Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00362804
Status:
COMPLETED
Last Update Posted:
2012-07-06
First Post:
2006-08-09
Brief Title:
Tetrabenazine for Partial Responders
Sponsor:
Centre for Addiction and Mental Health
Organization:
Centre for Addiction and Mental Health
Study Overview
Official Title:
Augmentation of Antipsychotic Partial Responders With Tetrabenazine
Status:
COMPLETED
Status Verified Date:
2012-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Purpose of Study
A To improve outcome in large population of antipsychotic patients with schizophrenia or schizoaffective who are only partial responders B To increase understanding of pharmacology and mechanisms of action underlying antipsychotic effect
HypothesisObjectives of the Study
Tetrabenazine through its pre-synaptic action should augment the post-synaptic effects of an antipsychotic
Background and Rationale for the study
Preliminary evidence that other amine-depleting agents eg reserpine can induce such an effect
A To improve outcome in large population of antipsychotic patients with schizophrenia or schizoaffective who are only partial responders B To increase understanding of pharmacology and mechanisms of action underlying antipsychotic effect
HypothesisObjectives of the Study
Tetrabenazine through its pre-synaptic action should augment the post-synaptic effects of an antipsychotic
Background and Rationale for the study
Preliminary evidence that other amine-depleting agents eg reserpine can induce such an effect
Detailed Description:
Since the 1950s antipsychotics have been used as the mainstay treatment to control symptoms of schizophrenia However soon after their introduction it became apparent that a substantial number of individuals show a less than optimal response to these drugs - as many as 30 of schizophrenics using conventional antipsychotics derive little benefit Furthermore atypical generation antipsychotics such as clozapine which proves to be the most beneficial for partial responders and represents the cornerstone of treatment-resistant schizophrenia offers a response rate as low as 30 in those showing an inadequate response Moreover many individuals decline clozapine as an option or cannot tolerate it
For these reasons augmentation strategies play an important role in the treatment of antipsychotic partial responders We have systematically reviewed the different augmentation options and reached the conclusion that most such strategies are theoretically speculative and empirically unsupported
At the same time though we recognize that augmentation strategies are common practice in the clinical setting With so many individuals showing only a partial response to antipsychotic treatment typical or atypical it has become a practical reality in efforts to offer further improvement Often this come in the form of adding one or even more antipsychotics although the evidence for such an approach is less than compelling and neuroimaging from our centre has cautioned against this approach
With a variety of other potential augmentation strategies available we have chosen to focus on tetrabenazine TBZ which is currently licensed here in Canada for the management of hyperkinetic movement disorders
The choice of TBZ as an augmentation strategy arises from several lines of investigation
TBZ like reserpine is a pre-synaptic monoamine-depleting agent or inhibitor of vesicular monoamine transporter and hence will act to dampen abnormal dopamine release in patients already on a primary post-synaptic D2 blocking compound as is the case to varying degrees with all antipsychotics currently available
There are anecdotal reports with reserpine indicating that it can augment response in patients showing only a partial response to antipsychotic atypical as well as typical partial responders
TBZ appears to have a low-affinity post-synaptic D2 effect still well below the 80 threshold where one begins to see motor side effects
TBZ has inherent anti-dyskinetic properties thereby offering an additional secondary benefit
We are proposing to carry out a controlled double-blind trial using TBZ off-label in patients with schizophrenia or schizoaffective disorder only partially responsive to antipsychotics We feel that the choice of this approach is empirically sound and in fact offers advantages to the more common approach of adding several antipsychotics Our decision to maintain out focus on the dopaminergic system arises from the growing body of evidence that dopamine blockade particularly at the level of the D2 receptor is central to antipsychotic activity in combination with the lack of current evidence supporting the distinct advantages of incorporating other systems
Given the limited success with augmentation strategies in schizophrenic patients to date any evidence of efficacy and safety with this combination will add considerably to options that might be considered in the clinical setting This same information could also prove very useful in shaping investigations related to the pharmacology of schizophrenia and development of future compounds
For these reasons augmentation strategies play an important role in the treatment of antipsychotic partial responders We have systematically reviewed the different augmentation options and reached the conclusion that most such strategies are theoretically speculative and empirically unsupported
At the same time though we recognize that augmentation strategies are common practice in the clinical setting With so many individuals showing only a partial response to antipsychotic treatment typical or atypical it has become a practical reality in efforts to offer further improvement Often this come in the form of adding one or even more antipsychotics although the evidence for such an approach is less than compelling and neuroimaging from our centre has cautioned against this approach
With a variety of other potential augmentation strategies available we have chosen to focus on tetrabenazine TBZ which is currently licensed here in Canada for the management of hyperkinetic movement disorders
The choice of TBZ as an augmentation strategy arises from several lines of investigation
TBZ like reserpine is a pre-synaptic monoamine-depleting agent or inhibitor of vesicular monoamine transporter and hence will act to dampen abnormal dopamine release in patients already on a primary post-synaptic D2 blocking compound as is the case to varying degrees with all antipsychotics currently available
There are anecdotal reports with reserpine indicating that it can augment response in patients showing only a partial response to antipsychotic atypical as well as typical partial responders
TBZ appears to have a low-affinity post-synaptic D2 effect still well below the 80 threshold where one begins to see motor side effects
TBZ has inherent anti-dyskinetic properties thereby offering an additional secondary benefit
We are proposing to carry out a controlled double-blind trial using TBZ off-label in patients with schizophrenia or schizoaffective disorder only partially responsive to antipsychotics We feel that the choice of this approach is empirically sound and in fact offers advantages to the more common approach of adding several antipsychotics Our decision to maintain out focus on the dopaminergic system arises from the growing body of evidence that dopamine blockade particularly at the level of the D2 receptor is central to antipsychotic activity in combination with the lack of current evidence supporting the distinct advantages of incorporating other systems
Given the limited success with augmentation strategies in schizophrenic patients to date any evidence of efficacy and safety with this combination will add considerably to options that might be considered in the clinical setting This same information could also prove very useful in shaping investigations related to the pharmacology of schizophrenia and development of future compounds
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None