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Electroconvulsive Therapy

Indications

A. Major depressive episode: 

Unipolar 

Bipolar in depressed phase

Prediction of response in depression

Positive Predictors                                                                             Negative Predictors electroconvulsive therapy, electroshock treatment, shock treatment, electric shock treatment, electro shock treatment

                                                        History

Acute, discrete episodes                                                                        Chronicity

Autonomous to circumstance                                                                  Reactive

Positive F.H. for affective disorder                                                          Hypochondriasis

Prior good response to ECT                                                                   Unstable relationships

 

Positive Predictors                                                                                Negative Predictors

Acute anhedonia                                                                                      Projection & externalization

Anergia                                                                                                    Denial

Anorexia                                                                                                  Blaming

Weight loss                                                                                              Inability to tolerate: anger, frustration, sadness

Terminal insomnia 

Speech latency 


Positive Predictors                                                                                 Negative Predictors

Motor restlessness                                                                                    Inability to assume responsibility

Impaired concentration                                                                             Substance abuse

Loss of sex drive                                                                                      Problem pain

A.M. worse than p.m.

Delusions: somatic, paranoid, self-deprecatory

 

Major depression can occur superimposed on lifelong character disorder. If a patient with longstanding character disorder complains of acute deterioration with neurovegetative signs, ECT is likely to be helpful.

Error of commission: administer treatment to patient with a disorder unresponsive to ECT (situational, characterological, organic).

Error of omission: to withhold ECT from such a patient because of failure to recognize the emergence of an acute major depression.

Since the treatment is relatively safe, and depression potentially devastating, the graver error is to withhold treatment from a patient who could benefit from it.

Errors of under- and over-use are less frequent if ECT practitioners are sensitive to character issues and adept at diagnosing character pathology. However, the most reliable predictors of response are the neurovegetative signs listed above.

Natural history of major depression

Bipolar: 

80% spontaneous remission at 6 months

88% response to ECT

Unipolar: 

46% spontaneous remission at 31 months

80% response to ECT

36% mortality at 31 months, half suicide, half medical

Biological markers may be confirmatory, but not diagnostic.

DST non-suppression in 60%

REM latency less than 60 minutes in 60%

Depressed TSH response to TRH in 40%

Neuropsychological testing

1. Diffuse deficits in attention and performance that mimic non-specific organic brain syndrome.

2. Specific deficits in sequencing and abstraction that suggest localization to frontal lobes and non-dominant hemisphere.

3. Intact memory

The bulk of the evidence suggests that ECT-responsive depression is a neuroendocrine disorder of the diencephalon, mainly involving the hypothalamus.

--Depressive symptoms affect functions that are mainly hypothalamically mediated,

--Demonstrable endocrine deregulation--mainly hypothalamic, ie, cortisol, TRH

--Diencephalic involvement in seizure is necessary for efficacy.

Efficacy of ECT in major depression:

Response rates in studies 1950-1970:

Placebo (sham ECT) 0-40% vs. ECT 90%

TCA 70-80% vs. ECT 90%

MAOI 50-60% vs. ECT 90%

Earlier studies from 1960s (Greenblatt in U.S., MRC in England) used inadequate doses of antidepressants. Recent work with higher doses significantly increases response rate with both TCA and MAOI. Contemporary drug treatment yields response rates approaching that of ECT. Overall, however, ECT remains the most effective available treatment for major depression .

There are still two problems. Some patients, particularly the elderly, have great difficulty tolerating side-effects at high dose. Main culprit: orthostatic hypotension. Also, a significant percent (10-20) remain refractory even at maximal doses. Surprisingly, a prospective comparison of ECT and drugs at high dosage has not been done, and will not be in the foreseeable future.

A. Problems of delusional depression

Independent studies consistently find response rate to TCA alone in

40% range. Basically no better than placebo.

ECT is still highly effective in this drug-resistant group (approximately 80% response rate).

Preliminary studies suggest TCA/neuroleptic combination may be quite effective, yielding response rates of up to 86%. Regimen is appropriate only for young, stable, healthy patients.

B. Catatonia

Mood disorder is the commonest underlying diagnosis.

Classical onset (Kahlbaum 1894): Acute manic or psychotic phase which soon switches to depression and rapidly progresses from akinesia to catatonia.

Symptoms: Fluctuating mutism, negativism, muscular rigidity, waxy flexibility, posturing, blepharospasm, tachycardia, fever, diaphoresis.

Complications: Embolism, contractures, fluid and electrolyte imbalance, pneumonia. These make prompt treatment important.

Support: IVs, daily weight, Foley, laxatives, feeding tube, physical therapy.

Treatment: If history consistent with schizophrenia, may respond to neuroleptic. If history consistent with affective disorder, should be treated immediately with ECT. The latter group are highly responsive to EC.

Caveats

1. Neuroleptic malignant syndrome. Suspect this in presence of: history of recent neuroleptic use opisthotonos and dystonia high fever

Some patients with a history of NMS eventually require a course of ECT. There are now over 40 case reports of these patients tolerating ECT uneventfully (19). The history of NMS does not predispose patients to malignant hyperthermia under general anesthesia. They appear to be syndromes which are similar in presentation but physiologically different. Nevertheless, treat with caution in general hospital setting. ECT has not been proven effective in the treatment of NMS, and therefore dantrolene and bromocriptine remain the standard treatment.

2. Complex partial seizures. EEG helpful only if markedly abnormal. About 20% of catatonics have mild abnormalities on EEG.

3. Intracranial event. CT scan obligatory.

Amytal interview:

Catatonia, NMS, seizure disorder all may remit temporarily with I.V. amytal or benzodiazepine, so this is not diagnostically specific. It does, however, help rule out metabolic causes such as porphyria, Wilson's disease, hepatic coma. On the other hand, many catatonics show no response to amytal or benzodiazepine, and these drugs do not provide a litmus test for catatonia. If the patient wakes up with amytal, it does not clinch the diagnosis, and if the patient remains catatonic through amytal, it does not exclude the diagnosis.

The only way to diagnose catatonia is on the basis of the history and clinical symptoms.

C. Schizophrenia

ECT may induce a dramatic remission in younger psychotic patients, particularly those with some of the features of schizophreniform illness

Acute onset

Good premorbid history

Precipitating event

FH of affective disorder

Confusion and affective symptoms prominent

Chronic, well-established, "process" schizophrenia may show temporary improvement, but no dramatic remission. Most of the data show neuroleptics to be superior to ECT in the treatment of chronic schizophrenia. ECT given simultaneously with neuroleptic shows promise, but controlled studies are needed in neuroleptic-resistant schizophrenia.

Number of Treatments

Most studies that report efficacy of ECT in schizophrenia used high numbers of treatments (20-25 per patient). This may reflect convention more than medical necessity, and one cannot assume automatically that high numbers of treatments are necessary to treat psychotic symptoms. There has been no direct comparison of high and low numbers of ECT in schizophrenia. Low numbers may suffice and clinical judgment should determine the endpoint.

In summary, ECT should be considered for:

1. Schizophreniformpresentation.

2. Schizophrenia refractory to neuroleptic treatment. (Therapeutic effect probably enhanced by concurrent neuroleptic, including clozapine).

D. Mania

ECT is an effective treatment for mania with overall response rate of about 80%. There are numerous older case reports, but two recent well-designed studies confirm this finding. In mania refractory to lithium, the response rate is over 50%, and when ECT and lithium are compared propectively, ECT is associated with a more rapid response, but after 2 months both groups do equally well. Bilateral ECT appeared to be more effective than unilateral in both studies.

Lithium remains the primary treatment for bipolar disorder, but ECT clearly has a role in treatment-resistant cases.

3. Use of ECT In Clinical Practice

A. Principal use in major depression, drug-resistant or drug-intolerant.

Resistance: Definition varies per patient. Young, healthy, stable patient should have trials of at least 2-3 different drugs. Elderly, debilitated, fragile patient may be at risk with 1 drug trial.

B. ECT as a Primary treatment

--Starvation or malnutrition. Rehydrate first!

--Delusional depression.

--Catatonia.

C. Risk Factors

There are no absolute contraindications to ECT. The risk of treatment must be balanced on an individual basis against the risk of remaining depressed.

Cardiovascular Risk Factors CNS Risk Factors

Coronary ischemia cerebral infarction

Hypertension cerebral hemorrhage

CHF tumor

Arrhythmia dementia

Recent MI hydrocephalus

Aneurysm AV malformation

Cardiac pacemaker multiple sclerosis

Seizure disorder

ECT has proven safe in pregnancy, but fetal monitoring is essential.

Special Risk Factors: -Digitalis toxicity

-Aortic stenosis

-Theophylline

-Increased intracranial pressure

4. Technique of ECT

A. Consent. Guardian ad litem may be necessary.

B. Discontinue psychotropics unless necessary.

--Benzodiazepines inhibit ictal process

--Tricyclics and MAOIs may make BP and cardiac rate less predictable and do not increase chance of response

--Lithium may be associated with severe OBS in some patients Data are ambiguous, but case reports continue to report severe OBS

--Neuroleptics remain the best treatment for depressive agitation, ie, perphenazine 4-8 mg p.o. t.i.d.

C. Lab tests: Electrocardiogram, chest x-ray, urinalysis, BUN, electrolytes, BS, CPK, SGOT, CBC, thyroid function tests. Also EEG and CT if clinically indicated.

D. Anesthesia

Administration of anesthesia for ECT has been considered a trivial exercise in anesthetic technique, but quite the opposite is true. ECT induces stresses on the heart and CNS that are unique to the surgical setting, and ECT patients cannot be safely managed according to routine protocols for brief surgery.

There are two prerequisites for safe treatment:

1. Training or independent study in ECT for the anesthesiologist

2. Consistency of staff. Frequent rotations are an invitation to mishap. Staff must be familiar both with the treatment and with each other's technique.

Specifics of patient management:

1. Medication: 

Methohexital .75-1.0 mg/kg 

Succinylcholine .75-1.0 mg/kg

Atropine is optional, probably indicated only for bradycardia. Does not reduce oral secretions.

2. Rule of parsimony with barbiturate, since it is an anticonvulsant.

3. Hyperventilation with ambu bag is very important. Most bags deliver 40-60% oxygen. ECT induces several minutes of marked increase in oxygen demands of heart, because of hypertension and tachycardia, and in brain, because of seizure. Color of patient is not an appropriate guide, and does not accurately reflect oxygenation of heart and brain tissue.

4. Blood pressure: Hypertension normally occurs during and for several minutes after the seizure. This is a sudden, centrally-mediated response. It is most severe in patients who are already hypertensive and can often be greatly improved by aggressive antihypertensive treatment of resting blood pressure between treatments. Beta blockers appear to be the most helpful agents for this purpose (ie, Atenolol 50 mg p.o. q.d.).

The drug of choice for attenuation of the ictal sympathetic response is a short-acting injectable beta blocker. Two are available, Labetolol (10-20 mg) and Esmolol (100-200 mg), both given as I.V. bolus 2 minutes prior to the stimulus. These give about 5-10 minutes of protection against tachycardia, hypertension, and ectopy in the patient with cardiac disease. They are not associated with hypotension or CHF, but may occasionally be associated with bradycardia, and atropine should be readily available.

Nifedipine 10 mg sublingually 15 minutes prior to treatment also offers a safe way to attenuate the sympathetic response. It is most useful in augmenting the antihypertensive effect of beta blockers. Its antiarrhythmic effect in the ECT setting is not known.

5. Cardiac monitor is mandatory.

6. Roll patient on side as soon as respirations resume to avoid aspiration.

7. Nausea: Droperidol (Inapsin) 1.25 mg I.V. immediately after seizure.

Headache: Tylenol or aspirin.

8. Prolonged seizures: Seizures of greater than 2 minutes' duration should be abbreviated since they are no more effective and are likely to cause severe confusion. Prolonged seizures may be partial, resulting in severe confusion and agitation without convulsion, particularly in young patients with low seizure threshold.

The drug of choice is Midazolam 2-5 mg I.V. bolus since it is potent and does not sclerose veins. It is also a potent respiratory depressant, so have ambu ready and monitor respirations carefully.

E. Seizure monitoring: Not all seizures are alike (52)

1. EEG

2. Blood pressure cuff on ipsilateral arm

F. Current dose

As low as possible consistent with fully generalized seizures. There is a subgroup of patients who are resistant to unilateral brief pulse stimulation at threshold intensity of stimulus. The problem is most likely due to inadequate seizure generalization and does not appear to occur as often with stimulus intensity well above the seizure threshold.

Solution: switch to sine wave or bilateral stimulus.

G. Electrode placement

1. The relative efficacy of unilateral and bilateral ECT remains an unresolved question, which is highly controversial.

Unilateral and bilateral are probably equally effective if unilateral is properly performed. Bilateral ECT should probably not be used as a routine technique, and should usually be reserved for cases refractory to 8-10 unilateral ECT.

2. Muller vs. d'Elia unilateral placements. D'Elia requires less current, gives less side effects.

H. Waveform

Sine wave and brief pulse are equally effective. Brief pulse induces generalized seizures with much less energy than sine wave, and is less disruptive to cognition. Mean sine wave stimulus = 120 ws. Mean brief pulse dose = 20 ws.

U.S. Manufacturers of ECT devices:

MECTA Corp., 7015 S.W. McEwan Rd, Lake Oswego, OR 97035 503-624-8778

Thymatron, Somatics, Inc., 910 Sherwood Drive, #18, Lake Bluff, IL 60044, 800-642-6761

Hittman Medical Systems, Inc., 9050 Red Branch Rd, Columbia, MD 21045, 800-638-2896

Elcot Inc., 14 East 60 St., NY; NY 10022, 212-688-0900

I. Seizure length

Aim for seizure of 30-40 sec. duration. Seizures of less than 20 sec. duration may be less effective. Over 60 sec. seizure duration is probably redundant.

J. Total seizure time

One unreplicated study purports to show that at least 200 sec. of seizure time is necessary to treat major depression. This is not true, and many patients have a full remission with 100 sec. or less of total seizure time.

If seizures are very brief, IV caffeine may increase seizure length and treatment efficacy.

K. Number of treatments

Average 7-8. Occasional patient requires up to 25. Persistence is indicated if diagnosis is unambiguous.

L. Multiple ECT 4-8 seizures per induction. A controlled comparison with conventional ECT has not been done. In the uncontrolled studies, investigators have found:

--Some patients remit quickly (after 2 sessions) but some remit slowly.

--Post-treatment confusion is increased.

--Memory impairment is in general not increased.

--Increased incidence of individual complications: severe amnesia, status epilepticus, persistent OBS.

Fink (1979): "We concluded that MECT, as now applied, carried more risks and fewer benefits than conventional ECT for our patients."

5. Adverse Effects of ECT

A. Memory impairment

Retrograde: for events nearest time of treatment.

Anterograde: up to 6 months post-treatment, objectively measured.

There are now over 40 studies comparing unilateral and bilateral ECT. They consistently show a dramatic reduction in both verbal and non-verbal cognitive disturbance with unilateral placement.

The findings with regards to relative efficacy are less clear, although the better designed studies tend to show equal efficacy. There may be some patients who are resistant or unresponsive to unilateral ECT, particularly when administered with very low intensity stimulus.

More Toxicity                                                                                                                                                     Less Toxicity

BSW                                                         BBP                                                     USW                                                     UBP

Brief pulse stimulus, with its lower energy, is associated with reduced cognitive deficit, although the difference is not as dramatic as that between bilateral and unilateral electrode placement.

With unilateral ECT, as stimulus intensity is increased above seizure threshold, efficacy approaches that of bilateral ECT. With bilateral ECT, as stimulus intensity is reduced towards seizure threshold, the side-effect profile approaches that of unilateral ECT. Therefore, if the goal is to achieve maximum effectiveness with a minimum of side-effects, one should administer either unilateral ECT well above threshold, or bilateral ECT as close as possible to threshold. It has not been determined which of these is preferable in specific circumstances.

B. Post-treatment confusion

The main determinants of post-ECT confusion are:

--Electrode placement

--Stimulus dose

--Length of seizure

--Adequacy of oxygenation

--Age of patient

Note: All but one of these are controllable by the clinician.

C. Structural damage

6. Mechanism of Action

Generalization of the seizure to the diencephalon is essential.

Postictal prolactin rise correlates with efficacy.

7. Post-ECT Maintenance

Note: Relapse is the most serious problem in the clinical use of ECT. Over 50% relapse rate at 1 year without maintenance antidepressant.

Relapse rate may be reduced with:

Imipramine 

Amitriptyline 

Lithium 

Phenelzine

MAOIs underutilized: effective and well tolerated in elderly. Probably the drug of choice for healthy patients. Tricyclics are poorly tolerated and are less effective.

Fluoxetine and bupropion are promising agents, but have not been evaluated as post-ECT therapies.

Maintenance ECT (one treatment every 1-4 weeks) probably has a place in the management of patients who are very prone to relapse, but there has never been a trial comparing it with aggressive drug therapy. Case reports have been positive.

Partial responders to ECT should be treated aggressively with MAOI. ECT appears to sensitize patients to drug therapy, and full remission often occurs after several weeks at therapeutic dose, even in patients who were drug-resistant before ECT.

8: Areas for Investigation

A. Mechanism of action--hormonal and receptor sensitivity assays

B. Cardiovascular response

C. Role of ECT in Parkinson's disease

D. Markers for hypothalamic seizure activity

Cardiac

EEG

E. Does ECT destabilize or irritate mood disorders?

F. Malpractice experience and clinical outcome studies

G. ECT in