Clinical trial NCT00947791: Treatment Study of Bipolar Depression
Official title: Intravenous Ketamine in Treatment-Resistant Bipolar Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Depression
Treatment-Resistant
ketamine
antidepressant
glutamate
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2009-07-28
Enrollment: 1
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 24 hrs post-infusion compared to baseline
Secondary outcomes:
measure: Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)
timeFrame: 24 hrs post-infusion compared to baseline
measure: Young Mania Rating Scale (YMRS)
timeFrame: 24 hrs post-infusion compared to baseline
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: 4 hrs post-infusion compared to baseline
measure: Clinician-Administered Dissociative States Scale (CADSS)
timeFrame: 4 hrs post-infusion compared to baseline
measure: Systematic Assessment for Treatment Emergent Effects (SAFTEE)
timeFrame: 4 hrs post-infusion compared to baseline
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James W Murrough, MD
role: PRINCIPAL_INVESTIGATOR
References: