Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
August 15, 2024
A placebo is a pill that does not contain any active medication. It is given to patients who form the control group in clinical trials. Comparing the effects of a treatment with placebo is essential because some patients will improve with the passage of time and some will get better due to the expectation of benefit they have from being enrolled in a clinical trial.
In studies of psychiatric conditions, patients in placebo groups typically show improvement. This can be induced by combinations of hope, suggestion, expectation, and consumption of what are presented as medications. It is reinforced by the context of receiving compassionate care from others, with supportive conversations.
A 2005 study found that placebo response is unequally distributed across psychiatric disorders, but did not address several disorders (including bipolar disorder) examined in the present meta-analysis conducted by a German research team.
Using only high-quality randomized clinical trials (RCTs) across major psychiatric diagnoses, the team quantified differences in the change of disorder symptoms within placebo groups.
They selected nine common and clinically significant psychiatric conditions: major depressive disorder (MDD), mania (bipolar disorder), schizophrenia, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), panic disorder, posttraumatic stress disorder (PTSD), and social phobia. For each of these, they selected the ten most recent high-quality RCTs of medicationsfor meta-analysis.
Of the ninety included RCTs, the team only looked at placebo groups. Because RCTs for the different diagnoses used differing established psychopathology rating scales, standardized pre-post effect sizes were used to compare outcomes across diagnoses.
Meta-analysis of the ten ADHD RCTs with a combined total of 1,189 participants reported large effect size improvements in symptoms, with no variation (heterogeneity) across RCTs and no sign of publication bias.
By contrast, the placebo effect size improvements in symptoms of major depressive disorder (10 RCTs, 1,598 participants) and generalized anxiety disorder (10 RCTs, 1,457 participants) were very large, well above those for ADHD, and with no overlap of 95% confidence intervals.
At the other end of the spectrum, the placebo effect size improvements in symptoms of schizophrenia (10 RCTs, 888 participants) were moderate, well below those for ADHD, and with no overlap of 95% confidence intervals.
There were absolutely no indications of publication bias.
The team noted, “In all diagnoses, there were improvements in symptom severity during placebo treatment (ie, the lower limit of the 95% CIs of the pooled pre-post placebo effect sizes were >0).” Although they stated, “The large and robust improvements observed in ADHD studies have not been reported to our knowledge.” they seemed to have missed this article by me and my colleagues: https://pubmed.ncbi.nlm.nih.gov/34232582/.
They also concluded, “Comparing the courses of different disorders under placebo indirectly may assist in understanding disease etiology, possibly providing insights into the proportionate influence of organic and psychogenic factors. Conditions with presumed substantial hereditary and biological components, such as schizophrenia, exhibited modest placebo responses in our analysis. Conversely, disorders with potentially less biological contribution, eg, depression and GAD, showed stronger responses. Our study may serve as an initial framework for incorporating the comprehensive insights derived from placebo groups of controlled trials into the etiopathogenetic exploration of mental illnesses.”
Yanli Zhang-James, John W.S. Clay, Rachel B. Aber, Hilary M. Gamble, Stephen V. Faraone,
Post–COVID-19 Mental Health Distress in 13 Million Youth: A Retrospective Cohort Study of Electronic Health Records,
Journal of the American Academy of Child & Adolescen
Tom Bschor, Lea Nagel, Josephine Unger, Guido Schwarzer, and Christopher Baethge, “Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders: A Systematic Review and Meta-Analysis,” JAMA Psychiatry (2024), https://doi.org/10.1001/jamapsychiatry.2024.0994.
Faraone, S. V., Newcorn, J. H., Cipriani, A., Brandeis, D., Kaiser, A., Hohmann, S., Haege, A. & Cortese, S. (2021). Placebo and nocebo responses in randomised, controlled trials of medications for ADHD: a systematic review and meta-analysis. Mol Psychiatry 27, 212-219.
Oppositional Defiant Disorder (ODD)—a pattern of chronic irritability, anger, arguing, or defiance—is one of the most challenging behavioral conditions families and clinicians face.
A new study involving 2,400 children ages 3–17 offers one of the clearest pictures yet. Using parent-reported data from the Pediatric Behavior Scale, researchers compared how often ODD appears in Autism spectrum disorder (ASD), ADHD-Combined presentation (ADHD-C), ADHD-Inattentive presentation (ADHD-I), and those with both ASD and ADHD.
Results:
Children with ADHD-Combined presentation show both hyperactivity/impulsivity and inattention. They had the highest ODD rates of any single diagnosis: 53% of kids with ADHD-Combined met criteria for ODD.
But when autism was added to ADHD-Combined, the prevalence jumped to 62%. This group also had the highest overall ODD scores, suggesting more severe or more impairing symptoms.
This synergy matters: while autism alone increases ODD risk, the presence of ADHD-Combined is what pushes prevalence into the majority range. Other groups showed lower, but still significant, rates of ODD:
These findings echo what clinicians often see: children with inattentive ADHD, while struggling significantly with attention and learning, tend to show fewer behavioral conflict patterns than those with hyperactive/impulsive symptoms.
It is important to note that ODD is considered to have two main components. Across all diagnostic groups, ODD consistently broke down into these two components: either Irritable/Angry (emotion-based) or Oppositional/Defiant (behavior-based). But the balance between these components differed depending on diagnosis. Notably, Autism + ADHD-Combined showed higher levels of the irritable/angry component than ADHD-Combined alone. The oppositional/defiant component did not differ much between groups. This suggests that autism elevates the emotional side of ODD more than the behavioral side, which is important for clinicians to note before tailoring interventions.
The study notes that autism, ADHD, and ODD often cluster together, with 55–90% comorbidity in some combinations.
As the authors explain, “The high co-occurrence of ADHD-Combined in autism (80% in our study) largely explains the high prevalence of ODD in autism.”
Clinical Implications: Why This Study Matters
The researchers point to a straightforward recommendation: clinicians shouldn’t evaluate these conditions in isolation. A child referred for autism concerns might also be struggling with ADHD. A child referred for ADHD might have undiagnosed ODD. And ignoring one disorder can undermine treatment for the others.
Evidence-based interventions (behavioral therapy, parent training, school supports, and/or medication) can reduce symptoms across all three diagnoses while improving long-term outcomes, including overall quality of life.
Background:
Sleep is more than simple rest. When discussing sleep, we tend to focus on the quantity rather than the quality, how many hours of sleep we get versus the quality or depth of sleep. Duration is an important part of the picture, but understanding the stages of sleep and how certain mental health disorders affect those stages is a crucial part of the discussion.
Sleep is an active mental process where the brain goes through distinct phases of complex electrical rhythms. These phases can be broken down into non-rapid eye movement (NREM) and rapid eye movement (REM). The non-rapid eye movement phase consists of three stages of the four stages of sleep, referred to as N1, N2(light sleep), and N3(deep sleep). N4 is the REM phase, during which time vivid dreaming typically occurs.
Two of the most important measurable brain rhythms occur during non-rapid eye movement (NREM) sleep. These electrical rhythms are referred to as slow waves and sleep spindles. Slow waves reflect deep, restorative sleep, while spindles are brief bursts of brain activity that support memory and learning.
The Study:
A new research review has compiled data on how these sleep oscillations differ across psychiatric conditions. The findings suggest that subtle changes in nightly brain rhythms may hold important clues about a range of disorders, from ADHD to schizophrenia.
The Results:
People with ADHD showed increased slow-spindle activity, meaning those brief bursts of NREM activity were more frequent or stronger than in people without ADHD. Why this happens isn’t fully understood, but it may reflect differences in how the ADHD brain organizes information during sleep. Evidence for slow-wave abnormalities was mixed, suggesting that deep sleep disruption is not a consistent hallmark of ADHD.
Among individuals with autism spectrum disorder (ASD), results were less consistent. However, some studies pointed to lower “spindle chirp” (the subtle shift in spindle frequency over time) and reduced slow-wave amplitude. Lower amplitude suggests that the brain’s deep-sleep signals may be weaker or less synchronized. Researchers are still working to understand how these patterns relate to sensory processing, learning differences, or daytime behavior.
People with depression tended to show reduced slow-wave activity and fewer or weaker sleep spindles, but this pattern appeared most strongly in patients taking antidepressant medications. Since antidepressants can influence sleep architecture, researchers are careful not to overinterpret the changes. Nevertheless, these changes raise interesting questions about how both depression and its treatments shape the sleeping brain.
In post-traumatic stress disorder (PTSD), the trend moved in the opposite direction. Patients showed higher spindle frequency and activity, and these changes were linked to symptom severity which suggests that the brain may be “overactive” during sleep in ways that relate to hyperarousal or intrusive memories. This strengthens the idea that sleep physiology plays a role in how traumatic memories are processed.
The clearest and most reliable findings emerged in psychotic disorders, including schizophrenia. Across multiple studies, individuals showed: Lower spindle density (fewer spindles overall), reduced spindle amplitude and duration, correlations with symptom severity, and cognitive deficits.
Lower slow-wave activity also appeared, especially in the early phases of illness. These results echo earlier research suggesting that sleep spindles, which are generated by thalamocortical circuits, might offer a window into the neural disruptions that underlie psychosis.
The Take-Away:
The review concludes with a key message: While sleep disturbances are clearly present across psychiatric conditions, the field needs larger, better-standardized, and more longitudinal studies. With more consistent methods and longer follow-ups, researchers may be able to determine whether these oscillations can serve as reliable biomarkers or future treatment targets.
For now, the take-home message is that the effects of these mental health disorders on sleep are real and measurable.
Many studies have shown that ADHD is associated with increased risks of suicidal behavior, substance misuse, injuries, and criminality. As we often discuss in our blogs, treatments for ADHD include medication and non-medication options, such as CBT (Cognitive Behavioral Therapy). While non-drug approaches are often used for young children or mild cases of ADHD, medications – both stimulants and non-stimulants – are common for adolescents and adults.
Global prescriptions for ADHD drugs have risen significantly in recent years, raising questions about their safety and effectiveness. Randomized controlled trials have demonstrated that medication can help reduce the core symptoms of ADHD. However, research from these trials still offers limited or inconclusive insights into wider and more significant clinical outcomes, such as suicidal behavior and substance use disorder.
An international study team conducted a nationwide population study using the Swedish national registers. Sweden has a single-payer national health insurance system, which covers nearly every resident, enabling such studies. The researchers examined all Swedish residents aged 6 to 64 who received their first ADHD diagnosis between 2007 and 2018. Analyses of criminal behavior and transport accidents focused on a subgroup aged 15 to 64, since individuals in Sweden must be at least 15 years old to be legally accountable for crimes or to drive.
The team controlled for confounding factors, including demographics (age at ADHD diagnosis, calendar year, sex, country of birth, highest education (using parental education for those under 25), psychiatric and physical diagnoses, dispensations of psychotropic drugs, and health care use (outpatient visits and hospital admissions for both psychiatric and non-psychiatric reasons).
Time-varying covariates from the previous month covered diagnoses, medication dispensations, and healthcare use. During the study, ADHD treatments licensed in Sweden included amphetamine, atomoxetine, dexamphetamine, guanfacine, lisdexamphetamine, and methylphenidate.
After accounting for covariates, individuals diagnosed with ADHD who received medication treatment showed better outcomes than those who did not. Specifically:
-Suicidal behaviors dropped by roughly 15% in both first-time and recurrent cases.
-Initial criminal activity decreased by 13%, with repeated offences falling by 25%.
-Substance abuse initiation declined by 15%, while recurring substance abuse was reduced
by 25%.
-First automotive crashes were down 12%, and subsequent crashes fell by 16%.
There was no notable reduction in first-time accidental injuries, and only a marginally significant 4% decrease in repeated injuries.
The team concluded, “Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality, but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes.”
_logo%201.svg)
