This will be an 8-week open-label trial, using daily doses of paliperidone (Invega) in the
treatment of children and adolescents who meet DSM-IV criteria of Bipolar I, Bipolar II, or
Bipolar Spectrum Disorder. Specific hypotheses are as follows:
Hypothesis 1: Bipolar Disorder symptomatology in children and adolescents with DSM-IV
Bipolar I, Bipolar II, or Bipolar Spectrum Disorder will be responsive to Invega treatment.
Hypothesis 2: Invega -associated improvement in bipolar disorder symptomatology in children
and adolescents will translate into improved functional capacities (neuropsychological,
social, and occupational), as well as an increased quality of life throughout treatment.
Hypothesis 2: Invega treatment will be safe and well tolerated as reflected by a low drop
out rate and absence of major side effects.
Invega (paliperidone), a second generation antipsychotic (SGA), is a psychotropic agent
belonging to the chemical class of benzisoxazole derivatives. Invega is approved by the FDA
for the treatment of schizophrenia in adults. Initial data suggest a promising role for
Invega in the treatment of bipolar disorder with minimal adverse events of weight gain. We
propose to study the safety and efficacy of Invega therapy in children and adolescents with
Bipolar I, Bipolar II, and Bipolar Spectrum Disorder. The study results will be used to
generate hypotheses for a larger, randomized, controlled clinical trial with explicit
hypotheses and sufficient statistical power.
The proposed study includes 1) use of a 8-week design to document the response rate, 2)
assessment of the impact of Invega on functional capacities (quality of life, psychosocial
function) and cognition, and 3) careful assessment of safety and tolerability.
1. Male and female outpatients 6-17 years of age (inclusive).
2. Subjects with the diagnosis of Bipolar or Bipolar Spectrum Disorder and currently
displaying manic, hypomanic, or mixed symptoms (with or without psychotic features),
by DSM-IV, as manifested in clinical evaluation and confirmed by structured
interview. Bipolar Spectrum Disorder (or sub- threshold bipolar disorder) is
operationalized as having severe mood disturbance, which meets DSM-IV Criteria A for
bipolar disorder but display fewer elements in Criteria B (only require 2 items for
elation category and 3 for irritability).
3. Subjects must score ≥ 20 on the YMRS.
4. Subjects and their legal representative must have a level of understanding sufficient
to communicate intelligently with the investigator and study coordinator, and to
cooperate with all tests and examinations required by the protocol.
5. Subjects and their legal representative must be considered reliable reporters.
6. Each subject and his/her authorized legal representative must understand the nature
of the study. The subject's authorized legal representative must sign an informed
consent document and the subject must sign an informed assent document (if ≥ 7 years
7. Subject must be able to participate in mandatory blood draws.
8. Subject must be able to swallow pills.
9. Subjects with comorbid ODD, CD, OCD, PDD, anxiety and depressive disorders will be
allowed to participate in the study provided they do not meet for any of the
10. For concomitant therapy used to treat ADHD, subjects must have been on a stable dose
of the medication for 1 month prior to study enrollment. The dose of the ADHD
therapy will not change throughout the duration of the study.
1. Investigator and his/her immediate family; defined as the investigator's spouse,
parent, child, grandparent, or grandchild.
2. Serious, unstable illness including hepatic, renal, gastroenterological, respiratory,
cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
immunologic, or hematologic disease.
3. Uncorrected hypothyroidism or hyperthyroidism.
4. Non-febrile seizures without a clear and resolved etiology.
5. DSM-IV substance (except nicotine or caffeine) dependence within past 6 months.
6. Judged clinically to be at serious suicidal risk.
7. Any other concomitant medication with primary central nervous system activity other
than specified in the Concomitant Medication portion of the protocol.
8. Current diagnosis of schizophrenia.
9. Mental retardation (IQ < 75).
10. Pregnant or nursing females.
11. Known hypersensitivity to Invega® or similar formulations (paliperidone,
12. A non-responder or history of intolerance to Invega®, after treatment at adequate
doses as determined by the clinician.
13. Severe allergies or multiple adverse drug reactions.
14. Subjects with a hematological disorder.
15. Subjects with diabetes.