Phenytoin as an Augmentation for SSRI Failures

This study has been completed.
Sponsor:
Collaborator:
The Rogosin Institute
Information provided by:
Beersheva Mental Health Center
ClinicalTrials.gov Identifier:
NCT00146237
First received: September 6, 2005
Last updated: November 23, 2009
Last verified: November 2009
  Purpose

About two-thirds of depressed patients respond to a standard course of serotonin specific reuptake inhibitor (SSRI's) within 3-4 weeks. While some clinicians advise continued watchful waiting after this time or switch to a different reuptake-blocker based antidepressant, result of such conservative strategies are usually disappointing. For severe depression electroconvulsive therapy (ECT) is an option and for atypical depressions monoamine oxide inhibitors (MAO) inhibitors often give relief at this point. A unique strategy with both theoretical and practical implications is lithium augmentation (Fava et al, 1994). Addition of lithium to SSRI failures at 3-4 weeks is consistently and sometimes dramatically found to be helpful. This is considered true even by those authors who advocate use of lithium under usual circumstances only in bipolar patients.

Lithium in recent years has been joined as a mood stabilizer by carbamazepine and valproate. Phenytoin, ignored for many years as a possible anticonvulsant mood stabilizer, has been recently reported in double-blind controlled trials to be anti-manic (Mishory et al, 2000) and also prophylactic in BP disorder (Mishory et al, 2003).

Data on mood stabilizers other than lithium as augmentors in SSRI failures are sparse. Carbamazepine (Steinacher et al, 2002) and valproate (Barbee et al, 2002) have been used. Given our recent preliminary results of phenytoin's efficacy in unipolar depression (Nemets et al, 2005) and its analogy to lithium as a mood stabilizer, it seems important to study phenytoin as a possible augmentation of SSRI failures.

We have published a negative study previously of inositol as an augmentation of SSRI failures, enrolling forty-two patients over two years (Nemets et al, 1999). Antidepressant failures are easier to recruit from referring physicians in our center than are untreated patients, whom clinicians are reluctant to refer for new drug studies given the adequacy of standard treatment in 2/3 of them. Thus we estimate that we could enroll 20 patients per year in such a study. Survey of the literature of Li augmentation suggests that 40 phenytoin vs. 40 placebo should give adequate power to detect a significant phenytoin effect if the phenytoin effect is similar to that of lithium.


Condition Intervention Phase
Depression
Drug: phenytoin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phenytoin as an Augmentation for SSRI Failures: A Controlled Study

Resource links provided by NLM:


Further study details as provided by Beersheva Mental Health Center:

Primary Outcome Measures:
  • Hamilton Depression Scale

Estimated Enrollment: 40
Study Start Date: November 2003
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age: 18-65
  • DSM-IV criteria for major depression without psychotic features
  • at least 3 weeks of treatment with SSRI at clinically adequate dose with at most mild improvement from onset of SSRI treatment
  • Hamilton Depression Scale score of at least 18

Exclusion Criteria:

  • ideations of suicide
  • pregnancy
  • drug or alcohol abuse
  • unstable medical illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00146237

Locations
Israel
Beersheva Mental Health Center
Beersheva, Israel
Sarah Herzog Memorial Hospital
Jerusalem, Israel
Sponsors and Collaborators
Beersheva Mental Health Center
The Rogosin Institute
Investigators
Study Director: RH Belmaker, MD Ben-Gurion University of the Negev
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00146237     History of Changes
Other Study ID Numbers: BMHC-3581
Study First Received: September 6, 2005
Last Updated: November 23, 2009
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Beersheva Mental Health Center:
phenytoin
SSRI failure
depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014