For major depressive disorder, is unilateral electroconvulsive therapy preferred over bilateral electroconvulsive therapy as first-line treatment?

Unilateral vs Bilateral ECT for Major Depressive Disorder

Begin with unilateral ECT as first-line treatment for major depressive disorder, then switch to bilateral ECT if response is inadequate after 3-4 treatments. 1

Standard Treatment Algorithm

The recommended approach follows a stepwise escalation:

• Start with right unilateral (RUL) electrode placement applied to the nondominant hemisphere as initial treatment 1
• Evaluate response at treatment 3-4 to determine whether bilateral placement is warranted 1
• Switch to bilateral ECT if unilateral treatment produces inadequate response 1

Exceptions Requiring Bilateral ECT from the Start

Bilateral ECT should be initiated immediately in specific clinical scenarios where speed of response is critical:

• Refusal to eat or drink 1
• Severe suicidality 1
• Florid psychosis 1
• Catatonia 1
• Acute mania (bilateral ECT may be more effective for manic patients) 1

Comparative Efficacy Evidence

The evidence reveals nuanced differences between electrode placements:

• High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy (no difference in depression rating change scores, remission rates, or 12-month relapse rates) 2
• Brief pulse RUL ECT is slightly more efficacious than ultrabrief pulse RUL ECT (standardized mean difference = 0.25, p = .004), requiring fewer treatment sessions (8.7 vs 9.6 sessions, p < .001) 3
• High-dose brief pulse RUL ECT achieves superior remission rates compared to ultrabrief pulse (68.4% vs 49.0%, p = .019) and faster speed of remission (7.1 vs 9.2 sessions, p = .008) 4

Cognitive Side Effect Profile

Unilateral ECT demonstrates clear cognitive advantages:

• Reorientation time after individual sessions is 8.28 minutes faster with unilateral compared to bilateral ECT (95% CI -12.86 to -3.70) 2
• Retrograde autobiographical memory is significantly better preserved with unilateral ECT (Hedges's g = -0.46,95% CI -0.87 to -0.04) 2
• Unilateral electrode placement produces less memory impairment in the immediate post-treatment period 1
• No significant differences exist between unilateral and bilateral groups in cognitive effects 2 months after treatment, though this finding suggests cognitive side effects are reversible 1

However, the most recent evidence using more sensitive assessment tools reveals:

• Significant long-term overall cognitive impairment persists (SMD = -0.94,95% CI [-1.33, -0.54], p < 0.00001) regardless of electrode placement 1, 5
• Long-term learning cognitive abilities remain adversely affected (SMD = -0.37,95% CI [-0.55, -0.18], p < 0.0001) 1, 5

Critical Clinical Considerations

Efficacy takes priority over cognitive side effects because cognitive impairments are reversible and no longer measurable a few months after the last treatment 1

The decision framework should prioritize:

1. Clinical urgency: Life-threatening situations warrant immediate bilateral ECT 1
2. Initial trial: Start with unilateral for less urgent cases 1
3. Response assessment: Evaluate at treatment 3-4 1
4. Escalation: Switch to bilateral if inadequate response 1

Common Pitfalls to Avoid

• Do not continue unilateral ECT beyond 3-4 treatments without response assessment, as this delays potentially more effective bilateral treatment 1
• Do not use low-dose unilateral ECT, as response rates are significantly lower than high-dose unilateral or bilateral treatment 1
• Do not assume bilateral ECT is always necessary for mania—while evidence suggests it may be more effective, this should be evaluated case-by-case 1
• Do not overlook the importance of determining cerebral dominance for language and verbal memory when applying unilateral electrodes, as approximately 15% of left-handed individuals have atypical lateralization 1