Treatment Study of Bipolar Depression

Intravenous Ketamine in Treatment-Resistant Bipolar Depression

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00947791

Enrollment

Registered

2009-07-28

Start date

2009-07-31

Completion date

2009-10-31

Last updated

2017-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder, Depression, Treatment-Resistant, ketamine, antidepressant, glutamate

Brief summary

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.

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).

Interventions

DRUGketamine

a single IV infusion of ketamine, IV 0.5 mg/kg

DRUGmidazolam

a single IV infusion of midazolam, 0.045 mg/kg

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Patient, doctor and rater are masked (triple masked). Only the research pharmacist is unblinded.

Eligibility

Sex/Gender

ALL

Age

21 Years to 70 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Ketamine/Midazolam Participants in this group/condition receive a single IV infusion of ketamine, IV 0.5 mg/kg then 2 weeks later receive Midazolam IV 0.45 mg/kg	0
Midazolam/Ketamine Participants in this group/condition receive a single IV infusion of midazolam, 0.45 mg/kg and then 2 weeks later received single IV infusion of Ketamine 0.50 mg/kg	0
Total	0

Baseline characteristics

Characteristic	Total
Sex: Female, Male Female	0
Sex: Female, Male Male	0

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0