Clozapine Versus Other Atypical Antipsychotics for Bipolar Disorder
Status:
Unknown status
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
Hospital de Clinicas de Porto Alegre
Collaborators:
Conselho Nacional de Desenvolvimento Científico e Tecnológico Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.