Treatment Study of Bipolar Depression

Intravenous Ketamine in Treatment-Resistant Bipolar Depression

The purpose of this study is to determine whether a single intravenous administration of an N-methyl-D-aspartate antagonist is safe and effective for the acute treatment of bipolar depression.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: ketamine; Drug: midazolam

Detailed Description

Bipolar disorder (BPD) is a common, recurrent, and disabling medical condition. Although mania is the defining feature of BPD, depression represents the majority of illness burden in patients with this devastating condition. Despite the high degree of morbidity and mortality associated with bipolar depression, currently available treatments are few and often inadequate. Recently, a single intravenous (IV) dose of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in severe unipolar depression. Therefore, the objective of the current study is to investigate the safety and efficacy of a single IV dose of ketamine in treatment-resistant bipolar depression (TRBD).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients, 21-70 years;
2. Primary diagnosis of bipolar I or II disorder as assessed by the SCID-P and confirmed by a study psychiatrist;
3. Current depressive episode ≥ 8 weeks duration;
4. History of a failure to respond to at least three (3) adequate pharmacotherapy trials in the current depressive episode (see above for definition for adequate trials);
5. Subjects must be on a stable dose of divalproex ER with serum levels greater than 55 mcg/ml prior to enrollment;
6. Subjects must be free of psychotropic medication for at least 2 weeks (4 weeks for fluoxetine) prior to enrollment (with the exception of divalproex ER as above);
7. Subjects must have scored ≥ 32 on the IDS-C30 at both Screening and Infusion Day #1 and #2;

Exclusion Criteria:

1. Women who plan to become pregnant, are pregnant or are breast-feeding;
2. Any unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease;
3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
4. Lifetime history of schizophrenia, schizoaffective disorder, OCD, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
5. Current presence of psychotic, mixed or manic symptoms;
6. Lifetime history of antidepressant-induced switch to a manic episode;
7. History of rapid cycling bipolar subtype;
8. Drug or alcohol abuse within the preceding 3 months or dependence within the preceding 5 years;
9. Lifetime exposure to ketamine or phencyclidine;
10. Patients judged by study investigator to be at high risk for suicide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine/Midazolam; Patients receive both treatment conditions (ketamine and midazolam) in a single arm, crossover design. Patients are randomized to ketamine-midazolam. Each treatment occurs as a single intravenous infusion on one treatment day. The two treatment conditions occur 2 weeks apart.	Drug: ketamine; a single IV infusion of ketamine, IV 0.5 mg/kg; Drug: midazolam; a single IV infusion of midazolam, 0.045 mg/kg
Experimental: Midazolam/Ketamine; Patients receive both treatment conditions (ketamine and midazolam) in a single arm, crossover design. Patients are randomized to midazolam-ketamine. Each treatment occurs as a single intravenous infusion on one treatment day. The two treatment conditions occur 2 weeks apart.	Drug: ketamine; a single IV infusion of ketamine, IV 0.5 mg/kg; Drug: midazolam; a single IV infusion of midazolam, 0.045 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)	24 hrs post-infusion compared to baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)	24 hrs post-infusion compared to baseline
Young Mania Rating Scale (YMRS)	24 hrs post-infusion compared to baseline
Brief Psychiatric Rating Scale (BPRS)	4 hrs post-infusion compared to baseline
Clinician-Administered Dissociative States Scale (CADSS)	4 hrs post-infusion compared to baseline
Systematic Assessment for Treatment Emergent Effects (SAFTEE)	4 hrs post-infusion compared to baseline

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 27, 2009
• First Submitted That Met QC Criteria: July 27, 2009
• First Posted (Estimate): July 28, 2009

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Depression; Bipolar Disorder; ketamine; antidepressant; Treatment-Resistant; glutamate
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Bipolar and Related Disorders; Depression; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: GCO 08-1422

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No