Risperdal Consta for Bipolar Disorder

OBJECTIVE:

To evaluate if a long acting injectable form of risperidone offers clinical advantages over
comparison oral second generation antipsychotic agents following titration and stabilization
in bipolar subjects. In keeping with current practice, it is expected the vast majority of
patients will also be receiving either lithium or valproate or other anticonvulsants.
Following the stabilization phase several clinical events will be evaluated for up to 15
months in the two treatment groups to examine differences in clinical outcomes between those
receiving the injectable versus oral medicines.

RESEARCH PLAN:

We intend to recruit 50 consenting adult subjects with DSM-IV TR diagnoses of bipolar
disorder who are about to initiate or to switch their antipsychotic agent. Patients will be
titrated and cross-tapered during a 3 month titration and stabilization phase. Those who
transition successfully and show some improvement will be followed for an additional 12
months. Clinical outcomes such as study drop out, adverse events, worsening of symptoms,
crisis interventions, need for additional medication, hospitalizations etc. will be
evaluated from months 3 to 15. The numbers of clinical events (pooled) will be used to
evaluate if the long acting injectable form of risperidone has an advantage over the oral
second generation antipsychotic agents in terms of treatment continuity and clinical
stability.

METHODS:

An open design, but treatment to either the long acting risperidone or to the oral second
generation antipsychotic agents is randomly assigned. A board independent of the day-to-day
clinical events will code the primary clinical outcomes of interest without knowledge of
treatment assignment. The board will be provided clinical summaries of these events without
revealing the treatment assignment.

SIGNIFICANCE:

The use of a long acting injectable second generation antipsychotic agent may offer
advantages of treatment continuity and adherence in bipolar patients permitting improved
clinical stability and improved psychosocial and functional outcomes. Such stability is
difficult to achieve in the face of frequent treatment discontinuations seen with oral
agents. The improved tolerability of the second generation antipsychotic agents may change
the perception of long acting injections. For instance, these agents are likely to be more
acceptable to patients, families and clinicians and therefore likely be used much sooner in
the treatment algorithms of bipolar patients than in the past. This study will provide a
treatment effect size to statistically power future comparisons of long-acting injectable
vs. oral antipsychotic agents in persons with bipolar disorder

Inclusion Criteria:

- DSM-IV - TR diagnoses of bipolar disorder (I or II or NOS).

- Age 18 to 70 years

- Men or women

- Any Ethnicity

- Currently receiving or willing to receive treatment at sites associated with the
Western Psychiatric Institute and Clinic -University of Pittsburgh Medical Center
(inpatient or ambulatory) or Mon Yough Community Services, Inc. or at Mayview State
Hospital, Bridgeville, PA (inpatient)

- Able to provide competent and sign an informed consent document

- It is clinically appropriate in the eligible individual to consider antipsychotic
treatment for at least 15 months (clinician and investigator determined)

- It is clinically appropriate to switch antipsychotic treatment to one of the second
generation antipsychotic agents being evaluated in this study.

- There is no known contraindication for the use of either risperidone or for more than
two of the antipsychotic agents being considered in the study (Investigator
determined)

- At entry (at the screening visit, and just prior to randomization) Y-MRS (Young-Mania
rating scale, Young et al., 1978) total score > 15 in bipolar disorder patients
entering in a manic or mixed or hypomanic or NOS episode.

- Either life-time or current comorbid substance abuse or dependence is permitted
(unless the Investigator and referring physician opines the substance abuse is likely
to significantly interfere with either the diagnosis of the Axis I condition or to
compromise patients safety due to withdrawal issues (Investigator determined).

- Screening physical and laboratory/EKG procedures are within acceptable limits

Exclusion Criteria:

- Actively suicidal or dangerous to others (Investigator opines that it is
inappropriate to involve the potential subject in the study)

- Pregnant or lactating women

- Women in the reproductive age group who are not using any acceptable contraception
(abstinence is not acceptable) or intend to become pregnant during the trial

- Subjects who are likely to face incarceration during the study duration (and for
those already in the study, the continued participation of such subjects will be
evaluated on a case-by-case basis)

- Patients currently receiving clozapine (or within six weeks prior to randomization)
are ineligible for the study

- Subjects currently receiving a depot neuroleptic injectable agent, or within 2
injection cycles of receiving the injection prior to randomization.

- Allergy or serious side effects (for instance - neuroleptic malignant syndrome) to
either risperidone or to more than two of the other second-generation antipsychotic
agents that have been approved for use in the U.S.A. (olanzapine, quetiapine,
ziprasidone, aripiprazole-per investigator and referring clinician).

- Treatment resistance to either risperidone, or to more than two of the other
antipsychotic agents in this trial (olanzapine, quetiapine, ziprasidone,
aripiprazole).

- This is the first episode of mania, mixed or hypomania for patients.

- Current (or within one month prior to randomization) participation in an
investigational drug/device study.

- Currently participating in another study that would confound the present study
objectives (per investigator)