Evidence Table 2Dysthymia

STUDY:Authors: Barrett, et. al.99
Year: 2001
Country: US
FUNDING:Hartford Foundation, MacArthur Foundation
DESIGN:Study design: RCT (also used a behavior therapy arm)
Setting: Primary care settings
Sample size: 241
INTERVENTION:
Drug:ParoxetinePlaceboBehavior Therapy
Dose:10–40 mg/dN/AN/A
Duration:11 weeks11 weeks11 weeks
INCLUSION:Age 18–59; met DSM II-R criteria for dysthymia or minor depression and score 10 or higher on HAM-D-17; illness at least 4 weeks with at least 3 symptoms; diagnosis made by research psychiatrist using PRIME-MD
EXCLUSION:(from Williams et al., 2000) major depression; psychosis; schizophrenia or schizoaffective disorder; bipolar disorder; alcohol or other substance abuse within the past 6 months; borderline or antisocial personality disorder; serious suicidal risk; moderate or severe cognitive impairment (MMSE ≤ 23); medical illness with prognosis ≤ 6 months to live; patients in current treatment excluded unless willing to discontinue and dose ≤ 50 mg of amitriptylline
OTHER MEDICATIONS/INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Age: Mean 44.1
Gender (% female): 63.9%
Ethnicity: Non-Hispanic white: 90%, Asian Pacific: 3%, African American: 3%, Native American: 3%, Hispanic: < 1%
Other population characteristics: Comorbid anxiety disorders: 25%, employed FT: 61.3%, mean # of chronic medical conditions: 2.1, Duke Severity of Illness mean 13.3
OUTCOME ASSESSMENT:Measures and timing of assessments: Primary Outcome was 13 items from the Hopkins Symptom Check list
Depression Scale (HSCL-D-20) plus 7 additional items. Timing: baseline and each treatment visit (1, 2, 4, 6, 8, 11), also measured: Ham-D-17 and SF36, mental health component and physical health component timing: baseline, 6 and 11 weeks
RESULTS:
  • ITT analysis: mean decrease in HSCL-D-20; paroxetine: 0.88 (0.08), placebo: 0.85 (0.09); behavior therapy: 0.79 (0.09), no significant differences between arms;
  • remission by HAM-D-17 score ≤ 6: paroxetine: 80%, placebo: 44.4%; behavior therapy: 56.8% (p = 0.008 for difference among all three arms)
  • minor depression: paroxetine 60.7%, placebo 65.6%; behavior therapy 65.5%(p = 0.906 for difference among all three arms)
  • SF 36 results were not compared head to head, they seem to only be compared within groups over time
ANALYSIS:ITT: Yes
Post randomization exclusions: No
ATTRITION:Loss to follow-up: 20.7
Withdrawals due to adverse events: PAR: 7.5
Loss to follow-up differential high: No
ADVERSE EVENTS:Not reported
QUALITY RATING:Fair
STUDY:Authors: Devanand DP, et al.100
Year: 2005
Country: US
FUNDING:NIMH and capsules provided by Eli Lilly
OBJECTIVE:To determine efficacy and side effects of fluoxetine in elderly patients with dysthymia
DESIGN:Study design: RCT
Setting: Depression clinic
Sample size: 90
INTERVENTION:
Drug:FluoxetinePlacebo
Dose:10–60 mg/dayN/A
Duration:12 weeks12 weeks
Sample size:4446
INCLUSION:Outpatients with a primary diagnosis dysthymia following DSM-IV criteria; at least 60 years of age; HAM-D score 8–25; and, CGI-S severity score of 3 or more
EXCLUSION:MDD; allergy to fluoxetine; previous lack of response to SSRI; suicide ideation or plan; Mini-Mental State exam less than 23 out of 30; alcohol or substance abuse in last 6 months; bipolar disorder, schizophrenia or other psychotic disorder; stroke, dementia or other major neurological disorder or insult
OTHER MEDICATIONS/INTERVENTIONS:Zolpidem (up to 10 mg/day) for insomnia and lorazepam (up to 2 mg/day) for anxiety
POPULATION CHARACTERISTICS:Groups similar at baseline: Uncertain; fluoxetine group more likely to be unmarried males with comorbid anxiety disorder and have a family history of affective disorder.
Mean age: fluoxetine: 69.0, placebo: 70.8
Gender (% female): fluoxetine: 32.5%, placebo: 40.9%
Ethnicity (% white): fluoxetine: 86.4%, placebo 89.1%
Other population characteristics:
Married: fluoxetine: 29.6%, placebo: 37%
Family history of affective disorder: fluoxetine: 38.6%, placebo 21.7%
Comorbid anxiety disorder: fluoxetine: 11.4%, placebo 6.5%
HAM-D: fluoxetine: 15.3 (+/− 5.1), placebo: 14.4 (+/− 3.0)
CGI-S: fluoxetine: 3.4 (+/− 0.5), placebo 3.2 (+/− 0.5)
CDRS: fluoxetine: 28.0 (+/− 8.8), placebo 25.2 (+/− 11.5)
OUTCOME ASSESSMENT:Primary Outcome Measures:
  • HAM-D and CDRS
  • Responders classified as having a ≥ 50% decrease in Ham-D scores at final assessment relative to baseline and have a CGI improvement score of 1 or 2
Timing of assessments:
RESULTS:
  • Response rates: fluoxetine: 27.3%, placebo: 19.6% (p < 0.4)
  • No differences between treatment groups in quality of life
  • Only the CDRS scores demonstrated a significant effect for treatment group in regression analysis: fluoxetine 26.2%, placebo 4.6% (p < 0.04)
ANALYSIS:ITT: Yes
Post randomization exclusions: No
ATTRITION:OverallFluoxetinePlacebo
Loss to follow-up:21127
Withdrawals due to adverse events:431
Withdrawals due to lack of efficacy:422
Loss to follow-up differential high:No
ADVERSE EVENTS:
  • The only side effect that differed significantly between the 2 groups was yawning: fluoxetine baseline 2.5%, endpoint 20% vs. placebo baseline 6.3%, endpoint 7.5% (% change p < 0.03)
QUALITY RATING:Good
STUDY:Authors: Ravindran et. al.101
Year: 2000
Country: Canada and Europe
FUNDING:Pfizer
DESIGN:Study design: RCT
Setting: Multi-center
Sample size: 310
INTERVENTION:
Drug:SertralinePlacebo
Dose:50–200 mg/dayN/A
Duration:12 weeks12 weeks
INCLUSION:18 yrs or older; DSM-III-R criteria for dysthymia disorder; duration ≥ 5yrs; ≥ 12 on HAM-D seasonal affective disorders version
EXCLUSION:Pregnancy, lactation or lack of adequate contraception; major depression; history of psychotic disorders; bipolar disorder; previous use of sertraline; clinically relevant disease; unstable medical conditions; use of psychotropic meds
OTHER MEDICATIONS/ INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: sertraline: 46.0; placebo: 44.2
Gender (% female): sertraline: 65.8, placebo: 67.8
Ethnicity: Not reported
Other population characteristics: Early onset (before 21 yrs): sertraline: 38.0%, placebo: 40.8%
Duration of illness: sertraline: 17 years, placebo: 15.9 years
OUTCOME ASSESSMENT:Measures: SIGH-SAD (Hamilton Depression Rating Scale, Seasonal Affective Disorders Version), HAM-A, CGI-I, CGI-S, MADRS, HAD-A, HAD-D (Hospital Anxiety and Depression scale), BQOLS (Batelle Quality of Life Scale)
Timing of assessments: Weeks 1, 2, 4, 6, 8, 12
RESULTS:
  • Patients in the sertraline group had significantly greater reductions in SIGH-SAD (p = 0.03), MADRS (p = 0.02), CGI-S (p = 0.02), CGI-I (p = 0.02), HAD-A (p = 0.003), and HAD-D (p = 0.004) scores compared to placebo
  • The number of responders was significantly higher in the sertraline group
  • HAM-A: sertraline: 51.9%, placebo: 33.8%, p = 0.001
  • MADRS: sertraline: 53.2%, placebo: 37.5%, p =0.006
  • CGI-I: sertraline: 60.1%, placebo: 39.5%, p < 0.001
  • The number of remitters was also significantly higher in the sertraline group 33.8% vs. 21.6%, p = 0.02
  • BQOLS showed significantly greater improvements in 8 of 9 domains in the sertraline group
ANALYSIS:ITT: Yes
Post randomization exclusions: Yes
ATTRITION:Loss to follow-up: 24.2%; sertraline: 23.4%, placebo: 25.0%
Withdrawals due to adverse events: sertraline: 13.3%, placebo: 7.9%
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • More patients in the sertraline group experienced adverse events: 75.3% vs. 64.5% (p = 0.047)
  • Increased sweating: sertraline: 13.9%, placebo: 2%
  • Tremor: sertraline: 13.9%, placebo: 0.7%
  • Nausea: sertraline: 20.9%, placebo: 17.8%
  • Ejaculation disorder: sertraline: 9.3%, placebo: 0
QUALITY RATING:Fair
STUDY:Authors: Thase et. al.,102 Kocsis et. al.,103 Hellerstein et. al.104
Year: 1996, 1997, 2000
Country: US
FUNDING:Not reported
DESIGN:Study design: RCT
Setting: Multi-center (17 US centers)
Sample size: 416
INTERVENTION:
Drug:SertralineImipraminePlacebo
Dose:50–200 mg/day50–300 mg/dayN/A
Duration:12 weeks12 weeks12 weeks
INCLUSION:Dysthymia for more than 5 years without depression-free period exceeding 2 consecutive months; HAM-D score ≥ 12; age 25–65 yrs.
EXCLUSION:Other Axis I disorders; pregnancy, lactation; failed to respond in previous trials; drug/alcohol dependency; suicidal risk
OTHER MEDICATIONS/ INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean Age: 42
Gender (% female): 65%
Ethnicity: Caucasian: 95%, black: 2%, Asian: 0.5%, other: 2%
Other population characteristics: Not reported
OUTCOME ASSESSMENT:Measures and timing of assessment: CGI weekly, HAM-D, MADRS biweekly, DSM-IV, Hopkins Symptom Checklist, Inventory for Depression Symptomatology, Social Adjustment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire weeks 8 and 12
RESULTS:
  • Sertraline group showed significantly more responders than placebo (59.0% vs. 44.3%; p < 0.02)
  • No significant differences in responders between sertraline and imipramine-treated patients
  • A significantly greater proportion of patients in the sertraline group increased in psychosocial functioning compared to placebo (61% vs. 45%; p = 0.01) as measured by the Global Assessment of Functioning Score of 71 or more
  • Significant improvements in family relationships, marital relationships, and parental role functioning
  • The harm avoidance scores (from the Tri-dimensional Personality Questionnaire) were significantly decreased in all treatment groups
  • Significantly more sertraline patients than placebo patients were classified as harm avoidance responders (p = 0.001)
ANALYSIS:ITT: Yes
Post randomization exclusions: Yes
ATTRITION:Loss to follow-up: 24.3%; sertraline: 15.7%; imipramine: 33.1%; placebo: 24.3%
Withdrawals due to adverse events: sertraline: 6.0%; imipramine: 18.4%; placebo: 3.6%
Loss to follow-up differential high: Yes
ADVERSE EVENTS:Not reported
QUALITY RATING:Fair
STUDY:Authors: Vanelle et al.105
Year: 1997
Country: France
FUNDING:NR
DESIGN:Study design: RCT
Setting: Psychiatric centers
Sample size: 140
INTERVENTION:
Drug:FluoxetinePlacebo
Dose:20–40 mgN/A
Duration:phase I: 3 monthsphase 1: 3 months
phase II: 6 monthsphase 2: 6 months
INCLUSION:Adults ≥ 18; minimum HAM-D score of 16; dysthymia not secondary to any other axis I disorder
~
EXCLUSION:Additional mental illnesses or organic mental disorder; MDD or other type of depression; secondary-type dysthymia; uncontrolled serious somatic disease; fluoxetine for a depressive disorder which had not been effective; received a psychotropic drug during the previous week (except for authorized benzodiazepines); requiring one of the following during the study: neuroleptic, lithium, or other mood regulator
OTHER MEDICATIONS/ INTERVENTIONS:NR
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: NR
Gender (% female): fluoxetine: 76.9%, placebo: 73.5%
Ethnicity: NR
Other population characteristics: Early onset of dysthymia: 22.9%, late onset: 77.1%
OUTCOME ASSESSMENT:Primary Outcome Measures: HDRS, CGI

Secondary Outcome Measures: HDRS, HARS, CGI, GAF-S, Paykel Life Event Questionnaire, HSCL-58, AMDP-5

Timing of assessments:
RESULTS:
  • # of responders at month 3 (>50% decrease in HAM-D associated with a score of 1 (very much improved) or 2 (much improved) on the CGI-I): fluoxetine = 42, placebo = 14 (p = 0.03)
  • Remission n at month 3 (HAM-D ≤ 7): fluoxetine = 32, placebo = 10 (p = 0.07) # of responders at month 6: fluoxetine =33, placebo = 9 (p = 0.48)
  • Remission n at month 6: fluoxetine = 29, placebo = 4 (p = 0.01)
  • Increase in GAF scores by month 3 significantly greater in fluoxetine (p = 0.02); mean score indicated return to functioning level compatible with normal social & relational life (mean GAF score = 70)
  • No significant change in GAF scores from month 3 to 6 for either treatment group
ANALYSIS:ITT: Yes
Post randomization exclusions: NR
ATTRITION:Loss to follow-up: Phase I: fluoxetine: 13.2%; placebo: 26.5% Phase II: fluoxetine: 7%; placebo: 31%
Withdrawals due to adverse events: NR
Loss to follow-up differential high: Yes (16.2%)
ADVERSE EVENTS:
QUALITY RATING:Fair
STUDY:Authors: Williams JW, et. al.106
Year: 2000
Country: US
FUNDING:Hartford Foundation, MacArthur Foundation, Smith Kline Beecham supplied meds and placebo, VA (career award to lead author)
DESIGN:Study design: RCT
Setting: Multi-center (Community, VA, and academic primary care clinics)
Sample size: 415
INTERVENTION:
Drug:ParoxetinePlaceboBehavior Therapy
Dose:10–40 mg/dN/AN/A
Duration:11 weeks11 weeks11 weeks
INCLUSION:Age 60 or older; met DSM II-R criteria for dysthymia or minor depression and score 10 or higher on HAM-D-17; symptoms for at least 4 weeks with 3–4 symptoms
EXCLUSION:Major depression; psychosis; schizophrenia or schizoaffective disorder; bipolar disorder; alcohol or other substance abuse within the past 6 months; borderline or antisocial personality disorder; serious suicidal risk; moderate or severe cognitive impairment (MMSE ≤ 23); medical illness with prognosis ≤ 6 months to live; patients in current treatment excluded unless willing to discontinue and dose ≤ 50 mg of amitriptylline
OTHER MEDICATIONS/ INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: 71
Ethnicity: paroxetine: 82.5% white, 11.0% Latino, 6.0% black, placebo: 75.7% white, 12.1% Latino, 10.0% black
Gender (% female): paroxetine: 39%, placebo: 45%
Other population characteristics: Mean of 3.4 medical conditions per patient
OUTCOME ASSESSMENT:Measures: Hopkins Symptom Checklist Depression Scale (HSCL-D-20), HDRS, and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components
Timing of assessments:
RESULTS:
  • Mean (SE) decrease in HSCL-D-20:
    Paroxetine: 0.61 ( p =0.05)
    Placebo: 0.40 (p = 0.05)
    Behavior Therapy 0.52 (p = 0.05)
    p = 0.004 for paroxetine vs. placebo
  • Paroxetine only statistically and clinically significantly better than placebo for subjects with dysthymia and high baseline mental health function.
  • HAM-D results not reported for the ITT population
ANALYSIS:ITT: Yes
Post randomization exclusions: Yes
ATTRITION:Loss to follow-up: 25.1% (for all 3 arms, including behavioral tx)
Withdrawals due to adverse events: Paroxetine: 8.8%, Placebo: 5.7%
Loss to follow-up differential high: No
ADVERSE EVENTS:Not reported
QUALITY RATING:Fair

From: Evidence Tables

Cover of Drug Class Review: Second-Generation Antidepressants
Drug Class Review: Second-Generation Antidepressants: Final Update 5 Report [Internet].
Gartlehner G, Hansen RA, Reichenpfader U, et al.
Portland (OR): Oregon Health & Science University; 2011 Mar.
Copyright © 2011 Oregon Health & Science University.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.