down
When someone is taking an
antidepressant for depression
accepting symptoms or side
effects without speaking up
Depressettling
(de • PRESS • seh • tuh • ling)
Related phrases include:
“Nah, I’m ok”, “Ah, it’s fine”, or “It is what it is”.
Despite many available
treatment options, including
psychotherapy and antidepressants,
depression remains the 
Despite many available
treatment options, including
psychotherapy and antidepressants,
depression remains the 
The ongoing COVID-19 pandemic has posed additional challenges for treating patients with depression.4
Antidepressants can be an effective option for the treatment of major depressive disorder (MDD).1 But for many, they can have limitations, like residual symptoms or side effects.5-13 It can be hard for patients to talk about them, so they might not speak up.14-16
We're here to help foster conversations about the MDD treatment experience.
What is
If patients with MDD are still experiencing residual symptoms or side effects with their antidepressant, they may brush them off, or put off talking about them with you.5-13
Whether they realize it or not, they may
be settling with them17 - depressettling.
See how
we're helping
patients open up.
Patient website
Antidepressants can have a number of limitations, including:
Delayed time to symptom relief6,18
Delayed onset is a major limitation of existing antidepressants.6
They often take weeks to months to achieve response and remission, which commonly disrupts patients' personal, professional and social lives.6
Reducing the delay in antidepressants' onset of effect and improving remission rates continues to be important research goals.6
Residual symptoms and
low remission rates5-12,19
The goal of MDD treatment has shifted from response to remission.17
The goal of MDD treatment has shifted from response to remission.17
While response has been defined as a ≥50% reduction in total symptom severity; symptomatic remission has been defined as minimal residual symptom as measured as an absolute cutoff score, such as ≤7 on the HAM-D or <5 on the PHQ-9, among others.17†‡
Helping patients with MDD achieve symptomatic remission is critical to helping them function as they did before they experienced MDD symptoms.17
Many patients experienced inadequate relief from the initial MDD treatment.20,21
of patients with MDD (67.1%) did not reach remission with the first-level treatment in the large STAR*D trial (N=3,761), measured by QIDS-SR16 score20*
*STAR*D=Sequenced Treatment Alternatives to Relieve Depression, a study in an adult outpatient sample with nonpsychotic major depressive disorder who received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. The first-level treatment was an antidepressant. QIDS-SR16=Quick Inventory of Depressive Symptomatology-Self-Report (16 items); Remission=QIDS-SR16 score ≤5 at exit from the indicated treatment step. †HAM-D=Hamilton Rating Scale for Depression (17 items). ‡PHQ-9=9-item Patient Health Questionnaire
A therapy's ability to help patients achieve remission is critical.
Patients who don't reach remission have been shown to be at greater risk for17,20-24:
- Relapse or recurrence
- More rapid relapse
- More long-term depressive episodes
- Fewer symptom-free weeks
Side effects13
Common side effects can include13:
- Sexual dysfunction
- Nausea and vomiting
- Weight gain
- Diarrhea
- Sleep disturbances
In a large review
of antidepressant efficacy trials,
of patients experienced at least one adverse event during their treatment.9*
*Based on 93 head-to-head studies and 48 additional studies (of both experimental and observational design), comparing the benefits and harms of second-generation antidepressants for treating major depressive disorder in adults.9
Along with interfering with patients' quality of life, side effects can25:
- Prevent the adequate dose titration patients need to receive a full therapeutic dose
- Disrupt the goal of helping patients stay on treatment long enough to achieve remission and prevent relapse and recurrence
- Of MDD patients who discontinued their antidepressant, ~1 in 4 did so due to undesirable side effects in a study (N=272)26,27â€
†Based on a study of MDD patients receiving antidepressant therapy, designed to investigate when and why patients stop treatment and whether they inform their doctors. Patients completed an antidepressant compliance questionnaire, and were telephoned monthly while they continued on antidepressant therapy, up to 6 months.26
What’s happening in MDD?
The monoamine hypothesis, involving serotonin, norepinephrine and dopamine, has dominated our understanding of depression and pharmacological approaches to its management.7,28,29
But, other neurotransmitters are
also thought to be involved in the pathophysiology of depression, including glutamate, the primary excitatory neurotransmitter in the brain.7,12,27,28,30
Fortunately, the understanding of MDD continues to evolve, and we are committed to highlighting the science of MDD and the experiences of patients living with this condition.6,7,17
We’re opening the conversation about the MDD treatment experience
We know you go above and beyond for your patients with MDD, and we want to help.
We're committed to helping foster open, ongoing discussions between patients being treated for major depressive disorder and their doctors, to help patients share more of what they're going through with their treatment. Because the more you know, the easier it may be to find the best option for them. And we're dedicated to creating resources for depression education, empowerment, and support.1,31
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for updates
from AXSOME
References: 1. Depression Basics. National Institute of Mental Health website; https://www.nimh.nih.gov/health/publications/depression/index.shtml. Updated 2016. Accessed February 4, 2021. 2. Depression - January 30, 2020. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/depression. Published 2020. Accessed February 4, 2020. 3. Depression and Other Mental Health Disorders: Global Health Estimates (2017). World Health Organization. https://apps.who.int/iris/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf. Accessed February 4, 2021. 4. Moreno C, Wykes T, Galderisi S, et al. How mental health care should change as a consequence of the COVID-19 pandemic. Lancet. 2020;7:813-824. doi:10.1016/ S2215- 0366(20)30307-2. 5. Goldberg JF and Rush AJ. Addressing the unmet needs of current antidepressants: does neuroscience help or hinder clinical psychopharmacology research? Exp Opin Pharmacotherapy. 2017;18(14):1417- 1420, doi: 10.1080/14656566.2017.1363178. 6. Machado-Viera R, Salvadore G, Luckenbaugh DA, et al. Rapid Onset of Antidepressant Action: A New Paradigm in the Research and Treatment of Major Depression. J Clin Psych. 2008;69(6): 946-958. doi: 10.4088/jcp.v69n0610. 7. Hillhouse TM and Porter JH. A brief history of the development of antidepressant drugs: From monoamines to glutamate. Exp Clin Psychopharmacol. 2015;23(1): 1–21. doi:10.1037/a0038550. 8. Corey-Lisle PK, Nash R, Stang P, et al. Response, Partial Response, and Nonresponse in Primary Care Treatment of Depression. Arch Intern Med. 2004;164:1197-1204. doi:10.1001/archinte.164.11.1197. 9. Gartlehner G, Hansen RA, Morgan LC, et al. Comparative Benefits and Harms of Second-Generation Antidepressants for Treating Major Depressive Disorder: An Updated Meta-analysis. Ann Intern Med. 2011;155:772-785. doi: 10.7326/0003- 4819-155-11-201112060-00009. 10. Machado M and Einarson TR. Comparison of SSRIs and SNRIs in major depressive disorder: a meta-analysis of head-to-head randomized clinical trials. J Clin Pharm Ther. 2010;35:177-188. doi:10.1111/j.1365-2710.2009.01050.x. 11. Dawson MY, Michalak EE, Waraich P, et al. Is remission of depressive symptoms in primary care a realistic goal? A meta-analysis. BMC Fam Practice. 2004;5(19) doi:10.1186/1471-2296-5-19. 12. Duman RS, Sanacora G, and Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019;102:75-90.doi:10.1016/j.neuron.2019.03.013. 13. Depression: FDA-Approved Medications May Help. U.S. Food & Drug Administration website. https://www.fda.gov. April 2017. Accessed February 4, 2020. 14. Unützer J and Park M. Strategies to Improve the Management of Depression in Primary Care. Prim Care. 2012;39(2):415-431. doi:10.1016/j.pop.2012.03.010. 15. Bell RA, Franks P, Duberstein PR, et al. Suffering in Silence: Reasons for Not Disclosing Depression in Primary Care. Ann Fam Med. 2011;9:439-446. doi:10.1370/afm.1277. 16. Mago R, Fagiolini A, Weiller E, et al. Understanding the emotions of patients with inadequate response to antidepressant treatments: results of an international online survey in patients with major depressive disorder. BMC Psychiatry. 2018;18(33): 1-9. doi:10.1186/s12888-018-1625-y. 17. Culpepper L, Muskin PR, and Stahl SM. Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability. Am J Med. 2015;128: S1-S15. doi: 10.1016/j.amjmed.2015.07.001. 18. Otte C, Gold SM, Penninx BW, et al. Major Depressive Disorder. Nature Rev. 2016;2:1-20. doi:10.1038/nrdp.2016.65. 19. Oluboka OJ, Katzman MA, Habert J, et al. Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient. Int J Neuropsychopharmacol. 2018;21(2):128-144. doi:10.1093/ijnp/pyx081. 20. Rush AJ, Trivedi MH, Wisniewski SR, et al. 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. doi: 10.1176/ajp.2006.163.11.1905. 21. Halfin A. Depression: The Benefits of Early and Appropriate Treatment. Am J Manag Care. 2007;13:S92-S97. PMID: 18041868. 22. Mendlewicz J. Towards achieving remission in the treatment of depression. Dialogues Clin Neurosci. 2008;10(4):371-375. doi: 10.31887/DCNS.2008.10.4/jmendlewicz. 23. Paykel ES. Partial remission, residual symptoms, and relapse in depression. Dialogues Clin Neurosci. 2008;10(4):431-437. doi:10.31887/ DCNS.2008.10.4/espaykel. 24. Kelsey JE. Achieving Remission in Major Depressive Disorder: The First Step to Long-Term Recovery. J Am Osteo Assoc. 2004;104:S6-S10. 25. Kelly K, Posternak M, and Alpert JE. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-418. doi: 10.31887/DCNS.2008.10.4/kkelly. 26. Demyttenaere K, Enzlin P, Dewé W, et al. Compliance with Antidepressants in a Primary Care Settling, 1: Beyond Lack of Efficacy and Adverse Events. J Clin Psychiatry. 2001;62(22):30-33. PMID: 11599645. 27. Musazzi L, Trecani G, and Popoli M. Glutamate hypothesis of depression and its consequences for antidepressant treatments. Exp Rev Neurother. 2012;12(10):1-4. doi:10.1586/ern.12.96. 28. Holtzheimer PE and Nemeroff CB. Future prospects in depression research. Dialogues Clin Neurosci. 2006;8:175-189. Available at: https://www.researchgate.net/publication/6897933_Future_prospects_in_depression_research. 29. Davoudian PA and Wilkinson ST. Clinical overview of NMDA-R antagonists and clinical practice. Adv Pharmacol. 2020;89:103-129. doi: 10.1016/bs.apha.2020.04.004. 30. Sanacora G, Trecani G, and Popoli M. Towards a glutamate hypothesis of depression: An emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacol. 2012;62(1): 63-77. doi:10.1016/j.neuropharm.2011.07.036. 31. Addressing Stigma. Centre for Addiction and Mental Health website; https://www.camh.ca/en/driving-change/addressing-stigma. Accessed February 4, 2020.
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