Depression, Parkinson Disease
Conditions
Keywords
Parkinson's disease, Parkinson disease, depression, antidepressants, nortriptyline, paroxetine
Brief summary
The goal of this study is to evaluate the effectiveness and safety of two antidepressants--nortriptyline and paroxetine, compared to placebo in patients with Parkinson's disease and depression.
Detailed description
Depression is the most common neuropsychiatric disorder found in patients with Parkinson's disease (PD). It causes immense personal suffering and is associated with increased disability and caregiver burden. Despite the adverse consequences of depression in patients with PD, there are virtually no empirical data to guide clinical treatment. This study will begin to answer some questions on the treatment of depression by testing a SSRI (selective serotonin reuptake inhibitor) antidepressant, paroxetine, a tricyclic antidepressant, nortriptyline, and placebo in a placebo-controlled trial. A total of 75 patients with PD will be randomized to each of the three arms in a balanced design.
Interventions
DRUGparoxetine
Paroxetine CR 12.5 - 25 mg q hs
DRUGNortriptyline
nortriptyline 25 - 75 mg q hs
OTHERplacebo
matching placebo
Sponsors
GlaxoSmithKline
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Parkinson's disease without dementia. * Depression. * Males or females.
Exclusion criteria
* Psychosis * Heart block
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Scale | 8 weeks | total score on HDRS (0-54 higher score is worse) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Responders | 8 weeks | Percent of patients who had a 50% decrease in total HDRS at 8 weeks |
Countries
United States
Participant flow
Recruitment details
Patients were recruited between 10/2003 and 7/2007, from the RWJMS movement disorder clinic and advertising to local support groups.
Pre-assignment details
Patients who met inclusion and not exclusion criteria were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Nortriptyline Dosing was flexible with decisions on dose being made at each visit (or between visits if the patient was having troublesome side effects) based on efficacy and tolerability. Nortriptyline was started at 25mg and could be increased up to 75 mg. | 17 |
| Paroxetine Paroxetine CR was started at 12.5 mg and could be increased up to 37.5 mg. | 18 |
| Placebo Placebo was started at 1 pill and could be increased up to three pills. | 17 |
| Total | 52 |
Baseline characteristics
| Characteristic | Paroxetine | Placebo | Nortriptyline | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 6 Participants | 7 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 10 Participants | 31 Participants |
| Age, Continuous | 62.8 years STANDARD_DEVIATION 8.1 | 61.4 years STANDARD_DEVIATION 9.2 | 62.9 years STANDARD_DEVIATION 9.3 | 62.2 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment United States | 18 participants | 17 participants | 17 participants | 52 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 6 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 17 | 7 / 18 | 11 / 17 |
| serious Total, serious adverse events | 0 / 17 | 1 / 18 | 2 / 17 |
Outcome results
Primary
Hamilton Depression Scale
total score on HDRS (0-54 higher score is worse)
Time frame: 8 weeks
Population: intent to treat - total patients in the arm
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nortriptyline | Hamilton Depression Scale | 10.84 units on a scale | Standard Deviation 6.2 |
| Paroxetine | Hamilton Depression Scale | 12.45 units on a scale | Standard Deviation 6.36 |
| Placebo | Hamilton Depression Scale | 15.81 units on a scale | Standard Deviation 5.78 |
Secondary
Percent Responders
Percent of patients who had a 50% decrease in total HDRS at 8 weeks
Time frame: 8 weeks
Population: intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nortriptyline | Percent Responders | 53 percent of patients who were responders |
| Paroxetine | Percent Responders | 11 percent of patients who were responders |
| Placebo | Percent Responders | 24 percent of patients who were responders |
Comparison: For the responder analysis, an LOCF approach was used in which a clinical response was operationally defined as at least a 50% reduction in the HAM-D score from baseline to 8 weeks. Clinical response was cross-tabulated with treatment and Fisher exact test was used to distinguish differences among these groups.p-value: <0.0595% CI: [0.8, 15.9]Fisher Exact