Magnetic Seizure Therapy (MST) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder

• 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) [ Time Frame: 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 ] [ Designated as safety issue: No ]

  i) The HRSD-24 is a semi-structured, clinician-administered scale used to assessed the severity of depressive symptoms.

  ii) The Y-BOCS is a clinician-rated scale used to assess the severity of OCD symptoms.

  iii) The BPRS is a clinician-administered scale used to assess the severity of various psychiatric symptoms, such as depression, anxiety, hallucinations, and delusions. In this study, it will be used with participants diagnosed with schizophrenia.

  
  
• Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 1 month after final treatment ] [ Designated as safety issue: No ]
  
• Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 2 months after final treatment ] [ Designated as safety issue: No ]
  
• Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 3 months after final treatment ] [ Designated as safety issue: No ]
  
• Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 6 months after final treatment ] [ Designated as safety issue: No ]
  

• Cognitive Functioning [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  Improvement or sparing of cognitive functioning, as assessed by standard tests of episodic memory and non-memory cognitive functions.
  
  
• Cognitive Functioning [ Time Frame: Change from baseline in cognitive functioning at 6 months after final treatment ] [ Designated as safety issue: Yes ]
  
• Neuroimaging (brain structure and activity) [ Time Frame: Changes from baseline in brain structure and activity within 48 hours after final treatment ] [ Designated as safety issue: No ]
  Improvements in cortical thickness in subgenual cingulate cortex on T1 MRI voxel-based morphometry; improved anatomical connectivity between anterior hippocampus, subgenual cingulate cortex, and retrosplenial cortex on voxel-based comparative DTI tractography; subgenual and orbitofrontal functional connectivity to amygdala and ventral striatum on T2* fMRI BOLD signal covariation.
  
  
• Neuroimaging (brain structure and activity) [ Time Frame: Changes from baseline in brain structure and activity at 6 months after final treatment ] [ Designated as safety issue: No ]
  Improvements in cortical thickness in subgenual cingulate cortex on T1 MRI voxel-based morphometry; improved anatomical connectivity between anterior hippocampus, subgenual cingulate cortex, and retrosplenial cortex on voxel-based comparative DTI tractography; subgenual and orbitofrontal functional connectivity to amygdala and ventral striatum on T2* fMRI BOLD signal covariation.
  
  

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, 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.