Advances in the Treatment of Depression: Brain Stimulation

Ketamine is under very active investigation

NMDA receptor antagonist

Advances in the

Treatment of Depression:

Zarate et al. A Randomized Trial of an N-methyl-D-aspartate

Antagonist in Treatment-Resistant Major Depression. Arch Gen Psychiatry. 2006;63:856-864

Tw: @DescartesLi

Brain Stimulation

Ketamine

not FDA approved for depression

electroconvulsive therapy

transcranial magnetic

stimulation

Primary indication is anesthesia

deep brain stimulation

ketamine

Case series in chronic pain

in terminally ill

http://healthland.time.com/2013/05/22/club-drug-ketamine-lifts-depression-in-hours/

Electroconvulsive Therapy (ECT)

Deep Brain Stimulation (DBS)

Transcranial Magnetic Stimulation (TMS)

not FDA approved for depression

http://www.mayoclinic.com/health/electroconvulsive-therapy/MY00129

Target: DLPFC

Application of a localized magnetic field to the scalp

Magnet powered by high-intensity electrical current

Magnetic field induces local electric currents in superficial cortex (2-3 cm)

no seizure

Target:

Brodmann Area 25

(subcallosal cingulate gyrus, SCG)

and others

Sherwin

Nuland, M.D.

ECT vs. Antidepressants

rTMS compared with ECT

3 randomized, non-blinded, non-placebo controlled studies rTMS vs. ECT

Patients ill enough to justify ECT

3-4 weeks of treatment

Close or equivalent for uncomplicated depression(?)

ECT superior for psychotic depression

Relapse rates similar at 6 months (~20%)

History of ECT

The UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361: 799–808

side effects

1932: Ladislav Meduna observed cell over- and under-growth in brains

1933: Animal trials to find medication that could reliably induce seizures

1934: First trial of camphor induced seizures in humans

1934: camphor replaced by pentylenetetrazol (Metrazol)

1938: Cerletti and Bini use electricity to stimulate seizures.

General Description

Recent Efficacy Rates

ECT

6-15 treatments

http://en.wikipedia.org/wiki/Deep_brain_stimulation

headache

muscle aches

nausea

post-treatment confusion

memory impairment

[rarely, mania/hypomania]

usually done 3X/week

Currently in clinical testing phase

medications

1940: Kalinowsky introduces ECT to the U.S.

rTMS Side Effects

How Effective, and for What?

entire procedure is 30min

one hour preop

1-2 hour recovery

http://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation

Prudic J et al. Effectiveness of Electroconvulsive Therapy in Community Settings. Biol Psychiatry 2004;55:301-312.

Kellner CH, Knapp RG, Petrides G, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006;63:1337-44.

Nelson, J. Craig. The STAR*D Study: A Four-Course Meal That Leaves Us Wanting More. Am J Psychiatry 2006 163: 1864-186.

Tapping noise – Use earplugs

Prickling sensation on the scalp

Transient headache (<10%)

Mild analgesics effective

8 reported seizures during early rTMS

No significant cognitive, cardio problems

rTMS for depression > effective than sham

Effect size of ~ .65 on average

Moderately effective

Patient sits or reclines in chair

Headrest / earplugs

5d/week, 40min per session

30-40 treatments

Office treatment

Non-invasive, No anesthesia

Patient awake, alert