May 15, 2021

Myths About The Treatment of ADHD

Myth:  ADHD medications "anesthetize" ADHD children.
 
The idea here is that the drug treatment of ADHD is no more than a chemical straightjacket intended to control a child's behavior to be less bothersome to parents and teachers. After all, everyone knows that if you shoot up a person with tranquilizers, they will calm down.

Fact:  ADHD medications are neither anesthetics nor tranquilizers.

The truth of the matter is that most ADHD medications are stimulants. They don't anesthetize the brain; they stimulate it. By speeding up the transmission of dopamine signals in the brain, ADHD medications improve brain functioning, which in turn leads to an increased ability to pay attention and control behavior.  The non-stimulant medications improve signaling by norepinephrine. They also improve the brain's ability to process signals. They are not sedatives or anesthetics. When taking their medication, ADHD patients can focus and control their behavior to be more effective in school, work, and relationships.  They are not "drugged" into submission.

Myth: ADHD medications cause drug and alcohol abuse
We know from many long-term studies of ADHD children that when they reach adolescence and adulthood, they are at high risk for alcohol and drug use disorders. Because of this fact, some media reports have implied that their drug use was caused by treatment of their ADHD with stimulant medications.

Fact: ADHD medications do not cause drug and alcohol abuse
Some ADHD medications indeed use the same chemicals that are found in street drugs, such as amphetamine.  But there is a very big difference between these medications and street drugs. When street drugs are injected or snorted, they can lead to addiction, but when they are taken in pill form as prescribed by a doctor, they do not cause addiction. When my colleagues and I examined the world literature on this topic, we found that rather than causing drug and alcohol abuse, stimulant medicine protected ADHD children from these problems later in life. One study from researchers at Harvard University and the Massachusetts General Hospital found that the drug treatment of ADHD reduced the risk for illicit drug use by84 a percent. These findings make intuitive sense. These medicines reduce the symptoms of the disorder that lead to illicit drug use. For example, an impulsive ADHD teenager who acts without thinking is much more likely to use drugs than an ADHD teen whose symptoms are controlled by medical drug treatment. After we published our study, other work appeared. Some of these studies did not agree that ADHD medications protected ADHD people from drug abuse, but they did not find that they caused drug abuse.

Myth:  Psychological or behavioral therapies should be tried before medication.  
Many people are cautious about taking medications, and that caution is even stronger when parents consider treatment options for their children.  Because medications can have side effects, shouldn't people with ADHD try to talk therapy before taking medicine?

Fact:  Treatment guidelines suggest that medication is the first-line treatment.
The problem with trying talk or behavior therapy before medication is that medication works much better.  For ADHD adults, one type of talk therapy(cognitive behavioral therapy) is recommended, but only when the patient is also taking medication.  The multimodal treatment of ADHD (MTA) study examined this issue in ADHD children from several academic medical centers in the United States. That study found that treating ADHD with medication was better than treating it with behavior therapy. Importantly, behavior therapy plus medication was no more effective than medication alone. That is why treatment guidelines from the American Academy of Pediatrics and the American Academy of Children and Adolescents recommend medicine as a first-line treatment for ADHD, except for preschool children. ADHD medications indeed have side effects, but these are usually mild and typically do not interfere with treatment.  And don't forget about the risks that a patient faces when they do not use medications for ADHD.  These untreated patients are at risk for worsening ADHD symptoms and complications.

Myth: Brain abnormalities of ADHD patients are caused by psychiatric medications
A large scientific literature shows that ADHD people have subtle problems with the structure and function of their brains.  Scientists believe that these problems are the cause of ADHD symptoms. Critics of ADHD claim that these brain problems are caused by the medications used to treat ADHD.  Who is right?

Fact: Brain abnormalities are found in never medicated ADHD patients.
Alan Zametkin, a scientist at the US National Institute of Mental Health, was the first to show brain abnormalities in ADHD patients who had never been treated for their ADHD.  He found that some parts of the brains of ADHD patients were underactive. His findings could not be due to medication because the patients had never been medicated. Since his study, many other researchers have used neuroimaging to examine the brains of ADHD patients. This work confirmed Dr. Zametkin’s observation of abnormal brain findings in unmediated patients. Reviews of the brain imaging literature have concluded that the brain abnormalities seen in ADHD cannot be attributed to ADHD medications.

Wilens, T., Faraone, S. V.,Biederman, J. &Gunawardene, S. (2003). Does Stimulant Therapy of Attention-Deficit hyperactivity disorder Beget Later Substance Abuse?  Aneta-Analytic Review of the Literature.Pediatrics111, 179-185.
Humphreys, K. L., Eng, T. &Lee, S. S.
(2013).Stimulant Medication and Substance Use Outcomes: A Meta-analysis. JAMA psychiatry, 1-9.
Chang, Z., Lichtenstein, P., Halldner,L., D'Onofrio, B., Serlachius, E., Fazel, S., Langstrom, N. & Larsson, H.
(2014). Stimulant ADHD medication and risk for substance abuse. J Child Psychol Psychiatry55,878-85.
Nakao, T., Radua, J., Rubia, K. &Mataix-Cols, D.
(2011 ). Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry168, 1154-63.
Rubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M.J. &Radua, J.
(2014). Effects of stimulants on brain function inattention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Biol Psychiatry76, 616-28.
Spencer, T. J., Brown, A., Seidman, L. J., Valera, E. M., Makris, N., Lomedico, A., Faraone, S. V. &Biederman,J.
(2013).Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies. J Clin Psychiatry74, 902-17.

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Meta-analysis finds little to no association between prenatal cannabis exposure and offspring ADHD

Meta-analysis Finds Little-to-No Association Between Prenatal Cannabis Exposure and Offspring ADHD

Prevalence of cannabis use among pregnant women is on the rise with the spread of legalization. The most frequently reported reasons for use are to relieve stress or anxiety, nausea or vomiting, pain, and for recreation.

Given that the primary psychoactive ingredient of cannabis, ∆9-tetrahydrocannabinol (THC) is a small fat-soluble molecule that can easily cross the placenta, an Israeli-U.S. research team conducted a systematic search of the peer-reviewed medical literature for studies exploring possible neuropsychiatric effects on offspring.  

They included not only studies evaluating likelihood of ADHD, but also autism spectrum disorder, anxiety, depression, and psychotic symptoms. For each of these, adjustment was made for known confounding variables.

With that adjustment, meta-analysis of six studies with a total of over half a million (503,661) participants reported a 13% increase in the odds of ADHD in offspring of mothers using cannabis during pregnancy compared with offspring of mothers not using cannabis while pregnant.

That is generally considered a small effect size increase in risk. But there are multiple reasons to question even this minimal finding:

  • It barely achieved statistical significance.
  • A few studies used more reliable clinical diagnoses, while most just used ADHD symptom rating scales.
  • It is virtually impossible to eliminate all confounding variables. Twin studies come closest to fully accounting for otherwise unmeasured environmental and genetic confounders, but no such studies were included.
  • The team made no effort to evaluate publication bias.  
  • Almost all the participants (497,821) were in a single study, and that study – which relied on clinical diagnoses – did not find a significant association.

Meta-analysis of two studies with a total of 741 individuals reported a 20% increase in offspring use of cannabis among mothers who used cannabis during pregnancy, but once again this was subject to methodological shortcomings:

  • Two studies do not make for a robust meta-analysis, even more so with only 741 participants.
  • The result barely achieved statistical significance.
  • Publication bias was unaddressed.
  • Small effect sizes are questionable due to the virtual impossibility of eliminating all confounding variables, especially without twin studies.

Some studies have suggested a link between cannabis and psychotic symptoms. But meta-analysis of four studies combining over nineteen thousand persons found no significant association between maternal cannabis use during pregnancy and offspring psychotic symptoms.

Many studies have pointed to commonalities in the etiology of ADHD and autism spectrum disorder (ASD). Yet meta-analysis of five studies encompassing over half a million participants found absolutely no association between maternal prenatal cannabis use and ASD.  

The remaining meta-analyses also reported no association with depression or anxiety.

With the caution that absence of evidence is not the same as evidence of absence, it is by no means clear from what is presently known that prenatal cannabis exposure has any significant neuropsychiatric effects on offspring. And if further research finds any effects, they are likely to be minor.

July 26, 2024

Meta-analysis Associates Dasotraline with Some Reduction in ADHD Symptoms

Meta-analysis Associates Dasotraline with Some Reduction in ADHD Symptoms

Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that had been under development by Sunovion for treating ADHD and binge eating disorder.  

An Indian research team conducted a systematic search of the peer-reviewed medical literature to perform meta-analyses of the quantitative outcomes of clinical trials. 

Meta-analysis of five double-blinded randomized clinical trials (RCTs) with a combined total of 1,498 participants reported a small-to-medium effect size reduction in ADHD symptoms in patients given dasotraline as opposed to those given placebo. 

There were, however, strong indications of publication bias. Using the trim-and-fill procedure to correct for that bias yielded a small effect size reduction in ADHD symptoms in patients given dasotraline compared with those given placebo. 

Insomnia were more than four times more frequent among patients given dasotraline than among those given placebo. There was no evidence of the frequency of insomnia being dose-dependent. 

Similarly, patients given dasotraline were more than four times more likely to report decreased appetite than those receiving placebo. In this case, however, the effect was clearly dose-dependent, rising from 3x for 2mg to 4x for 4mg to 5x for 6mg and almost 8x for 8mg. 

The authors concluded, “dasotraline can reduce the core symptoms of ADHD, that is, hyperactivity/impulsivity and inattentiveness, leading to an overall improvement of ADHD compared to placebo. Dasotraline can also improve clinician-determined patients’ global functioning compared to the placebo. The most common adverse drug reactions related to dasotraline were insomnia and decreased appetite. However, to fill the knowledge gap, multicentric randomized active-controlled clinical trials are warranted in this domain for a successful translation into clinical practice.” 

Weighing these less than impressive initial results against the cost of further RCTs, Sunovion withdrew its application for approval by the Food and Drug Administration, stating, “while Sunovion considers dasotraline to be a promising, novel treatment for binge eating disorder and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications.” 

July 25, 2024

Meta-Analysis: Young People with ADHD Experience Serious Social Cognition Impairments

Meta-analysis Concludes Children and Adolescents with ADHD Experience Serious Impairments in Social Cognition, Affecting Social Functioning

Children and adolescents with ADHD are known to have difficulties in relating to family members, peers, and teachers. Over the long run this can contribute to anxiety or even delinquency. 

Several cognitive functions that allow individuals to process social information and interact with others contribute to shaping everyday social interactions. These include: 

  • Theory of mind (ToM): Being able to attribute mental states to others, and thus explain and predict their behaviors. 
  • Empathy: Being able to feel an appropriate emotion in response to another person’s mental state, and thereby understand others’ feelings. 
  • Emotion recognition: Being able to identify emotions in facial expressions and other communication cues, such as voice and body position. 

A European research team performed a systematic search of the peer-reviewed medical literature to conduct meta-analyses of ToM, Empathy, Facial and Non-Facial Emotion Recognition in children and adolescents with ADHD when compared to typical development. As a comparison measure, they also included Everyday Social Skills (using self, parent, teacher, or clinician questionnaires/interviews of social skills) as an outcome. 

The search yielded 142 case-control studies (including dissertations) with a total of 16,283 participants. 

Meta-analysis of 82 studies with a combined total of 10,770 participants found a very large effect size impairment in everyday social skills among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates only strengthened the finding. There was no sign of publication bias. 

This was mirrored in three out of five measures of social cognition: 

  • Theory of mind (ToM): Meta-analysis of 49 studies with a total of 2,449 participants identified a large effect size impairment among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates made no difference in the outcome. There was no sign of publication bias. 
  • Empathy: Meta-analysis of twelve studies combining 916 individuals yielded a medium effect size impairment among children and adolescents with ADHD. But there were strong signs of publication bias, and the outcome lost significance after adjusting for covariates (perhaps because it became under-powered with three studies pooling only 151 persons). 
  • Facial emotion recognition: Meta-analysis of 43 studies with a total of 3,369 participants reported a medium effect size impairment among children and adolescents with ADHD after adjusting for covariates. There was absolutely no indication of publication bias. 
  • Non-facial emotion recognition: Meta-analysis of eight studies encompassing 707 persons reported a small effect size impairment with signs of publication bias that became insignificant after adjusting for covariates. 

The team concluded, “Our findings show that children and adolescents with ADHD have deficits in ToM, Facial Emotion Recognition, and Everyday Social Skills, three domains that warrant clinical attention.” 

July 22, 2024