Table 1.
Characteristics of the included studies.
| Study | Design, setting and country | Patients and sample size | ECT method | Intervention | Control condition | Outcome measures of interest | Results |
|---|---|---|---|---|---|---|---|
| Randomized controlled trials on adjuvant TCA | |||||||
| Imlah et al. (1965)a | RCT, inpatient clinic, UK | Depressive disorder (clinical observation) Total sample n = 150 ECT + placebo n = 50 ECT + IMI n = 50 ECT + PHE n = 50 |
No information available on electrode placement, waveform and dose strategy; 2 ECT sessions/week until favourable clinical response, maximum of 12 treatments. | ECT + IMI 75 mg | ECT + placebo | Number of ECT sessions until response, based on ‘5-point scale’ | Mean number of ECT sessions until
response: ECT + placebo 7.93 ECT + IMI 7.15 ECT + PHE 6.90 No significant difference between intervention and control group. |
| Kay et al. (1970) | RCT, inpatient clinic, UK | Depressive disorder (clinical observation) Total sample n = 132 ECT + diazepam n = 73 ECT + AMI n = 59 |
No information available on ECT method. | ECT + AMI 50–150 mg | ECT + diazepam 4–12 mg |
HRSD | Mean decrease in HRSD score at
1 month: ECT + diazepam 24.4 ECT + AMI 28.7 No significant difference between intervention and control group. |
| Mayur et al. (2000)a | RCT (discontinuation study), inpatient clinic, India | Major depressive disorder (DSM-IV) Total sample n = 30 ECT + placebo n = 15 ECT + TCA n = 15 |
UL; pulse, square wave; dose titration (stimulus: 2.5× ST); 3 ECT sessions/week for 4 weeks or until remission, whichever was earlier. | ECT + TCA | ECT + placebo | 17-item HRSD, MADRS | Mean HRSD score and mean MADRS score at week 4 not
reported. No significant differences between intervention and control group. |
| Sackeim et al. (2009)b | RCT, inpatient clinic, USA | Major depressive disorder (DSM-IV) Total sample n = 319 ECT + placebo n = 135 ECT + NOR n = 93 ECT + VEN n = 91 |
RUL or BL; pulse, square wave; dose titration (stimulus RUL 6× ST, BL 1.5× ST); 3 ECT sessions/week until remission. | ECT + NOR (mean blood level 82.1 ± 52.2 ng/mL) | ECT + placebo | 24-item HRSD Remission: reduction HRSD score ⩾ 60% and post-ECT HRSD ⩽ 10 |
Remission rate: ECT + placebo 41.4% ECT + NOR 54.8% ECT + VEN 52.8% Difference between intervention and control group shows trend in favour of NOR. Mean post-ECT HRSD score: |
| ECT + placebo 15.9 ± 10.7 ECT + NOR 12.6 ± 9.8 ECT + VEN 13.0 ± 9.7 Significant difference between ECT + NOR and ECT + placebo in favour of NOR; ECT + VEN did not differ from the other conditions. |
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| Seager and Bird (1962)a | RCT, inpatient clinic, UK | Depressive disorder (clinical observation) Total sample n = 43, analysed sample n = 40 (drop-outs excluded for analysis) ECT + placebo n = 21 ECT + IMI n = 19 |
No information available on electrode placement and dose strategy; sine wave; 2 ECT sessions/week until favourable clinical response. | ECT + IMI 150 mg | ECT + placebo | Number of ECT sessions until response, based on clinical observation | Mean number of ECT sessions until
response: ECT + placebo 7.0 ECT + IMI 6.3 No significant difference between intervention and control group. |
| Wilson et al. (1963)c | RCT, inpatient clinic, USA | Depressive disorder (clinical observation) Total sample n = 10 ECT + atropine n = 6 ECT + IMI n = 4 |
No information available on electrode placement, waveform and dose strategy; 2 ECT sessions/week for six treatments. | ECT + IMI 150 mg | ECT + atropine 0.1 mg | HRSD | Mean decrease in HRSD score at week 5: ECT + atropine 22.3 ± 1.6 ECT + IMI 20.7 ± 1.9 Difference between intervention and control group not statistically analysed. |
| Randomized controlled trials on adjuvant SSRI/SNRI | |||||||
| Lauritzen et al. (1996)a,d | RCT, inpatient clinic, Denmark | Major depressive disorder (DSM-III-R) Total sample n = 87, of which n = 35 in this study arm |
First 3 ECT sessions BL, thereafter UL; pulse, square wave; no information available on dose strategy; 3 ECT sessions/week until remission. | ECT + PAR 30 mg | ECT + placebo | HRSD, number of ECT sessions | Mean post-ECT HRSD score: ECT + placebo 9.2 ± 3.4 ECT + PAR 8.9 ± 4.7 Mean number of ECT sessions until response: ECT + placebo 11.1 ± 3.8 |
| ECT + placebo n = 17 ECT + PAR n = 18 |
ECT + PAR 12.1 ± 6.3 No significant difference between intervention and control group in mean post-ECT HRSD score and number of ECT sessions until response. |
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| Sackeim et al. (2009)b | RCT, inpatient clinic, USA | Major depressive disorder (DSM-IV) Total sample n = 319 ECT + placebo n = 135 ECT + NOR n = 93 ECT + VEN n = 91 |
RUL or BL; pulse, square wave; dose titration (stimulus RUL 6× ST, BL 1.5× ST); 3 ECT sessions/week until remission. | ECT + VEN (mean dose 187 mg/day) | ECT + placebo | 24-item HRSDR emission: reduction HRSD score ⩾ 60% and post-ECT HRSD ⩽ 10 | Remission rate: ECT + placebo 41.4% ECT + NOR 54.8% ECT + VEN 52.8% Difference between intervention and control group shows trend in favour of NOR. Mean post-ECT HRSD score: ECT + placebo 15.9 ± 10.7 ECT + NOR 12.6 ± 9.8 ECT + VEN 13.0 ± 9.7 Significant difference between ECT + NOR and ECT + placebo in favour of NOR; ECT + VEN did not differ from the other conditions. |
| Randomized controlled trials on adjuvant MAOI | |||||||
| Imlah et al. (1965)a | RCT, inpatient clinic, UK | Depressive disorder (clinical observation) Total sample n = 150 ECT + placebo n = 50 ECT + IMI n = 50 ECT + PHE n = 50 |
No information available on electrode placement, waveform and dose strategy; 2 ECT sessions/week until favourable clinical response, maximum of 12 treatments. | ECT + PHE 45 mg | ECT + placebo | Number of ECT sessions until response, based on ‘5-point scale’ | Mean number of ECT sessions until
response: ECT + placebo 7.93 ECT + IMI 7.15 ECT + PHE 6.90 No significant difference between intervention and control group. |
| Monaco and Delaplaine (1964) b | RCT, inpatient clinic, USA | Depressive disorder (clinical observation) Total sample n = 26 ECT + placebo n = 12 ECT + TRA n = 14 |
No information available on ECT method. | ECT + TRA 20 mg | ECT + placebo | Clinical observation | Improvement rate at week 4: ECT + placebo 91.7% ECT + TRA 78.6% Difference between intervention and control group not statistically analysed. |
| Muller (1961) | RCT, outpatient clinic, UK | Depressive disorder (clinical observation) Total sample n = 100 ECT + placebo n = 45 ECT + PHE n = 55 |
No information available on electrode placement, waveform and dose strategy; 2 ECT sessions/week until clinical response. | ECT + PHE 45 mg | ECT + placebo | ‘25-point scale’ | Mean post-ECT score on ‘25-point
scale’: ECT + placebo 6.62 ± 4.04 ECT + PHE 4.82 ± 2.75 Mean decrease on ‘25 point scale’ at end of ECT: ECT + placebo 4.31 ± 5.28 ECT + PHE 7.24 ± 4.37 Significant differences between intervention and control group in mean post-ECT score and mean decrease on ‘25-point scale’. |
| Retrospective cohort studies | |||||||
| Baghai et al. (2006) | Cohort study, inpatient clinic, Germany | Major depression (ICD-10) Total sample n = 358 ECT alone n = 170 ECT + TCA n = 78 ECT + TTCA n = 40 ECT + SSRI n = 30 ECT + other AD n = 40 |
UL or BL; pulse, square wave; dose titration in < 5% of
patients; dose strategy in remaining patients: based on age
in UL, based on half-age in BL; 2.8 ECT sessions/week (mean). |
ECT + AD | ECT alone | CGI | Scores on CGI not reported. Significantly higher severity of illness and less improvement in control group and ECT + SNRI group compared to ECT + TCA, ECT + TTCA and ECT + SSRI groups. |
| Kho et al. (2005) | Cohort study, setting unclear, The Netherlands | Major depressive disorder (DSM-IV) Total sample n = 73 ECT alone n = 26 ECT + TCA n = 19 ECT + SSRI n = 12 ECT + combination treatment and or lithium and or antipsychotic medication n = 49 |
UL, UL > BL or BL; pulse, square wave; dose strategy based on age, adjusted upwards if patients used benzodiazepines and or anticonvulsants; 2 ECT sessions/week until remission. | ECT + psychotropic medication (among which AD) | ECT alone | 17-item HRSD Remission: reduction HRSD score ⩾ 60% and post-ECT HRSD < 8 |
Remission rate: ECT alone 61.5% ECT + psychotropic 68.1% No significant difference between intervention and control group. |
| Nelson and Benjamin (1989) | Cohort study, inpatient clinic, USA | Depressive disorder (clinical observation) Total sample n = 84 ECT alone n = 44 ECT + partial TCA n = 23 ECT + full TCA n = 17 |
UL; pulse, square wave; dose strategy: ‘Initial middle setting’ so that seizures of > 30s were obtained; no information available on frequency of ECT; ECT sessions administered until favourable clinical response. |
ECT + partial TCA (IMI blood level 75–149 ng/mL or daily
dose 50–99 mg) ECT + full TCA (IMI blood level 150–300 ng/mL or daily dose > 100 mg) |
ECT alone | Number of ECT sessions, ‘clinical observation scale’ (no (0), slight (1), moderate (2) and marked (3) improvement) | Mean post-ECT score on ‘clinical observation
scale’ ECT alone 2.0 ECT + partial TCA 2.4 ECT + full TCA 2.6 Significant difference between ECT + full TCA and ECT alone; no significant difference between ECT + partial TCA and ECT alone. Mean number of ECT sessions until response: ECT alone 9.8 ECT + partial TCA 8.0 ECT + full TCA 8.2 Significant difference between control group and both intervention groups; no significant difference between ECT + partial TCA and ECT + full ECT. |
RCT: randomized controlled trial; UK: United Kingdom; USA: United States of America; TCA: tricyclic antidepressant; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin noradrenaline reuptake inhibitor; MAOI: monoamine oxidase inhibitor; TTCA: tetracyclic antidepressant; AD: antidepressant; IMI: imipramine; AMI: amitriptyline; NOR: nortriptyline; PAR: paroxetine; VEN: venlafaxine; PHE: phenelzine; TRA: tranylcypromine; DSM: Diagnostic and Statistical Manual of Mental Disorders; ECT: electroconvulsive therapy; RUL: right unilateral ECT; UL: unilateral ECT; BL: bilateral ECT; ST: seizure threshold; HRSD: Hamilton Rating Scale for Depression; MADRS: Montgomery Asberg Depression Rating Scale; CGI: Clinical Global Impression; ICD-10: International Classification of Diseases, tenth edition.
a
These studies consisted of two phases: (1) acute treatment and (2) follow-up. We only included the first phase in our systematic review and meta-analysis.
b
These studies had a crossover design. We only included the part prior to crossover in our systematic review and meta-analysis.
c
This study consisted of two phases: (1) ECT + IMI versus ECT + atropine and sham ECT + IMI versus sham ECT + atropine and (2) ECT + atropine versus IMI alone. We only included the ECT + IMI versus ECT + atropine arm of the first phase in our systematic review and meta-analysis.
d
This study consisted of two study arms: (1) ECT + PAR versus ECT + placebo and (2) ECT + IMI versus ECT + PAR. We only included the first study arm in our systematic review and meta-analysis.