A Review of the Clinical, Economic, and Societal Burden of Treatment-Resistant Depression: 1996–2013
Abstract
Objective
Methods
Results
Conclusions
Methods
Results
Literature search and study characteristics
Treatment-resistant depression | Treatment-responsive depression | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N | % | Median(%) | Minimum(%) | Maximum(%) | N ofstudies | N | % | Median(%) | Minimum(%) | Maximum(%) | N ofstudies | |||||
Characteristic | M | SD | M | SD | M | SD | M | SD | ||||||||
Sample size | 1,239 | 4,756 | 42 | 6 | 24,415 | 49 | ||||||||||
Age (M±SD) | 46.7 | 5.3 | 47.0 | 27.4 | 74.7 | 39 | ||||||||||
Age at onset (M±SD) | 31.5 | 6.8 | 27.7 | 2.9 | 51.2 | 12 | ||||||||||
Duration of illness (M±SD years) | 4.4 | 3.3 | 16.7 | 2.5 | 26.7 | 20 | ||||||||||
Previous episodes of depression (M±SD) | 3.8 | 2.1 | 2.6 | .8 | 7.2 | 16 | ||||||||||
Women | 14,310 | 6,086 | 71 | 4 | 65 | 0 | 93 | 42 | ||||||||
Race-ethnicity | ||||||||||||||||
Caucasian | 3,060 | 1,765 | 89 | 4 | 91 | 78 | 97 | 12 | ||||||||
African American | 29 | 24 | 13 | 9 | 3 | 2 | 18 | 3 | ||||||||
Other | 6 | 3 | 4 | 3 | 3 | 0 | 7 | 3 | ||||||||
Comorbid conditionb | ||||||||||||||||
Joint, limb, or back pain | 3,386 | 73 | 1 | 5,267 | 70 | 1 | ||||||||||
Hypertension | 3,095 | 607 | 67 | 0 | 40 | 12 | 68 | 2 | 5,035 | 903 | 67 | 9 | 43 | 17 | 68 | 2 |
Dyslipidemia | 2,821 | 556 | 61 | 0 | 32 | 1 | 62 | 2 | 4,739 | 853 | 63 | 11 | 34 | 3 | 64 | 2 |
Cardiovascular disease | 2,598 | 56 | 1 | 3,702 | 666 | 49 | 9 | 25 | 1 | 50 | 2 | |||||
Malaise and fatigue | 2,412 | 52 | 1 | 3,311 | 44 | 1 | ||||||||||
Anxiety | 1,767 | 1,265 | 44 | 0 | 21 | 7 | 59 | 6 | 2,512 | 1,557 | 36 | 16 | 13 | 9 | 43 | 3 |
Anemia | 3 | 39 | 1 | 2,633 | 35 | 1 | ||||||||||
Hypothyroidism | 1,593 | 312 | 35 | 5 | 23 | 11 | 35 | 2 | 2,147 | 385 | 29 | 4 | 18 | 7 | 29 | 2 |
Chronic obstructive pulmonary disease | 1,577 | 34 | 1 | 2,257 | 30 | 1 | ||||||||||
Diabetes | 1,358 | 499 | 30 | 0 | 15 | 8 | 32 | 3 | 2,295 | 411 | 31 | 4 | 20 | 10 | 31 | 2 |
Alcohol abuse, lifetime | 16 | 10 | 27 | 7 | 28 | 14 | 30 | 3 | 47 | 34 | 1 | |||||
Alcohol abuse, current | 231 | 173 | 6 | 2 | 5 | 3 | 8 | 3 | 180 | 116 | 3 | 1 | 2 | 1 | 3 | 2 |
Avoidant personality disorder | 18 | 2 | 24 | 7 | 28 | 20 | 30 | 2 | 35 | 33 | 1 | |||||
Asthma | 974 | 21 | 1 | 1,354 | 18 | 1 | ||||||||||
Self-defeating personality disorder | 11 | 21 | 1 | 15 | 14 | 1 | ||||||||||
Chronic pain | 878 | 251 | 20 | 1 | 16 | 15 | 20 | 3 | 1,162 | 490 | 19 | 3 | 21 | 18 | 23 | 2 |
Substance use disorder, lifetime | 8 | 4 | 18 | 12 | 14 | 7 | 39 | 3 | 30 | 22 | 1 | |||||
Substance use disorder, current | 56 | 42 | 3 | 1 | 43 | 1 | 4 | 2 | 37 | 2 | 1 | |||||
Obsessive-compulsive disorder | 13 | 2 | 17 | 4 | 18 | 15 | 21 | 2 | 39 | 37 | 1 | |||||
Panic disorder | 48 | 34 | 17 | 7 | 18 | 7 | 25 | 5 | 17 | 12 | 1 | |||||
Delusions and other psychoses | 774 | 151 | 17 | 2 | 13 | 9 | 17 | 2 | 444 | 80 | 6 | 1 | 4 | 2 | 6 | 2 |
Obesity | 774 | 152 | 17 | 3 | 10 | 3 | 17 | 2 | 1,037 | 185 | 14 | 1 | 104 | 6 | 14 | 2 |
Personality disorder | 728 | 142 | 16 | 2 | 11 | 6 | 16 | 2 | 296 | 53 | 4 | 0 | 43 | 2 | 4 | 2 |
Sleep disorder | 694 | 252 | 16 | 2 | 13 | 9 | 16 | 2 | 978 | 13 | 1 |
Baseline patient characteristics
Scale range | |||||||||
---|---|---|---|---|---|---|---|---|---|
Variable | M | SD | Median | Lowest | Highest | N of studies | Remissionor mild | Severe ormarkedly ill | Reference |
Failed drug trialsb | 4.7 | 2.7 | 2.6 | 1.0 | 10.0 | 11 | |||
Failed drug classesb | 2.1 | .3 | 2 | 2.0 | 3.0 | 6 | |||
Depression-specific scale score | |||||||||
HAM-D-17 | 21.9 | 1.7 | 22.6 | 19.2 | 28.4 | 18 | 0–13 | 20–52 | 22 |
HAM-D-21 | 19.8 | 5.2 | 19.5 | 15.8 | 23.2 | 2 | 0–15 | 23–64 | 22 |
HAM-D-24 | 27.9 | 4.2 | 27.9 | 21.0 | 33.7 | 4 | 0–18 | 27–75 | 22 |
HAM-D-28 | 30.4 | 5.5 | 32.2 | 23.7 | 34.3 | 3 | 0–10 | 21–52 | 23 |
MADRS | 31.8 | 3.0 | 33.0 | 25.0 | 50.0 | 12 | 0–19 | 35–60 | 22 |
CGI-S | 4.6 | .4 | 4.8 | 3.8 | 6.3 | 11 | 1–3 | 6–7 | 24 |
BDI | 30.9 | 6.6 | 31.7 | 16.5 | 38.2 | 5 | 0–18 | 30–63 | 22 |
IDS-SR-30 | 41.3 | 2.0 | 40.8 | 38.2 | 43.4 | 3 | 0–25 | 39–84 | 22 |
IDS-C-30 | 35.4 | 1 | 0–23 | 37–84 | 22 | ||||
QIDS-SR-16 | 15.8 | 2.5 | 15.8 | 14.0 | 17.6 | 2 | 0–10 | 16–27 | 22 |
QIDS-C-16 | 14.4 | 1 | 0–10 | 16–27 | 22 | ||||
Other scale score | |||||||||
GAF | 50.0 | 7.0 | 42.3 | 28.7 | 55.0 | 6 | 100–61 | 50–0 | 25 |
HAMA | 17.8 | 1.1 | 19.6 | 17.5 | 23.3 | 4 | 0–17 | 31–56 | 26 |
Q-LES-Q | 37.4 | 1.2 | 37.3 | 34.6 | 41.0 | 3 | 100 | 0 | 26 |
BPRS | 17.3 | 6.9 | 25.9 | 16.0 | 35.8 | 2 | 16–31 | 53–126 | 27 |
SF–36 MCS | 22.5 | 2.7 | 21.6 | 19.4 | 23.7 | 2 | 100 | 0 | 28 |
SF–36 PCS | 37.5 | 3.1 | 36.5 | 34.0 | 38.9 | 2 | 100 | 0 | 28 |
BAI | 14.1 | 1 | 0–15 | 26–63 | 29 | ||||
MMSE | 27.7 | 1 | 24–30 | 0–23 | 30 | ||||
SQ-SS | 6.6 | 1 | 0 | 18 | 31 | ||||
SQ-SWB | 1.4 | 1 | 6 | 0 | 31 | ||||
POMS | 52.5 | 1 | 0 | 200 | 32 |
Symptom severity
Comorbid conditions
Response and remission rates
Study | Ratingscaleb | Lengthof study(weeks) | N ofpatients | Treatment with lowest rate of response or remission | Treatment with highest rate of response or remission | Response (%) | Remission (%) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
Average | Lowest | Highest | Average | Lowest | Highest | ||||||
Inoue et al., 1996 (50) | HAM-D-17 | 6 | 6 | Bromocriptine | 67 | ||||||
Shelton et al., 2001 (51) | MADRS | 8 | 34 | Olanzapine | Olanzapine and fluoxetine | 25 | 0 | 60 | |||
Papakostas et al., 2003 (35) | HAM-D-17 | 6 | 92 | Nortriptyline; patients with comorbid avoidant personality disorder | Nortriptyline; patients without comorbid avoidant personality disorder | 42 | 17 | 49 | |||
Seidman et al., 2005 (49) | HAM-D-17 | 6 | 23 | Placebo | Testosterone | — | 23 | 54 | |||
Corya et al., 2006 (52) | MADRS | 7 | 483 | Olanzapine | Venlafaxine (response); olanzapine and fluoxetine combination (remission) | 38 | 25 | 50 | 23 | 14 | 30 |
Fava et al., 2006 (8) | QIDS-SR-16 | 14 | 235 | Mirtazapine | Nortriptyline | 15 | 13 | 17 | 10 | 8 | 12 |
Fava et al., 2006 (8) | HAM-D-17 | 14 | 235 | Mirtazapine | Nortriptyline | 16 | 12 | 20 | |||
Doree et al., 2007 (46) | HAM-D-17 | 8 | 20 | Lithium | Quetiapine | 65 | 50 | 80 | 60 | 40 | 80 |
Doree et al., 2007 (46) | MADRS | 8 | 20 | Lithium | Quetiapine | 65 | 50 | 80 | 55 | 30 | 80 |
Mahmoud et al., 2007 (48) | HAM-D-17 | 6 | 258 | Placebo | Risperidone | — | 30 | 46 | 25 | 11 | 25 |
Schindler and Anghelescu, 2007 (45) | HAM-D-17 | 8 | 34 | Lithium | Lamotrigine | 47 | 41 | 53 | 21 | 18 | 23 |
Avery et al., 2008 (17) | MADRS | 9 | 158 | Sham, then transcranial magnetic stimulation (TMS) | Extended TMS | 40 | 34 | 45 | 25 | 18 | 31 |
Avery et al., 2008 (17) | MADRS | 6 | 158 | Sham, then TMS | Extended TMS | 35 | 26 | 42 | 16 | 11 | 20 |
Avery et al., 2008 (17) | HAM-D-24 | 6 | 158 | Sham, then TMS | Extended TMS | 37 | 32 | 42 | 22 | 16 | 27 |
Avery et al., 2008 (17) | HAM-D-24 | 9 | 158 | Sham, then TMS | Extended TMS | 39 | 32 | 46 | 29 | 19 | 37 |
Bares et al., 2008 (9) | MADRS | 4 | 25 | Venlafaxine | 48 | ||||||
Karp et al., 2008 (47) | HAM-D-17 | 6.9 | 20 | Duloxetine | 50 | ||||||
Lozano et al., 2008 (53) | HAM-D-17 | 26 | 20 | Deep brain stimulation | 60 | ||||||
Lozano et al., 2008 (53) | HAM-D-17 | 52 | 20 | Deep brain stimulation | 55 | 35 | |||||
Bewernick et al., 2010 (23) | HAM-D-28 | 52 | 11 | Deep brain stimulation | 46 | 9 | |||||
Kopell et al., 2011 (44) | HAM-D-28 | 91 | 11 | Epidural cortical stimulation | 46 | 36 | |||||
Taneja et al., 2012 (54) | MADRS | 6 | 1,034 | Meta-analysis: antidepressant | 30 | 20 | 39 | ||||
Taneja et al., 2012 (54) | MADRS | 6 | 540 | Meta-analysis: aripiprazole with antidepressant | 49 | 41 | 60 | ||||
Taneja et al., 2012 (54) | MADRS | 6 | 309 | Meta-analysis: quetiapine 150 mg with antidepressant | 34 | 28 | 40 | ||||
Taneja et al., 2012 (54) | MADRS | 6 | 312 | Meta-analysis: quetiapine 300 mg with antidepressant | 38 | 32 | 44 | ||||
Taneja et al., 2012 (54) | MADRS | 6 | 200 | Meta-analysis: olanzapine and fluoxetine | 45 | 32 | 64 | ||||
Average±SD (weighted)c | 6±20 | 176±234 | 36±1 | 26±1 | 45±1 | 20±1 | 13±1 | 25±1 |
Medication-related adverse events
Quality of life and costs
Category | M | SDb | Median | Lowest | Highest | N ofstudies |
---|---|---|---|---|---|---|
Treatment-resistant depression | ||||||
Health care (direct costs) | ||||||
Depression drugs | 2,667 | 1,026 | 3,736 | 1,346 | 7,568 | 4 |
Nondepression drugs | 2,556 | 141 | 2,580 | 2,216 | 2,963 | 3 |
Hospitalizations | ||||||
Emergency care | 392 | — | — | — | — | 1 |
Nonpsychiatric medical care | 2,508 | 786 | 2,986 | 2,253 | 3,719 | 2 |
Psychiatric visits | 593 | 324 | 790 | 488 | 1,092 | 2 |
Physician visits | 4,829 | 2,431 | 3,351 | 1,085 | 5,618 | 2 |
Psychotherapy | 978 | 344 | 770 | 449 | 1,090 | 2 |
Totalc | 13,196 | 219 | 13,402 | 13,152 | 14,417 | 3 |
Productivity (indirect costs) | ||||||
Absenteeism | 2,625 | 987 | 2,025 | 1,105 | 2,945 | 2 |
Disability | 4,299 | 815 | 3,804 | 3,044 | 4,564 | 2 |
Total | 6,924 | 1,801 | 5,829 | 4,149 | 7,509 | 2 |
Total direct and indirect costs | 20,120 | |||||
Treatment-responsive depression | ||||||
Health care (direct costs) | ||||||
Depression drugs | 898 | 162 | 561 | 385 | 939 | 3 |
Nondepression drugs | 1,407 | 75 | 1,369 | 1,094 | 1,422 | 3 |
Hospitalizations | ||||||
Emergency care | 224 | — | — | — | — | 1 |
Nonpsychiatric medical care | 1,438 | 119 | 1,418 | 1,332 | 1,505 | 2 |
Psychiatric visits | 99 | 23 | 95 | 79 | 112 | 2 |
Physician visits | 1,708 | 1,864 | 2,021 | 666 | 3,376 | 2 |
Psychotherapy | 255 | 176 | 284 | 156 | 412 | 2 |
Totalc | 7,715 | 456 | 6,902 | 6,375 | 7,832 | 3 |
Productivity (indirect costs) | ||||||
Absenteeism | 1,125 | 849 | 1,268 | 651 | 1,885 | 2 |
Productivity | 1,751 | 464 | 1,829 | 1,492 | 2,166 | 2 |
Total | 2,876 | 1,312 | 3,096 | 2,142 | 4,050 | 2 |
Total direct and indirect costs | 10,592 |
Discussion
Conclusions
Acknowledgments and disclosures
Supplementary Material
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