DepressionPhase 4NCT00602290
Effectiveness of Methylphenidate in Improving Cognition and Function in Older Adults With Depression
A Phase 4 study testing Citalopram and Methylphenidate (MPH) in people with Depression, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of methylphenidate in improving cognition and function in older adults with depression. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Depression
- What is being tested?
- Citalopram and Methylphenidate (MPH)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 181 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Feb 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
- Score of 16 or higher on the 24-item Hamilton Depression Rating Scale (HDRS) at study entry
- Score of 26 or higher on the Mini-Mental State Exam (MMSE)
Who cannot join
- History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
- Presence of psychotic symptoms
- Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
- Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
- Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
- Toxic or metabolic abnormalities on laboratory examination
Show all 19Show fewer
- Medications taken or medical illnesses present that could account for depression
- Active heart failure categorized as Class III or greater according to New York Heart Association criteria
- Heart attack or crescendo angina within the 3 months prior to study entry
- Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease
- Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds
- Second or third degree atrioventricular block
- Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry
- Treated with depot neuroleptic therapy within 6 months prior to study entry
- Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors (MAOIs)) prior to the first administration of study medication
- Known allergy to citalopram or MPH or history of ineffective treatment with citalopram or MPH for current depressive episode
- Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either citalopram or MPH
- Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry
- Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Semel Institute - Neuropsychiatric Institute (NPI)
Los Angeles, California, 90095
About this study
Official title: The Use of Methylphenidate to Improve Clinical Outcomes in Geriatric Depression: A Double-blind Placebo-Controlled Trial of Methylphenidate (Ritalin) Augmentation of Citalopram (Celexa) in Depressed Elderly Patients
This study will evaluate the safety and effectiveness of methylphenidate in improving cognition and function in older adults with depression.
Read the detailed description
Less than 50% of older adults with depression achieve remission and functional recovery in response to first-line antidepressant treatment. Most are left with significant residual symptoms, putting them at risk for illness relapse, frailty, and suicide. Improved understanding of the neurobiology of depression in older adults and mechanisms of treatment response may lead to better clinical management of depression. Methylphenidate (MPH) has long been used in the elderly and the medically ill to provide rapid improvement in depression, apathy, and fatigue. However, its potential beneficial effects on cognitive and functional outcomes in older adults with depression have not been studied. Combining MPH with the serotonergic antidepressant citalopram may result in better clinical outcomes than would using citalopram alone. This study will compare the safety and effectiveness of MPH combined with citalopram, MPH combined with placebo, and citalopram combined with placebo in improving thinking, memory, and speed of recovery in older adults with depression. The study will also evaluate selected dopamine- and serotonin-related gene relationships with mood, cognitive symptoms, and treatment response to MPH and citalopram.
Participation in this double-blind study will last 16 weeks. All potential participants will initially undergo comprehensive medical, neuropsychiatric, and cognitive assessments and genetic testing. These initial assessments will include questionnaires about depressive symptoms, a medical history, an electrocardiogram (ECG), and a blood draw for the genetic testing. Eligible participants will then be randomly assigned to one of three groups: MPH and citalopram, MPH and placebo, or citalopram and placebo. All participants will receive 16 weeks of treatment with their assigned medications. Study visits will occur weekly for the first 6 weeks of treatment and bi-weekly for the remainder of the study. During study visits, participants will undergo vital sign and weight measurements, answer questionnaires, and report any medication side effects. Blood will again be drawn at Visits 4 and 10, and the ECG will be repeated at Visit 10 if any cardiac symptoms occur. Most initial assessments will be repeated on Visit 13, the last study visit. Participants will also be contacted weekly by phone throughout the study to answer questions on how they are feeling and any possible side effects.
- Conditions
- Depression
- Being tested
- Citalopram, Methylphenidate (MPH), Placebo
- Keywords
- Major Depression, Geriatric Major Unipolar Depression, Executive Cognitive Dysfunction, Elderly, Geriatric, Executive Cognitive Impairment, Quality of Life, Disability, Comorbidity, Medical Burden, Safety, Candidate Genes
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramDrug
Also called Celexa
Citalopram dosage will be 20 to 60 mg a day prior to FDA warning limiting it to 20-40 mg in 2011. Participants will begin taking one 20-mg capsule once per day for 4 weeks, and this dosage may be increased or decreased depending on the participant's response to the medication or side-effect profile. Participants will continue on their assigned dosage of citalopram that will be titrated up after week 4 if clinical global impressions (CGI) scores were > 2 until treatment completion.
Methylphenidate (MPH)Drug
Also called Ritalin
MPH dosage will be 5 to 40 mg a day. Participants will initially take 1 capsule (2.5 mg) twice per day, which will be increased to a maximum up to 8 x 2.5 mg capsules twice per day. After Visit 11, MPH dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
PlaceboDrug
Placebo pills will be taken in combination with the active pills. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 16 capsules twice per day matching methylphenidate, and 1-3 capsules matching citalopram. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
| Study group | Role | What they receive |
|---|---|---|
| 1 - Citalopram and placebo | Active comparator | Participants will take a combination of citalopram and placebo for 16 weeks Receives: Drug: Citalopram; Drug: Placebo |
| 2 - Methylphenidate and placebo | Active comparator | Participants will take a combination of methylphenidate and placebo for 16 weeks Receives: Drug: Methylphenidate (MPH); Drug: Placebo |
| 3 - Methylphenidate and Citalopram | Active comparator | Participants will take a combination of methylphenidate and citalopram for 16 weeks Receives: Drug: Citalopram; Drug: Methylphenidate (MPH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16
The Hamilton Depression Rating Scale (HDRS) is a 24-item depression scale and the total score is summed with a minimum score=0 and maximum score=76. There are no subscales and the higher values represent a worse outcome. Outcomes are measured and defined as follows: 1) Response will be defined as HDRS scores of 10 or less; 2) Sustained response will be defined as maintained response at week 16; 4) Remission will be defined as HDRS scores of 6 or less.
Measured: Maintained response measured at Week 16
Secondary outcomes (1)
Quality of Life Assessment
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16 item self-administered questionnaire that captures life satisfaction over the past week. Each question is rated on a 5 point scale from 1 (Very Poor) to 5 (Very Good). The total score is reported for items 1-14. The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70 with higher values representing a better outcome.
Measured: Measured at Baseline and Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study startFeb 2008
- Primary completionJan 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Helen Lavretsky, MD, University of California, Los Angeles
- Investigators
- Helen Lavretsky, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00602290
- Sponsor's protocol ID
- R01MH077650
- Other IDs
- R01MH077650, DATR A4-GPX
- Status last verified
- Dec 2017
- First submitted
- 23 Jan 2008
- Last updated
- 11 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Schneider B, Ercoli L, Siddarth P, Lavretsky H. Vascular burden and cognitive functioning in depressed older adults. Am J Geriatr Psychiatry. 2012 Aug;20(8):673-81. doi: 10.1097/JGP.0b013e31822ccd64.
PubMed 21857219Eyre HA, Eskin A, Nelson SF, St Cyr NM, Siddarth P, Baune BT, Lavretsky H. Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study. Int J Geriatr Psychiatry. 2016 May;31(5):510-7. doi: 10.1002/gps.4356. Epub 2015 Oct 15.
PubMed 26471432
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Methylphenidate to Improve Clinical Outcomes in Geriatric Depression: A Double-blind Placebo-Controlled Trial of Methylphenidate (Ritalin) Augmentation of Citalopram (Celexa) in Depressed Elderly Patients
- ClinicalTrials.gov ID
- NCT00602290
- Acronym / sponsor ID
- R01MH077650
- Conditions
- Depression
- Keywords
- Major Depression, Geriatric Major Unipolar Depression, Executive Cognitive Dysfunction, Elderly, Geriatric, Executive Cognitive Impairment, Quality of Life, Disability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2008
- Primary completion
- Jan 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 28 Jan 2008 (estimated)
- Results
- Posted 1 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of methylphenidate in improving cognition and function in older adults with depression.
Detailed description
Less than 50% of older adults with depression achieve remission and functional recovery in response to first-line antidepressant treatment. Most are left with significant residual symptoms, putting them at risk for illness relapse, frailty, and suicide. Improved understanding of the neurobiology of depression in older adults and mechanisms of treatment response may lead to better clinical management of depression. Methylphenidate (MPH) has long been used in the elderly and the medically ill to provide rapid improvement in depression, apathy, and fatigue. However, its potential beneficial effects on cognitive and functional outcomes in older adults with depression have not been studied. Combining MPH with the serotonergic antidepressant citalopram may result in better clinical outcomes than would using citalopram alone. This study will compare the safety and effectiveness of MPH combined with citalopram, MPH combined with placebo, and citalopram combined with placebo in improving thinking, memory, and speed of recovery in older adults with depression. The study will also evaluate selected dopamine- and serotonin-related gene relationships with mood, cognitive symptoms, and treatment response to MPH and citalopram.
Participation in this double-blind study will last 16 weeks. All potential participants will initially undergo comprehensive medical, neuropsychiatric, and cognitive assessments and genetic testing. These initial assessments will include questionnaires about depressive symptoms, a medical history, an electrocardiogram (ECG), and a blood draw for the genetic testing. Eligible participants will then be randomly assigned to one of three groups: MPH and citalopram, MPH and placebo, or citalopram and placebo. All participants will receive 16 weeks of treatment with their assigned medications. Study visits will occur weekly for the first 6 weeks of treatment and bi-weekly for the remainder of the study. During study visits, participants will undergo vital sign and weight measurements, answer questionnaires, and report any medication side effects. Blood will again be drawn at Visits 4 and 10, and the ECG will be repeated at Visit 10 if any cardiac symptoms occur. Most initial assessments will be repeated on Visit 13, the last study visit. Participants will also be contacted weekly by phone throughout the study to answer questions on how they are feeling and any possible side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 - Citalopram and placebo | Active comparator | Drug: Citalopram, Drug: PlaceboParticipants will take a combination of citalopram and placebo for 16 weeks |
| 2 - Methylphenidate and placebo | Active comparator | Drug: Methylphenidate (MPH), Drug: PlaceboParticipants will take a combination of methylphenidate and placebo for 16 weeks |
| 3 - Methylphenidate and Citalopram | Active comparator | Drug: Citalopram, Drug: Methylphenidate (MPH)Participants will take a combination of methylphenidate and citalopram for 16 weeks |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Meets Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
- Score of 16 or higher on the 24-item Hamilton Depression Rating Scale (HDRS) at study entry
- Score of 26 or higher on the Mini-Mental State Exam (MMSE)
Key exclusion criteria (19 listed)
- History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
- Presence of psychotic symptoms
- Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
- Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
- Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CitalopramAlso: CelexaCitalopram dosage will be 20 to 60 mg a day prior to FDA warning limiting it to 20-40 mg in 2011. Participants will begin taking one 20-mg capsule once per day for 4 weeks, and this dosage may be increased or decreased depending on the participant's response to the medication or side-effect profile. Participants will continue on their assigned dosage of citalopram that will be titrated up after week 4 if clinical global impressions (CGI) scores were > 2 until treatment completion. | Drug | 1 - Citalopram and placebo, 3 - Methylphenidate and Citalopram |
| Methylphenidate (MPH)Also: RitalinMPH dosage will be 5 to 40 mg a day. Participants will initially take 1 capsule (2.5 mg) twice per day, which will be increased to a maximum up to 8 x 2.5 mg capsules twice per day. After Visit 11, MPH dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules. | Drug | 2 - Methylphenidate and placebo, 3 - Methylphenidate and Citalopram |
| PlaceboPlacebo pills will be taken in combination with the active pills. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 16 capsules twice per day matching methylphenidate, and 1-3 capsules matching citalopram. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules. | Drug | 1 - Citalopram and placebo, 2 - Methylphenidate and placebo |
Primary outcome
Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16
Time frame: Maintained response measured at Week 16
The Hamilton Depression Rating Scale (HDRS) is a 24-item depression scale and the total score is summed with a minimum score=0 and maximum score=76. There are no subscales and the higher values represent a worse outcome. Outcomes are measured and defined as follows: 1) Response will be defined as HDRS scores of 10 or less; 2) Sustained response will be defined as maintained response at week 16; 4) Remission will be defined as HDRS scores of 6 or less.
1 secondary outcome
Quality of Life Assessment
Time frame: Measured at Baseline and Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21857219Schneider B, Ercoli L, Siddarth P, Lavretsky H. Vascular burden and cognitive functioning in depressed older adults. Am J Geriatr Psychiatry. 2012 Aug;20(8):673-81. doi: 10.1097/JGP.0b013e31822ccd64.
- Derived from this study: PubMed 26471432Eyre HA, Eskin A, Nelson SF, St Cyr NM, Siddarth P, Baune BT, Lavretsky H. Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study. Int J Geriatr Psychiatry. 2016 May;31(5):510-7. doi: 10.1002/gps.4356. Epub 2015 Oct 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Lavretsky, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Citalopram and Methylphenidate (MPH) in people with Depression, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16 (time frame: Maintained response measured at Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00602290, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2018.