SOMATIC TREATMENT INTERVENTIONS 1 Electroconvulsive Therapy (ECT)

BACKGROUND

Electroconvulsive therapy (ECT) has advanced in terms of its importance in treating severe MDD, especially in its psychotic and treatment-resistant forms. Refinements in anesthetic, physiologic monitoring, stimulus control, and neuromuscular blockade techniques are largely responsible for the advances and have contributed to ECT’s improved safety profile.

ACTION STATEMENT

Electroconvulsive therapy (ECT) should be considered in patients with severe MDD who cannot tolerate, or have not responded to, several trials of antidepressant treatment, unless the patient has significant co-morbid medical conditions that would increase the risks of ECT (e.g., recent myocardial infarction or intracerebral hemorrhage, currently taking MAOIs, or retinal detachment).

RECOMMENDATIONS

1. Electroconvulsive therapy (ECT) should be considered in patients with severe MDD and any of the following conditions: [A]

a. Catatonia or other psychotic symptoms b. Severe suicidality

c. A history of prior good response to ECT

d. Need for rapid, definitive treatment response on either medical or psychiatric grounds

e. Risks of other treatments outweigh the risks of ECT (i.e., comorbid medical conditions make ECT the safest treatment alternative)

f. A history of poor response to multiple antidepressants

g. Intolerable side effects to all classes of antidepressant medications (e.g., seizures, hyponatremia, severe anxiety)

h. Patient preference.

2. In patients with the following potential contraindications for electroconvulsive therapy (ECT), the trade-off between risk and benefit must be weighed for each individual: [B]

a. Space-occupying cerebral lesion or other conditions resulting in elevated intracranial pressure confers added risk of brainstem herniation

b. Significant cardiovascular problems such as recent myocardial infarction, severe cardiac ischemic disease or profound hypertensive illness

c. Recent intracerebral hemorrhage, or patients with bleeding or unstable vascular aneurysms or malformations

d. Degenerative diseases of the axial or appendicular skeleton - use of anesthetic and muscle relaxant techniques have added to the safety profile of ECT in these individuals.

e. Patient currently taking monoamine oxidase inhibitor medication (MAOI). MAOIs should be discontinued two weeks prior to initiating ECT in order to prevent a possible hypertensive crisis.

f. Patient currently taking lithium may develop a neurotoxic syndrome marked by increased mental confusion, disorientation, and unresponsiveness

g. Retinal detachment h. Pheochromocytoma

i. High anesthesia risk – American Society of Anesthesiologists level 4 or 5.

3. Electroconvulsive therapy (ECT) should be considered a short-term therapy that requires maintenance treatment with antidepressants or if antidepressants are not tolerated, repeated treatment with ECT. [A]

4. There is insufficient evidence to recommend for or against ECT in the elderly. [I]

EVIDENCE STATEMENTS

o ECT is more efficacious than simulated ECT in patients with MDD (standardized effect size 0.91 in 6 trials involving 256 patients). ECT is more efficacious than pharmacotherapy in patients with MDD (standardized effect size 0.80 in 8 trials involving 1144 patients) (UK ECT review group, 2003).

o Different regimens of ECT may have different effects on depression symptoms:

Bilateral compared with unilateral electrode placement ECT improved symptoms (standardized effect size 0.32 in 22 trials involving 1137 patients)

High dose ECT also compared with low dose significantly improved symptoms (standardized effect size 0.58 in 6 trials, 337 patients)

There is no significant difference in outcomes between twice weekly and three times weekly treatment or between brief pulse waveform and sine wave (UK ECT review group, 2003).

o Symptom improvement with ECT is short-term and should be followed by maintenance treatment with antidepressants, or if antidepressants are not tolerated, repeated treatment with ECT (Kellner et al., 2006; Sackeim et al., 2001; van den Broek et al., 2006).

o ECT is effective in the acute treatment of late life depression and is generally safe. There is insufficient evidence regarding the relative efficacy of ECT over antidepressants, the long-term efficacy of ECT, morbidity and mortality related to ECT, cost-effectiveness and the efficacy of ECT in subgroups of patients (Van der Wurff et al., 2004).

o The impact of ECT on short- and long-term cognitive functioning was inconsistently assessed across studies and results reported vary across studies included in the systematic reviews. One RCT found that ECT compared to simulated ECT had a greater impact on short-term cognitive functioning, but not on cognitive function at 6 months. Compared to antidepressants, one RCT found ECT had a greater impact on short-term cognitive function and another RCT found there was no difference in short-term cognitive function (UK ECT Review Group, 2003).

EVIDENCE TABLE

Evidence Source QE Overall

Quality SR 1 ECT is efficacious for severe

MDD

Kho et al., 2003 NICE, 2003 Pagnin et al., 2004

UK ECT Review Group, 2003

I Good A

2 Different regimens of ECT Kho et al., 2003 NICE, 2003 Pagnin et al., 2004

UK ECT Review Group, 2003

I Good A

3 ECT should be followed by maintenance antidepressants

Kellner et al., 2006 Sackeim et al., 2001 van den Broek et al., 2006

I Good A

4 Insufficient evidence to recommend for or against ECT in the elderly

Van der Wurff et al., 2003 II Poor I

5 Effect of ECT on cognitive

functioning UK ECT Review Group, 2003 II Poor C

QE = Quality of Evidence; SR = Strength of Recommendation (See Appendix A)

22.2. Vagus Nerve Stimulation (VNS)

BACKGROUND

Vagus nerve stimulation (VNS) for treatment of depression involves implanting a device that sends electrical pulses to the brain. The device consists of three parts: 1) a pulse generator implanted under the skin in the chest wall, 2) two electrodes that are wrapped around the vagus nerve, and 3) a programming wand for non-invasive programming of the device. This device was first approved by the FDA for treatment of refractory epilepsy. In patients with refractory epilepsy who received a VNS, it was noted that their mood improved, thus leading to consideration of VNS for depression.

ACTION STATEMENT

Vagus nerve stimulation (VNS) has not been demonstrated to be safe and effective and should not be routinely considered in patients with treatment resistant depression.

RECOMMENDATIONS

1. Vagus nerve stimulation (VNS) should not be routinely considered for patients with severe treatment resistant depression. [D]

RATIONALE

Several important issues surround the use of VNS for treatment of depression. First, VNS is a proposed treatment for patients with “treatment resistant depression.” However, the definition of treatment resistance is not clear and is highly variable even across researchers (Rush et al., 2003). This makes it extremely difficult to determine who might benefit from this treatment if it is efficacious. Of note, in FDA testimony from patients, patients who received VNS described receiving over 20 different treatments for their depression prior to VNS (Phurrough et al., 2007). This is in contrast to the definition used by NICE (2004) - “[depression] which fails to respond to two or more antidepressants given sequentially at an adequate dose for an adequate time." Second, there have been significant adverse events reported in > 5percent of implanted patients, including voice alteration, dypshagia, dyspnea, increased cough, asthenia, chest pain, headache, vocal cord paralysis, palpitations, dizziness, infection, and incision site reaction. Third, the cost of the device and surgical implantation is estimated to be $25,000. Finally, although there have been multiple calls for a second RCT of VNS for treatment resistant depression, there has been reluctance to pursue another RCT due to the manufacturer’s resistance (Shuchman, 2007).

EVIDENCE STATEMENTS

There is good evidence to recommend that VNS not be used for severe treatment resistant depression except as a last resort.

o One double-blind RCT of 235 outpatients found no difference between VNS and a sham- placebo (Rush, Marangell et al., 2005). VNS was compared to a sham control (patients received the VNS but it was not turned on). Concomitant treatments were held stable. After 3 months, 15 percent (17/111) of patients receiving VNS had a 50 percent reduction in symptoms based on the HRSD-24 compared to 10 percent (11/110) in the sham control group. This difference was not statistically significant (p = 0.238).

o The remainder of the studies are 12-month non-blinded follow-up of study participants (Rush, Sackeim et al., 2005), comparison of intervention group patients to a non-concurrent cohort of treatment as usual patients (George et al., 2005), or observational studies (Corcoran et al., 2006; Marangell et al., 2002; Nahas et al., 2005; Sackeim et al., 2001). Of note, most VNS studies have been done by a single group of researchers.

EVIDENCE TABLE

Evidence Source QE Overall

Quality SR 1 VNS compared to sham control

group found no difference in outcomes at 3 months

Blue Cross Blue Shield Association Technology Assessment, 2006 ICSI, 2006 Rush et al., 2005 I Good D 2 VNS might be considered as a treatment of last resort for patients with severe treatment resistant depression

Expert Opinion III Poor I

23. OTHER TREATMENT INTERVENTIONS