Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: An open-label clinical trial

Probably not a substantial claim: may not pass S3 (load-bearing).

A small number of patients with bipolar disorder have been included in randomized trials comparing magnetic seizure therapy and electroconvulsive therapy.

“A small number of patients with bipolar disorder have also been included in randomized trials that compared MST and ECT.17,23”

• cites [17] 17. Fitzgerald PB, Hoy KE, Elliot D, et al. A pilot study of the compar- ative efficacy of 100 Hz magnetic seizure therapy and electrocon- vulsive therapy in persistent depression. Depress Anxiety 2018; 35: 393-401. sourceSupported
• cites [23] 23. Kayser S, Bewernick BH, Grubert C, et al. Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression. J Psychiatr Res 2011;45:569-76. sourceNot checked — no full text of the source

May combine two claims.

Studies of magnetic seizure therapy in treatment-resistant depression have focused on major depressive disorder, and only case studies have described its use for bipolar disorder.

“To date, studies of MST in treatment-resistant depression have focused on major depressive disorder, 17,18 and only case studies have described the use of MST for bipolar disorder. 21,22”

• cites [17] 17. Fitzgerald PB, Hoy KE, Elliot D, et al. A pilot study of the compar- ative efficacy of 100 Hz magnetic seizure therapy and electrocon- vulsive therapy in persistent depression. Depress Anxiety 2018; 35: 393-401. sourceSupported
• cites [18] 18. Kayser S, Bewernick BH, Matusch A, et al. Magnetic seizure ther- apy in treatment-resistant depression: clinical, neuropsychological and metabolic effects. Psychol Med 2015;45:1073-92. sourceNot checked — no full text of the source
• cites [21] 21. Noda Y, Daskalakis ZJ, Fitzgerald PB, et al. Magnetic seizure therapy- induced mania: a report of 2 cases. J ECT 2015;31:e4-6. sourceNot checked — no full text of the source

May combine two claims.

Compared with electroconvulsive therapy, magnetic seizure therapy is unaffected by scalp or skull impedance, leading to less stimulation of deeper brain structures such as the hippocampus that are associated with memory.

“Relative to ECT, MST is unaffected by impedance from the scalp or skull.As a result, there tends to be less stimulation of deeper brain structures (e.g., hippocampus) that are associated with memory function.16”

• cites [16] 16. Deng Z-D, Lisanby SH, Peterchev AV. Electric field strength and focality in electroconvulsive therapy and magnetic seizure ther- apy: a finite element simulation study. J Neural Eng 2011;8:016007. sourcePartly supported

  The Discussion (§4.1; page unavailable) reports that MST stimulation is more confined to superficial cortex than ECT and that direct stimulation of medial-temporal structures such as the hippocampus is limited. The paper does not establish that MST is unaffected by scalp or skull impedance, or that this is the reason for the difference in deep-brain stimulation; its Methods (§2.1; page unavailable) instead model scalp and skull conductivity for both treatments. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Emerging clinical evidence supports antidepressant effects of magnetic seizure therapy in treatment-resistant unipolar depression, and it may have efficacy comparable to electroconvulsive therapy.

“Emerging clinical evidence supports the antidepressant effects of MST in treatment-resistant unipolar depression, and it may have efficacy comparable to ECT. [17][18][19]”

• cites [17] 17. Fitzgerald PB, Hoy KE, Elliot D, et al. A pilot study of the compar- ative efficacy of 100 Hz magnetic seizure therapy and electrocon- vulsive therapy in persistent depression. Depress Anxiety 2018; 35: 393-401. sourcePartly supported

  The Abstract and Discussion report antidepressant activity with MST and similar outcomes to right-unilateral ECT, while cautioning that the small pilot study could not establish equivalence. The Participants section and Table 1 show that the sample included both unipolar and bipolar depression; the reported comparison was not specific to unipolar patients or to all forms of ECT. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [18] 18. Kayser S, Bewernick BH, Matusch A, et al. Magnetic seizure ther- apy in treatment-resistant depression: clinical, neuropsychological and metabolic effects. Psychol Med 2015;45:1073-92. sourceNot checked — no full text of the source
• cites [19] 19. Daskalakis ZJ, Dimitrova J, McClintock SM, et al. Magnetic seizure therapy (MST) for major depressive disorder. Neuropsychopharma- cology 2020;45:276-82. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Magnetic seizure therapy studies have most commonly used high-frequency 100 Hz stimulation, while earlier studies used medium-frequency ranges between 40 and 60 Hz.

“The MST studies have most commonly used high-frequency 100 Hz stimulation; 17,18,24 however, earlier studies of MST were conducted with medium-frequency ranges between 40 and 60 Hz.25,26”

• cites [17] 17. Fitzgerald PB, Hoy KE, Elliot D, et al. A pilot study of the compar- ative efficacy of 100 Hz magnetic seizure therapy and electrocon- vulsive therapy in persistent depression. Depress Anxiety 2018; 35: 393-401. sourceSupported
• cites [18] 18. Kayser S, Bewernick BH, Matusch A, et al. Magnetic seizure ther- apy in treatment-resistant depression: clinical, neuropsychological and metabolic effects. Psychol Med 2015;45:1073-92. sourceNot checked — no full text of the source
• cites [24] 24. Fitzgerald PB, Hoy KE, Herring SE, et al. Pilot study of the clinical and cognitive effects of high-frequency magnetic seizure therapy in major depressive disorder. Depress Anxiety 2013;30:129-36. sourceSupported

May combine two claims.

Magnetic seizure therapy has been associated with shorter reorientation times and fewer cognitive adverse effects, suggesting it may be cognitively safer and better tolerated than electroconvulsive therapy.

“As well, MST has been associated with shorter reorientation times and fewer cognitive adverse effects, 20 suggesting that MST may be cognitively safer and better tolerated than ECT.”

• cites [20] 20. McClintock SM, Tirmizi O, Chansard M, et al. A systematic review of the neurocognitive effects of magnetic seizure therapy. Int Rev Psychiatry 2011;23:413-23. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Electroconvulsive therapy is an effective treatment for bipolar disorder.

“Electroconvulsive therapy (ECT) is an effective treatment for bipolar disorder.7”

• cites [7] 7. Kellner CH, Ahle GM, Geduldig ET. Electroconvulsive therapy for bipolar disorder: evidence supporting what clinicians have long known. J Clin Psychiatry 2015;76:e1151-2. sourceSupported

Classified as probably not a substantial claim. May combine two claims.

Because bipolar disorder pathophysiology is strongly associated with prefrontal cortex neurocircuitry, it is important to determine whether stimulating over this area has advantages compared with the vertex.

“Because the pathophysiology of bipolar disorder is strongly associated with prefrontal cortex neurocircuitry, 28 it is important to determine if there are advantages to stimulating over this area compared with the vertex.”

• cites [28] 28. Altshuler L, Bookheimer S, Townsend J, et al. Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study. Bipolar Disord 2008;10:708-17. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Preclinical research has suggested that lower-frequency ranges may be more effective in seizure induction, with magnetic seizure therapy at approximately 22 Hz.

“Furthermore, preclinical research has suggested that lower-frequency ranges may be more effective in seizure induction, with MST at approximately 22 Hz.27”

• cites [27] 27. Peterchev AV, Rosa MA, Deng ZD, et al. Electroconvulsive ther- apy stimulus parameters: rethinking dosage. J ECT 2010;26:159-74. sourcePartly supported

  Section III.2 says lower frequencies may be more efficient than higher frequencies for seizure induction, while noting that an optimum has not been determined. The evidence discussed there concerns ECT and related stimulation; our copy does not support the specific attribution to preclinical MST research at approximately 22 Hz. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

A large naturalistic study of 295 bipolar depression patients found a 68.1% response rate in those receiving electroconvulsive therapy with at least three treatments, as measured by the Clinical Global Impression Improvement Subscale.

“A recent large naturalistic study that included 295 patients with bipolar depression found a 68.1% response rate in those receiving ECT (with a minimum trial of ≥ 3 treatments), as measured”

• cites [12] 12. Perugi G, Medda P, Toni C, et al. The role of electroconvulsive therapy (ECT) in bipolar disorder: effectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic fea- tures. Curr Neuropharmacol 2017;15:359-71. sourceSupported

May combine two claims.

Ultra-brief pulse width with right unilateral electrode configuration, compared with brief pulse width, has slower response but better cognitive outcomes.

“However, ultra-brief pulse width stimulation relative to brief pulse width, combined with right unilateral electrode configuration, has a slower speed of response in conjunction with better cognitive outcomes.43”

• cites [43] 43. Loo CK, Sainsbury K, Sheehan P, et al. A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT. Int J Neuro- psychopharmacol 2008;11:883-90. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

ECT speed of response varies with electrode placement and pulse width; right unilateral placement and ultra-brief pulse width require the most treatments.

“Speed of response varies in ECT depending on the electrode placement and pulse width; the greatest number of treatments is required for right unilateral placement and ultra-brief pulse width.42,43”

• cites [42] 42. Kellner CH, Tobias KG, Wiegand J. Electrode placement in electroconvulsive therapy (ECT): a review of the literature. J ECT 2010; 26:175-80. sourceNot checked — no full text of the source
• cites [43] 43. Loo CK, Sainsbury K, Sheehan P, et al. A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT. Int J Neuro- psychopharmacol 2008;11:883-90. sourcePartly supported

  The Discussion reports that right-unilateral ultrabrief-pulse ECT required more sessions than standard right-unilateral ECT and may have a slower response. The study did not compare treatment counts across electrode placements, so it does not establish that right-unilateral ultrabrief ECT requires the greatest number of treatments overall. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Historically, cognitive adverse effects and patients' self-reported cognitive concerns have contributed to ECT stigma.

“Historically, these cognitive adverse effects and patient selfreport of cognitive concerns have contributed to the stigma associated with ECT.51,52”

• cites [51] 51. Rose D, Fleischmann P, Wykes T, et al. Patients' perspectives on electroconvulsive therapy: systematic review. BMJ 2003;326:1363. sourcePartly supported

  The Introduction says patients report severe, long-lasting memory loss after ECT and that these reports influence how they weigh its risks and benefits. The Results and Discussion also document patients’ reported memory loss, but do not establish that cognitive effects or concerns contributed to ECT stigma; that causal part of the claim is unsupported. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [52] 52. McFarquhar TF, Thompson J. Knowledge and attitudes regarding electroconvulsive therapy among medical students and the general public. J ECT 2008;24:244-53. sourceNot checked — no full text of the source

May combine two claims.

The pharmacotherapy group's 19.2% consistency loss was similar to this study's MST AMI-SF decrease of 18.9%, and both were smaller than the 27.1% decrease in Kessler's ECT group.

“The consistency loss in the pharmacotherapy group was similar to the decreased AMI-SF total score in our study with MST (18.9%), which was also less of a decrease than observed in the ECT group of the study by Kessler and colleagues (27.1%).54”

• cites [54] 54. Kessler U, Schoeyen HK, Andreassen OA, et al. The effect of electroconvulsive therapy on neurocognitive function in treatment- resistant bipolar disorder depression. J Clin Psychiatry 2014;75:e1306-13. sourceSupported

May combine two claims.

In unipolar depression, research to date shows MST is cognitively safe and has a better cognitive safety profile than all standard ECT delivery methods.

“In unipolar depression, research to date has demonstrated that MST is cognitively safe, and relative to all standard methods of ECT delivery has a superior cognitive safety profile.17,20”

• cites [17] 17. Fitzgerald PB, Hoy KE, Elliot D, et al. A pilot study of the compar- ative efficacy of 100 Hz magnetic seizure therapy and electrocon- vulsive therapy in persistent depression. Depress Anxiety 2018; 35: 393-401. sourcePartly supported

  The Cognition results and Discussion (page not provided) report no significant cognitive decline after MST and some evidence of a better cognitive profile than the right unilateral ECT method tested. They do not establish superiority over all standard ECT methods: the paper explicitly says that the cognitive comparison with ultrabrief ECT remains unexplored. The Participants section also includes people with bipolar as well as major depressive disorder, rather than a unipolar-only sample. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [20] 20. McClintock SM, Tirmizi O, Chansard M, et al. A systematic review of the neurocognitive effects of magnetic seizure therapy. Int Rev Psychiatry 2011;23:413-23. sourcePartly supported

  The Summary of findings and discussion (page unavailable) concludes that the available studies found MST cognitively safe. Clinical study findings (page unavailable) report better overall neurocognitive performance and faster reorientation after MST than after ECT. The review does not establish a superior cognitive safety profile relative to every standard ECT delivery method; it also calls for further research to confirm and characterize MST’s cognitive effects. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In adequate trial completers, the mean number of adequate medication trials was 2.36 ± 1.50 for the current depressive episode.

“In adequate trial completers, the mean number (± standard deviation [SD]) of adequate medication trials was 2.36 ± 1.50 for the current depressive episode.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Among 26 adequate trial completers, 8 received high-frequency prefrontal stimulation, 9 medium-frequency prefrontal, 3 low-frequency prefrontal, and 6 high-frequency vertex stimulation.

“Of the 26 patients who completed a minimally adequate trial of 8 MST sessions or more, 8 received prefrontal-placement high-frequency stimulation; 9 received prefrontal-placement medium -frequency stimulation; 3 received prefrontalplacement low-frequency stimulation; and 6 received vertexplacement high-frequency stimulation.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Twenty patients completed the per-protocol magnetic seizure therapy trial, with 5 high-frequency prefrontal, 7 medium-frequency prefrontal, 2 low-frequency prefrontal, and 6 high-frequency vertex.

“Twenty patients completed the per-protocol MST trial (a maximum of 24 treatments or remission on the HRSD-24): 5 received prefrontal-placement high-frequency stimulation; 7 received prefrontal-placement mediumfrequency stimulation; 2 received prefrontal-placement lowfrequency stimulation; and 6 received vertex-placement highfrequency stimulation.”

• Also stated in: § Abstract · plain

  “Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol.”

Probably not a substantial claim: may not pass S3 (load-bearing).

For per-protocol completers, the average time to reorientation was 8.76 ± 4.52 minutes.

“For per-protocol completers, the average time to reorientation was 8.76 ± 4.52 minutes.”

May combine two claims.

Among adequate trial completers, the remission rate was 23.1% and the response rate was 38.5%.

“Among the minimally adequate trial completers, remission and response rates were 23.1% and 38.5%, respectively (Fig. 2A).”

• Also stated in: § Abstract · plain

  “Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%.”

May combine two claims.

One participant had a hypomanic episode several days after finishing the per-protocol trial; it resolved quickly after medication was increased.

“Several days after completing the trial per-protocol, 1 participant had a hypomanic episode that resolved quickly with an increase in medication.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

One participant was hospitalized for a fall and dislocated shoulder, then resumed the trial after stabilization.

“Another participant was hospitalized because of a fall and a dislocated shoulder; after stabilization, this participant resumed the trial.”

May combine two claims.

The smallest number of sessions required to achieve response or remission was 9, and the largest was 24.

“The smallest number of sessions required to achieve response or remission was 9, and the largest was 24.”

Probably not a substantial claim: may not pass S3 (load-bearing).

For adequate trial completers, the average time to reorientation was 8.51 ± 4.79 minutes.

“For adequate trial completers, the average time to re orientation was 8.51 ± 4.79 minutes.”

May combine two claims.

Among per-protocol completers, the remission rate was 30% and the response rate was 50%.

“Among the per-protocol completers, the remission and response rates were 30% and 50%, respectively.”

• Also stated in: § Abstract · plain

  “Per-protocol completers had a remission rate of 30% and a response rate of 50%.”

May combine two claims.

Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory.

“Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory.”

May combine two claims.

In per-protocol completers, response and remission rates by treatment subtype were: 100 Hz prefrontal 60% and 60% (n=5); 60 Hz prefrontal 57.1% and 14.3% (n=7); 25 Hz prefrontal 100% and 100% (n=2); and 100 Hz vertex 16.7% and 0% (n=6).

“By treatment subtype, response and remission rates, respectively, were as follows: 100 Hz prefrontal, 60% and 60% (n = 5); 60 Hz prefrontal, 57.1% and 14.3% (n = 7); 25 Hz prefrontal, 100% and 100% (n = 2); and 100 Hz vertex, 16.7% and 0% (n = 6).”

May combine two claims.

The effect size for change from baseline to end of treatment in adequate trial completers was large, with Cohen's d of 1.25 and 95% confidence interval 0.42 to 1.57.

“The corresponding effect size for the level of change from baseline to the end of treatment was large (d = 1.25; 95% CI 0.42-1.57).”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the event, cardiology's impression was that MST was unrelated to the patient's chest pain.

“After the event, the impression from cardiology was that the MST treatment was unrelated to the chest pain the patient experienced.”

May combine two claims.

Mean electroencephalographic seizure duration was 44.12 ± 21.99 seconds in adequate trial completers and 45.20 ± 23.48 seconds in per-protocol completers.

“Mean seizure duration (± SD) in adequate trial completers was 44.12 ± 21.99 seconds, and in per-protocol completers was 45.20 ± 23.48 seconds.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In adequate trial completers, the mean cumulative Antidepressant Treatment History Form score was 12.5 ± 8.41 for the current episode.

“The cumulative ATHF score mean (± SD) was 12.5 ± 8.41 for the current episode.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Before MST, this patient had a pre-existing heart condition but had been medically cleared for the trial.

“Before MST treatment, this patient was identified as having a pre-existing heart condition but was medically cleared for participation in the trial.”

May combine two claims.

In adequate trial completers, response and remission rates by treatment subtype were: 100 Hz prefrontal 37.5% and 37.5% (n=8); 60 Hz prefrontal 57.1% and 14.3% (n=7); 50 Hz prefrontal 0% and 0% (n=2); 25 Hz prefrontal 66.7% and 66.7% (n=3); and 100 Hz vertex 16.7% and 0% (n=6).

“By treatment subtype, response and remission rates, respectively, were as follows: 100 Hz prefrontal, 37.5% and 37.5% (n = 8); 60 Hz prefrontal, 57.1% and 14.3% (n = 7); 50 Hz prefrontal, 0% and 0% (n = 2); 25 Hz prefrontal, 66.7% and 66.7% (n = 3); and 100 Hz vertex, 16.7% and 0% (n = 6).”

May combine two claims.

Minimally adequate trial completers had a large and significant reduction in depressive symptoms.

“Minimally adequate trial completers experienced a large and significant reduction in their depressive symptoms, resulting in a 38.5% response rate and 23.1% remission rate.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant was hospitalized for gallbladder removal.

“One participant was hospitalized for a gallbladder removal.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In per-protocol completers, the number of adequate medication trials was 2.25 ± 1.48 and the cumulative Antidepressant Treatment History Form score was 11.35 ± 7.43.

“In per-protocol completers, the number of adequate medication trials was 2.25 ± 1.48 and the cumulative ATHF score was 11.35 ± 7.43.”

May combine two claims.

Two patients stopped before completing an adequate course because of medical complications, and those two serious adverse events were judged unrelated to the intervention.

“Two other serious adverse events were deemed unrelated to the intervention: 2 patients were discontinued from the study before completing an adequate course because of medical complications.”

Classified as probably not a substantial claim.

Treatment guidelines recommend electroconvulsive therapy for bipolar depression patients who do not respond to first-line pharmacotherapy or who have high suicide risk or severe symptoms.

“Treatment guidelines for bipolar de-pression consistently recommend ECT in those who do not respond to first-line pharmacotherapy and those with a high risk of suicide or with severe symptoms, including catatonia or psychotic features.8”

• cites [8] 8. Parker GB, Graham RK, Tavella G. Is there consensus across inter- national evidence-based guidelines for the management of bipolar disorder? Acta Psychiatr Scand 2017;135:515-26. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Of 44 patients who consented, 7 did not meet inclusion criteria, 1 discontinued because of mania before treatment, and 5 withdrew consent.

“Of the 44 patients who consented to participate in the study, 7 did not meet the inclusion criteria, 1 discontinued because of the emergence of mania before treatment initiation and 5 withdrew consent.”

May combine two claims.

The use of electroconvulsive therapy is limited by cognitive adverse effects and stigma.

“However, use of ECT remains limited because of associated cognitive J Psychiatry Neurosci 2020;45(5) adverse effects (e.g., memory impairment) 13 and the stigma associated with ECT. 14”

• cites [13] 13. Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a sys- tematic review and meta-analysis. Biol Psychiatry 2010;68:568-77. sourceNot checked — no full text of the source
• cites [14] 14. Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med 2007;357:1939-45. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent randomized clinical trial in bipolar depression found electroconvulsive therapy superior in response rates compared with algorithm-based pharmacotherapy.

“A recent randomized clinical trial in patients with bipolar depression, ECT demonstrated superiority in response rates compared with algorithmbased pharmacotherapy.11”

• cites [11] 11. Schoeyen HK, Kessler U, Andreassen OA, et al. Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. Am J Psychiatry 2015;172:41-51. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The analyses were repeated using paired-sample t tests to corroborate the findings.

“We repeated the analyses using paired-sample t tests to corroborate the findings.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

From the adequate trial group, one patient withdrew because of anxiety about anesthesia and three were discontinued because of no perceived benefit.

“1 withdrew because of anxiety about anesthesia (50 Hz prefrontal) and 3 were discontinued because of no perceived benefit (100 Hz prefrontal, 50 Hz prefrontal and 25 Hz prefrontal).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Three other patients discontinued treatment: one could not adequately elicit seizures, and two had medical complications unrelated to treatment.

“Three others discontinued treatment: 1 participant was unable to adequately elicit seizures (100 Hz prefrontal), and 2 participants had medical complications unrelated to the treatment (1 investigated for possible pericarditis with inconclusive ultrasound findings and spontaneous remission of chest symptoms at follow-up; and 1 with myocardial infarction on the day after the third MST session).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Electroconvulsive therapy is considered equally effective in unipolar and bipolar depression, with meta-analyses estimating remission rates above 50%.

“Electroconvulsive therapy is considered to be equally effective in both unipolar and bipolar depression; recent meta-analyses have estimated that remission rates exceeded 50%.9,10”

• cites [9] 9. Dierckx B, Heijnen WT, van den Broek WW, et al. Efficacy of elec- troconvulsive therapy in bipolar versus unipolar major depres- sion: a meta-analysis. Bipolar Disord 2012;14:146-50. sourceNot checked — no full text of the source
• cites [10] 10. Bahji A, Hawken ER, Sepehry AA, et al. ECT beyond unipolar major depression: systematic review and meta-analysis of electroconvulsive therapy in bipolar depression. Acta Psychiatr Scand 2019;139:214-26. sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

The primary outcome was tested at a two-tailed significance level of 0.05, while neurocognitive measures used a stricter 0.005 level to reduce false positives given 24 comparisons.

“Tests were 2-tailed, and significance was set at α = 0.05 for the primary outcome, except for the neurocognitive measures, for which significance was set at α = 0.005 to minimize falsepositive findings, given the 24 comparisons performed.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Two cases of treatment-emergent mania have been reported with magnetic seizure therapy, including in one patient with a diagnosis of bipolar disorder before treatment.

“Two cases of treatment-emergent mania have also been reported, 21 including in 1 patient with a diagnosis of bipolar disorder before MST.”

• cites [21] 21. Noda Y, Daskalakis ZJ, Fitzgerald PB, et al. Magnetic seizure therapy- induced mania: a report of 2 cases. J ECT 2015;31:e4-6. sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Magnetic seizure therapy is a newer noninvasive neuromodulation therapy that induces generalized seizures using high-frequency repetitive transcranial magnetic stimulation.

“Magnetic seizure therapy (MST) is a newer noninvasive neuromodulation therapy that induces generalized seizures using high-frequency repetitive transcranial magnetic stimulation.15”

• cites [15] 15. Lisanby SH. Update on magnetic seizure therapy: a novel form of convulsive therapy. J ECT 2002;18:182-8. sourceNot checked — no full text of the source

May combine two claims.

Thirty-one patients with bipolar disorder were enrolled and received magnetic seizure therapy, and 26 received an adequate trial of at least eight sessions.

“Thirty-one patients with bipolar disorder were enrolled in the study and received MST treatment; 26 received an adequate trial of treatment, defined as a minimum of 8 sessions.”

May combine two claims.

A recent randomized trial of algorithm-based pharmacotherapy versus right unilateral brief pulse ECT in bipolar depression found ECT superior for response (73.9% v. 35.0%) but not remission (34.8% v. 30.0%).

“A recent randomized controlled trial of algorithm-based pharmacotherapy versus right unilateral brief pulse ECT in patients with bipolar depression demonstrated superiority of ECT relative to pharmacotherapy for response rates (73.9% v. 35.0%, respectively) but not for remission rates (34.8% v. 30.0%, respectively).11”

• cites [11] 11. Schoeyen HK, Kessler U, Andreassen OA, et al. Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. Am J Psychiatry 2015;172:41-51. sourceNot checked — no full text of the source

May combine two claims.

In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance.

“In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance.”

• AssumptionRests on an assumption: The observed symptom improvements were not due to factors other than magnetic seizure therapy, such as placebo response or concurrent treatment changes.

May combine two claims.

MST is well tolerated and has minimal effects on most cognitive functions.

“Our study also suggests that MST is well tolerated and has minimal effects on most cognitive functions.”

May combine two claims.

This study's remission rate was somewhat lower than the pooled ECT rate, but that difference should be viewed alongside cognitive adverse effects not covered by the meta-analysis.

“The remission rate in our study was somewhat lower, but it needs to be considered in the context of the cognitive adverse effects that were not addressed in the meta-analysis.”

• AssumptionRests on an assumption: ECT is the standard noninvasive neuromodulation antidepressant for treatment-resistant bipolar depression and has high response and remission rates and quick speed of response.

May combine two claims.

This open-label, nonrandomized trial suggests MST can be effective and safe for treatment-resistant bipolar depression.

“This open-label, nonrandomized clinical trial suggests that MST can be an effective and safe treatment for TRBD.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Medication trial data were not available for one participant.

“Data for medication trials were not available for 1 participant.”

May combine two claims.

The current study's mean treatments to response was comparable to those ECT studies, but remission was somewhat faster in those studies.

“In studies of right unilateral ultra-brief-pulse ECT that included patients with bipolar depression, the mean number of treatments to achieve response was approximately 12, 44,45 which was comparable to the current study but somewhat faster in achieving remission.”

• AssumptionRests on an assumption: ECT is the standard noninvasive neuromodulation antidepressant for treatment-resistant bipolar depression and has high response and remission rates and quick speed of response.

May combine two claims.

ECT is known to cause cognitive adverse effects, shown by objective cognitive measures and by patients' subjective reports.

“Electroconvulsive therapy is known to produce cognitive adverse effects: this has been consistently demonstrated using objective cognitive measures, 13 and in subjective reports from patients who described these cognitive effects as a deterrent to initiating or completing ECT therapy.”

• cites [13] 13. Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a sys- tematic review and meta-analysis. Biol Psychiatry 2010;68:568-77. sourceNot checked — no full text of the source

May combine two claims.

MST is an effective treatment for treatment-resistant bipolar depression, with minimal adverse effects on cognitive function.

“Our results showed that MST is an effective treatment for TRBD, with minimal adverse effects on cognitive function.”

May combine two claims.

Although the AMI-SF decrease may indicate a potential adverse MST effect on autobiographical recall consistency, it is more likely due to passage of time than to MST.

“Although our results may indicate a potential adverse effect of MST on this domain of autobiographical recall consistency, it is more likely that the effect we observed was associated with the passage of time, rather than with MST.”

• AssumptionRests on an assumption: The AMI-SF score can only stay stable or decrease; it can never improve.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The present study's clear limitations were its small sample size, open-label design, and lack of a comparator group.

“Clear limitations of the present study were its small sample size, its open-label design and the lack of a comparator group.”

May combine two claims.

This study adds to growing evidence for MST's neurocognitive safety, because no neurocognitive test except AMI-SF changed significantly after MST.

“This study adds to a growing body of evidence that substantiates the neurocognitive safety of MST, because no neurocognitive test except for the AMI-SF showed a significant change after MST.”