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Welcome to this presentation. I'm Denise Vanacore, a Board-Certified Nurse Practitioner in Psych Mental Health and as a Family Nurse Practitioner. I'm Associate Dean and Professor of Nursing at Eastern University. It is a pleasure today to talk to you about defining inadequate response. What do suboptimal treatment, treatment resistance, pseudo resistance look like in patients with major depressive disorder within the clinical setting?
Experts in the treatment of depression have suggested that achieving remission is the primary goal of treatment, but questions remain about how remission should be defined. To get to remission, we need to understand the phases of treatment. The most desired outcome of the acute phase of treatment is remission, which ideally occurs within the first 6 to 12 weeks of treatment. The primary goal of the second phase, the continuation phase, is to sustain remission and prevent relapse. The third phase, maintenance, targets patients who are at high risk for recurrent depressive episodes. The maintenance phase begins at the time that the healthcare provider considers the patient to be recovered, but still at risk for recurrence, and it may last many years or even indefinitely. Remission may be defined differently from the provider’s perspective and from the patient's perspective. In antidepressant efficacy trials, remission is defined according to the scores on symptom severity scales. So as we look at the Hamilton-D depression score, a cut-off of 7 is remission, whereas for the PHQ9, a score of 4 is remission. But from the patient's perspective, being in remission means that the depressed individual has returned to normal functioning.
Treatment-resistant depression is a subset of major depressive disorder that does not respond to traditional and first-line therapy options. There are several definitions as well as staging models of treatment resistance, and a consensus for each has yet to be established. One, and the most common criteria in each model, is to have an inadequate response to at least 2 trials of antidepressant pharmacotherapy. Several staging models to classify levels of treatment resistance have been proposed, but nothing has been agreed upon. Several large-scale clinical trials have examined response rates to traditional therapeutic approaches for depression. In the STAR*D trial, the cumulative remission rate after 4 trials is resulted to be about 33 to 44% of patients being treatment resistant. Treatment-resistant approaches includes switching therapies, augmentation, and combining therapies.
As far as suboptimal treatment goes, we have a number of criteria that we must take a look at. So the first one is, did we get to an adequate dose? In about 50% of patient, they actually have not received an adequate dose of antidepressants. The next one is inadequate time. Have we waited a significant amount of time to make sure that the current dosing is adequate for the patients’ time they've been on medication? For some medications, it's shorter, and for others, it can be longer. It's been suggested that prolonged trials of treatment lasting more than 10 weeks may lead to treatment-resistant depression. Most SSRIs have a half-life of 20 to 58 hours, which results in patients on average being 5 to 12 days beginning any particular dose. This may account for continued evolution of treatment over an extended period of time. There's a current lack of compelling evidence to support the advantage of prolonged trials over 6 to 8 weeks. And the final component is non-adherence. Patient non-adherence is the most common cause of failure. This means the patients either reduce the dose themselves, or they have stopped the medication, possibly due to side effects.
So pseudo-resistance means that they haven't actually had adequate treatment. So in a patient who has pseudo-resistance, they actually had some optimal treatment. Pseudo-resistance may encompass the profile of patients who unfortunately were prescribed either suboptimal doses of antidepressants, have not had the exact time, or they've not adhere to their dosing regimen. There is strong evidence that up to 60% of depression patients initially classified as being treatment-resistant fall into the category of pseudo depression.
So in summary, we examine the scores of the Hamilton-Depression rating scale and the PHQ9 depression scale, we discuss treatment-resistant depression, suboptimal treatment, pseudo-resistance. Thank you for your participation in this activity.
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