Clinical TrialBipolar DisorderKetamineCompleted

Neural Correlates of Ketamine’s Anti-suicidal Effects in Bipolar Depression (DEEPP)

This open-label pilot study (n=30) aims to examine the effect of intravenous (IV) ketamine treatment on acute suicidality (SI) in patients with bipolar depression (BD).

Target Enrollment
16 participants
Study Type
Phase NA interventional
Design
Non-randomized

Detailed Description

This open-label pilot examines IV ketamine given as 40-minute sub-anesthetic infusions twice weekly for four weeks in people with bipolar depression and current suicidal ideation to evaluate acute anti‑suicidal effects.

Neurophysiological mechanisms are assessed using TMS‑EMG and TMS‑EEG to index cortical excitation and inhibition as proxies of NMDA‑receptor mediated activity and to explore predictors of clinical response.

Safety and tolerability are monitored with vital signs, liver function tests, adverse event reporting and clinical assessments; dosing is weight‑based (0.5 mg/kg starting dose, up to 0.8 mg/kg) with close medical supervision.

Study Protocol

Preparation

sessions

Dosing

8 sessions
40 min each

Integration

sessions

Study Arms & Interventions

IV ketamine

experimental

Open-label series of IV ketamine infusions (twice weekly for 4 weeks) with neurophysiological assessment.

Interventions

  • Ketamine0.5 - 0.8 mg/kg
    via IV• twice per week• 8 doses total

    Initial dose 0.5 mg/kg; may be increased up to 0.8 mg/kg per clinician decision; 40-min infusion; 2-h monitoring per session.

Participants

Ages
24 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Individual meeting DSM-IV diagnostic criteria for Bipolar Disorder, current depressive episode as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
  • 2. Individuals capable to provide consent and able to communicate, read and write in English
  • 3. Individuals currently depressed defined as scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
  • 4. Individuals currently experiencing suicidal ideation as defined by a score of 9 or higher on the scale for suicide ideation (SSI)

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Individuals with history of a DSM-IV substance use disorder (i.e. dependence or abuse) within the past month; and lifetime history of ketamine substance use disorder as confirmed by the MINI
  • 2. Concomitant major unstable medical illness such as poorly controlled high blood pressure or patients diagnosed with enlarged prostate or reporting any other urinary related issues
  • 3. Stage 2 hypertension defined as a systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher on three consecutive readings taken 5 minutes apart
  • 4. Results of liver function tests (ALT, AST) are three times or greater than the upper limit of normal readings
  • 5. Pregnancy or the intention to become pregnant and breastfeeding during the study as confirmed by self-report. Female participants of reproductive potential must be willing to use a medically acceptable method of birth control which include highly effective (e.g. approved hormonal contraceptives, IUD, tubal ligation) or double barrier (e.g. male condom with diaphragm, male condom with cervical cap) methods of contraception or abstinence if that is the usual and preferred lifestyle of the participant
  • 6. Presence of cardiac decompensation/heart failure
  • 7. DSM-IV diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
  • 8. Current episode meeting criteria for mania/hypomania or mixed episode as per DSM-IV criteria on the MINI or as determined by the study team
  • 9. Diagnosis of severe personality disorder as assessed during the initial consultation with a physician at the Temerty Centre prior to study entry
  • 10. Any significant neurological disorder (e.g., a space occupying brain lesion, a history of stroke, a cerebral aneurysm, a seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
  • 11. Individuals presenting with a medical condition, a medication, or a laboratory abnormality that could cause a major depressive episode or significant cognitive impairment in the opinion of the investigator
  • 12. Individuals requiring a benzodiazepine with a dose equivalent to lorazepam 2 mg/day or higher; being on any anticonvulsant(e.g. Lamotrigine) and/or opioid medication due to the potential of these medications to limit the efficacy of ketamine
  • 13. Individuals unable to communicate in spoken and written English fluently enough to complete the required study assessments due to a language barrier or a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete clinical assessments)
  • 14. Individuals with cognitive or physical impairment which may potentially interfere with IN ketamine administration and subject's ability to stay in the same place for a 2-hr monitoring supervision as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
  • 15. Any intracranial implant (e.g., aneurysm clips, shunts, cochlear implants) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed given that we will be using TMS-EMG/EEG
  • 16. Those unable to secure escort to accompany them back home after ketamine sessions will also be excluded from this study
  • 17. Any known allergy to the study medication or any component/ingredient of the ketamine preparation

Study Details

  • Status
    Completed
  • Phase
    Phase NA
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment16 participants
  • Timeline
    Start: 2022-05-04
    End: 2024-08-19
  • Compound
    Ketamine
  • Topic
    Bipolar Disorder

Locations

Centre for Addiction and Mental Health — Toronto, Ontario, Canada

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