Topiramate and Schizophrenia: Effects on Weight and Psychopathology

  • STATUS
    Recruiting
  • End date
    Dec 29, 2023
  • participants needed
    50
  • sponsor
    Centre for Addiction and Mental Health
Updated on 23 February 2022

Summary

Clozapine is the sole AP agent with superiority in treatment refractory schizophrenia, but it also is associated with the greatest risk of weight gain and other metabolic abnormalities. Topiramate, an anticonvulsant agent, possesses a weight-reducing effect. Furthermore, some studies have suggested that Topiramate may be associated with improvements in psychopathology in treatment refractory schizophrenia. Here the investigators propose to determine the role of topiramate for augmentation purposes (psychopathology) and as an adjunctive pharmacological intervention for weight loss in overweight/obese individuals with Ultra-Treatment Resistant Schizophrenia or Schizoaffective disorder taking clozapine.

Description

Schizophrenia is a chronic illness characterized by social and vocational disruptive functioning. While >70% of individuals with first episode illness respond to antipsychotics (APs), there remains a subgroup left with persisting psychotic symptoms. For these individuals, clozapine (CLZ) is also the sole drug with treatment superiority, but also carries the greatest metabolic liability. Another complicating factor in those treated with CLZ is the observation that while effective in some, 40-70% of individuals fail to show significant improvement with CLZ, often leading to augmentation strategies. While controlled trials are, in general lacking, a number of agents have been suggested as useful. One such group of medications includes the anticonvulsants.

Topiramate represents one of the newer anticonvulsant agents approved for the treatment of epilepsy and prophylaxis of migraines. Importantly, topiramate possesses a weight-reducing effect that has been substantiated by a meta-analysis in non-psychiatric patients. Interestingly, topiramate has been studied as an adjunctive therapy in treatment-resistant schizophrenia with some evidence demonstrating small to moderate benefits with topiramate augmentation on psychopathology. However, these benefits must also be weighed against reports (primarily from epilepsy populations), that topiramate may cause cognitive dysfunction.

This study will examine:

  1. Topiramate-related effects on weight
  2. Topiramate-related effects on glucose tolerance and insulin sensitivity
  3. Topiramate-related effects on psychopathology and cognition
  4. Topiramate-related effects on adiposity

Details
Condition Schizophrenia, Schizoaffective Disorder
Treatment Placebo, Topiramate
Clinical Study IdentifierNCT02808533
SponsorCentre for Addiction and Mental Health
Last Modified on23 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Schizophrenia or Schizoaffective disorder
-59 years of age
Clozapine treatment for at least 12 weeks at a dose 350 mg/d or greater and/or plasma clozapine levels of 300 ng/mL or greater
CGI must be 4 or higher and/or GAF < 50
BMI greater than or equal to 25

Exclusion Criteria

Alcohol use disorder
Patients with liver, or renal dysfunction
Females of child bearing age not on a regular contraceptive, females who are nursing
Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematological, or pulmonary disease
HbA1c > 9%, or symptomatic hyperglycemia with metabolic decompensation
Prior lack of efficacy or tolerability of Topiramate
Addition of new hypoglycemic or lipid lowering medication within 2 months of starting study
Patients treated with Valproic Acid
Patients treated with hydrochlorothiazide
Switch in antipsychotic medications within 3 months of study entry
Major medical or surgical event within the preceding 3 months
History of renal stones
Use of Carbonic Anhydrase Inhibitor
History of glaucoma
Acute Suicidal risk
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note