Common positions for lead placement includes Bilateral (Bitemporal), Right Unilateral or Bifrontal Placement. According to the meta-analysis that looked at Bitemporal (Bilateral) ECT vs. RUL ECT by Kolshus et al. 2017, RUL worked just as well for treating depression but has some advantages for time to reorientation and retrograde memory.

Many patients respond well to RUL treatment with an ultra brief pulse width (0.3-0.37ms). The benefit of this approach is clinical effect with less memory side effects. There are some patients that dont respond to RUL ultra brief in which case the patient is switched to bilateral treatments. Bilateral treatment has the benefits of working faster for some patients at the expense of possibly leading to more memory issues. Reasons to start with bilateral ECT for a patient may include catatonia, neuro-vegetation, psychosis or severe suicidality.

What medications are used in treatment?

Most patients receive several medications for each ECT treatment. Most are administered via an IV. The medications typically include an anesthetic, paralytic, analgesic, anti-emetic and an anti-muscarinic. The medications and dosages are individualized to the patients body mass and specific requirements.

Common medications can include:

• Anesthetic:

  • Brevital (1 mg/kg range)

  • Etomidate (0.2 - 0.3 mg/kg range)

• Paralytic:

  • Succinylcholine (1 mg/kg range)

  • Rocuronium (0.5 - 1mg/kg range)

• Analgesic:

  • Tylenol 500 mg -1000 mg PO

  • Toradol 15 - 30 mg

• Anti-emetic:

  • Zofran 4 - 8 mg

  • Phenergan 6.25 -12.5 mg

• Miscellaneous:

  • glycopyrrolate (0.1 - 0.4 mg) for bradycardia and salivation

  • labetalol (5 - 10 mg) for hypertension

  • ketamine (15 - 60 mg) for anesthetic, analgesia and lowering seizure threshold

  • flumazenil (0.25 - 1 mg) for benzodiazepine reversal

  • caffeine (125 - 500 mg) for increased seizure duration

  • versed (1 - 4 mg) for postictal agitation/anxiety or prolonged seizure

  • sugammadex for rocuronium reversal (weight based)

• Monoamine Hypothesis: Similar to antidepressant medications, ECT causes changes in the relative amounts of serotonin, norepinephrine and dopamine that is utilized in the synapses which is thought to lead to adaptive changes in receptors and thus functioning of the circuits associated with those receptors.

• Genetic Changes: There appear to be many genetic changes that occur following ECT in animal models. Dyrviget al. 2014 stated “We find significant increases for c-Fos, Egr1, Neuritin 1 (Nrn 1), Bdnf, Snap29, Synaptotagmin III (Syt 3), Synapsin I (Syn 1), and Psd95.”

• Neurotrophic Factors: Brain Derived Neurotrophic Factor (BDNF) was found to be elevated in patients after ECT according to Brunoni et al. 2014. It is important to remember that there has been no established correlation found between clinical improvement with ECT and BDNF levels.

  • Vascular Endothelial Growth Factor (VEGF) was found to be increased 1 month after patients received ECT. Minelli et al. 2011

• Hypothalmic- Pituitary- Adrenal axis (HPA). Patients with depression tend to show elevated cortisol levels. ECT appears to help restore cortisol to normal levels although it is unclear if could be a direct cause of improvement or a result of some other mechanism. Hasket et al. 2014

• Functional Connectivity: There is some evidence that ECT leads to physiological changes that better enable different networks in the brain to communicate more effectively. Beal et al. 2012 demonstrated the anterior cingulate cortex (aCC) showed increased connectivity to the right dorsal lateral prefrontal cortex (rDLPC) and the Posterior Cingulate Cortex (PCC). This paper is also interesting in that there appears to be a correlation in the increased connectivity and clinical improvement. It’s important to pointout there are other studies that do not show a positive correlation between increased connectivity and clinical improvement. (Abbott et al., 2013; Li et al., 2013, Posner et al., 2013)

• GABA Hypothesis: ECT appears to increase GABA in patients receiving ECT. Esel et al. 2008

According to the article by Anderson 2021 there are 11 RCT’s comparing sham ECT to real ECT and 5 meta analysis. In the article he states “despite their methodological differences, there is a consistent direction in the findings of the RCTs of at least a numerical benefit for ECT over sham ECT at the end of the comparison treatment period, and all meta-analyses report a significant pooled result in favor of ECT irrespective of the combination of studies they include.”

• UK ECT group 2003: Reviewed efficacy and safety of ECT vs. Sham ECT in RCT’s in addition to ECT vs. medications and different types of ECT. That paper concluded, “Real ECT was significantly more effective than simulated ECT (six trials, 256 patients, standardised effect size [SES] -0.91, 95% CI -1.27 to -0.54). Treatment with ECT was significantly more effective than pharmacotherapy (18 trials, 1144 participants, SES -0.80, 95% CI -1.29 to -0.29). Bilateral ECT was more effective than unipolar ECT (22 trials, 1408 participants, SES -0.32, 95% CI -0.46 to -0.19).”

• Berlim et al. 2013: A systematic review and meta-analysis (n = 294) comparing ECT with rTMS. This analysis showed a higher rate of remission for ECT (52%) as compared to rTMS (34%). OR = 0.46 [95% CI: 0.22 to 0.96; z = -2.06; p = 0.04]

• Ren et al. 2014: A meta-analysis ( n = 429) comparing ECT with rTMS. This analysis showed a higher rate of response with ECT (52.9%) as compared to rTMS (33.6%). RR = 1.38, P = 0.006. The study also showed a higher rate of response with ECT (64.4%) as compared to rTMS ( 48.7%). RR = 1.41, p = 0.03.

• Sackeim et al. 1987: Randomized control trial (n = 52) showed that low dose bilateral ECT had a higher response (70%) when compared to low dose right unilateral ECT (28%).

• Sackeim et al. 1993: Randomized control trial (n = 96) comparing threshold vs. 2.5x threshold ECT in either Bilateral or Right Unilateral placement. The response rates were 63% in the 2.5x threshold bilateral group, 65% in the threshold bilateral group, 43% in the 2.5x threshold right unilateral group and 17 % in the threshold right unilateral group.

• Sackeim et al. 2000: Randomized controlled trial (n = 80) comparing response rates of Bilateral placement 150 % above seizure threshold (65% response) and right unilateral placement 500% above seizure threshold (65% response) with right unilateral placement dosed at 50% above seizure threshold (35% response) and 150% above seizure threshold (30%response).

• McCall et al. 2000: Randomized control trial comparing fixed dose of 403 mC (higher dose) right unilateral placement with 2.25 x seizure threshold with right unilateral placement. The response rates were 67% vs. 39% respectively.

• Semkovska et al 2010: “Cognitive abnormalities associated with ECT are mainly limited to the first 3 days posttreatment. Pretreatment functioning levels are subsequently recovered. After 15 days, processing speed, working memory, anterograde memory, and some aspects of executive function improve beyond baseline levels.”

• Rhee et al. 2022: A systematic review and meta-analysis of 6 clinical trials (5 of which were randomized clinical trials), composed of 340 patients, who either received ECT (n = 162) or ketamine (n = 178). The SMD per this paper was -0.69 (95% CI, -0.89 to -0.48; Cochran Q, P = 0.15; I^2 = 39%). This study concluded “ECT may be superior to ketamine for improving symptom severity in the acute phase, but treatment options should be individualized and patient-centered.”

Electricity is simply the flow of charged ions (electrons). The electricity that comes out of the wall in most homes is a sine wave. (see diagram to the right) This is the wave form of electricity that used to be used in ECT. Advances in ECT lead to the development of a square wave stimulation. (See diagram to the right)

The optimal pulse width for depolarization of a neuron is approximately 0.1 to 0.2 ms according to Geddes et al. 1987.

The advantages of square wave stimulation include a lesser amount of charge (electrons) that are used. Studies show that square wave administration is just as effective as sine wave but helps to cut down on the cognitive side effects that are common with ECT treatment. Weiner et al. 1986

Most modern ECT machines generate a biphasic wave form. This in reality doubles the frequency. As such this needs to be considered when calculating the charge being delivered.

An ECT stimulation dose is measured in millicoulumbs.(abbreviated mC) This is a measure of charge. The charge (dose) is a function of the amplitude of the wave form, the frequency, the pulse width and the total duration of the stimulus. Think of the dose (aka charge) as measuring the area of the boxes and then counting the total number of boxes. That is the charge (dose) given during the stimulation. According to Kho et al. 2003, “No evidence was found for a superior speed of action of ECT or for a difference in efficacy between sine wave and brief pulse stimulation.”

Shortening the pulse width can help reduce the cognitive side effects associated with ECT. There were two randomized controlled trials that compared brief pulse to ultrabrief pulse ECT. Pisvejc et al. 1998 and Sackeim et al. 2008. Both studies showed ultrabrief (<0.5 ms) is just as effective as brief (0.5-2.0 ms). Per Sackeim et al. 2008, “The use of an ultrabrief stimulus markedly reduces adverse cognitive effects, and when coupled with markedly suprathreshold right unilateral ECT, also preserves efficacy.”

Coulomb is a unit of electrical charge. 1 Coulomb = 6.241 x 10^18 electrons

or

1 e (electron) = 1.602176634 x 10^-19 Coulombs

Charge = current x time

So charge is the number of electrons passing through a conductor over a certain period of time

Charge = frequency (x2 for biphasic waveform) x duration x pulse width x amplitude

As an example: A stimulus with a current of 800 mA (0.8 amps) x pulse width of 0.37 ms (0.00037 seconds) x a frequency of 120 (120 hz x 2 since the wave form is biphasic) x duration (8 seconds)

0.8 x 0.00037 x (120 x 2) x 8 = .568 C or 568 mC

Energy (Joules) = Charge (coulombs) x Time (seconds) x impedance (Ohms)

or

Energy (Joules) = current(amps)^2 x resistance (Ohms) x time (seconds)

Think of the time variable as the total duration of boxes. You are just adding them up. So many boxes (pulses per second) x pulse width (measured in milliseconds) x total duration of stimulation.

Continuing with the example above: A current with 0.8 amps (x 0.8) x 220 Ohms x (0.00037 x 240 x 8)

or

0.64 Amps x 220 Ohms x 0.7104 seconds = 100.02 Joules

Voltage = Energy/Charge or V = J/C

or

100.02 Joules/0.568 Coulombs = 176 Voltz