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

Phase 2

Withdrawn

• Conditions: Head and Neck Cancer; Depression
• Interventions: Drug: Placebo; Drug: Venlafaxine

• Registration Number: NCT05724849
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

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).

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 Timeline

• Study First Submitted: 2023-01-31
• Study First Submitted QC: 2023-02-09
• Study First Posted: 2023-02-13
• Study Start: 2023-08-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-15
• Last Update Posted: 2024-01-18
• Primary Completion: 2026-08-01
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

6. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Venlafaxine	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.
Observation	Venlafaxine	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.

Primary Outcome Measures

Name	Time	Method
Prevention of Depression	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.

Secondary Outcome Measures

Name	Time	Method
Prevention of Pain	4 months post-operatively	Duration of opioid use post-surgery in all patients enrolled. This will be assessed using the opioid diary.
Prevention of Anxiety	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.
Quality of Life Improvement	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.
Treatment of Depression	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.