Placebos Work for Some Psychiatric Conditions, but Not Others, Study Finds

New research shows depression and ADHD have lower placebo study dropout rates than schizophrenia and panic disorder.

TanyaJoy/Shutterstock

Placebos may be more effective for some psychiatric conditions and less effective for others, a new study suggests.

Compared to patients with panic disorder or schizophrenia, those with depression or attention-deficit/hyperactivity disorder (ADHD) are less likely to drop out of clinical trials when assigned to the placebo group.

“The psychological and emotional state of patients can significantly affect their response to placebo treatment. Patients who have more positive expectations might experience more improvements compared to those who do not,” Dr. Michael McGrath, psychiatrist, chief clinical officer, and medical director at The Ohana Hawaii rehab center, told The Epoch Times.

Placebos are inert substances used as controls in clinical trials to determine whether a new medication is truly effective or if observed improvements are due to the placebo effect, which occurs when a person gets better because they believe they are receiving treatment.

Understanding the Dropout Rates in Placebo Studies

The study, recently published in JAMA Psychiatry, sheds light on how placebo treatments can affect people with different psychiatric conditions.

Researchers analyzed information from 90 high-quality clinical trials involving 10,056 participants. They found that patients with certain psychiatric conditions may observe a larger placebo effect, as demonstrated by lower dropout rates in clinical trials.

Patients with post-traumatic stress disorder, major depressive disorder (MDD), and ADHD reported the lowest dropout rates of 17 percent when put on a placebo.

In contrast, schizophrenia had a dropout rate of 41 percent, followed by panic disorder and mania, which also had high rates.

The researchers found that most participants dropped out of studies due to adverse side effects in obsessive-compulsive disorder and panic disorder studies, while the fewest dropouts were seen in MDD and ADHD trials.

Researchers found that schizophrenia and mania showed higher dropout rates, likely because patients saw no to few improvements while on placebo drugs, while patients with ADHD and MDD reported lower dropout rates due to perceived benefits.

The researchers systematically identified the most reliable studies for each major psychiatric disorder they sought to investigate, selecting the 10 best placebo-controlled trials for each condition. Out of 90 studies, 86 reported on the total number of participant dropouts.

Placebos Can Have Negative Effects

The findings suggest that while placebo treatments can sometimes help, they can also have a range of adverse effects depending on the type of psychiatric diagnosis.

The main adverse effect observed with placebos was a lack of therapeutic benefit, with variations depending on the specific diagnosis. When patients experience no improvement in their symptoms, this can be discouraging and lead to discontinuation of treatment.

The next biggest factor was the “nocebo effect.” This is the opposite of the placebo effect, which occurs when a negative outcome occurs due to a belief that the intervention will cause harm.

Researchers said that the high dropout rates seen in studies on schizophrenia and mania might be due to the severe symptoms these patients experience, making it hard for them to stick with placebo treatment.

Patients with psychotic disorders—such as schizophrenia—are especially influenced by their expectations and mistrust of medications, Dr. Carole Lieberman, a psychiatrist and bestselling author, told The Epoch Times.

“Paranoid subtypes, in particular, tend to suspect harm from treatment, leading to high dropout rates,” she said. “Panic and manic patients also abandon trials quickly because they seek immediate relief and lack the patience for delayed outcomes.”

In contrast, Lieberman added, those with major depression often remain enrolled longer because they are more willing to believe that any treatment might finally help, even if it’s a placebo. However, in the case of patients with obsessive-compulsive disorder, they tend to exit due to hypersensitivity to physical changes and their aversion to unpredictability.

In cases of panic disorder, the intense distress felt during attacks could also be a significant factor in why patients leave the study, according to researchers.

However, they noted that the low dropout rates in MDD could be related to the way the condition occurs in episodes, which aligns with earlier findings showing that MDD patients often respond well to placebo treatment.

Dr. Anissa Abi-Dargham, chair of the Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, told The Epoch Times that taking “precautions and safeguards” during the eligibility evaluation is the best way to reduce likelihood of dropout.

“For example including patients who are not extremely ill or acute, and those who tolerate drug free periods well,” she said, emphasizing that placebo-controlled studies are often necessary to show the efficacy and safety of a new drug.

“They are often also mandated by the FDA. The best approach is to minimize risks via rigorous eligibility evaluation and close monitoring.”

The Placebo Effect in Depression

The placebo effect is a significant factor in many treatments, including those for pain, depression, and fatigue.

It can significantly contribute to the apparent effectiveness of depression treatments. The positive expectations about the treatment can lead to physiological changes in the brain, reducing depressive symptoms.

A person’s belief in the treatment can also lead to changes in their behavior, such as improved diet, exercise, or rest, contributing to symptom relief.

Researcher also suggests that placebo is not just a passive effect but a partially active treatment itself, potentially inducing neuroplasticity, or changes in brain structure and function.

While the extent of the placebo effect varies, it can account for a substantial portion of the measured effect of a treatment, especially in conditions where the body’s response is influenced by the mind-body connection—the relationship between our mental and emotional states and our physical health. It suggests that our thoughts, feelings, and attitudes can influence our physical well-being, and conversely, physical health can impact mental and emotional states. 

Researchers have zeroed in on the part of the brain involved in this phenomenon. A study conducted at Northwestern University used magnetic resonance imaging (MRI) to investigate brain activity as patients with chronic pain from knee osteoarthritis experienced the placebo effect. A placebo pill ingestion was associated with a strong pain-relieving effect, with more than half of the patients reporting significant pain relief.

The researchers found that when people experienced pain relief from a placebo, a specific area of their brain showed more activity. The increased activity helped the researchers predict who was feeling the effect of the placebo.

A 2024 study examined the Neuroplasticity Placebo Theory, which posits that placebo treatments stimulate neuroplasticity in brain areas sensitized by depression. Neuroplasticity is suggested as the unifying factor explaining the placebo response in depression clinical trials and the placebo effect in clinical care. The study referenced neuro-radiological evidence showing brain changes in placebo arms of antidepressant trials and highlighted that placebo response accounts for about 70 percent of improvement in these trials.