IDENTIFYING THE UNMET NEEDS IN THE TREATMENT OF MDD

Stephen M. Stahl, MD, PhD, discusses the unmet needs and treatment challenges in MDD.

WATCH NOW

CHALLENGES OF PATIENT MANAGEMENT IN MDD

/Views/Home/~2/3 of patients do not achieve remission following their first antidepressant therapy.1

Improving remission rates remains an area of need.

According to the STAR*D study, approximately 2 out of 3 patients did not reach remission following their first antidepressant treatment.1 Of those patients who did achieve remission, over 90% had at least 1 residual symptom.2

Remission rates decreased while discontinuation due to side effects increased with each additional change in therapy1
chart showing % rate on left axis, with numbers from 0 to 100, and across bottom copy reads, Step 1, Step 2, Step 3, Step 4, with bar charts above each step - left bar in blue is response, right bar in green is remission. Results - Step 1 shows 48.6 and 36.8; Step 2 shows 28.5 and 30.6, Step 3 shows 16.8 and 13.7, and Step 4 shows 16.3 and 13.0.

In the STAR*D trial, a large study of 3671 patients with MDD, each additional line of antidepressant therapy was associated with decreased rates of remission and increased rates of discontinuation.1

Remission rates decreased while discontinuation due to side effects increased with each additional change in therapy1
chart showing % rate on left axis, with numbers from 0 to 100, and across bottom copy reads, Step 1, Step 2, Step 3, Step 4, with bar charts above each step - left bar in blue is response, right bar in green is remission. Results - Step 1 shows 48.6 and 36.8; Step 2 shows 28.5 and 30.6, Step 3 shows 16.8 and 13.7, and Step 4 shows 16.3 and 13.0.

In the STAR*D trial, a large study of 3671 patients with MDD, each additional line of antidepressant therapy was associated with decreased rates of remission and increased rates of discontinuation.1

Residual symptoms increase risks in MDD

Patients with residual symptoms are at an increased risk for relapse and other serious consequences, including3,4

  • Greater likelihood of experiencing recurrent episodes of MDD
  • Significant psychosocial disability
  • Faster relapse rate
  • More chronic future course of disease
  • Work impairment

Common residual symptoms seen in patients with MDD are depressed mood or diminished interest (anhedonia), cognitive problems, insomnia, and fatigue.2,5

Watch a video on evolving theories in MDD pathophysiology and patient management.

WHAT ARE THE CHALLENGES IN ACHIEVING REMISSION?

Larry Culpepper, MD, MPH, discusses achieving treatment goals for patients with MDD.

WATCH NOW

In one study following patients with MDD in remission after 15 months6

Not all patients with MDD are the same

MDD presents a complex challenge—symptoms, progression, and response vary greatly from patient to patient.7

  • There are over 227 different ways to meet the criteria for MDD in the DSM-5; this means it is possible for 2 patients with MDD to have no symptoms in common.8
  • The neurological basis of depression or the rationale for such symptomatic heterogeneity in these patients has yet to be fully understood.7

DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Not all patients with MDD are the same

MDD presents a complex challenge—symptoms, progression, and response vary greatly from patient to patient.7

  • There are over 227 different ways to meet the criteria for MDD in the DSM-5; this means it is possible for 2 patients with MDD to have no symptoms in common.8
  • The neurological basis of depression or the rationale for such symptomatic heterogeneity in these patients has yet to be fully understood.7

DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Looking beyond the monoaminergic system may be necessary

MDD has been recognized as a heterogeneous disorder that may involve dysfunction in several neural networks that rely on non-monoaminergic signaling.9,10

Currently, all FDA-approved oral antidepressant medications for MDD primarily target the monoamine neurotransmitter system, including the serotonin, norepinephrine, and dopamine receptors.

Primary targets of FDA-approved oral antidepressants are monoaminergic
Chart showing how FDA-approved oral antidepressants target monoamine pathways. On left of chart is listing, from top to bottom TCAs, MAOIs, SSRIs, NDRI, SNRIs, Atypical antipsychotics.  Across top is Monoamines as header, with Serotonin column on left, Norepinephrine column in center, and Dopamine column on right. Across from each name on listing are checkmarks that apply to different pathways: TCAs has serotonin and norepinephrine checked, MAOIs has all 3 checked, SSRIs only has serotonin checked, NDRI has norepinephrine and dopamine checked, SNRIs has serotonin and norepinephrine checked, and Atypical antipsychotics has all 3 checked

MAOIs, monoamine oxidase inhibitors; NDRIs, norepinephrine-dopamine reuptake inhibitors; SNRIs, serotonin-norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.

Exploring how non-monoaminergic systems may contribute to MDD is important in furthering our understanding of MDD. Non-monoaminergic systems may be particularly important in understanding why patients may be unresponsive or partially responsive to antidepressant therapies.
Watch a video on evolving theories in MDD pathophysiology and patient management.

Living with depression – Keith

WATCH NOW

References: 1. 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. 2. Nierenberg AA, Husain MM, Trivedi MH, et al. Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report. Psychol Med. 2010;40(1):41-50. 3. American Psychiatric Association. Practice guideline for the treatment of patent with major depressive disorder, third edition. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Published October 2010. Accessed. April 30, 2019. 4. Miller IW, Keitner GI, Schatzberg AF, et al. The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine. J Clin Pyschiatry. 1998;59(11):608-619. 5. Conradi HJ, Ormel J, de Jonge P. Symptom profiles of DSM-IV-defined remission, recovery, relapse, and recurrence of depression: the role of the core symptoms. Depress Anxiety. 2012;29(7):638-645. 6. Paykel ES, Ramana R, Cooper Z, et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995;25(6):1171-1180. 7. Nelson JC, Pikalov A, Berman RM. Augmentation treatment in major depressive disorder: focus on aripiprazole. Neuropsychiatr Dis Treat. 2008;4(5):937-948. 8. Zimmerman M, Ellison W, Young D, Chelminski I, Dalrymple K. How many different ways do patients meet the diagnostic criteria for major depressive disorder? Compr Psychiatry. 2015;56:29-34. 9. Dale E, Bang-Andersen B, Sánchez C. Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochem Pharmacol. 2015;95(2):81-97. 10. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci (Landmark Ed). 2009;14:5291-5338. 11. Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. New York, NY: Cambridge University Press; 2013. 12. Viibryd [prescribing information]. Madison, NJ: Allergan USA Inc; 2018. 13. Trintellix [prescribing information]. Deerfield, IL: Takeda Pharmacueticals America, Inc; 2018.

close
 
close
close
close
 

Thank you for your response.
An email reminder will be sent to you prior to the event.
To learn more about MDD targets beyond the monoamine pathway,

Visit ChallengeMDD.com

Thank you for your response.
To learn more about MDD targets beyond the monoamine pathway,

Visit ChallengeMDD.com

close

Sign Up for E-mail Updates

Submit your e-mail address to receive notifications about updates to this website and announcements and information from Alkermes about major depressive disorder (MDD).


Please enter your first name.

Please enter your last name.

Please enter a valid e-mail address.

Please enter a valid zip code.

Please enter a valid specialty.
Please check the box if you want to proceed.

*Required field.

Thank you!

close

Share information about challenges in
MDD patient management

*Please include a valid e-mail address.
*Please include a valid e-mail address.

*Required field.

close

Help us create a better, more informed experience for you.

Please answer these 2 questions to help shape this site for you and your peers. Your answers will remain anonymous:

Has the information on this page given you insight into how the modulation of the endogenous opioid system could lead to an antidepressant effect?

Help us create a better, more informed experience for you.

Please answer these 2 questions to help shape this site for you and your peers. Your answers will remain anonymous:

Was this information consistent with what you expected to learn here?

Thank you!