Tapering Off Antidepressants

• ClinicalTrials.gov Identifier: NCT02661828
• Recruitment Status: Terminated
• First Posted: January 25, 2016
• Results First Posted: September 25, 2018
• Last Update Posted: September 25, 2018
• Sponsor: Emory University
• Information provided by (Responsible Party): Boadie W. Dunlop, Emory University

Study Description

Brief Summary:

The purpose of this study is to compare two ways to stop taking an antidepressant medication and determine whether a faster or slower taper is better tolerated.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; Anxiety Disorder; Obsessive Compulsive Disorder; Post-Traumatic Stress Disorder	Other: Two-Week Antidepressant Taper Regimen; Other: One-Week Antidepressant Taper Regimen	Not Applicable

Detailed Description:

As abrupt cessation of antidepressant medication can cause distressing symptoms (including and not limited to worsened mood, irritability/agitation, anxiety, dizziness, confusion, and headache), the aim of this study is to compare the tolerance of two tapering regimens with the hypothesis that tapering the antidepressant dose over the course of two weeks will yield less discontinuation symptoms than a one week taper regimen. Additionally, it is suspected that discontinuing medications that inhibit the serotonin transporter , such as selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) will have a greater difference in the frequency of discontinuation symptoms between the two and one-week tapering regimens versus antidepressants that don't inhibit serotonin transporter.

Demographic and clinical features will also be identified that may predict discontinuation symptoms with the hypothesis that patients on SSRIs and SNRIs may experience more discontinuation symptoms versus patients on non-SSRI/SNRI medications. Whether or not the treatment duration is positively associated with the number of discontinuation symptoms will also be determined.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparison of Two Antidepressant Tapering Regimens
• Study Start Date: January 2016
• Actual Primary Completion Date: March 17, 2017
• Actual Study Completion Date: March 17, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Taper A Regimen; Participants taking an antidepressant for at least four weeks and no longer wish to take the antidepressant medication will undergo a Two-Week Taper Regimen to discontinue their medication.	Other: Two-Week Antidepressant Taper Regimen; Days 1-7: 50% of baseline antidepressant dose taken; Days 8-14: 25% of baseline antidepressant dose taken; Day 15: Stop antidepressant.
Active Comparator: Taper B Regimen; Participants taking an antidepressant for at least four weeks and no longer wish to take the antidepressant medication will undergo a One-Week Taper Regimen to discontinue their medication.	Other: One-Week Antidepressant Taper Regimen; Days 1-3: 50% of baseline antidepressant dose taken; Days 4-7: 25% of baseline antidepressant dose taken; Day 8: Stop antidepressant.

Outcome Measures

Primary Outcome Measures :

1. Discontinuation Emergent Signs and Symptoms Scale (DESS) Scores [ Time Frame: Baseline (Post-Taper), Visit 4 (3 Weeks Post Baseline) ]

   To determine a change in the frequency of Discontinuation symptoms, the Discontinuation Emergent Signs and Symptoms Scale (DESS) will be administered by a trained clinician/rater to assess the frequency of discontinuation symptoms. The assessment has 43 items to evaluate discontinuation-emergent symptoms resulting from withdrawal from their antidepressant medication. Symptoms are rated on a scale of 1-5:

   1. New symptom
   2. Old symptom but worse
   3. Old symptom but improved
   4. Old symptom but unchanged
   5. Symptom not present

   Total score = sum of number of new symptoms and old (but worse) symptoms (score = 1) and old and unchanged symptom, absent, or old symptom but improved (score = 0); total possible range 0 to 43. Higher score = more symptoms.

Secondary Outcome Measures :

1. Physician Withdrawal Checklist (PWC-20) Scores [ Time Frame: Baseline (Post-Taper), Visit 4 (3 Weeks Post Baseline) ]

   To determine a change in the Intensity of Discontinuation symptoms, the Physician Withdrawal Checklist (PWC-20) will be administered by a trained clinician/rater to assess the intensity of discontinuation symptoms. The assessment has 20 items evaluated to detect withdrawal symptoms. Symptoms are rated on a scale of 0-3.

   0. Not present

   1. Mild
   2. Moderate
   3. Severe

   Total scores range from 0 to 60 with higher scores indicating more severe symptoms.

2. Number of Participants Who Meet Criteria for Antidepressant Discontinuation Syndrome [ Time Frame: Duration of Study (Up to 14 Months) ]

   Antidepressant Discontinuation Syndrome is defined as greater than or equal to 4 new or worsened Discontinuation Emergent Signs and Symptoms Scale (DESS) symptoms at a visit during the study.

   Symptoms are rated on a scale of 1-5:

   1. New symptom
   2. Old symptom but worse
   3. Old symptom but improved
   4. Old symptom but unchanged
   5. Symptom not present

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Currently taking an FDA-approved antidepressant for at least four weeks on the list of approved medications: SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vilazodone or vortioxetine), SNRIs (desvenlafaxine, duloxetine, levomilnacipran, venlafaxine) and other classes (amitriptyline, bupropion, desipramine, doxepin, mirtazapine, nefazodone, nortriptyline, phenelzine, selegiline, or tranylcypromine). Clomipramine, a tricyclic antidepressant approved for the treatment of OCD, will also be included, but will be classed as an SSRI for this study because inhibition of the serotonin transporter is its primary therapeutic mechanism.
• No longer wish to take the antidepressant medication they are currently prescribed, due to one of the following reasons: 1) ineffective for symptoms; 2) intolerable side effect; 3) improvement of their illness for sufficient duration that it is clinically appropriate to consider tapering the medication.
• Primary psychiatric diagnosis of major depressive disorder, an anxiety disorder, OCD, or PTSD.
• Ability to read and understand English language.

Exclusion Criteria:

• Has met criteria at any time during their life for a primary psychotic disorder (e.g. schizophrenia), or dementia.
• Meets criteria for DSM-5-defined substance use disorder within three months of the screening visit.
• Currently taking two or more antidepressants.
• Presents with a clinically significant suicide risk, as assessed by a study physician.
• Presence of any unstable or central nervous system-related medical illness that would interfere with cognition or participation.
• Women who are currently pregnant or lactating, or plan to become pregnant during the study.

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

The Emory Clinic

Atlanta, Georgia, United States, 30322

12 Executive Park Drive, 3rd floor

Atlanta, Georgia, United States, 30329

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Boadie Dunlop, MD; Emory University

  Study Documents (Full-Text)

Documents provided by Boadie W. Dunlop, Emory University:

Study Protocol and Statistical Analysis Plan  [PDF] January 29, 2016

More Information

• Responsible Party: Boadie W. Dunlop, Boadie W. Dunlop, MD, Emory University
• ClinicalTrials.gov Identifier: NCT02661828
• Other Study ID Numbers: IRB00084849
• First Posted: January 25, 2016
• Results First Posted: September 25, 2018
• Last Update Posted: September 25, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Boadie W. Dunlop, Emory University:

Tapering Antidepressant Regimen; Antidepressant Discontinuation Syndrome

Additional relevant MeSH terms:

Disease; Depressive Disorder; Depressive Disorder, Major; Stress Disorders, Traumatic; Anxiety Disorders; Stress Disorders, Post-Traumatic; Obsessive-Compulsive Disorder; Pathologic Processes; Mood Disorders; Mental Disorders; Trauma and Stressor Related Disorders; Antidepressive Agents; Psychotropic Drugs