Neurostimulation and neuromodulatory devices other than vns

Electroconvulsive therapy (ECT)

Is non-surgical

FDA approved for depression although currently the FDA is discussing revising its FDA-approved device status as many devices were grandfathered an approval for MDD treatment

Generally is accepted as very effective for the acute treatment of resistant depression, psychotic depression

Works in the acute setting (whereas VNS works chronically) but long-term maintenance ECT may not be as effective

Transcranial magnetic stimulation (TMS)

Is non-surgical

FDA approved since 2008 for depression that is resistant to initial antidepressant therapy or for patients who cannot tolerate an initial antidepressant. (Patients failing four or more antidepressants were not part of regulatory trials, although many insurances insist on four trials)

Works acutely over four to six weeks of treatment

Magnetic coil is placed over the left DLPFC and stimulation is given every day

Magnet creates electrical cortical impulses and neuronal activity in a focused brain area that may be associated with generating depressive symptoms when hypoactive

Side effects are minimal: headache, toothache, ear pain. Rarely may induce a seizure

Deep brain stimulation (DBS)

FDA approved to treat intractable tremors and for compassionate use in refractory obsessive compulsive disorder (OCD). Is being actively studied in TRD and has prior approvals for Parkinson’s disease tremors and dyskinesias

Requires more invasive, sterotactic insertion of two electrodes in deeper brain areas (i.e., Brodmann Area 25) and implantation of a pacemaker/generator device (similar to VNS)

Stimulation side effects may include dizziness, insomnia, or hypomania. Acute clinical antidepressant effects appear to be rapid and within minutes of activating electrodes in some cases

Magnetic seizure therapy (MST)

Is non-surgical

Is experimental and not FDA approved

Uses a device similar to TMS but with a stronger magnet and the ability to stimulate the cortex to a focal seizure (instead of generalized seizure, like those in ECT)

May avoid the cognitive side effects of ECT

Transcranial direct current stimulation

Is non-surgical

Limited FDA approval with limited data available, this noninvasive brain stimulation technique involves the application of a low-amplitude direct current by two small electrodes placed on the scalp skin surface for up to 20 minutes at a time

A small amount of current passes through the scalp where it induces changes in cortical excitability

Modulation of neuronal resting membrane potentials appears to be the antidepressant mechanism. Alterations in glutamate NMDA receptor efficacy have also been noted

Epidural prefrontal cortical stimulation (EpCS)

In this application, a Band-Aid size electrode is placed underneath the skull but on the surface of the prefrontal cortex. This is more invasive than TMS, MST, and VNS but less invasive than DBS, as EpCS electrodes are not placed into brain matter. These electrodes are also stimulated by a pacemaker/generator-type device

Figure 4.2. The VNS device placement, VNS generator, and wire leads.

Posttest self-assessment question and answer

Which of the following is(are) not an invasive surgical treatment for resistant depression?

A. TMS

B. VNS

C. ECT

D. DBS

E. EpCS

F. A and C

G. B and D

H. All of the above

Answer: F

TMS and ECT are treatments that are not invasive and rendered at or near to the surface of the scalp. VNS, DNS, EpCS all require invasive surgeries.

References

1.http://dynamic.cyberonics.com/depression/hcp/THESYNAPSE/conway.htm. Accessed March 25, 2011.

2.Stahl SM. Stahl’s Essential Psychopharmacology, 4th edn, New York, NY: Cambridge University Press, 2013; Ch. 12.

3.Stahl SM. Stahl’s Essential Psychopharmacology: The Prescriber’s Guide, 5th edn. New York, NY: Cambridge University Press, 2014.

4.American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd edn. Washington, DC: American Psychiatric Association Press, 2010.

5.George MS, Rush AJ, Marangell LB, et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry 2005; 58:364–73.

6.Dorr AE, Debonnel G. Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther 2006; 318:890–8.

7.Follesa P, Biggio F, Gorini G, et al. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res 2007; 1179:28–34.

8.Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology 2002; 59:S3–14.

9.Huynh N, McIntyre R. Algorithms: STAR*D, positives, negatives and implications for clinical practice. In: Schwartz TL, Petersen T, eds. Depression Treatment Strategies and Management, 2nd edn. New York, NY: Informa, 2009; Ch. 5.

10.Conway CR, Sheline YI, Chibnall JT, et al. Cerebral blood flow changes during vagus nerve stimulation for depression. Psychiatry Res Neuroimaging 2006; 146:179–84.

11.Zimmerman M, Chelminski I, Young D, Dalrymple K. Using outcome measures to promote better outcomes. Clin Neuropsychiatry 2011; 8:21–36.

12.Nahas Z, Teneback C, Chae JH, et al. Serial vagus nerve stimulation functional MRI in treatment-resistant depression. Neuropsychopharmacology 2007;32:1649–60.

13.Carpenter LL, Philip NS, O’Reardon J. Advances in neurostimulation for depression: electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation and deep brain stimulation. In: Schwartz TL, Petersen T, eds. Depression Treatment Strategies and Management, 2nd edn. New York, NY: Informa, 2009; Ch. 9.

14.Carpenter LL, Megna JL, Herrera-Rojas M, Siddiqui UA. When medications fail. Neurostimulation therapies for depression. Clin Neuropsychiatry 2011; 8:61–80.

15.Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163:1905–17.

Patient file

The Case:

The primary care physician who went the prescribing distance but came up short

The Question:

Do atypical antipsychotics treat generalized anxiety?

The Psychopharmacological dilemma:

Finding an effective treatment for chronic treatment-resistant generalized anxiety in an elderly patient

Pretest self-assessment question (answer at the end of the case)

What pharmacologic properties of quetiapine (Seroquel) lend themselves to providing clinical antidepressant and anxiolytic properties?

A. 5-HT1A partial receptor agonism (similar to buspirone [BuSpar], vilazodone [Viibryd])

B. Norepinephrine reuptake inhibition (NRI) properties (similar to bupropion-XL [Wellbutrin-XL])

C. Histamine-1 (H1) receptor antagonism (similar to hydroxyzine [Vistaril], doxepin [Silenor])

D. Selective serotonin reuptake inhibitor (SSRI) properties similar to fluoxetine (Prozac)

E. GABA-A receptor modulating properties similar to diazepam (Valium)

F. A, B, and C

G. All of the above