~6x
Patients who showed
early improvement* with an antidepressant (within 2 weeks) were ~6x more likely to achieve remission5
*In a meta-analysis of 17 randomized, double-blind, placebo-controlled trials of 14,779 adult patients with MDD, early improvement was defined as a ≥20% or ≥25% reduction in Hamilton Depression Rating Scale (HAMD)/Montgomery-Åsberg Depression Rating Scale (MADRS) sum score of depression severity from baseline to day 7 or 14 of treatment. Remission was defined as a cut-off score ≤7 in the HAMD or ≤12 in the MADRS at the end of treatment.5
Achieving response and remission with current antidepressants can take 5–8 weeks—if it occurs at all3,4
The challenge of achieving response3
Nearly half of patients on antidepressants failed to respond (46% vs 63% with placebo)†
The challenge of achieving remission4
- Mean time to remission was >6 weeks with a first-line antidepressant‡
- ~2 in 3 patients failed to achieve remission with a first-line antidepressant‡
Mean time to remission was >6 weeks with a first-line antidepressant‡
~2 in 3 patients failed to achieve remission with a first-line antidepressant‡
†Meta-analysis of 182 randomized double-blind, placebo-controlled trials (between 1980-2007) of acute antidepressant monotherapy for treatment of adults with MDD. Clinical response was defined as a ≥50% reduction in Hamilton Depression Rating Scale or Montgomery-Åsberg Depression Rating Scale scores from baseline to endpoint or a Clinical Global Impression Scale score <3 at final visit.3
‡The STAR*D Study enrolled 4,041 adult patients with MDD. In treatment step 1, patients (N=3,671) received antidepressant monotherapy. Those who did not achieve remission (QIDS-SR16 score <5) or were unable to tolerate treatment were eligible for the next step. Steps 2 to 4 included several switch and augmentation choices. QIDS-SR16=Quick Inventory of Depressive Symptomology (Self-Report)-16 item.4
Delayed onset of antidepressants was associated with prolonged depressive episodes that limit quality of life5,6§||
Lack of early response to antidepressants was associated with6||:
Multiple patient visits to the physician’s office
Long-term psychological dysfunction
Treatment adherence challenges
§Based on a meta-analysis of 17, randomized, double-blind, placebo-controlled trials of 14,779 adult patients with MDD that assessed the predictive power of early improvement on later response and remission of MDD.5
||According to a 2010 review assessing the impact of the timing of antidepressant effects on various therapies used to treat MDD.6
Inadequate therapeutic response to a first-line antidepressant may lead to dose increases, switching, and/or augmentation7,8
~3 in 4 patients initiating an antidepressant had a treatment change by the end of a 1-year follow-up period.9¶
According to an analysis of 2,280 adults with MDD treated with an antidepressant, the proportion of patients with severely impaired quality of life increased from10#:
~50% after 1 line of therapy
~70% after 4 lines of therapy
~50%after 1 line of therapy
~70% after 4 lines of therapy
¶Based on a retrospective, observational analysis of IBM MarketScan US commercial claims data from January 1, 2017– December 31, 2018. Treatment patterns (persistence, discontinuation, switch, combination, and augmentation) were analyzed for patients with MDD starting first-line antidepressant monotherapy for up to 12 months following their antidepressant initiation index date.9
#Based on an analysis of 2,280 adult MDD out-patients treated with an antidepressant therapy that examined quality of life at the entry and exit of each of the four levels of the acute treatment phase, as well as the 12-month follow-up phase, of the STAR*D study. Quality of life (QOL) was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q).10
Antidepressant side effects can have a negative impact on patients and their adherence to treatment1,2,11
- Side effects frequently persist well past the initial treatment period1,11
- Up to one third of patients who discontinued antidepressants early** cited side effects as a reason2,11**
**Based on a telephone survey of patients (N=272) on antidepressant therapy in general practitioner practices published in 2001 in which 23% of patients dropped out due to adverse events after a mean period of 6.5 weeks, and a 6-month study from January 2004–January 2005 of patients newly treated for MDD (N=135) in a general psychiatric clinic. In the latter study, early discontinuation was defined as within 2 months from starting the antidepressant.2,11
Early symptom improvement in PPD
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The multiple mechanisms involved in depression
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References: 1. Hu XH, Bull SA, Hunkeler EM. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry. 2004;65(7):959-965. 2. Hung C-I, Wang S-J, Liu C-Y. Comorbidities and factors related to discontinuation of pharmacotherapy among outpatients with major depressive disorder. Compr Psychiatry. 2011;52(4):370-377. 3. Papakostas GI, Fava M. Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol. 2009;19:34-40. 4. Rush AJ, Travedi MH, Wisniewski SR. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11)1905-1917. 5. Wagner S, Engel A, Engelmann J, et al. Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with major depressive disorder: systematic review and meta-analysis. J Psychiatric Res. 2017;94:96-106. 6. Machado-Vieira R, Baumann J, Wheeler-Castillo C, et al. The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and Somatic Treatments. Pharmaceuticals (Basel). 2010;3(1):19-41. 7. Sicras-Mainar, Maurino J, Cordero L, et al. Assessment of pharmacological strategies for management of major depressive disorder and their costs after an inadequate response to first-line antidepressant treatment in primary care. Ann Gen Psychiatry. 2012;11:22-3. 8. Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009:70(suppl 6):16-25. 9. Zhu L, Ferries E, Suthoff E, et al. Economic burden and antidepressant treatment patterns among patients with major depressive disorder in the United States. JCMP. 2022;28(11):S1-S13. 10. IsHak WW, Mirocha J, James D, et al. Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up. Acta Psychiatr Scand. 2015;131(1):51-60. 11. Demyttenaere K-O, Enzlin P, Dewé W. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J Clin Psychiatry. 2001;62(suppl 22):30-33.