Clinical trial NCT01596608: Magnetic Seizure Therapy (MST) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder
Official title: Efficacy and Tolerability of Magnetic Seizure Therapy (MST) as an Alternative to Electroconvulsive Therapy (ECT) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depressive Disorder
Schizophrenia
Schizoaffective Disorder
Obsessive-Compulsive Disorder
Keywords: Magnetic seizure therapy
Treatment resistance
Open-label trial
Treatment resistant depression
Treatment resistant schizophrenia
Treatment resistant obsessive-compulsive disorder
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2012-05-11
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Electroconvulsive therapy (ECT) has unparalleled efficacy in treating severe depression, and is also useful in treatment-refractory cases of schizophrenia and obsessive compulsive disorder (OCD). However, its use is limited by significant adverse effects on memory and cognition. In addition, ECT cannot be precisely targeted, since it relies on unpredictable pathways of electrical conduction through the brain. Magnetic seizure therapy (MST) is currently under investigation as a targetable, cognition-sparing alternative to ECT. MST uses magnetic fields rather than electrical stimuli for seizure induction, dramatically reducing the passage of induced current through undesired brain regions. 10 years of experimental studies have established the safety of MST in animal and human subjects. This pilot study will investigate whether MST has similar efficacy to ECT, with fewer cognitive side effects, in patients with severe depression, schizophrenia, and OCD.

Detailed description: Although ECT is effective against severe depression, psychosis, and OCD, it also produces significant impairments of autobiographical memory and other cognitive functions. These side effects limit the acceptability and tolerability of ECT in many patient populations. They also limit the number of treatments that can be administered in a course of ECT, leading to high relapse rates once ECT is discontinued. In animal studies, MST has been shown to have far fewer adverse cognitive effects than ECT. In small human studies, humans have shown faster subjective and objective recovery of orientation after MST than with ECT. However, the precise degree of cognitive sparing in MST versus ECT has yet to be established. Likewise, the comparative efficacy of MST versus ECT in severe depression, schizophrenia, and OCD remains to be seen. The investigators aim to determine whether MST spares autobiographical memory and other cognitive functions, while retaining comparable efficacy to that of ECT.

Objective 1: To compare the efficacy of MST and ECT in treating patients with severe depression, schizophrenia, and OCD.

Hypothesis 1: MST will have equivalent efficacy to ECT on objective measures of mood, schizophrenia, and OCD symptoms.

Objective 2: To compare the effects of MST and ECT on autobiographical memory and other cognitive functions in patients with severe depression, schizophrenia, schizoaffective disorder and OCD.

Hypothesis 2: MST will have significantly lower adverse effects on objective measures of autobiographical memory and other cognitive functions in patients with severe depression, schizophrenia, and OCD.

Objective 3: To compare the changes in brain function that result from MST and ECT.

Hypothesis 3: Both MST and ECT will produce changes in functional brain activity consistent with antidepressant response, antipsychotic response, and antiobsessive response, along with a sparing of cognitive functions.

The discovery of a viable alternative to ECT, with equivalent efficacy but fewer side effects, would have a transformative effect on the treatment of several forms of severe mental illness. At present, many patients who could benefit from ECT do not pursue this treatment due to concerns about cognitive side effects, as well as the enduring social stigma of ECT itself. In addition, many patients who have benefited from ECT are obliged to discontinue this effective treatment because of mounting cognitive side effects; high rates of relapse then ensue.

If MST could be shown to spare autobiographical memory and other forms of cognition, many more patients would be willing to take advantage of the treatment. They would also be able to continue the treatment, when effective, for longer periods. The potential result would be a dramatic improvement in the rates of remission and relapse for patients with severe depression and other forms of mental illness.

Eligibility criteria: Inclusion Criteria:

* ages 18 to 85
* DSM-IV diagnosis of major depressive episode with or without psychotic features in the context of MDD or bipolar disorder; OCD or Schizophrenia
* 24-item HRSD score of ≥ 21 (for depression subjects)
* 18-item BPRS score of ≥ 37 (for schizophrenia subjects)
* Y-BOCS score of ≥ 16 (for OCD subjects)
* demonstrate capacity to give informed consent
* are a Canadian resident

Exclusion Criteria:

* have an unstable medical and/or neurological condition
* are currently pregnant or lactating
* are not considered sufficiently well to undergo general anesthesia for any reason
* have a cardiac pacemaker, cochlear implant, implanted electronic device or non-electric metallic implant
* are taking a benzodiazepine at a dose greater than lorazepam 2mg or equivalent
* are taking any non-benzodiazepine anticonvulsant
* have active substance misuse or dependence within the past 3 months
* have a current diagnosis of delirium, dementia or another cognitive disorder secondary to a general medical condition
* have a co-morbid borderline personality disorder and/or antisocial personality disorder
* have had a history of any suicide attempts in the past 6 months

Primary outcomes:
measure: Score on rating scale that corresponds to diagnosis: i) Hamilton Rating Scale for Depression, 24-item (HRSD-24); or ii) Yale-Brown Obsessive Compulsive Scale (Y-BOCS); or iii) Brief Psychiatric Rating Scale (BPRS)
timeFrame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at date of symptom remission or date of the 24th treatment, whichever comes first, assessed up to 12 weeks
measure: Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS
timeFrame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 1 month after final treatment
measure: Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS
timeFrame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 2 months after final treatment
measure: Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS
timeFrame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 3 months after final treatment
measure: Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS
timeFrame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 6 months after final treatment
Secondary outcomes:
measure: Cognitive Functioning
timeFrame: Change from baseline in cognitive functioning at date of symptom remission or at date of 24th treatment, whichever comes first, assessed up to 12 weeks
measure: Cognitive Functioning
timeFrame: Change from baseline in cognitive functioning at 6 months after final treatment
measure: Neuroimaging (brain structure and activity)
timeFrame: Changes from baseline in brain structure and activity within 48 hours after final treatment
measure: Neuroimaging (brain structure and activity)
timeFrame: Changes from baseline in brain structure and activity at 6 months after final treatment
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Z. Jeffrey Daskalakis, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang VM, Blumberger DM, Throop A, McClintock SM, Voineskos D, Downar J, Knyahnytska Y, Mulsant BH, Fitzgerald PB, Daskalakis ZJ. Continuation Magnetic Seizure Therapy for Treatment-Resistant Unipolar or Bipolar Depression. J Clin Psychiatry. 2021 Oct 19;82(6):20m13677. doi: 10.4088/JCP.20m13677.
citation: Weissman CR, Blumberger DM, Dimitrova J, Throop A, Voineskos D, Downar J, Mulsant BH, Rajji TK, Fitzgerald PB, Daskalakis ZJ. Magnetic Seizure Therapy for Suicidality in Treatment-Resistant Depression. JAMA Netw Open. 2020 Aug 3;3(8):e207434. doi: 10.1001/jamanetworkopen.2020.7434.
citation: Tang VM, Blumberger DM, Dimitrova J, Throop A, McClintock SM, Voineskos D, Downar J, Knyahnytska Y, Mulsant BH, Fitzgerald PB, Daskalakis ZJ. Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: an open-label clinical trial. J Psychiatry Neurosci. 2020 Sep 1;45(5):313-321. doi: 10.1503/jpn.190098.
citation: Tang VM, Blumberger DM, McClintock SM, Kaster TS, Rajji TK, Downar J, Fitzgerald PB, Daskalakis ZJ. Magnetic Seizure Therapy in Treatment-Resistant Schizophrenia: A Pilot Study. Front Psychiatry. 2018 Jan 16;8:310. doi: 10.3389/fpsyt.2017.00310. eCollection 2017.