Clozapine Versus Other Atypical Antipsychotics for Bipolar Disorder

NCT ID: NCT02562287

Last Updated: 2018-10-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2020-12-31

Brief Summary

The clinical use of clozapine has been an unequivocal advance in the treatment of schizophrenia, a chronic and severe mental illness. A wealth of clinical data demonstrates it offers enhanced efficacy on both positive and negative symptomatology, improving cognition, functioning and quality of life. It is also associated with improved compliance and a continued efficacy in long-term treatment that can be translated into a reduction of suicidality and all-cause mortality. Because of preclinical evidence that it modulates neuroplasticity and prefrontal cortex connectivity, clozapine may be an interesting strategy for further severe psychotic illnesses. Nevertheless, even considering the growing use of other atypical antipsychotics in the management of bipolar disorder, a role for clozapine has been poorly defined. The clinical evidence-base for its use in this condition is largely based on uncontrolled naturalistic trials and retrospective studies and chart reviews. Several of these have supported clozapine's efficacy in treatment-resistant bipolar disorder. Possibly because of clozapine's profile of adverse effects and lack of interest from pharmaceutical companies, only two randomized trials have examined its effectiveness. Both suggest clinically relevant antimanic and mood-stabilizing properties. Therefore, the primary objective of this trial is to determine the effectiveness of clozapine for treatment-resistant bipolar disorder. Secondary objectives include examining the effects of treatment with clozapine on cognition and functioning of patients with bipolar disorder. Tolerability and safety of long-term clozapine use will also be examined. To that end, the investigators will conduct a clinical trial with 54 patients with a history of treatment resistance. Patients will be randomized to either open-label treatment with clozapine, in combination with lithium or valproate, or open-label treatment with an atypical antipsychotic with consistent evidence of efficacy in the treatment of bipolar disorder (olanzapine, quetiapine or risperidone), also in combination with lithium or valproate. Patients will be followed for one-year and time to all-cause treatment failure will be the primary outcome measure. It is the belief of the investigators that this study will generate meaningful clinical data of tremendous importance to validate clozapine as a legitimate treatment option for treatment-resistant bipolar disorder.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clozapine

Clozapine, P.O., flexible dose, for up to 6 months

Group Type: EXPERIMENTAL

Clozapine

Intervention Type: DRUG

Flexible dosage, with up-titration according to standard schedules employed for schezophrenia

Risperidone, olanzapine or quetiapine

Risperidone, olanzapine or quetiapine, according to clinical indication, flexible dose, for up to 6 months

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Risperidone, in a flexible dosage

Olanzapine

Intervention Type: DRUG

Olanzapine, flexible dosage

Quetiapine

Intervention Type: DRUG

Quetiapine, flexible dosage

Interventions

Clozapine

Flexible dosage, with up-titration according to standard schedules employed for schezophrenia

Intervention Type: DRUG

Risperidone

Risperidone, in a flexible dosage

Intervention Type: DRUG

Olanzapine

Olanzapine, flexible dosage

Intervention Type: DRUG

Quetiapine

Quetiapine, flexible dosage

Intervention Type: DRUG

Other Intervention Names

Clozaril; Risperdal; Zyprexa; Seroquel

Eligibility Criteria

Inclusion Criteria

• DSM-IV Bipolar I Disorder;
• having had a mood episode within the preceding year; DSM-IV rapid cyclers will be permitted to participate in this study;
• males or females between 18 and 65 years of age;
• ongoing illness symptoms including significant functional impairment;
• documented history of treatment resistance, defined as persistent symptoms despite simultaneous, adequate treatment with at least two medications: one mood stabilizer (lithium or valproate) + antipsychotic OR two mood stabilizers (at least one of them being lithium or valproate).
• each patient must have a level of understanding sufficient to agree to all the tests required by the protocol and must sign an informed consent document

Exclusion Criteria

• patients with onset of illness after age 40 or illness resulting from secondary causes
• women who are pregnant or breastfeeding, or not using adequate contraception
• unstable medical illnesses
• clinically significant abnormal laboratory tests
• current active alcohol or substance abuse
• severe personality disorders
• contraindication to the use of clozapine or previous treatment with clozapine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

OTHER_GOV

Sponsor Role: collaborator

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Pedro Vieira da Silva Magalhães

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

PEDRO V MAGALHAES, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clínicas de Porto Alegre / Universidade Federal do Rio Grande do Sul

Locations

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

PEDRO V MAGALHAES, M.D., Ph.D.

Role: CONTACT

pedromaga2@gmail.com

+555191123773

Facility Contacts

PEDRO V MAGALHAES, M.D., Ph.D.

Role: primary

Other Identifiers

32356214200005327

Identifier Type: -

Identifier Source: org_study_id