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When your patient is not responding to treatment, could it be TRD?
They've been through multiple medication trials, prolonged depressive episodes, relapses, and yet they keep trying, waiting for something to change.1,6-8
~1 in 3 patients receiving drug treatment for depression may have TRD9
(Zhdanava et al.,2021)
Patients with TRD can show up in various ways, but if they've been failed by two or more antidepressants, a standard approach may not be enough to help them.1
Listen for these negative cognitive patterns in patients with TRD
Even when other symptoms have improved, your patient could still be struggling with maladaptive cognitive patterns,10,11 including:
Cognitive Inflexibility12
Rigid, automatic, negative thoughts, including self-devaluation, worthlessness, helplessness, pessimism, and overgeneralization
Negative Cognitive Bias13,14
Biased perception of self and environment. Heightened attention to negative stimuli with reduced likelihood of updating negative beliefs when confronted with positive information
Rumination/Negative Self-focused Thinking15
Repetitive dwelling on negative thoughts about oneself that can lead to reduced behavioral activation and sociability
Emotional Dysregulation/Reward Processing2,16,17
Reduced responsivity to positive or rewarding stimuli related to anhedonia and treatment resistance
“It is an illness, and it has a name, and naming it early would have helped.”
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These patterns may Reflect the Biologyof trd3,4
You've done what all careful clinicians do: started with standard of care, adjusted, monitored, and tried again.1 But the maladaptive cognitive and behavioral pattern you recognize in patients with TRD may reflect changes at the brain network level.3,4 Research suggests that these network changes deepen with recurrent illness,5 which could explain why more of the same approach rarely moves things.1,6,7
The Human Brain contains several separate but interacting networks of brain regions18,19
How do these brain networks relate to the patterns in TRD?
In depression, the brain's capacity to shift flexibly between states across large-scale networks is reduced,3 which is linked to:
Rumination
Linked to disrupted flexibility of certain brain network states involving the DMN3
Negativity bias
Associated with unbalanced patterns of DMN-SN connectivity23
Anhedonia
Associated with abnormal activation patterns of SN during reward tasks, disrupting adaptation of DMN and CEN activity4,24
If patients have been failed by multiple antidepressants, it may be because these underlying network changes have not been addressed25,26
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Your Patient WITH TRD could be running out of hope27,28
You know what is at stake. Depression can be debilitating, but with TRD their suffering could be even greater.6-8
TRD leads to worse outcomes than major depressive disorder (MDD)7,8
almost3x
longer depressive episodes vs MDD8*
(Wu et al., 2019)
13%
remission rate vs 42% in patients with MDD7†
(Pappa et al., 2024)
53%
relapse rate vs 31% in patients with MDD7‡
(Pappa et al., 2024)
**571 days with TRD vs 200 days with MDD. Based on depressive episodes in patients with filled antidepressant prescriptions (N=48,440). TRD defined as an MDD episode with ≥3 antidepressant regimens, in which a regimen was defined as any combination of antidepressants used with a continuous segment of ≥28 days' supply (allowing a maximum 60-day gap).8
†Based on real-world prescription claims (N=110,406). Remission defined as a prescription of a single treatment sequence for at least 180 days with no change other than dose or no antidepressant prescription in the 60 days following the end of a sequence of ≥90 days.7
‡1-year relapse rate. Relapse was signified by prescription of an antidepressant treatment sequence within 60-180 days after the end of a previous sequence that had resulted in a response.7
Continuing standard of care carries its own cost6,7,29
Patients with TRD/MDD may have to contend with side effects from antidepressant treatment.29 This could add to the burden patients with TRD already face the longer remission is out of reach.6,7
UP TO62%
of patients with depression who are taking antidepressants have reported side effects such as:29
(Read et al., 2014)
Sexual difficulties
Drowsiness
Weight gain
Emotional blunting
And with each delay or failed treatment, patients' demoralization and hopelessness grow.27,28
“With each episode, it becomes harder to engage with life… you start to become the thing you had to be in order to survive it, and not what you were before.”
If the TRD pattern won't change, the Conversation Can
TRD can feel hopeless for the patients living with it,27,28 but it doesn't have to be this way.
Once the pattern is clear, you can reassess and lead a conversation about a different next step, whether that means referral to a collaborative specialty or adapting your care approach.
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