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A Parallel-group, Double-blind, Placebo-controlled Study of Methylphenidate as an Add on Therapy for Mirtazapine in the Treatment of Major Depressive Disorder in Cancer Patients Under Palliative Care


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Depression

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Trial Information

A Parallel-group, Double-blind, Placebo-controlled Study of Methylphenidate as an Add on Therapy for Mirtazapine in the Treatment of Major Depressive Disorder in Cancer Patients Under Palliative Care


Background

Cancer remains one of the most feared illnesses and the diagnosis of cancer has huge
psychological impact on the patients and their care-takers (Knobf, 2007). Depression is one
the most common psychiatric sequella (Derogatis et al., 1983)2 and affects the quality of
life, compliance to treatment, disease advancement, tolerability to pain and fatigue in
cancer patients (Bennett et al., 2004; Sommerset, 2004; Green et al., 2009). However, it is
likely that depression is under-recognized and under-treated in cancer patients
(Kadan-Lottick et al., 2005).

Depressed feelings manifest in a spectrum ranging from normal sadness to a variety of mood
disturbances and clinical presentations. It is challenging to differentiate clinical
depression from "normal" emotional distress in cancer patients and the somatic symptoms such
as fatigue, loss of appetite or weight, sleep difficulties, poor memory and concentration
may mirror the physiological symptoms caused by cancer or its treatment (McDaniel and
Musselman, 1995; Masie and Popkin, 1998; Cochinov, 2001; Jesse et al., 2008). This
complicates the diagnosis of depression in cancer patients (McDaniel and Musselman, 1995;
Masie and Popkin, 1998; Cochinov, 2001; Pasquini and Biond, 2007; Jesse et al., 2008).

Many studies have investigated the prevalence of depression in cancer in the past decades. A
previous review by Mc Daniel et al, reported a prevalence of major depression ranging from
4.8% to 9.2% based on studies using standardized diagnostic interviews on cancer
outpatients. Prevalence rates were higher in the admitted cancer patients (8% for Major
Depression and 15% to 36% for all depressive disorders)(McDaniel and Musselman, 1995). A
preliminary systematic review on the prevalence of depression in cancer patients was
conducted by the investigator of this study. It showed that major depressive disorder was as
high as 10.8% in cancer patients based on structured clinical interview.

In addition to the high prevalence, uncertainty exists with respect to the optimal treatment
of depression in cancer. Although a huge number of studies investigated the efficacy of
pharmacotherapy for depression in general population, the number of randomized, controlled
trials of antidepressants on depression in cancer patient conducted is limited(Challman and
Lipsky, 2000; Raison and Miller, 2003). A comprehensive systematic review looking into the
effectiveness and tolerability of antidepressant treatment in depressed cancer patients was
performed and published by Rodin et al in 2007. Although 7 trials were identified, the
authors commented that the number of positive randomized trials was limited and there is a
need for more rigorous studies on other newer agents or alternative treatment option (Raison
and Miller, 2003). The preliminary systematic review conducted by the investigator of this
study also came to the same conclusion.

Psychostimulants such as methylphenidate have been proposed for the treatment of depressed
patients because of their rapid onset of action (Masand and Tesar, 1995; Challman and
Lipsky, 2000; Rozans et al., 2002; Kaminski and Sjogren, 2007). They may have antidepressant
effects and may be advantageous due to the rapid onset of action (Candy et al., 2008). Some
studies suggest they provide a safe and effective treatment of depression in cancer patients
(Masand and Tesar, 1995) and alleviates opioid induced somnolence, improve cognitive
function and ameliorate pain in cancer patients. Another potential advantage of the use of
psychostimulant in the cancer patients is the ability to improve multiple somatic symptoms
irrespective of the etiology (Vigano et al., 1995). However, the number of studies looking
into the efficacy of psychostimulant in improving depressive mood in cancer is limited.

Five studies were identified from the review conducted by the investigator of this study.
Although they showed positive result on the use of methylphenidate in depressed cancer
patients, they were open-label and without control group. There is only one double blind,
randomised placebo controlled study on the use of methylphenidate in cancer patients which
was published in French language (Laval, 2008).Considering the lack of randomized controlled
trial on the topic, the need of study on the efficacy and tolerability of psychostimulant
such as methylphenidate as an add on therapy of depression in cancer patients is inevitably
needed.

Primary Objective To determine the efficacy of Methylphenidate as add on therapy to
mirtazapine in the treatment of depression in cancer patients

Secondary Objective

1. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in the
treatment of anxiety in cancer patients.

2. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in
reducing distress in cancer patients.

3. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in
improving function in cancer patients.

4. To determine the efficacy of Methylphenidate as add on therapy to mirtazapine in
reducing somatic complaints in cancer patients.

Study Design

Design An open label, parallel group, placebo controlled study on methylphenidate as add on
therapy to mirtazapine.

Procedure Subjects will be male or female with current diagnosis of cancer of any types and
DSM-IV diagnoses of major depressive disorder. They are identified from the oncology,
surgical and palliative clinics and wards. Depressive symptoms will be measured at screening
with the MADRS.

Sixty (120) subjects will be recruited and started on the mirtazapine 30mg at night. They
will be then randomized to one of two groups (60 subjects per group): Methylphenidate or
Placebo as add on therapy. All treatment will be initiated after screening and continued for
28 days of outpatient or inpatient treatment. Efficacy evaluation will be take place at
baseline, day 3, day 6, 9, 14, 21 and day 28.

At the end of the 28 days, the continuation of treatment will be depends on the
investigator's clinical judgment and End of Medication Evaluation will be perform. Every
effort will be made to continue to evaluate all subjects who are randomized even if they
decide to discontinue the medication.

Project Timetable The project will take 2 years. The plan is to randomize 2 subjects per
week, taking about 15 month to acquire 120 subjects. All subjects will have completed study
drug treatments before 18 months have elapsed. Follow-up evaluations will be completed 2
year from the start of the project.

Primary Study Endpoints

The primary endpoints to be measured in this study are:

- MADRS at the baseline, Day 3, 6, 9, 14, 21 and 28.

Secondary Study Endpoints

The secondary endpoints to be measured are:

- Anxiety with HADS at baseline, Day 3, 6, 9, 14, 21 and 28

- Distress score with distress thermometer at baseline, Day 3, 6, 9, 14, 21 and 28

- Karnofsky Scale at the baseline, Day 3, 6, 9, 14, 21 and 28

- Numeric Rating Scale (NRS) for Pain at the baseline, Day 3, 6, 9, 14, 21 and 28

- Visual Analogue Scale (VAS) for Fatigue at the baseline, Day 3, 6, 9, 14, 21 and 28

Primary Safety Endpoints The primary safety endpoint will be measurement and collection of
any serious adverse event that occurs from initial study treatment through and including 14
days after cessation of study treatment.


Inclusion Criteria:



1. Male or female, aged >18 years.

2. Current DSM IV diagnosis of Major Depressive Disorder.

3. Under palliative care.

4. Confirmed diagnosis of cancer.

5. Not on any antidepressants

Exclusion Criteria:

1. Clinical significant abnormal laboratory values.

2. Clinically significant abnormal ECG.

3. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder,
organic brain disorder, dementia etc.)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

depressive symptoms

Outcome Description:

measured with Montgomery-├ůsberg Depression Rating Scale

Outcome Time Frame:

3 to 28 days

Safety Issue:

No

Principal Investigator

Chong Guan Ng, MBBS, MPM

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Psychological Medicine, University Malaya Medical Centre

Authority:

Malaysia: Medical Ethical Comittee, University Malaya Medical Centre

Study ID:

NCG001

NCT ID:

NCT01497548

Start Date:

March 2011

Completion Date:

October 2012

Related Keywords:

  • Depression
  • Depression
  • cancer
  • methylphenidate
  • pharmacotherapy
  • Depression
  • Depressive Disorder
  • Depressive Disorder, Major

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