Not all placebo effects are the same

While the placebo effect is a known effect in treatments across various specialties, one study in psychiatry found that the degree of response varies between different diagnoses.A meta-analysis of 90 studies found that beneficial effects from placebo treatment was greatest in patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD), but those with schizophrenia had the least effect. Findings were published by researchers in Germany in JAMA Psychiatry.“However, other factors in trials might contribute to improvements in psychopathology such as the fact psychiatric disorders often have episodic courses. Or “contextual factors, such as attentive study personnel, compassionate care, supportive conversations and psychoeducation, can influence outcomes positively,” they wrote. The researchers did not respond to requests for interviews.Read: We need a new word for anxietyThe authors noted that technically, placebo is the most extensively investigated therapeutic agent in the world because of it’s ubiquitous use in randomized controlled trials. And because it is so commonly used, more needs to be learned about it.While some studies have suggested that the placebo response appears to differ across different disorders, there hasn’t been much study on the topic in psychiatry.For the metanalysis, the researchers used 10 recent high-quality studies for each of nine psychiatric conditions in which patients often are prescribed drug treatments These conditions were: MDD, mania, GAD, schizophrenia, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), panic disorder, post-traumatic stress disorder (PTSD), and social phobia. This amounted to a total of 90 studies comprising an overall total of 9,985 placebo treatedpatients. Of these, 1,598 participants had MDD, 967 had mania, 888 schizophrenia, 803 OCD, 1,189 ADHD, 1,457 GAD, 1,180 social phobia, 1,248 panic disorder and 655 patients with PTSD. The duration of the studies varied, ranging from three weeks for mania up to 12 weeks for OCD, social phobia and GAD—a time period known to encompass the strongest placebo effects.It was generally found that for all the diagnoses in the collection of studies, patients had notable improvements in symptom severity during placebo treatment as compared to baseline. But the strength of the effect varied between the different diagnoses. The largest effect size was seen in patients with MDD, followed by GAD. Schizophrenia had the smallest effect size and OCD had the second weakest. But the placebo response also varied significantly between different studies of the same condition.Overall, the authors said there were five key findings:Symptom improvement occurred in all conditions during placebo treatment. The improvements were of considerable magnitude. Improvement varied significantly among disorders. It was especially strong in MDD and GAD, while schizophrenia, OCD and mania had only modest improvements.For most diagnoses, there was substantial or considerable variability in the improvements across all of the studies.Women tended to have larger improvements in placebo groups.However, to really know the power of placebo, a placebo group needs to be compared to an untreated group. “This is required due to confounding factors that may ‘mimic’ the placebo effect, e.g. natural evolution of the disease,” according to a 2022 review in Naunyn Schmiedeberg’s Archive of Pharmacology (the official journal of the German Society of Experimental and Clinical Pharmacology and Toxicology).That review stated that: “Findings over the last two decades have shown that placebo, as an inactive substance, triggers a series of neurohormonal responses in the brains of patients and healthy subjects that could be the anatomic-physiological basis for its effects.” Placebo effects and placebo responses are known to occur across medicine. It’s seen in dermatology, gastroenterology, urology, cardiology and even in surgery with sham surgery. It has effects in pain, nausea, insomnia, in neuropsychiatric conditions and more. It tends to help with symptoms, but, not surprisingly, lacks curative power. The effects tend to be of short duration, but sometimes effects can last for days after discontinuation.Interestingly, in Parkinson’s disease the placebo effects works only in certain patients.“For the placebo response to occur, it is essential that the cortex and its connections are unaffected or only slightly affected, because in Parkinson’s patients with an interruption of these pathways, the response does not occur. The same happens in dementias where a large number of frontal pole neurons are destroyed,” the review said.There are two types of placebo. “Pure” placebo which is an inert substance such as starch, dextromaltose, lactose, talc, mentholated water and saline. The other is “impure” placebo which could be vitamins, minerals, antibacterials and psychotropic substances used in subtherapeutic doses.The authors stated that is not uncommon for placebo to be used clinically and that about 40% of prescriptions end up working as a placebo, sometimes with doctors being aware of this and sometimes not. One study found that an average of 63% of physicians use it, with many using impure placebos.The review stated that there could be personality types that are more prone to the placebo, with differences in effect between optimistic and pessimistic people.“Factors associated with the placebo effect also include prior conditioning; the environment and place where it is administered; the patient’s positive expectations about the treatment to be received, by whom and where it is carried out,” it said. Being conscious when it is used is important too “as the placebo effect does not appear in subjects in coma or with severe dementia.”Another review, in the NEJM, authors point out nocebo effects can occur too where the administered placebo ends up blocking treatments, or worsening or triggering symptoms. Some studies suggest that directly suggesting potential side effects can become self-fulfilling, it said.There is debate in research as to whether or not placebos should be used in studies, along with debate around the ethics and efficacy of it being used in clinical practice. There is a lot of study on the topic too, and there is even a Journal Interdisciplinary Placebo Studies devoted to the subject.

Not all placebo effects are the same

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