Systematic review & meta-analysis of 208 RCTs - #5 - Dec 21, 2024

Speaker: 00:00:15

Welcome to the Neurostimulation Podcast.

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I'm Michael Passmore, Clinical

Associate Professor in the Department

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of Psychiatry at the University of

British Columbia in Vancouver, Canada.

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The Neurostimulation Podcast is all

about bringing cutting edge neuroscience

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and neurostimulation education to

you every week, free of charge.

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We're going to look at the latest

research breakthroughs, how the

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technology works and most importantly,

how all of this is being translated

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into real world treatments that

can improve health and wellbeing.

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So whether you are a researcher, a

clinician, a student, or just somebody

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who's curious about how our brains

work and what we can do to help them to

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work better, this podcast is for you.

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My mission is to make the

science accessible, inspiring,

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and relevant to your daily life.

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As part of my commitment to evidence based

analysis, in every episode that we discuss

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a specific study, I'm going to include an

advanced critical appraisal of that study.

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If you're not interested in this

deeper dive into the methodology

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and analysis, feel free to skip

ahead on the timeline to focus in

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on other aspects of the discussion.

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This podcast is separate from my clinical

and academic roles and is part of my

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personal effort to bring neuroscience

education to the general public.

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Accordingly, I would like to emphasize

that the information shared in

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this podcast is for educational

purposes only, and is not intended

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as medical advice or a substitute

for professional medical guidance.

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Always consult with your health care

provider to discuss your own specific

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health needs and treatment options.

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By listening to or watching this

podcast, you acknowledge and agree that

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any decisions related to your health

care are your own responsibility and

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should be made in consultation with

a qualified medical professional.

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This episode is presented

by ZipStim Neurostimulation.

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Full disclosure, ZipStim is

the neurostimulation clinic

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that I own and operate.

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You can find out more about our clinical

neurostimulation programs at zipstim.com.

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That's Z I P S T I M dot com.

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Now let's get started.

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Mike: Today we're going to explore

a groundbreaking study that could

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change how we view non invasive

brain stimulation for mental health.

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This episode focuses on a comprehensive

review and meta analysis titled,

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Efficacy of Neurostimulation Across

Mental Disorders, Systematic Review

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and Meta Analysis of 208 Randomized

Controlled Trials, published in

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the journal Molecular Psychiatry.

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We're spotlighting the largest meta

analysis to date on neurostimulation,

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covering an incredible 208

randomized controlled trials.

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This study provides a comprehensive

look at two key techniques,

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transcranial magnetic stimulation,

or TMS, and transcranial direct

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current stimulation, or tDCS.

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It evaluates their effectiveness across

a range of mental health conditions.

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from depression and anxiety

to schizophrenia and PTSD.

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So why does this matter?

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As mental health challenges continue

to rise globally, especially in

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the wake of the COVID 19 pandemic,

there is an urgent need for safe,

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effective, and accessible treatments.

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Neurostimulation is emerging as a

powerful tool, offering hope where

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traditional therapies might fall

short or are poorly tolerated.

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But what do the numbers say?

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Which conditions show the most promise?

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And how do we navigate the

challenges of translating this

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research into real world practice?

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In this episode, we'll break down the

findings of this monumental study and

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we're going to explore the mental health

conditions, where neurostimulation

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has shown the greatest potential.

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So grab a cup of coffee or your

favourite beverage and let's get started.

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By the end of the episode you'll

have a clearer understanding of

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how neurostimulation fits into the

broader landscape of mental health

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care and where it's headed next.

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Let's start by setting the stage.

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The study that we're discussing

today is a meta analysis, which is

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essentially a way to synthesize data

from multiple high quality studies.

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It provides a bird's eye view of how

effective neurostimulation really is

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for various mental health conditions.

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Now what makes this particular meta

analysis stand out is its scope.

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It includes 208 randomized controlled

trials, making it the largest synthesis

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of its kind for transcranial magnetic

stimulation, or TMS, and transcranial

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direct current stimulation, or tDCS.

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So what exactly are TMS and tDCS?

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If you're new to the podcast,

here's a quick refresher.

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TMS uses magnetic fields to induce

electrical currents in targeted brain

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regions, altering neural activity.

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It's most commonly delivered as repetitive

TMS or rTMS and can be either high

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frequency or low frequency stimulation.

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tDCS, on the other hand, uses

low electrical currents delivered

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through electrodes on the scalp.

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It doesn't induce neuronal firing

directly, but modulates brain

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activity, making the neurons more

or less likely to fire, depending

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on the polarity of the current.

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This meta analysis doesn't

just look at one condition.

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It spans multiple disorders, including

depression, which is by far the most

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studied, generalized anxiety disorder,

or GAD, Obsessive Compulsive Disorder,

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or OCD, Post Traumatic Stress Disorder,

or PTSD, Schizophrenia, focusing on both

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positive and negative symptoms, Substance

Use Disorders, and even cognitive

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deficits like attention and working memory

issues in disorders like Schizophrenia.

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So what did they measure?

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Outcomes included reductions in core

symptoms like depression or anxiety

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severity and improvements in cognitive

functions such as attention, working

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memory, and executive functioning.

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This broad approach provides

us with valuable insights into

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where neurostimulation excels and

where it might need refinement.

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/ . Let's break down the

findings of this study.

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The results of this meta analysis

are both exciting and nuanced.

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Let's go through them condition

by condition, highlighting where

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neurostimulation shows the most promise.

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First, let's look at generalized

anxiety disorder, or GAD.

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TMS was a clear standout

here, with a large effect

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size, or SMD of negative 1.8.

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Only three RCTs were included, but all

use different stimulation protocols,

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including both high frequency and

low frequency stimulation of the

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right dorsolateral prefrontal cortex,

or DLPFC, and parietal cortex.

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This consistency across protocols

suggests a strong potential for TMS in

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treating GAD, although more research is

needed to refine the best parameters.

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Second is Substance Use Disorder, or SUD.

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tDCS showed a medium to large

effect size, an SMD of negative

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0.73 , for reducing cravings and

symptoms related to substance use.

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No significant heterogeneity was

found, which means that these

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results were fairly consistent.

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This is exciting because SUD, Substance

Use Disorder, is notoriously difficult

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to treat and tDCS could provide a new

non invasive option for helping patients.

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Third is Obsessive

Compulsive Disorder, or OCD.

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TMS demonstrated a medium effect size, or

SMD, around negative 0.66, with specific

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protocols showing even stronger results.

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The bilateral DLPFC stimulation

stood out as particularly

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effective, with low heterogeneity.

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Low frequency stimulation of the

supplementary motor area, or SMA, and

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also right DLPFC also showed promise.

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These findings highlight the importance

of tailoring TMS protocols to specific

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brain regions and symptom profiles.

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What about unipolar depression

or major depressive disorder?

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TMS and tDCS were both effective.

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High frequency stimulation of

the left DLPFC, a commonly used

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protocol, had a medium effect size.

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Bilateral stimulation showed

a smaller but more consistent

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effect with less heterogeneity.

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This reinforces the idea that TMS

can be a game changer for patients

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with treatment resistant depression,

but protocol optimization is key.

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Fifth is schizophrenia.

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TMS and tDCS were effective for

negative symptoms with medium

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effect sizes, but results for

positive symptoms were less clear.

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tDCS was particularly promising

for improving attention and working

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memory, addressing cognitive deficits

that medications often fail to treat.

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This is a significant step forward, as

cognitive symptoms are a major barrier

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to functional recovery in schizophrenia.

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Sixth is post traumatic

stress disorder, or PTSD.

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TMS demonstrated a large effect

size with an SMD of negative 1.09,

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especially with low frequency

stimulation of the right DLPFC.

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This aligns with growing evidence

that targeting specific brain

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regions can effectively alleviate

PTSD symptoms, including hyper

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arousal and intrusive thoughts.

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Across these findings, what's clear

is that both TMS and tDCS hold

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incredible potential for treating

mental health conditions that are often

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resistant to traditional therapies.

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But it's not just about

whether these techniques work.

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It's also about fine tuning the

protocols to maximize their effectiveness

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and ensure consistent results.

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Now that we've unpacked the findings of

this study, let's explore what they mean

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for clinical practice and patient care.

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Neurostimulation techniques like TMS

and tDCS are not just promising, they're

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already reshaping how we approach

some of the most challenging mental

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health conditions First, let's look at

standardizing protocols for effectiveness.

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One of the most striking takeaways

from this meta analysis is the

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importance of session frequency

and protocol standardization.

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For example, the analysis suggests that 10

to 20 sessions of TMS are optimal across

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conditions like depression, PTSD, and OCD.

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Interestingly, extending beyond

20 sessions doesn't appear to

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necessarily lead to greater benefits.

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What about treatment resistant cases?

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Conditions like unipolar depression

or major depressive disorder,

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PTSD and negative symptoms in

schizophrenia are notoriously

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difficult to treat with traditional

pharmacotherapy and/or psychotherapy.

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Neurostimulation offers a viable

alternative or complement to these

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other therapies, giving clinicians

more tools to help their patients.

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For example, transcranial magnetic

stimulation can help patients

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who haven't responded to multiple

antidepressant trials, reinforcing

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its role as a frontline treatment

for treatment resistant depression.

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What about cognitive deficits?

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Cognitive symptoms, especially

in conditions like schizophrenia,

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are often under-addressed

by conventional treatments.

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These findings suggest that tDCS can

improve attention and working memory.

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which could significantly enhance

functional outcomes for patients.

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These kinds of improvements can translate

into better everyday functioning,

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such as improved job performance or

general ability to manage daily tasks.

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What about combining treatments

for a synergistic effect?

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The study focused on neurostimulation

as a standalone therapy.

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But previous research indicates

that combining it with other

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interventions can amplify its effects.

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For instance, TMS plus cognitive

behavioral therapy, or CBT, particularly

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promising for anxiety and PTSD.

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tDCS plus cognitive training, a

potential game changer for ADHD and

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cognitive deficits in other disorders.

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These approaches suggest that

future protocols might pair

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neurostimulation with existing

therapies for a more holistic approach.

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How about expanding accessibility?

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One exciting aspect of tDCS is its

potential for home-based treatment,

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particularly for conditions like

substance use disorders and depression.

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This could make neurostimulation more

accessible, especially for individuals

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who face barriers to in-clinic treatment.

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There's also the potential for app-based

monitoring or remote supervision to

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help ensure safety and improve efficacy.

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Ultimately, the findings of this

study remind us that neurostimulation

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isn't just about treating symptoms.

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It's about restoring function, hope,

and agency to patients who may have felt

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left behind by other treatment options.

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While the results of this meta

analysis are promising, They're also a

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reminder that the journey of advancing

neurostimulation is far from over.

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Let's discuss the key challenges

and where we go from here.

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First, there are still

significant research gaps.

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For example, conditions like ADHD and

tic disorders remain underexplored with

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too few studies to draw firm conclusions.

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We also need more RCTs exploring

long-term effects and how well

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benefits are sustained over time.

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Ongoing research is going to

be very important to address

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these gaps in our knowledge.

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What about managing heterogeneity?

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One of this study's major

limitations was heterogeneity or

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variability in results across trials.

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Factors like stimulation site,

frequency intensity, and patient

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demographics all influence outcomes.

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For instance, high frequency TMS

on the left DLPFC shows promise for

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treating depression, but results vary

widely depending on the number of

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sessions and patient characteristics.

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Future research must identify the best

parameters for each condition, tailoring

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treatments to maximize efficacy.

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How about ethical and

practical considerations?

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Accessibility and

affordability are crucial.

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While tDCS offers potential for home-based

treatment, ensuring proper supervision and

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preventing misuse is going to be critical.

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Similarly, TMS's cost and reliance on

specialized equipment can limit its reach.

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There is a need for policies and

programs to help make neurostimulation

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more affordable and available

to underserved populations.

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What are some innovations on the horizon?

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Emerging technologies like closed

loop neurostimulation, which adapts

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stimulation in real time based on

brain activity, could dramatically

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improve precision and outcomes.

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We need to explore the potential for AI

driven personalization, where machine

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learning algorithms help to identify the

best protocols for individual patients.

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What about combining

modalities for greater impact?

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We've discussed combining neurostimulation

with CBT or cognitive training approaches,

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but what about pairing TMS with tDCS?

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Could these two techniques work

synergistically to address both symptoms

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and underlying brain dysfunction?

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This might be an exciting

area for future exploration.

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The future of neurostimulation is bright.

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But it requires collaboration across

research clinical practice and policy

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in order to fully unlock its potential

Now i'd love to hear from you.

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What are your thoughts on these

challenges and opportunities?

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Reach out to share your

perspective or suggest topics

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for future podcast episodes.

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Now I'm going to offer an advanced

evidence-based critical analysis of this

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study using the PRISMA analysis, PRISMA

stands for the Preferred Reporting Items

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for Systematic Reviews and Meta Analyses,

is a checklist and a framework that allows

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us to highlight both the study's strengths

and potential areas for improvement.

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First, let's look at the

title and the abstract.

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What about the strengths?

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The study's title clearly

conveys its purpose.

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A systematic review and meta analysis

of neurostimulation techniques, TMS and

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tDCS, across mental health disorders.

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The abstract effectively summarizes

the key findings, objectives,

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and methods, providing a

comprehensive snapshot for readers.

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What are some areas for improvement?

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Well, the abstract could provide more

detailed information on limitations,

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such as heterogeneity or publication

bias to give a balanced view up front.

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Second, let's look at the introduction.

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What were the strengths?

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The introduction establishes a strong

rationale for the study by highlighting

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gaps in neurostimulation research and

the need for comprehensive synthesis.

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The objectives are clearly

stated, aligning with PRISMA

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guidelines to ensure transparency.

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What are some areas for improvement?

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It could elaborate on how this study

builds on previous meta analyses or

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systematic reviews, differentiating its

contribution to the field in general.

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Third, let's look at the methods.

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What were the strengths?

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The study adheres to PRISMA's

emphasis on a detailed methodology.

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It specifies inclusion

and exclusion criteria.

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search strategies across

databases, and the statistical

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methods used for meta analysis.

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The use of randomized controlled trials,

or RCTs, ensures high quality data,

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minimizing the potential for bias.

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While the study includes 208 RCTs, it

doesn't clarify how grey literature,

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such as unpublished studies or non

English studies, were handled, which

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may introduce some publication bias.

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The heterogeneity of the protocols,

for example, variation in stimulation

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sites, frequencies, and session

counts, is acknowledged, but not fully

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addressed in terms of its potential

impact on pooled effect sizes.

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Fourth are results.

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What were the strengths?

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Well, the results were well organized

with clear subgroup analyses for specific

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disorders, like GAD, OCD, and depression.

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The effect sizes, or SMDs, are

reported with confidence intervals.

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which helps in assessing the

precision and reliability of findings.

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What about the limitations in reporting?

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High heterogeneity, or I squared

values, is reported for some outcomes,

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but not consistently explained.

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The PRISMA guidelines recommend

sensitivity analyses, or meta regression,

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in order to address heterogeneity,

which could strengthen the findings.

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There's no discussion of small

study effects or potential biases in

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specific subgroups, such as studies

with high versus low risk of bias.

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Fifth is the discussion.

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What were the strengths?

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Well, the discussion contextualized the

findings within existing literature,

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highlighting where neurostimulation has

strong evidence and where gaps remain.

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The clinical implications are

thoughtfully explored, including the

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importance of protocol standardization

and the potential for home-based tDCS.

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What would be some areas for improvement?

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Well, the study does not sufficiently

address limitations such as the

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reliance on studies with small sample

sizes, short follow-up durations,

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or lack of blinding in some trials.

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The discussion could also include a

more robust critique of the variability

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in effect sizes, particularly for

conditions like depression, where

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multiple protocols are in use.

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Then there's the risk of bias assessment.

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What were the strengths?

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Well, the study included a risk of

bias assessment for included RCTs,

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which is a key PRISMA requirement.

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Use of standardization tools,

for example, the Cochrane risk of

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bias tool, ensures credibility.

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But what about the limitations?

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While the assessment identifies high

risk studies, it doesn't adequately

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explore how these studies may have

influenced the meta analysis results.

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Exclusion or subgroup analyses for high

risk studies could have added clarity.

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Limitations and future directions.

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What were the strengths?

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The authors acknowledge heterogeneity

and the need for more targeted

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studies in underrepresented conditions

like ADHD and tic disorders.

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Calls for standardizing protocols,

for example, session count,

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stimulation parameters, are

valuable for advancing the field.

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: 00:22:41

What could be some areas for improvement?

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: 00:22:43

Well, the study could expand on

the ethical and practical barriers

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to implementing neurostimulation

more widely, such as cost,

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accessibility, and patient adherence.

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: 00:22:54

There could have been a greater emphasis

on the need for large scale, multi center

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trials with longer term follow up, which

could help to guide future research.

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: 00:23:03

Let's look at the overall

quality and contribution.

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: 00:23:06

What were the strengths?

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: 00:23:08

This study is a landmark synthesis

offering the most comprehensive

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: 00:23:11

evidence to date on TMS and tDCS

across mental health conditions.

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: 00:23:17

Its findings provide actionable insights

for clinicians and researchers reinforcing

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: 00:23:24

neurostimulation's role in treating

treatment-resistant conditions, and

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: 00:23:29

in offering patients an alternative

to traditional treatment options.

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: 00:23:34

As a final critique, this study excels

in scope and rigor, but it could benefit

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: 00:23:39

from a deeper analysis of variability

and publication bias, as well as more

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: 00:23:44

practical recommendations for integrating

the findings into clinical practice.

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: 00:23:49

Using the PRISMA framework to critique

this study highlights its strength

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: 00:23:53

as a comprehensive meta analysis

while pointing out areas where future

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: 00:23:58

reviews and research could improve.

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: 00:24:01

By addressing these limitations, the

field of clinical neurostimulation can

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: 00:24:05

advance even further, offering more

precise, effective, and accessible

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: 00:24:11

care options for mental health.

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: 00:24:13

Okay, let's quickly recap the

highlights of what we've covered.

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: 00:24:18

Let's summarize the key takeaways

from today's discussion.

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: 00:24:21

We started by exploring the largest

meta analysis to date, which evaluated

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: 00:24:25

208 randomized controlled trials on

TMS and tDCS across various conditions.

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: 00:24:32

We learned that TMS shows strong

potential for treating conditions like

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: 00:24:36

GAD, OCD, PTSD, and major depressive

disorder, while tDCS excels in addressing

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: 00:24:42

cognitive deficits in schizophrenia

and symptoms of substance use disorder.

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: 00:24:47

We discussed how tailoring protocols

like focusing on specific stimulation

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: 00:24:51

sites, or standardizing session counts

can optimize outcomes for patients.

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: 00:24:57

And finally, we tackle the challenges,

including research gaps, heterogeneity

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: 00:25:03

in results, and the need for greater

accessibility and affordability in

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: 00:25:08

neurostimulation treatment options.

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: 00:25:11

These findings aren't just numbers.

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: 00:25:12

They're a testament to how far we've

come in understanding and harnessing

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: 00:25:17

the power of neurostimulation

in helping the brain to heal.

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: 00:25:21

Neurostimulation represents a frontier in

mental health care, but it's also a field

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: 00:25:26

where there's so much more to discover.

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: 00:25:29

Every study, every clinical trial,

and every patient experience

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: 00:25:33

adds another piece to the puzzle.

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: 00:25:35

Did today's discussion

spark your curiosity?

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: 00:25:38

Maybe you're a clinician thinking about

incorporating neurostimulation into your

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: 00:25:44

own practice, or maybe you're a researcher

interested in the next big questions.

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: 00:25:49

I would love to hear your thoughts.

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: 00:25:51

Share them with me on our social

media outlets or through the podcast

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: 00:25:55

website on the comment section below

any way that works best for you.

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: 00:26:00

If you're a researcher or a clinician,

consider joining the movement to

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: 00:26:04

push neurostimulation forward.

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: 00:26:06

Collaborate on studies, refine protocols,

or explore how these techniques can

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: 00:26:11

complement traditional therapy options.

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: 00:26:14

And don't forget to tune in next

time, where we're going to be

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: 00:26:17

looking in a fascinating direction

that could redefine how we approach

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: 00:26:21

personalized mental health care.

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: 00:26:24

For more resources, insights, or to catch

up on previous episodes, please visit

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: 00:26:29

our website or follow us on social media.

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: 00:26:33

If you've enjoyed today's episode,

don't forget to like and subscribe,

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: 00:26:37

and also feel free to leave a review.

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: 00:26:40

It really helps us to reach

more people who are passionate

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: 00:26:42

about mental health innovation,

neuroscience, and neurostimulation.

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: 00:26:48

Thank you so much for joining me

today on the Neurostimulation Podcast.

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: 00:26:52

I sincerely appreciate your time,

your interest, and your attention.

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: 00:26:56

Until next time, stay curious, stay

compassionate, and let's keep exploring

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: 00:27:01

the future of mental health care together.