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PAL May Newsletter - Placebo Response in Antidepressant Treatment
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Partnership Access Line

 

1-866-599-7257

Monday - Friday, 8AM - 5PM

The Partnership Access Line (PAL) supports primary care providers (doctors, nurse practitioners and physician assistants) with questions about mental health care such as diagnostic clarification, medication adjustment, or treatment planning. PAL is available throughout the state of Washington and is funded by the Health Care Authority. The phone consultation is covered by HIPAA, section 45 CFR 164.506, no additional release of patient information is required to consult.

The PAL team consists of child and adolescent psychiatrists affiliated with the University of Washington School of Medicine and Seattle Children’s Hospital to deliver its phone consultation services. In addition, PAL has a master’s-level social worker who can assist with finding mental health resources for patients.


The PAL team is available to any primary care provider in Washington State to discuss the care of any pediatric patient regardless of insurance type (state, private, or no insurance).

Placebo Response in Antidepressant Treatment


Jim Peacey, MD
PAL Consultant

Clinical trials of antidepressants in children and adolescents are often burdened by very high placebo response rates making it very difficult to show any additional benefit from the drug being studied. Is most of what we see when youth get better after starting an antidepressant due to placebo effect? If so, is that a problem? If the depression is getting better, shouldn't we want to make the most of whatever can contribute to that improvement?

It's useful to distinguish between placebo response and the placebo effect. The term "placebo response" describes improvement seen in the placebo arm of a study and may be due to factors in addition to classic placebo effect. Placebo effect is usually attributed to belief that a treatment will be effective. We know that there are biological changes associated with placebo effect, and that improvement is not just imaginary. Placebo effect can account for a portion of placebo response. Belief in a treatment may be enhanced by confidence communicated by the one recommending it or testimonials from others. There are other cognitive and behavioral elements of medication treatment that may also be important such as the daily practice of taking medication with the intention of feeling better. Patients may be paying attention to possible changes or signals that they may be getting better, and we can encourage that process by asking about changes that may signal improvement. Regular follow-up appointments can produce an additional psychotherapy effect: the benefit of regular interaction with someone who is not only expressing expectation of improvement but also concern about their life and an interest in wanting to help as well as supporting changes in behavior such as better sleep hygiene, exercise, and more involvement in activities.

There are still other reasons that patients may be getting better in the months following the start of an antidepressant that may have nothing to do with treatment response at all. The most typical course of an episode of untreated depression is eventual recovery with average illness duration of a year. When antidepressant trials and titration can take a few months, spontaneous recovery will account for a portion of the response we see. We often start antidepressants when people are at a particularly low point in mood, so subsequent improvement might be expected just due to "regression to the mean" regardless of treatment decisions. And there are depressive episodes that will be, in retrospect, better described as adjustment disorders that improve spontaneously when stressors improve.

Patients and clinician should be glad to see improvement regardless of the best explanation for it. But there are elements that contribute to placebo response that are less salutary. There may be observer bias in parents and clinicians with overinvestment in a treatment and grasping for signs that it may be working even when there is no actual improvement so that an ineffective treatment is prolonged. And patients may try to please adults who are very invested in a treatment by minimizing symptoms that are still there; rating scales may not always give us an accurate picture of symptoms. We can develop opinions from "clinical experience" that can mislead us to either become overly confident in treatments that we know have a specific benefit in a minority of patients ("Number Needed to Treat" for antidepressants is 4 at best) or think that we are doing something wrong when response doesn't happen. A more realistic view of the effectiveness of our treatments does make it easier to understand certain phenomena. The observation of antidepressant "poop out" where a treatment that had been working well stops working or doesn't work when it is restarted at a later time may not be that surprising if much of the improvement we see in clinical practice was never due to the pharmacologic properties of the drug in the first place.

What we can tell patients and families is that more than half of patients have meaningful improvement when treated with one of our first-line SSRIs, and that half of those that don't will respond to an alternative SSRI or SNRI. We can enhance basic psychotherapy effects by having regular follow-up with patients to inquire about their mood and life circumstances, encourage healthy habits of sleep, exercise, and social activity, and troubleshoot any problems with residual symptoms or side effects. We can encourage engagement in evidence-based psychotherapies that not only increase the likelihood of improvement but can improve the durability of response. And we should be trying to take people off their antidepressants after a year or so of recovery with supports in place and stressors managed. We will discover some who do have a more persistent disorder with a specific life-changing response to medication treatment that will need to be continued. And we will spare many others who never did have a specific drug response from the burden and risk (though minimal!) of prolonged drug treatment.

News & Notes


Our June 3, 2023 virtual conference is this weekend!
  • Time: 8:00 am - 12:30 pm PST
  • Featured topics & presenters:
    • Being solution-focused: a transdiagnostic approach to developing treatment in primary care | Dr. Lawrence Wissow
    • Postpartum Psychosis | Dr. Amritha Bhat | University of Washington Perinatal Psychiatry
    • Psychiatric Management of Child and Adolescent Anxiety | Dr. Erin Dillon-Naftolin
  • Register here!
 


 
PAL will be closed on the following days:
  • Juneteenth - Monday, June 19, 2023
  • Independence Day - Tuesday, July 4, 2023

PAL Spotlight

Dr. Jim Peacey first joined the PAL team in December 2013 and returned in March 2018 after a two year hiatus. He is a native Washingtonian, now living in Seattle just five miles south of where he grew up in the suburbs at the north end of Lake Washington. After receiving his undergraduate degree in chemistry in the Bay Area, he returned to Washington for medical school, followed by psychiatry and child and adolescent psychiatry residencies at the University of Washington. After finishing training in the mid-90s, he worked in private practice, community mental health and residential treatment settings. His work with PAL has heightened his awareness of mental health treatment resource scarcity in many communities. Dr. Peacey also is a courtesy clinical faculty member at the University of Washington and supervises child and adolescent psychiatry fellows. In his spare time, he enjoys a number of the outdoor activities available in the Pacific Northwest. He is a member of the Puget Sound Mycological Society, and when not in the mountains hunting for mushrooms, he might be found tending to his backyard orchard of dwarf apple trees.

Upcoming CME Conferences



June 3, 2023
Location: virtual conference
Register here!


Visit our website for the most updated information on upcoming conferences and to view slides from our previous conferences.

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