Treatment-resistant depression (TRD) represents a considerable global health concern. The goal of the InSight study was to investigate the prevalence of TRD and to evaluate its clinical characterization and management, compared with nonresistant depression, in primary care centres.
Methods:
Physicians completed a case report on a consecutive series of patients with major depressive disorder (n = 1212), which captured patient demographics and comorbidity, as well as current and past medication.
Results:
Using failure to respond to at least 2 antidepressants (ADs) from different classes as the definition of TRD, the overall prevalence was 21.7%. There were no differences in prevalence between men and women or among ethnicities. Patients with TRD had longer episode duration, were more likely to receive polypharmacy (for example, psychotropic, lipid-lowering, and antiinflammatory agents), and reported more AD related side effects. Higher rates of disability and comorbidity (axes I to III) were associated with treatment resistance. Obesity and being overweight were also associated with treatment resistance. While the selection and sequencing of pharmacotherapy by family physicians in this sample was in line with recommendations from evidence-based treatment guidelines, the wait time to make a change in treatment was 6 to 8 weeks in both groups, which exceeds guideline recommendations.
Conclusions:
These real-world data demonstrate the high prevalence of TRD in primary care settings, and underscore the substantial burden of illness associated with TRD.
UstunTBAyuso-MateosJLChatterjiS.Global burden of unipolar depressive disorders in the year 2000. Br J Psychiatry. 2004;184:386–392.
2.
LernerDHenkeRM. What does research tell us about depression, job performance, and work productivity?J Occ Environ Med. 2008;50:401–410.
3.
OlchanskiNMcInnis MyersM, The economic burden of treatment-resistant depression. Clin Ther. 2013;35:512–522.
4.
MalhiGSParkerGBCrawfordJ, Treatment-resistant depression: Resistant to definition?Acta Psychiatr Scand. 2005;112:302–309.
5.
GibsonTBJingYSmith CarlsG, Cost burden of treatment resistance in patients with depression. Am J Manag Care. 2010;16:370–377.
6.
IvanovaJIBirnbaumHGKidoleziY, Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder. Curr Med Res Opin. 2010;26:2475–2484.
RushAJTrivediMHWisniewskiSR, Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Am J Psychiatry. 2006;163:1905–1917.
10.
SheltonRCOsuntokunOHeinlothAN, Therapeutic options for treatment-resistant depression. CNS Drugs. 2010;24:131–161.
11.
ThaseMECoryaSAOsuntokunO, A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007;68:224–236.
12.
PapakostasGISheltonRC. Use of atypical antipsychotics for treatment-resistant major depressive disorder. Curr Psychiatry Rep. 2008;10:481–486.
13.
BermanRMFavaMThaseME, Aripiprazole augmentation in major depressive disorder: A double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14:197–206.
14.
El-KhaliliNJoyceMAtkinsonS, Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: A multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2010;23:1–16.
15.
RizviSJDonovanMGiacobbeP, Neurostimulation therapies for treatment resistant depression: A focus on vagus nerve stimulation and deep brain stimulation. Int Rev Psychiatry. 2011;23:424–436.
16.
FagioliniAKupferDJ. Is treatment-resistant depression a unique subtype of depression?Biol Psychiatry. 2003;53:640–648.
17.
FekaduAWoodersonSCMarkopouloK, What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies. J Affect Disord. 2009;116:4–11.
18.
SoueryDOswaldPMassatI, Clinical factors associated with treatment resistance in major depressive disorder: Results from a European multicenter study. J Clin Psychiatry. 2007;68:1062–1070.
19.
CarneyRMFreedlandKE. Treatment-resistant depression and mortality after acute coronary syndrome. Am J Psychiatry. 2009;166:410–417.
20.
DuhameauBFerréJCJanninP, Chronic and treatment-resistant depression: A study using arterial spin labeling perfusion MRI at 3Tesla. Psychiatry Res. 2010;182:111–116.
21.
LambertGJohanssonMAgrenH, Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: Evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry. 2000;57:787–793.
22.
PriceRBShunguDCMaoX, Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: Relationship to treatment resistance in major depressive disorder. Biol Psychiatry. 2009;65:792–800.
23.
AnttilaSViikkiMHuuhkaK, TPH2 polymorphisms may modify clinical picture in treatment-resistant depression. Neurosci Lett. 2009;464:43–46.
24.
ViikkiMSamiAOlliK, Vascular endothelial growth factor (VEGF) polymorphism is associated with treatment resistant depression. Neurosci Lett. 2010;477:105–108.
GaynesBNRushAJTrivediMH, Major depression symptoms in primary care and psychiatric care settings: A cross-sectional analysis. Ann Fam Med. 2007;5:126–134.
27.
StegengaBTKamphuisMHKingM, The natural course and outcome of major depressive disorder in primary care: The PREDICT-NL study. Soc Psychiatry Psychiatr Epidemiol. 2012;47:87–95.
28.
OrnsteinSStuartGJenkinsR.Depression diagnoses and antidepressant use in primary care practices: A study from the Practice Partner Research Network (PPRNet). J Fam Pract. 2000;49:68–72.
29.
RegierDANarrowWERaeDS, The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50:85–94.
30.
StaffordRSAusielloJCMisraB, National patterns of depression treatment in primary care. Prim Care Companion J Clin Psychiatry. 2000;2:211–216.
31.
WittchenHUPittrowD.Prevalence, recognition and management of depression in primary care in Germany: The Depression 2000 study. Hum Psychopharmacol. 2002;17(Suppl 1):S1–S11.
32.
PattenSBBeckC.Major depression and mental health care utilization in Canada: 1994 to 2000. Can J Psychiatry. 2004;49:303–309.
33.
KennedySH. A review of antidepressant therapy in primary care: Current practices and future directions. Prim Care Companion CNS Disord. 2013;15:e1–e9.
34.
McIntyreRSKonarskiJZManciniDA, Measuring the severity of depression and remission in primary care: Validation of the HAMD-7 scale. CMAJ. 2005;173:1327–1334.
35.
KroenkeKSpitzerRLWilliamsJB. The PHQ-9: Validity of a brief depression severity measure. J Gen Int Med. 2001;16:606–613.
36.
MontgomerySAÅsbergM.New depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:3829.
37.
BeckATSteerRABallR, Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996;67:588–597.
38.
WardenDTrivediMHWisniewskiSR, Predictors of attrition during initial (citalopram) treatment for depression: A STAR*D report. Am J Psychiatry. 2007;164:1189–1197.
39.
DudekDRybakowskiJKSiwekM, Risk factors of treatment resistance in major depression: Association with bipolarity. J Affect Disord. 2010;126:268–271.
40.
ShergillSSRobertsonMMSteinG, Outcome in refractory depression. J Affect Disord. 1999;54:287–294.
41.
O'LearyDALeeAS. Seven year prognosis in depression: Mortality and readmission risk in the Nottingham ECT cohort. Br J Psychiatry. 1996;169:423–429.
42.
McIntyreRSMcCannSMKennedySH. Antipsychotic metabolic effects: Weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry. 2001;46:273–281.
43.
KloiberSIsingMReppermundS, Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62:321–326.
44.
KhanASchwartzKAKoltsRL, BMI, sex and antidepressant response. J Affect Disord. 2007;99:101–106.
45.
UherRMorsOHauserJ, Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affect Disord. 2009;118:147–154.
46.
CapuronLPoitouCMachaux-TholliezD, Relationship between adiposity, emotional status and eating behaviour in obese women: Role of inflammation. Psychol Med. 2011;41:1517–1528.
47.
VicennatiVPasqualiR.Abnormalities of the hypothalamic–pituitary–adrenal axis in non-depressed women with abdominal obesity and relations with insulin resistance: Evidence for a central and a peripheral alteration. J Clin Endocrinol Metab. 2000;85:4093–4098.
48.
AholaKVirtanenMHonkonenT, Common mental disorders and subsequent work disability: A population-based Health 2000 Study. J Affect Disord. 2011;134:365–372.
49.
BirnbaumHGKesslerRCKelleyD, Employer burden of mild, moderate, and severe major depressive disorder: Mental health services utilization and costs, and work performance. Depress Anxiety. 2010;27:78–89.
50.
LernerDAdlerDARogersWH, Work performance of employees with depression: The impact of work stressors. Am J Health Promot. 2010;24:205–213.
51.
PattenSBWangJLWilliamsJV, Prospective evaluation of the effect of major depression on working status in a population sample. Can J Psychiatry. 2009;54:841–845.
52.
PattenSBKennedySHLamRW, Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. I. Classification, burden and principles of management. J Affect Disord. 2009;117(Suppl 1):S5–S14.
53.
SharmaVKhanMSmithA.A closer look at treatment resistant depression: Is it due to a bipolar diathesis?J Affect Disord. 2005;84:251–257.
54.
CorreaRAkiskalHGilmerW, Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?J Affect Disord. 2010;127:10–18.
55.
LamRWKennedySHGrigoriadisS, Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009;117(Suppl 1):S26–S43.
56.
KennedySHMilevRGiacobbeP, Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Affect Disord. 2009;117(Suppl 1):S44–S53.
57.
SzegediAJansenWTvan WilligenburgAP, Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: A meta-analysis including 6562 patients. J Clin Psychiatry. 2009;70:344–353.
58.
KudlowPAChaDSMcIntyreRS. Predicting treatment response in major depressive disorder: The impact of early symptomatic improvement. Can J Psychiatry. 2012;57:782–788.
59.
CravenMABlandR.Depression in primary care: Current and future challenges. Can J Psychiatry. 2013;58:442–448.
60.
GaskL.Educating family physicians to recognize and manage depression: Where are we now?Can J Psychiatry. 2013;58:449–455.
61.
ZisookSRushAJHaightBR, Use of bupropion in combination with serotonin reuptake inhibitors. Biol Psychiatry. 2006;59:203–210.
62.
DavidsonJR. Major depressive disorder treatment guidelines in America and Europe. J Clin Psychiatry. 2010;71(Suppl E1):e04.
