Cognitive Training as an Adjunct to Ketamine in Real-world Clinics

Inclusion criteria

• be between the ages of 18 and 80 years
• score ≥20 on the Montgomery-Asberg Depression Rating Scale (MADRS)
• per SCID-5-RV interview, meet DSM-5 diagnostic criteria for at least one of the following: Major Depressive Disorder, Bipolar Disorder (I or II), Persistent Depressive Disorder, or Other Specified Depressive or Bipolar Disorder
• exhibit treatment resistance, defined as: (a) failure to respond to ≥1 adequate trials of an evidence-based treatment for mood disorder \[per the Antidepressant Treatment History Form-Short Form Modified Score Sheet (ATHF-SF-Modified)\] and/or (b) failure to respond to ≥1 adequate mood stabilizer or other evidence-based treatment trials (for bipolar depression patients) and/or (c) a history of intolerance during attempted trials of evidence-based treatments for mood disorders and/or (d) failure to respond to ≥1 prior treatment trials (e.g., medication, psychotherapy) for Post Traumatic Stress Disorder (PTSD)
• be eligible and clinically enrolled for an upcoming ketamine or esketamine induction series at one of our study clinics according to that clinic's standard intake procedures
• agree to maintain a stable schedule of concomitant psychiatric medications throughout the ketamine induction phase (minor adjustments to PRN meds and timing of meds are allowable), and for 4 weeks post-induction phase
• possess a level of judgment and understanding sufficient to agree to all procedures required by the protocol and must sign an informed consent document
• be willing and able to provide names and contact information for at least 1 additional emergency contact in the patient's proximal geographic area (in addition to the ketamine treatment team at the enrolling site)

Exclusion criteria

• Presence of current/acute psychosis, mania, or dementia, or a diagnosis of developmental disorder with significant language and/or intellectual impairment (e.g., autism spectrum disorder)
• Current/acute suicide risk with intent to act, defined as CSSRS past-week ideation score ≥ 4 among outpatients; patients engaged in residential or inpatient care at the time of enrollment need not meet this CSSRS score criterion, as their current/acute suicide risk is extremely low by virtue of the residential/inpatient, round-the-clock care they are already receiving at time of enrollment
• Concern for dementia or significant cognitive decline, per interviewer observations and impressions during screening assessments
• Current pregnancy
• English reading level \<5th grade as per patient self-report Rationale: to ensure adequate reading comprehension for verbal ASAT/sham stimuli which are presented in English