Pilot Study to Evaluate Individualized Choice of Antidepressants in Patients With Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01725048
First received: November 7, 2012
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

This is a pilot study to test the hypothesis that the antidepressants mirtazapine and citalopram are effective treatment for major depressive disorder (MDD) in cancer patients.


Condition Intervention Phase
Major Depressive Disorder
Neoplasms
Drug: Mirtazapine
Drug: Citalopram
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Pilot Study to Evaluate Individualized Choice of Antidepressant in Patients With Cancer

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Feasibility [ Time Frame: One year ] [ Designated as safety issue: No ]
    To determine the feasibility of this pilot study to recruit subjects, as measured by the number of individuals enrolled per month, such that the goal of the study is met in a timely manner.


Secondary Outcome Measures:
  • Depression Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    To assess the short-term (9 week) outcome of mirtazapine or citalopram in cancer patients with major depressive disorder based on mean improvement in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)


Enrollment: 21
Study Start Date: January 2011
Study Completion Date: October 2013
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mirtazapine
Treatment with oral mirtazapine, dosed once daily, for 9 weeks, with starting dose of 7.5 milligrams (mg) daily up to 30mg daily.
Drug: Mirtazapine
7.5mg by mouth once a day at night. If subject has not had a 50% or greater reduction in the PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable adverse effects, then the dose may be escalated first to 15mg by mouth every night and then to 30mg by mouth every night.
Other Name: Remeron
Active Comparator: Citalopram
Treatment with Citalopram, once daily, for 9 weeks, with dosages starting at 10mg once daily to 40mg once daily.
Drug: Citalopram
Citalopram 10mg by mouth once daily. If the subject has not had a 50% or greater reduction in PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable side effects, then the dose may be escalated first to 20mg by mouth every day and then to 40mg by mouth once a day.
Other Name: Celexa

Detailed Description:

Major depressive disorder (MDD) is a debilitating illness associated with increased mortality and significant impairment in quality of life. The prevalence of MDD is particularly high in patients with cancer, as much as 38% in some studies.

The study of depression in cancer patients is particularly important, as these co-morbid illnesses can frequently complicate the management of each other. In addition to affecting quality of life, poorly controlled depression can affect cancer treatment adherence and can lead to poor treatment outcomes.

Depression can be challenging to diagnose in patients with cancer. A spectrum of depressive symptoms can be seen, ranging from appropriate sadness in response to a life threatening diagnosis, to a major depressive episode. The diagnosis is confounded by the symptoms brought on by the cancer and its treatment, such as fatigue, insomnia, anorexia, and pain. Medications commonly used in cancer patients such as narcotics, benzodiazepines, antihistamines, steroids, antibiotics, chemotherapy, and endocrine therapy can all lead to side effects that further confuse the picture. However, while challenging, evidence does suggest that a valid diagnosis of depression can be made in this patient population.

The current standard for diagnosing MDD is the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR), which was published in 2000 by the American Psychiatric Association. The diagnosis is made based on an interview between the patient and physician in which nine criteria are assessed, including depressed mood, anhedonia, weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and recurrent thoughts of death. In patients with cancer, the diagnosis of MDD is more often based on anhedonia and feelings of worthlessness, as depressed mood, weight fluctuation, and sleep disturbance can be symptoms of the underlying cancer itself. Once the diagnosis has been made, there are several tools which have been created and validated for the purpose of assessing the severity of depression and for following the severity over time. The tool we intend to use in this study is the PHQ-9.

Therapy for MDD in the general population includes both psychotherapy and pharmacological intervention. However, the optimal therapy of MDD in cancer patients remains uncertain. Very few placebo controlled trials have been performed in this population, and there is currently no uniformly accepted standard of care. Some of the evidence from studies in depressed but otherwise medically healthy patients may be applicable to cancer patients, but there are several factors which complicate the treatment of depression in this group. For example, the overlap of symptoms between depression and the underlying malignancy can confound the diagnosis, as discussed earlier. Simultaneous treatment of the underlying malignancy introduces adverse effects from surgery, chemotherapy, or radiation, as well as an increased likelihood of drug-drug interactions. Finally, co-morbid conditions such as cancer pain can contribute to the depression, requiring simultaneous therapy. As a result of these unique factors, the treatment of MDD in cancer patients cannot necessarily be approached using the standard recommendations for the general population.

There is scant evidence supporting the effectiveness of pharmacologic therapy in cancer patients with MDD. In the last 25 years only four placebo controlled trials have been published, and of these only two have shown a statistically significant improvement in depression scores with active treatment.

Additional studies are needed to evaluate some of the newer antidepressants within the cancer population and to assess whether this strategy of matching side effects to symptoms is beneficial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with a malignancy
  • Informed consent obtained and signed
  • Greater than or equal to 18 years of age
  • Life expectancy determined to be greater than or equal to 6 months
  • Diagnosed with Major Depressive Disorder based on clinical examination and the DSM-IV-TR criteria
  • PHQ-9 depression assessment completed by subject, with a score of 10 or greater
  • Able to take whole or crushed tablets by mouth or by feeding tube

Exclusion Criteria:

  • Unable to complete self-report instruments due to illiteracy, neurologic illness, visual problems, inability to speak or read English, or other causes
  • Treatment with antidepressants or antipsychotics within the last 3 months
  • Psychotic or manic behavior
  • Active suicidal ideation or plan
  • Current illicit substance abuse
  • Severe renal impairment as defined by creatinine clearance of <15 milliliters/minute/1.73 meters squared (mL/min/m2)
  • Severe hepatic impairment as defined by Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit of normal, or a total bilirubin > 3.0 milliliters/deciliter (mL/dL)
  • History of congenital long QT syndrome
  • Clinically significant congestive heart failure or bradyarrhythmias
  • Treatment with a concomitant medication that is known to have a strong association with corrected QT interval (QTc) prolongation AND a QTc >460 for men or >470 for women. Applicable to the citalopram arm only
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725048

Locations
United States, North Carolina
University of North Carolina Hospital
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Eliza Park, MD University of North Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01725048     History of Changes
Other Study ID Numbers: LCCC1021
Study First Received: November 7, 2012
Last Updated: October 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Major depressive disorder
Neoplasms

Additional relevant MeSH terms:
Neoplasms
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Citalopram
Mirtazapine
Dexetimide
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antidepressive Agents, Second-Generation
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on July 23, 2014