Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy
Condition: Depressive Disorder
MeSH terms: Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      Ketamine has been used successfully as the sole medication for anesthesia in the setting of
      electroconvulsive therapy (ECT), and has more recently been studied as an adjunct agent in
      combination with propofol (the most commonly used anesthetic agent) to induce anesthesia for
      ECT. New literature postulates an anti-depressant effect of ketamine, which in ECT
      specifically may be helpful with regards to the overall goals of therapy (i.e. ECT indicated
      for severe or treatment-resistant depression).

      Current research focusing on ketamine with respect to its anti-depressant effect suggests it
      may even represent an alternative to ECT. This study will seek to determine whether ketamine
      when used in low-doses as an adjunct to propofol-based anesthesia for ECT has anti-depressant
      effects and whether it influences the characteristics of recovery from anesthesia in the ECT
      setting (i.e. vital sign parameters such as blood pressure and heart rate, quality of
      recovery, etc.).
    

Detailed description: 
      This is a proof-of-concept study to elucidate whether the use of low-dose ketamine as an
      adjunct to propofol-based anesthesia for electroconvulsive therapy has beneficial
      anti-depressant effects in a population of adults with major depressive disorder presenting
      for ECT.

      Since thiopental is no longer widely available in North America as an induction agent for
      anesthesia, other agents have supplanted it for various uses, including for induction of
      anesthesia for electroconvulsive therapy (ECT). Induction is most commonly achieved using
      propofol in doses of 0.75 - 1 mg/kg IV bolus.

      Propofol as an induction agent for ECT may not be the ideal agent in this setting as its
      anticonvulsant effects may result in less-than-ideal seizure quality and duration. Ketamine
      has been studied in the ECT setting but at full induction doses has well-known
      psychotomimetic and dissociative effects. However, the anti-depressant effects of ketamine,
      even at low-doses, may have a beneficial effect on depressive symptoms after ECT as compared
      with propofol alone.

      Ketamine also has been used successfully as the sole induction agent for anesthesia in this
      setting, and has more recently been studied as an adjunct or co-induction agent in
      combination with propofol. Drawbacks of using ketamine as the sole induction agent are
      related to its hemodynamic and psychotomimetic effects (e.g. post-treatment hypertension and
      hallucinogenic activity).

      New literature postulates a putative anti-depressant effect of ketamine via the
      N-Methyl-D-aspartate (NMDA) receptor, which in the ECT setting specifically may be helpful
      with regards to the overall goals of therapy (i.e. ECT indicated for severe or
      treatment-resistant depression). Current research focusing on the efficacy of ketamine with
      respect to anti-depressant effects suggests that ketamine may even represent an alternative
      to ECT.

      As per the investigators' standard practice for ECT, treatment for each patient would be 3
      times per week up to a total of 12 treatments (i.e. 4 weeks of treatment). The total study
      duration for each patient will be not more than 6 weeks. As discussed below, patients will be
      withdrawn from the study at anytime upon their own request or when the treating psychiatrist
      feels the clinical improvement is strong enough to justify doing so.

      An interim analysis will be completed after the first 14 patients have completed treatment.
      If after these first 14 patients the investigators find a lower than expected difference in
      efficacy in favor of the ketamine group, able to achieve alpha error >0.2 and power <80%, all
      subsequently recruited patients will be randomized to receive either propofol at usual
      induction doses for ECT (0.75 - 1 mg/kg IV bolus) with placebo (normal saline), or with a
      slightly higher dose of ketamine of 0.5 mg/kg. Should this turn out to be the case, thirty
      new patients will be recruited from that point.
    

Intervention name(s): Ketamine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Low dose ketamine 0.2 mg/kg (or 0.5 mg/kg depending on results of interim analysis) administered with usual induction drugs for ECT; Normal saline administered with usual induction drugs for ECT
Other intervention name(s): Ketalar; Normal saline; 0.9% NS
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Moderate to severe depression; Monopolar; Bipolar; Ketamine; ECT; Electroconvulsive therapy; NMDA