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Phenytoin as an Augmentation for SSRI Failures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00146237
Recruitment Status : Completed
First Posted : September 7, 2005
Last Update Posted : November 25, 2009
The Rogosin Institute
Information provided by:
Beersheva Mental Health Center

Brief Summary:

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 or disease Intervention/treatment Phase
Depression Drug: phenytoin Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Phenytoin as an Augmentation for SSRI Failures: A Controlled Study
Study Start Date : November 2003
Actual Primary Completion Date : January 2005
Actual Study Completion Date : January 2005

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Hamilton Depression Scale

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00146237

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

Layout table for additonal information Identifier: NCT00146237     History of Changes
Other Study ID Numbers: BMHC-3581
First Posted: September 7, 2005    Key Record Dates
Last Update Posted: November 25, 2009
Last Verified: November 2009
Keywords provided by Beersheva Mental Health Center:
SSRI failure
Additional relevant MeSH terms:
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Behavioral Symptoms
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers