Venlafaxine for the Prevention of Depression in Patients With Head and Neck Cancer

January 15, 2024 updated by: Michael Topf, Vanderbilt University Medical Center
This is a pilot double-blinded, randomized, placebo-controlled trial to determine if venlafaxine prevents depression in patients undergoing surgery for Head and Neck Cancer (HNC).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Patients with head and neck cancer (HNC) are disproportionately affected by major depressive disorder (MDD), with up to 50% developing MDD compared to 15-25% of patients with other solid malignancies. The higher rates of depression seen in HNC patients are likely related to treatment-associated disfigurement, voice and swallow dysfunction, and other physical alterations that significantly diminish quality of life. Survivors of HNC have a significantly increased risk of suicide when compared to other cancers. The rate of suicide among HNC survivors is 63.4 suicides per 100,000 person-years, which is three times that of other cancer survivors and second highest only behind pancreatic cancer.

There is evidence to suggest that depression plays a role in HNC prognosis, with studies showing a 25% decrease in overall survival in HNC patients with depression. Despite the prevalence and impact of depression in HNC patients, there has only been one randomized control trial to prevent depression in patients with HNC that showed potential benefit. This study used escitalopram, a selective-serotonin reuptake inhibitor (SSRI). A more appropriate medication would be one that provided mood stabilization as well as pain modulation, since it is known that HNC treatment can lead to long-term opioid use. Serotonin-norepinephrine reuptake inhibitors (SNRIs) provide dual action against serotonergic and noradrenergic receptors and have shown to provide superior pain relief than monoaminergic drugs such as SSRIs.

The investigators hypothesize that venlafaxine will provide mood stabilization and improved pain control in patients undergoing surgical treatment for HNC. The investigators plan to conduct a pilot double-blinded, randomized, placebo-controlled trial using venlafaxine in HNC patients treated with surgery. Patients who screen negative for Bipolar disorder (BPD) based on the screening tool The Mood Disorder Questionnaire (MDQ) as well as for MDD using the Patient Health Questionnaire (PHQ-9) preoperatively (Cohort A) will be randomized to either venlafaxine or placebo and will be assessed throughout the perioperative period with a series of validated self-reported questionnaires regarding depression, anxiety, pain, and other quality of life measures.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

COHORT A (RCT)

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Male or female, aged 18 years or older
  4. Have a recently diagnosed cutaneous or mucosal malignancy
  5. Scheduled to undergo surgical treatment for their malignancy with curative intent
  6. Ability to take medication orally or via gastric tube feeds
  7. Willing to adhere to the study drug's dosing protocol
  8. Score <10 on the PHQ-9

COHORT B (Observation cohort)

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Male or female, aged 18 years or older
  4. Have a recently diagnosed cutaneous or mucosal malignancy
  5. Scheduled to undergo surgical treatment for their malignancy with curative intent
  6. Ability to take medication orally or via gastric tube feeds
  7. Willing to adhere to the study drug's dosing protocol
  8. Score >10 on the PHQ-9

Exclusion Criteria:

COHORT A (RCT)

  1. Score >10 on PHQ-9
  2. Score between 5-9 on PHQ-9 and elect for psychotherapy
  3. Age less than 18 years
  4. Primary malignancy of thyroid or parathyroid origin
  5. Currently meet diagnostic criteria for psychosis, schizophrenia, or bipolar disorder
  6. Currently receiving medication as treatment for depression or anxiety including: MAO inhibitors, Linezolid, Other SNRIs or SSRIs, Bupropion
  7. Known allergic reaction to components of study drug
  8. Treatment with another investigational drug or other intervention within 30 days
  9. Females of child-bearing age who are pregnant or nursing
  10. Inability to speak or understand English

COHORT B (Observation cohort)

  1. Score <10 on PHQ-9
  2. Unwillingness or inability to take venlafaxine
  3. Age less than 18 years
  4. Primary malignancy of thyroid or parathyroid origin
  5. Currently receiving medication as treatment for depression or anxiety including: MAO inhibitors, Linezolid, Other SNRIs or SSRIs, Bupropion

7. Known allergic reaction to components of study drug 8. Treatment with another investigational drug or other intervention within 30 days 9. Females of child-bearing age who are pregnant or nursing 10. Inability to speak or understand English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venlafaxine

Patients who screen negative or meet criteria for mild MDD are eligible for the randomized control trial (RCT) portion of this study in which patients are randomized into either the intervention (venlafaxine) arm or placebo. Participants randomized into the intervention group will be prescribed a starting dose of venlafaxine immediate release (IR) 75mg once daily. The dosing will be increased at the following rate:

Week 1: 75mg in AM

Week 2: 75mg BID

Week 3: 150mg in AM, 75mg in PM

Week 4: 150mg BID

For patients with hepatic impairment, severe renal impairment, or end stage kidney disease, the starting dose is 37.5 mg once daily, increased by increments of 37.5 mg per day to reach a maximum of 187.5 mg per day, given in two divided doses.
Drug: Venlafaxine
See arm/group description.
Other Names:
  • Effexor
Placebo Comparator: Placebo
Patients who screen negative or meet criteria for mild MDD are eligible for the randomized control trial (RCT) portion of this study in which patients are randomized into either the intervention (venlafaxine) arm or placebo. Participants randomized to the placebo group will receive a placebo capsule with the same dosing schedule as the intervention group.
Drug: Placebo
See arm/group description.
Other: Observation
Patients who screen positive for moderate, moderately-severe, or severe MDD are excluded from the RCT and will be enrolled in the study as an observation cohort. These patients will be offered initiation of venlafaxine and will be referred to our collaborating oncologic psychiatrist. Patients in cohort B will still complete the same patient-reported outcome measures (PROMs) as patients in cohort A, allowing us to collect data and better understand what effects venlafaxine has on patients who are already diagnosed with depression at the start of treatment for HNC.
Drug: Venlafaxine
See arm/group description.
Other Names:
  • Effexor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevention of Depression
Time Frame: 4 months post-operatively
Rate of depression at any time interval within the 4-month post-surgery period in patients with no or mild MDD. This will be assessed using the Patient-Health Questionnaire (PHQ-9) which is scored ranging from 0-27 with a higher score indicating more severe depression. Four months was chosen as the duration to capture the adjuvant radiation period, which is typically 3 months post-surgery.
4 months post-operatively

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevention of Pain
Time Frame: 4 months post-operatively
Rate of pain control at 4-months post-surgery in all patients enrolled. This will be assessed using the Brief Pain Inventory-short form which is scored on a scale of 0 to 10 with a higher score indicating a worse outcome.
4 months post-operatively
Prevention of Pain
Time Frame: 4 months post-operatively
Duration of opioid use post-surgery in all patients enrolled. This will be assessed using the opioid diary.
4 months post-operatively
Quality of Life Improvement
Time Frame: 4 months post-operatively
Quality of life at 4 months post-surgery in all patients enrolled. This will be assessed using the FACE-Q HNC which is scored on a scale. The scale ranges from 0 to 100 with a higher score meaning a better outcome.
4 months post-operatively
Treatment of Depression
Time Frame: 4 months post-operatively
Rate of depression at 4 months post-surgery in patients who initially screened positive for moderate, moderately-severe, or severe MDD. This will be assessed using the Patient-Health Questionnaire (PHQ-9) which is scored ranging from 0-27 with a higher score indicating more severe depression.
4 months post-operatively
Prevention of Anxiety
Time Frame: 4 months post-operatively
Rate of anxiety at 4-months post-surgery in all patients enrolled. This will be assessed using the Generalized Anxiety Disorder-7 (GAD-7) which reports scores on a scale, ranging from 0 to 21 with higher scores indicating worse outcomes.
4 months post-operatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Michael C Topf, MD, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2023

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

January 31, 2023

First Submitted That Met QC Criteria

February 9, 2023

First Posted (Actual)

February 13, 2023

Study Record Updates

Last Update Posted (Estimated)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 15, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 230054

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression

Clinical Trials on Venlafaxine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe