Study of the Efficacy of Adjunctive Lithium Treatment for the Treatment of Psychotic Mania

Study Overview
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Brief Summary
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The proposed pilot study is a placebo-controlled, parallel group, randomized clinical trial comparing two treatment strategies in adolescents with mania and prominent psychotic features. One group will receive a second generation antipsychotic (SGA) and placebo and the other will receive a SGA and lithium. The primary double-blind phase of the study will last 8 weeks, followed by a 24-week extension-phase.

Official Title
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A Randomized, Double-blind, Placebo Controlled Study of the Efficacy of Adjunctive Lithium for the Treatment of Psychotic Mania Followed by an Open Label Long-term Safety Period.

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: Lithium treatment in combination with a SGA (Second Generation Antipsychotic)
* Drug: Placebo/Adjunctive SGA treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 12-18 years old, inpatients or outpatients meet DSM-IV criteria for Bipolar I disorder - manic or mixed episode psychotic symptoms present Exclusion criteria: current serious homicidal/suicidal ideation prior non-response or intolerance to an adequate trial of lithium prior non-response or intolerance to adequate trials of both aripiprazole and risperidone any unstable medical condition or medical contraindication to treatment with lithium, aripiprazole or risperidone inability or unwillingness to discontinue concomitant medication that interferes with the pharmacokinetics of either lithium, aripiprazole, or risperidone seizure disorder pregnant or, if sexually active, not using birth control, such as oral contraceptives, two barrier methods, long-acting depot preparations or an intra-uterine device Full Scale IQ less than 70 meets criteria for a DSM-IV diagnosis of substance-induced mood disorder or mood disorder due to a general medical condition.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium/Adjunctive SGA<br> | Drug: Lithium treatment in combination with a SGA (Second Generation Antipsychotic)<br>* All patients will be treated with aripiprazole with a target dose of 10 mg/day and a max daily dose of 30 mg. If aripiprazole is ineffective or not tolerated, it will be tapered and risperidone treatment will be started. If patient had an adequate aripiprazole trial in the past as described above, risperidone will be the initial treatment. Risperidone dosing will begin with 0.5 mg/day on day 1 with a target dose of 2.5 mg/day and a max daily dose of 6mg. Subjects in the lithium /adjunctive SGA group will be started at 900 mg/day lithium in thrice daily dosing. The lithium dose will be increased to 1200mg/day on day 4 if lithium has been well-tolerated and symptoms of mania remain, as determined by a phone assessment done by a blinded study physician. The target serum level of lithium will be 1.2 mEq/L (range 0.8 to 1.4 mEq/L).<br>|
| Placebo Comparator: Placebo/Adjunctive SGA<br> | Drug: Placebo/Adjunctive SGA treatment<br>* All patients will be treated with aripiprazole with a target dose of 10 mg/day and a max daily dose of 30 mg. If aripiprazole is ineffective or not tolerated, it will be tapered and risperidone treatment will be started. If patient had an adequate aripiprazole trial in the past as described above, risperidone will be the initial treatment. Risperidone dosing will begin with 0.5 mg/day on day 1 with a target dose of 2.5 mg/day and a max daily dose of 6mg. Subjects in the placebo /adjunctive SGA group will receive placebo for the entire trial in addition to the adjunctive SGA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute phase :Time to partial or full response | Acute phase: Partial response is defined as at least a 25% -49% reduction in YMRS score and a CGI improvement item score of 2. Full response is defined as a reduction in YMRS score of 50% or more and a CGI improvement item score of 1 very much improved. | 8 weeks | 
| Continuation Phase: time to recurrence of a subsyndromal mood episode | We will measure the amount of time for patients to have a recurrance of a subsyndomal mood episode during the Continuation Phase | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute phase: number of suicidal events |  | 8 weeks | 
| Acute phase: positive urine toxicology screens (yes/no variable) |  | 8 weeks | 
| Acute phase: adherence to medication regimen. |  | 8 weeks |