burns, inflammation, bacteria in the bloodstream, and even death.” He discusses the depth of the problem. “This problem, of course, is much larger and older than coffee enemas, Ms. Brogan and her book. Snake-oil salesmen have been around forever, but it was in the late 19th and early 20th centuries that a guy named Clark Stanley sold actual ‘snake oil liniment’ as a cure-all for various health conditions – incidentally, it didn’t work, and it didn’t even contain actual snake oil. The problem is that snake-oil salesmen, in the spirit of Clark Stanley, never went away.”
He continues: “In the world of mental-health care, scientists have estimated that there are at least 600 ‘brands’ of psychotherapy, an unreasonably and quickly growing number, many of which are ineffective and could be harmful… Beyond that world exist countless unregulated providers of mental-health-related services in the wellness industry and alternative-medicine community who market themselves as ‘life coaches,’ ‘wellness consultants’ and – depending on particular countries and jurisdictions – other various non-legally protected titles, such as ‘therapists,’ ‘psychotherapists,’ ‘counsellors’ and ‘practitioners.’”
“The tidal wave of pseudoscientific mental-health practices originates both within and outside of the mental-health professions. The global health and wellness industry has an estimated value of more than US $5.6-trillion, which includes legitimate sources of health – such as club memberships and exercise classes – as well as alternative-medicine products and services that purport to improve health, based on baseless or exaggerated claims and questionable evidence of safety and effectiveness.”
He adds that the stakes are high. “At the end of the day, your mental health is on the line. And your mental health is precious.”
“Yet, in the wellness industry, your mental health is for sale. You’ve been told you lack it and it’s available for purchase. You just need to buy the latest book with the latest 30-day diet plan, swallow 15 supplements ‘they’ don’t want you to know about, cleanse the toxins from your body by following ‘10 easy steps,’ spiritually awaken on a five-day wellness retreat, or undergo the revolutionary new therapy that most doctors haven’t heard about. That cheapened, commodified version of mental health is a wolf in sheep’s clothing. It’s sexy. It’s alluring. And it’s a sham.”
He notes the dangers. “Providers that advertise their services to address mental-health concerns but that do not value, respect or understand the role of science in mental-health care risk compromising the safety of patients. And unfortunately for patients, it can very much be a buyer-beware approach to their mental health, both within our health care systems and in the unregulated space where mental-health care is marketed and sold.”
What then is to be done? “Improving the science and mental-health literacy skills of both the general public and health care professionals can help mitigate this alarming problem. In part, this involves learning how to spot and avoid false information and pseudoscientific practices.”
1. This is a clever and persuasive essay.
2. We have all had patients who hesitate on our recommendations, excited instead by the latest pseudoscience fad.
3. Stea mentions many “cures.” He doesn’t discuss apps. While some apps provide people thoughtful, evidence-based strategies, others are the digital equivalent of snake oil.
4. What’s a way forward? He sees a role for regulations, but emphasizes the importance of empowerment. “The onus is also on us to empower ourselves with knowledge, such that we can protect ourselves from mental-health scams, charlatanry, and poor or misguided health practices.” Is there a role for us clinicians to help empower our patients?
The full Globe essay can be found here:
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.
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