Clinical trial NCT00183443: Treatment of Mania Symptoms With Drug Therapy
Official title: Divalproex Extended Release and Placebo, Lithium, or Quetiapine for Mania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Schizophrenia
Keywords: Mania
Manic-depressive
Psychotic disorder
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-09-16
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine the effectiveness of three different drug therapies in treating the symptoms of mania.

Detailed description: Mania is a serious condition characterized by extreme excitement, mental and physical hyperactivity, insomnia, and disconnected thoughts. Symptoms of mania are common in patients with schizophrenia or bipolar disorder. When associated with these conditions, mania reaches psychotic proportions and often includes hallucinations, paranoia, and feelings of omnipotence. Such symptoms may put individuals with mania and those around them at risk for physical harm. Drug therapies that can safely and effectively treat symptoms of mania are needed. This study will compare three drug combinations in their ability to treat symptoms of mania in people with schizophrenia or bipolar I disorder.

This study will comprise a 12-week acute phase and a 14-week continuation phase. While the acute phase is the primary component of this study, the continuation phase will provide extended data on the characteristics and course of responders to the initial treatment combinations. Results from the continuation phase will be reported elsewhere. In the acute phase, participants will be randomly assigned to receive one of three treatments: divalproex-extended release (DV-ER) and lithium, DV-ER and quetiapine, or DV-ER and placebo. Participants will receive their intervention for 12 weeks. Participants will have weekly study visits for the first 4 weeks of the acute phase; biweekly study visits will occur for the following 8 weeks. After the acute phase, participants who have not responded to their drug regimen will complete their participation in the study.

Participants whose symptoms of mania have decreased will be offered enrollment in the 14-week continuation phase, during which time participants will continue the drug regimen they began in the acute phase. Participants will have biweekly study visits in the continuation phase. During each study visit in both phases, participants will be interviewed about their mania symptoms. Mania, depression, quality of life, and overall functioning scales will assess participants at study entry, at the end of the acute phase, and at the end of the continuation phase. Participants over 50 years of age will have an electrocardiogram (EKG) at study entry to determine cardiac function.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of bipolar I disorder or schizophrenia
* Experiencing symptoms of mania at study entry
* Able to speak and understand English
* Willing and able to comply with all study requirements

Exclusion Criteria:

* History of partial response or nonresponse to any of the drugs or drug combinations given in this study
* History of intolerance to DVP, DVP-ER, lithium, or quetiapine
* Disorders that would contraindicate the use of DV, DV-ER, lithium, or quetiapine
* Use of antidepressants within 1 month prior to study entry
* Use of fluoxetine within 3 months prior to study entry
* Impaired cardiac function, as evidenced by abnormal EKG in participants 50 or over
* Unstable medical illness within 2 months prior to study entry
* At risk for suicide
* Substance abuse or dependence within 1 month prior to study entry
* Pregnancy, breastfeeding, or plans to become pregnant during the study

Primary outcomes:
measure: Symptoms of Mania, as Measured by Young Mania Rating Scale
timeFrame: Week 12
Secondary outcomes:
measure: Hamilton Rating Scale for Depression (HAM-D,17)
timeFrame: Week 12
measure: Clinical Global Impression Scale for Bipolar Disorder (CGI-BD)
timeFrame: Week 12
measure: Global Assessment of Functioning
timeFrame: Week 12
measure: Social and Occupational Functioning Assessment Scale (SOFAS)
timeFrame: Week 12
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
Study officials:
affiliation: Stanford School of Medicine and VA Palo Alto Health Care System
name: Trisha Suppes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cosgrove VE, Allende S, Gwizdowski I, Grace Fischer E, Ostacher M, Suppes T. A pilot trial of quetiapine, lithium, or placebo added to divalproex sodium for hypomanic or manic episodes in ambulatory adults with bipolar I disorder. Int J Bipolar Disord. 2022 Mar 2;10(1):7. doi: 10.1186/s40345-022-00252-w.