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

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.

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.

Study Overview

• Status: Withdrawn
• Conditions: Bipolar I Disorder
• Intervention / Treatment: Drug: Lithium treatment in combination with a SGA (Second Generation Antipsychotic); Drug: Placebo/Adjunctive SGA treatment

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Glen Oaks, New York, United States, 11004
      • The Zucker Hillside Hospital, North Shore-LIJ Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lithium/Adjunctive SGA	Drug: Lithium treatment in combination with a SGA (Second Generation Antipsychotic); 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).
Placebo Comparator: Placebo/Adjunctive SGA	Drug: Placebo/Adjunctive SGA treatment; 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.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: November 22, 2011
• First Submitted That Met QC Criteria: December 15, 2011
• First Posted (Estimate): December 19, 2011

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 21, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antipsychotic Agents
• Other Study ID Numbers: 11-185