treating treatment refractory depression with tms

$: Treating Treatment Refractory Depression With TMS$
copyright 2014 MTPC 1

Treating Treatment Refractory Depression with

TMSMidtown Psychiatry and TMS Center Data


Adult, adolescent and child psychiatristMidtown Psychiatry and TMS CenterFocus of treatment for mental illness : Integrative Approach Contact: www.danielawhite-md.com [email protected] office : 713 426 3100 cell : 713 252 5689

Daniela M White, MD

http://www.danielawhite-md.com/


It’s a collection of retrospective data; the process was not intended as a study;

The results obtained in the clinic were looking better than the data from the FDA clearance studies done for TMS approval as therapy;

Reviewing of the literature showed similar results in the outpatient population;

We decided to present our results to increase awareness in the community about the results of the therapy

Few words about this presentation…


Transcranial Magnetical Stimulation One of four ways of neurostimulation used to

treat depression: Deep Brain Stimulation, Vagal Nerve Stimulation, ECT

The only noninvasive office based method to treat refractory depression;

Cleared by FDA for the treatment of refractory MDD, in 2008

What is TMS


Major Depression: A Large Patient Population that is Currently Being

Underserved

14 Million US Adults with MDD

• Inadequate response• Intolerant to side effects

7.2 Million Treated

4 Million Poorly Served

Kessler RC et al. JAMA. 2003;289(23):3095-3105.


Major Depressive Disorder

prefrontalcortex

In MDD, some areas of the

brain are hypoactive and

others are hyperactive.

amygdala

brainstem neurotransmitter centers

thalamus

striatum

anterior cingulate

cortex

hippocampus

hypothalamus

LOW

HIGH

Neural Activity


FMRI of the Depressed Brain

STAR*D Study demonstrates that current treatments have limited effectiveness

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


Treatment Resistant Depression ( TRD) is an episode of MDD that does not respond to an adequate trial of ( at least 6 weeks) of an antidepressant

The definition of response is a decrement of 50 % on HAM-D between the initial presentation symptoms and at the end point of treatment.

TMS was cleared for the TRD treatment after the failure of at least one trial

What Defines

Chemical Antidepressants

Antidepressant

weight gainsexual

dysfunction

insomnia

nausea

GI distress

blood pressure changes

blurred vision

AntidepressantTherapeutic ffects such as :Side Effects such as:

improved mood

increased concentration

reduced feelings of guilt, suicidality, and worthlessness

weight gain

insomnia

agitation dry mouth fatigue


H0w is it done?

NeuroStar TMS Therapy


How does TMS work?

Electric current through the coil induces MRI-strength ( 1.2-2 Tesla) magnetic field pulses

Magnetic field pulses pass unimpeded 2-3 cm into the cortex

This produces a depolarization of the cortex and connected brain regions

This stimulates the firing of nerve cells and the release of neurotransmitters

NeuroStar Releases Neurotransmitters in the Brain

Depolarization of neurons in the DLPFC causes local neurotransmitter release

Depolarization of pyramidal neurons in the DLPFC also

causes neurotransmitter release in deeper brain neurons

Activation of deeper brain neurons then exerts secondary effects on remaining portions of

targeted mood circuits

Dorsolateral prefrontal

cortex

Kito (2008) J Neuropsychiatry Clin Neurosci

These effects are associated with improvements in

depressive symptoms

• Primary diagnosis: DSM-IV Major Depressive Disorder• Unipolar type, non-psychotic• Moderate to severe symptoms at baseline• Approximately one-third of patients had a co-morbid anxiety disorder

• Indicated patient population (164) had extensive prior antidepressant drug exposure• Average number of antidepressant medication trials in

current episode = 4 (range: 1 to 23 attempts)• Majority of treatment attempts were unable to achieve

adequate dose and duration of treatment due to intolerance

• Indicated patients had failed to achieve satisfactory benefit from one antidepressant medication at an adequate dose and duration in the current episode

17

Randomized Controlled Trial Conducted in a Difficult to Treat

Population

O’Reardon JP, et al. (2007). Biol Psychiatry 62(11):1208-1216.; Demitrack MA, Thase ME (2009). Psychopharmacol Bull 42(2):5-38.

Independent Study Reinforces Efficacy for NeuroStar TMS

Mark S. George, MD; Sarah H. Lisanby, MD; David Avery, MD; William M. McDonald, MD; Valerie Durkalski, PhD; Martina Pavlicova, Phd; Berry Anderson, Phd, RN; Ziad Nahas, MD; Peter Bulow, MD; Paul Zarkowski, MD;Paul E. Holtzheimer III, MD; Theresa Schwartz, MS; Harold A. Sackeim, PHD

• National Institute of Mental Health (NIMH) sponsored Optimization of TMS (‘OPT-TMS’) Study– Independent of industry– Rigorous Randomized Controlled Trial– 190 patients treated at 4 premier academic sites

• Primary outcome measure: Percent Remission at 3 weeks

‒ 4 times greater likelihood of achieving remission with active treatment vs. sham treatment

George, Arch Gen Psychiatry, 2010

Series10

10

20

30

40

50

60

70

58.0% 56.4%

37.1%

28.7%

Perc

en

t of

Pati

en

ts (

N=

30

7)

LOCF Analysis of intent-to-treat population

Remission is Possible with NeuroStar TMS Therapy,

1 in 2 Patients Respond, 1 in 3 Patients Achieve RemissionClinician Rating

(CGI-Severity of Illness)

Patient Rating(PHQ-9 Scale)

Responders (CGI-S ≤3, PHQ-9 <10) Remitters (CGI-S ≤2, PHQ-9 <5)

Carpenter (2012), Depression and Anxiety


High frequency delivered over the L DLPFC Low frequency delivered over the L or R

DLPFC Bi-lateral delivery Deep TMS- that has a deeper penetrating

action

Various protocols have been studied


High frequency L side stimulation and low frequency R side both have been shown to have antidepressant effects

The study evaluated sequentially combined applications for TRD

50 patients, 6 weeks randomized trial Sequentially applying both types of stimulation has

substantial treatment efficacy in patents with TRD

Bilateral rTMS


Daily doses of L DLPFC TMS at 120 % MT 10 Hz 5 sec on 10 sec off 6800 stimuli per session

High frequency r TMS


Patient meets with MD for a consultation, when the recommendation for TMS is made;

Patient receives daily sessions, or twice daily therapy;

Number of sessions is tailored based on individual needs, minimum 25 treatments;

Patient meets with MD once a week, when the HAM-D, GAD-7. QISD and PHQ-9 are completed.

Midtown TMS protocol


L r TMS stimulation at 120 % MT delivering 3000 stimuli

R rTMS at 1 HZ, at 120 % MT delivering 1000 stimuli

Total 4000 stimuli per session

Midtown TMS protocol


27 patients treated in total, 19 females and 8 males

10 patients had only a diagnosis of MDD 17 patient had MDD and comorbidities One patient was younger then 21 25 patients completed the questionnaires

Midtown Patients group


Sicker, on average they failed more than one trial of medication, some of them more then 6, theoretically less prone to improve

Most of them had comorbidities with MDD ( 17 OUT OF 27)

Heterogeneous group, age, diagnosis, comorbidities

Characteristics of the Midtown patients


Diagnosis Breakdowns

19 females with the following diagnosis

9 with MDD 5 with MDD+GAD 1 with MDD+PTSD 1 with MDD+OCD 1 with MDD+GAD+ADHD 1 with a dx of Pain + GAD 1 with MDD+PD

8 males with the following diagnosis

1 with MDD 1 with BP depression 1 with MDD + PD 2 with MDD+GAD 1 with GAD + PD 1 with

GAD+MDD+ADHD+PD 1 with MDD + OCD


PHQ-9

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

Midtown TMS Outcome DataPHQ-9

Response

Remission

85.7%Response

61.9%Remission

25 Patients

Response =End Score below 10

Remission = End Score below 5


GAD-7

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

Midtown TMS Outcome DataGAD-7

Response

Remission

85.7%Response 80.1%

Remission

25 Patients

Reponse =50% score reduction

Remission =End Score 8 or be-

low


HAMD-21

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

Midtown TMS Outcome DataHAMD-21

Remission

Response

80.9%Remission 72.2%

Response

25 Patients

Response =50% reduction in

score

Remission = End Score 10 or

below


This sample showed improvement of HAM-D score for TRD with combined r TMS high frequency for the L DLPFC and low rTMS for the R DLPFC

The improvement was measured at 4 weeks and follow up.

Conclusions


22 y/o WF who reported that she has been depressed for her entire life, and has been seen by a psychiatrist for several years.

She had tried ‘all antidepressants’ and augmentations. She came from out of town, hoping that this last resort

therapy would help. Was unemployed, spent her days in bed, lost previous

interests, had high levels of sadness and anhedonia “ I wanted to get my motivation back’ was her goal for

the TMS treatment

Helen ( not her real name)


Psychometric scales scores:initial HAM-D 23, final HAM-D 7

At the end of her treatment she had decreased levels of anxiety and sadness, had regained her motivation, started exercising more regularly, and felt ready to go back to schoolThis year, 2 years after finishing treatment she texted us that she had returned to school and graduated. Her depression is still in remission.

Helen


28 y/o WF, with depression diagnosed as a preteen

She had tried at least 6 other medications (antidepressants and augmentation)

Her complaints were: severe depression, hopelessness, lack of energy, difficulty concentrating, low performance at work, extreme, paralyzing anxiety, decreased initiative

Received bilateral TMS, while on Viibryd 40 mg po qd

Luisa ( not her real name)


At the end of the treatment she reported feeling ‘really good,’ able to relax and enjoy her weekends, able to stay ‘cool’ in situations that would ‘freak her out’ before the treatment.

Still in remission at 6 months. Psychometric scales numbers: initial HAM-D :

25, final HAM-D 4

Luisa


HAM-D graph


MADRID-XVI World Congress of Psychiatry September 14-18, 2014


Please contact Kristin McDermott for scheduling a consultation at (713) 426-3100

We love your referrals!!


Adult, adolescent and child psychiatristMidtown Psychiatry and TMS CenterFocus of treatment for mental illness : integrative approach Contact: www.danielawhite-md.com [email protected] office : 713 426 3100 cell : 713 252 5689

Daniela M White, MD

http://www.danielawhite-md.com/

treating treatment refractory depression with tms

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