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