rTMS &

Treatment of Depression

Michelle Cochran MD

rTMS

• Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive ‘neurostimulation’ treatment for patients with Depression

• Magnetic stimulation of targeted brain areas helps improve mood symptoms.

1. Review current treatments for depression with emphasis on treatment resistance & practical guidelines

2. rTMS: review of the science and a brief review of studies showing efficacy & safety

3. Review the Role of rTMS for depression

PURPOSE

Current Treatments

• Review 2006 STAR*D study (Sequenced Treatment Alternatives to Relieve Depression)

- NIH sponsored, largest & most definitive research that showed inadequacies of depression treatments.

Good Treatment Is Difficult to Achieve

•Adequacy of treatment has been estimated to be as low as 18%, regardless of agent used

•The ratio of inadequate-to-adequate treatment attempts is 4:1

5

…adequate treatment in depression is the exception (unfortunately), not the norm

Adequate Dosage

Adequate Duration

Poor tolerability

Lack of adherence to recommended

treatment

Lack of efficacy

Medical and Psychiatric

Comorbidities

Factors contributing to inadequate treatment

STAR*D Study revealed that current treatment has limited effectiveness

Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry

Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry; Neuronetics, Inc. (data on file)

LIKELIHOOD OF DISCONTINUING TREATMENT INCREASES WITH EACH NEW MEDICATION ATTEMPT

Weight GainConstipationDiarrheaNauseaDrowsinessInsomniaDecreased LibidoNervous AnxietyIncreased AppetiteDecreased Appetite

FatigueHeadache/MigraineAbnormal EjaculationImpotenceSweatingTremorDiscontinuation (Flu-like)WeaknessDry MouthDizziness

Most common systemic side effects with current medications:

Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010)

Antidepressant Switch:

Non MAOI Class

AugmentationStrategies

NEXT

NEXT

Switch to another non-MAOI antidepressant medication

[likelihood of remission declines with each step]

Switch to an MAOI or TCA

[Usually requires sufficient time for medication washout]

Augmentation with second generation antipsychotic or other medications (Li, thyroid hormone, stimulants)

[Potential side effects and drug interaction are considered]

Antidepressant Switch:

MAOIs/TCAs

WHAT’S BEEN THE NEXT STEP WHEN INITIAL TREATMENT FAILS…

Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010)

TREATMENT GUIDELINES FOR DEPRESSION

Systemic Drug Side Effects: Most common side effects per antidepressant medication labels (occurring 5% and two times placebo)

SSRI-Celexa (citalopram)-Lexapro (escitalopram)-Prozac (fluoxetine)-Luvox (fluvoxamine)-Paxil/Pexeva (paroxetine)-Zoloft (sertraline)

SNRI-Cymbalta (duloxetine)-Effexor (venlafaxine)-Pristiq (desvenlafaxine)

Other options:-Wellbutrin (buproprion)-Serzone (nefazadone)-Oleptro (trazadone ER) -Remeron (mirtazapine)-Tricyclic Antidepressants-Viibryd (vilazadone)

Weight Gain Nervousness Weakness Abnormal Ejaculation

Constipation Anxiety Dry Mouth Impotence

Diarrhea Increased Appetite Dizziness Sweating

Nausae Decreased Appetite Fatigue Tremor

Insomnia Less Sexual Interest Headache/Migraine Treatment Discontinuation

Drowsiness

TMS side effects: minor scalp and head painor a headache at first

Maintenance: with medications or taper from all medications depending on patient response

Psychotherapy & Medication

• The FDA approved the use of TMS via the Neurostar device for patients who failed to achieve satisfactory improvement from one course of pharmacological treatment (medication).

No Depression

A PET scan measures vital functions such as blood flow,

oxygen use and blood

sugar (glucose)

metabolism.

Depression

A PET scan measures vital functions such as blood flow,

oxygen use and blood sugar (glucose)

metabolism.

Major Depression is a Brain Disease

PET ScanNO DEPRESSION DEPRESSION

• rTMS uses focused magnetic impulses to non-invasively stimulate the brain in the pre-frontal cortex (the region of the brain associated with mood regulation).

How does rTMS work?

• magnetic fields penetrate directly into the brain to produce currents, which activate cells within the brain that increase neural activity

• TMS helps restore balance and thereby relieves the symptoms of depression.

How rTMS works . . .

Major brain regions known to be involved in mood regulation

Amygdala

VentromedialPrefrontal Cortex

PrefrontalCortex

Anterior Cingulate Gyrus• Brain activity can be altered

• Chemically (eg, via drugs) or

• Electrically (eg, via TMS or ECT)

– Drug action is anatomically diffuse and systemic

– TMS is focused, non-invasive and non-systemic

Pizzigalli (2011) Neuropsychopharmacology

TREATING THE BRAIN AS AN ELECTROCHEMICAL TARGET

• Activation of fronto-cingulate brain circuit following a course of TMS applied to the left dorsolateral prefrontal cortex in patients with Major Depression

Kito (2008) J Neuropsychiatry Clin Neurosci

TMS Coil

L

L

R

R

TARGETED EFFECTS ON MOOD CIRCUITS IN BRAIN

• Early scientific literature provided evidence of antidepressant efficacy of TMS

• Two large, multisite, randomized controlled trials confirmed the clinical significance of TMS as an antidepressant

• The treatment benefit of TMS over control condition (effect size) compares favorably to those seen with antidepressant medications*

Review of Research

• No systemic side effects• No adverse effect on cognition• Most common adverse event associated with treatment was

scalp pain or discomfort– < 5% of patients discontinued due to side effects

• No seizures with NeuroStar device during clinical studies (over 10,000 treatments)

• Rare risk of seizure with NeuroStar TMS in post-market use (0.003% per treatment, <0.1% per patient),(~100,000 treatments in post-marketing experience to date)

• Long term safety demonstrated

Safety overview

• No treatment emergent suicidal ideation, in the studies with NeuroStar TMS treatment.

Safety overview, cont.H

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Baseline Week 2 Week 4 Week 6

NeuroStar TMS Therapy (n=155)

Sham TMS (n=146)

Janicak (2008) J Clinical Psychiatry.

• non-invasive• requires no anesthesia or sedation • procedure typically lasts around 30-40 minutes daily (5 days per week)• patients are awake and alert• patients can immediately return to regular activity.

The advantages of TMS

• NeuroStar® TMS Therapy is contraindicated in patients with implanted metallic devices or non-removable metallic objects in or around the head

• Refer to www.NeuroStar.com for complete product safety information

Contraindications

• NeuroStar TMS Therapy is:

• An effective, proven treatment for major depression when initial drugs fail

• Included in APA Practice Guidelines

• A valuable treatment for patients who want to reduce medications and the side effect burden that goes along with them

Conclusion

• Refer to www.NeuroStar.com for

complete product prescribing and

safety information

Thank you!

For complete Prescribing and safety information