Ziprasidone in Pediatric Bipolar Disorder

This study will enroll approximately 60 children and adolescents aged 10-17 years who have been diagnosed with bipolar disorder. Their participation will last about 8 weeks (2 weeks of screening and 6 weeks of medication management) and enrollment will last for two years. After the screening period, all subjects who meet inclusion/exclusion criteria will be randomized to either rapid or slow dose titration of ziprasidone. Subjects in the rapid titration group will reach their maximum dose of study drug over 2 weeks, subjects in the slow titration group over 4 weeks. The study doctor may deviate from the dosing schedule if clinically indicated. The primary data analysis of this pilot study will examine the effect of rapid- versus slow-dose titration of ziprasidone on manic symptoms.

Inclusion criteria

• Outpatients aged 10-17 years
• Currently meet Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-IV-TR) criteria for bipolar disorder, type I, II or Not Otherwise Specified (NOS) as determined by the Schedule for Affective Disorders and Schizophrenia -Present/Lifetime (Kiddie-SADS-PL)
• Experiencing manic, hypomanic or mixed states as determined by clinical diagnosis and Kiddie- Young Mania rating scale (K-YMRS) equal to or more than 14
• General good health as determined by medical history, physical examination, and laboratory evaluations
• Female adolescents, if sexually active, must practice birth control methods approved by the primary investigator
• Ability to swallow tablets
• Subject's parent or guardian must be fully capable of monitoring the subject's disease process and compliance to treatment
• Parent(s) or legal guardian(s) must read and sign the informed consent form after the nature of the study has been fully explained and assent must be obtained from subjects.

Exclusion criteria

• Have a lifetime DSM-IV-TR Axis I disorder diagnosis of autistic disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders
• DSM-IV-TR diagnosis of alcohol or substance abuse or dependence within the past 6 months
• Serious or unstable medical or neurological conditions which require concomitant medications
• Judged by the principal investigator (PI) to be acutely suicidal or homicidal, or at imminent risk of injuring self or others or causing significant damage to property-i.e., subject needs to be in an inpatient facility
• Known or suspected intelligence quotient (IQ) less than 70
• Have a DSM-IV-TR diagnosis of anorexia and/or bulimia at the time of screening or within the last six months
• Female who is pregnant or nursing
• Subjects with a history of syncopal episodes (sudden loss of consciousness with loss of postural tone and not preceded by a pre-syncopal phase) or unexplained loss of consciousness
• Subjects with a history of significant cardiovascular disease or significant concurrent cardiovascular disease, including uncontrolled hypertension, hypotension, congestive heart failure or congenital heart disease
• Subjects with a history of cardiac arrhythmias, conduction abnormalities or known personal history or corrected QT prolongation (including congenital long QT syndrome)
• Subjects with a known genetic risk for QT syndrome determined by family history in first degree relatives
• Subjects taking any medications known to interact with ziprasidone or subjects taking any medications which have been consistently observed to prolong the QT interval
• Subjects with a clinically significant ECG abnormality at screening
• Subjects with persistent QTc (Fridericia) * 460 msec at screening
• Screening laboratory values outside the normal range and judged to be clinically significant by the investigator
• Patients and families that are Spanish speaking only will be excluded from the study as some instruments used in the study have not been validated in Spanish