Should We Use an Open-Label Placebo for Moderate Depression Treatment? Protocol for a Randomised Controlled Trial.

Pavlo Kolesnyk, Andrii Kolesnyk, Michael Harris

Keywords: Open-label placebo, Depression, General practice/family medicine, Primary care, Randomised controlled trial

Background:

Randomised controlled trials (RCTs) in patients with subjective symptoms in chronic low back pain, knee pain, cancer-related fatigue, migraine headaches, irritable bowel disease and allergic rhinitis have suggested that open-label placebo (OLP) may be an effective method to produce placebo effects without deception in these conditions.
However, there is insufficient evidence on their effects in mental disorders management.
Millions of people in Ukraine suffer from mental disorders, including depression, because of the full-scale russian invasion. So there is a need for an easily available, effective and low-cost treatment.

Research questions:

In Ukrainian patients with moderate depression:
- How does the effectiveness of OLP compare with no-pill control (NPC)?
- How does the effectiveness of OLP compare with double-blind placebo(DB-P)?

Method:

Primary care patients with newly diagnosed moderate depression (14–18 points according to Hamilton Rating Scale for Depression (HRSD) will be randomised to one of four 6-week treatment arms:
- OLP(unblinded)
- NPC(unblinded)
- DB-P
- DB-SSRI(double-blind selective serotonin reuptake inhibitor). Inclusion of this arm establishes double-blind conditions without deceiving patients or clinicians.
The differences in groups' clinical outcomes will be tested by one-way analysis of covariance.
A reduction in HRSD score in 6 weeks will be considered clinically important and used for the outcome measures. All patients will continue their treatment with SSRI after 6 weeks participating in the study.

Results:

This RCT seeks to explore the counter-intuitive finding from other studies about OLP, DB-P and NPC differences by studying it in patients with moderate depression. We are not aware a study with such a design has ever been performed.

Conclusions:

Open-label placebo effects research may suggest alternative ways of managing patients with mental disorders in primary care. This could be particularly useful in low-income countries, or those where pharmaceutical supplies are unreliable.

Points for discussion:

Do EGPRN members sometimes prescribe medicines that they believe will not have any pharmacological effects in the hope of inducing a placebo effect (‘impure’ placebos)?

Existing evidence suggests that patients are willing to try OLP. Is this something that EGPRN members would consider using in their own practices?

What other illnesses with subjective symptoms might be suitable for similar research?

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