Long term evaluation of ADD treatment

[Moonbear]

I just came across this thought-provoking opinion article in the NY Times.
http://www.nytimes.com/2012/01/29/o...gs-dont-work-long-term.html?pagewanted=1&_r=1

It raises some important questions so many years into using medications to treat ADD, including whether we're really treating the problem or slapping a temporary band-aid on it, and if these medications really improve educational outcomes in the kids taking them.

They've been in use a long time now, so it's a good time to look back and make sure they're working, having the intended effect, and aren't having any long-term detrimental effects. This evaluation should be done for any therapy or treatment regimen. Afterall, I think the major reason people worry about treating the behavioral condition is that it is generally perceived that the behavior hinders learning and treatment will improve learning. If treating the behavior doesn't improve learning, does the behavior still warrant treatment?

There are other issues the article raises as well, such as what NIH currently funds and how it is limiting scientific progress to very narrow views, but I'll save that more political debate for another day.

That is an opinion piece, so for the remainder of the thread, the goal is to explore the peer-reviewed literature to date on this issue to verify or refute those claims.

 

[Pythagorean]

Well, this is anecdotal:

I have friends, some clinically diagnoses, some not, that use aderall to treat ADD. Some other friends that don't claim to have ADD at all will occasionally get some from these friends to power study the night before a test. So there's some benefit to the drug whether you have ADD or not; so that it shows improvement shouldn't be proof that it's treating anything, I guess.

But I often have a feeling that the regular users of aderall tend to get caught up on the trees, completely missing the forest.

 

[Moonbear]

Well, this is anecdotal:

I have friends, some clinically diagnoses, some not, that use aderall to treat ADD. Some other friends that don't claim to have ADD at all will occasionally get some from these friends to power study the night before a test. So there's some benefit to the drug whether you have ADD or not; so that it shows improvement shouldn't be proof that it's treating anything, I guess.

But I often have a feeling that the regular users of aderall tend to get caught up on the trees, completely missing the forest.

That's actually discussed in the article, that there has been an assumption that the stimulants help focus on repetitive tasks because the ADD brain is different than a normal brain, but the meds have the same effect on normal subjects, which is why they are being abused by students without ADD. And, it further adds that as with other addictive substances, after about 3 years of use, they stop working due to development of tolerance. So, are we just creating amphetamine addicts while treating the wrong cause of the behavior problems? We could be masking symptoms, not treating them.

 

[Pythagorean]

College abuse statistics:

Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey

Sean Esteban McCabe1,*, John R. Knight2, Christian J. Teter3, Henry Wechsler4
Article first published online: 10 DEC 2004
DOI: 10.1111/j.1360-0443.2005.00944.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2005.00944.x/full

Long-term considerations

ATTENTION DEFICIT/HYPERACTIVITY DISORDER ACROSS THE LIFESPAN
Annual Review of Medicine
Vol. 53: 113-131 (Volume publication date February 2002)
DOI: 10.1146/annurev.med.53.082901.103945
Timothy E. Wilens, Joseph Biederman, and Thomas J. Spencer

http://www.annualreviews.org/doi/pdf/10.1146/annurev.med.53.082901.103945
I'm seeing lots of positive articles; one even suggests how we should move towards healthy people using cognition-enhancing drugs like aderall!:

Towards responsible use of cognitive-enhancing drugs by the healthy
Henry Greely, Barbara Sahakian, John Harris, Ronald C. Kessler, Michael Gazzaniga, Philip Campbell & Martha J. Farah
Nature 456, 702-705 (11 December 2008) | doi:10.1038/456702a;Cynical me wonders how well funded positive studies are vs. negative studies.

 

[Moonbear]

Cynical me wonders how well funded positive studies are vs. negative studies.

I'm concerned that's happening in a lot of biomedical research right now, not just this area. But, we can't really evaluate what hasn't been done. Instead, we can look at existing studies and see if they are flawed or biased in a way that would lead us to question the conclusions. I'm suspect of an article suggesting everyone use these drugs, so maybe that one will go to the top of my reading pile on the subject.

 

[atyy]

Well, there is this movement not to accept the results of any study, unless the study is made public at its inception.

Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors
http://www.nejm.org/doi/full/10.1056/NEJMe048225

"Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision-making. ...

The ICMJE member journals will require, as a condition of consideration for publication, registration in a public trials registry. Trials must register at or before the onset of patient enrollment."

 

[Pythagorean]

So, John Ioannidis has become known as somewhat of a watchdog in medical sciences. So I've been including him in searches. In one search, I got a hit for adderall and Ioannidis on this article, but I have no access. May be nothing, but I figured I'd mention it.

Withdrawals of drugs for safety reasons: how do regulators decide if they are too unsafe?
Lexchin, Joel
Adverse Drug Reaction Bulletin:
February 2006 - Volume - Issue 236 - p 903-906

 

[wphurley]

Pardon the sparseness of this contribution give some of the points I'll assert. I stumbled across this thread and, with other obligations pressing, I don't have time to coalesce the supporting citations at the moment.

I've read and reread Dr Souffe's essay several times. I find it earnest though wanting and curiously selective. My primary objection to the Dr Srouffe's essay is that he, like far too many others who have published on this subject in the popular press, conflates the effects of what is symptomatically called ADHD on individuals diagnosed with the disorder with the "issues" of cognitive performance in highly specified task-based scenarios among the general population. Cutting to the chase, and echoing my caveat above, there is to date no substantive, peer-reviewed study that affirms or denies the hypothesis that the use of stimulant drugs improve a subject's ability to perform to a higher standard of achievement or consistency than not. A meta-analysis of the body of research on the subject published in 2010 - if memory serves me correctly - arrived at the conclusion I paraphrased above. I'll see if I can located it in the immediate future and post the link/citation info. One thread of discussion in this meta-analysis addressed the placebo effect and its influence on an individual's subjective interpretation of his/her experiences and perceived benefits of occasional stimulant use.

Analyses of task performance are a useful but insufficient grounds upon which to evaluate the breadth of effects ADHD may have on an individual. By analogy, an individual's ability to accurately read a "traditional" eye chart test is useful but insufficient to determine the specific contours of a subject's deficiencies in vision and the "real-time" effect of such deficiencies across the spectrum of the a subject's daily experiences.

In addition to this error of conflation, Dr Srouffe makes no mention of studies of ADHD done in countries across the globe. The body of international research includes peer-reviewed studies conducted in Canada, Japan, S. Africa, Israel, China, Taiwan, UK, Germany, Brazil and many other nations. Among the many universal findings that these studies, in the aggregate, purport to have discovered is that a) the age of onset of ~7 years of age (though possibly earlier) is not nation/culture specific, b) subjects behavioral responses to the effects of ADHD are globally consistent, c) academic achievement whether classroom or test-based performance is statistically the same and, c) though limited in number, studies of working memory abilities (qualitative, quantitative and fMRI) of ADHD diagnosed children, teens and adults have found a marked WM deficiency in ADHD subjects regardless of nationality, gender, SES or age. I'll not speculate as to why Dr Srouffe chose to forgo including the various findings (some I've summarized) of non-US studies. I will however say that to address the matter of ADHD and what is, to date, the most common regime of treatment within and beyond US national borders begs many questions and skews the import of his essay's applicability as learned advice or clinical advice for the non-clinician.

Lastly, for now, Dr Srouffe's own history of engagement as an ADHD researcher demonstrates the complexities of studying and accurately identifying not only the etiologies of neurological and cognitive disorders - and the maladapted behaviors these disorders give rise to - but also that his history shows itself is instructive in that it demonstrates that what had been the "state-of-art" understanding can and often is overturned. Specifically, ADHD had long been "determined" to be a disorder of childhood, one that puberty and neurological maturation "resolved". Dr Srouffe had been an advocate of that out-moded understanding. As research has now determined, ADHD is not a disorder that "resolves" as a child matures into adulthood. ADHD is present life-long effecting a majority of afflictees from onset to death. I raise this before/after "state-of-art" understanding not to sully Dr Srouffe, but to highlight the complexities as I noted above and also to highlight the complexities of clinicians' own certitude in the efficacy and robustness of contemporary consensus.

My thoughts on the totality of Dr Srouffe's essay are not all critical. I found that his encouragement of a "combined" pharmaceutical/therapeutic model of treatment to be outstanding guidance. Still, I do wish he and others from within the medical professions writing on the matter in both professional and "lay" mediums speak to the issue of stimulant abuse, specifically Ritalin & Adderal, make mention of new pharmaceutical offerings such as lisdexamphetamine (vyvanse) that are designed with the abuse issue in mind. Vyvanse in particular is almost impossible for a sporadic/task-driven abuser to abuse due to the time-release mechanisms and, more importantly, the means by which it's metabolized. Since it must be digested to be metabolized, a process by which trypsin released from the pancreas splits lysine off of the amphetamine. Moreover, the dosing model facilitates a true "once-a-day" regime for patients of all ages - a regime that concerned parents can actively monitor or college-connected pharmacists can tack more readily.

Were Dr Srouffe and his fellows to advocate a move - by qualified patients - to drugs to drugs of such manufacture, the amount of abusable amphetamine in the "wild" would be reduced greatly.

Lastly lastly, I would also be overjoyed to see essays such as Dr Srouffe's make mention of the actual numbers the current "state-of-art" accepts regarding the population of affected individuals. If the general and/or non-specialist public knew that ADHD is thought to effect ~7-12% of the under-18 demographic and ~5-10 of the over-18 population - globally - then a context by which a rational understanding of the scale of the disorder can be understood and the "growth" in diagnosed individuals is not "scary" nor anecdotally useful to insinuate bad-motives to various constituencies. Of course, adding to the public's statistical understanding would also require one more data point, that being that consensus suggests that (using US stats alone) less than 50% of under-18 ADHD sufferers have been diagnosed and that less than 25% of adults have been diagnosed (with women in both demos representing a bulk of the undiagnosed afflictees). This being a physics forum, I'm sure many here are better at working out the math than I.

I'll conclude by revisiting the caveat I penned at the opening and that I'll endeavor to back-fill this post with citations and/or links.

 

[neyzenyelda]

I don't have ADD but I have depression and anger issues.
medications make wonders for me.
so I am always pro-medication.
I believe psyciatric disorders are organic brain disorders and non-drug treatments always fail.

 

[Thevic]

Well, there is this movement not to accept the results of any study, unless the study is made public at its inception.

Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors
http://www.nejm.org/doi/full/10.1056/NEJMe048225

"Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision-making. ...

The ICMJE member journals will require, as a condition of consideration for publication, registration in a public trials registry. Trials must register at or before the onset of patient enrollment."

I think it's pretty important to remember that a lot of these studies are made on pharmaceutical industries' money.

I don't have ADD but I have depression and anger issues.
medications make wonders for me.
so I am always pro-medication.
I believe psyciatric disorders are organic brain disorders and non-drug treatments always fail.

As a psychology undergrad who loves psychopharmacology, I must point out that most drug treatments fail in long-term, while the highest long-term healing rates are for both psychotherapy and pharmacology use.

Also, please refer to the Philosophy forums, specifically to the thread of Body/Mind and understand that under current philosophy development, organic brain disorders MEAN psychological issues.
Recent studies point that therapy causes healing re-wiring of the patient's brain.

Last, but not least, psychoanalysis has been having great results in neuroses and psychoses treatment in the last decades, and it's based solely on psychotherapy.

 

[Thermodave]

I don't have ADD but I have depression and anger issues.
medications make wonders for me.
so I am always pro-medication.
I believe psyciatric disorders are organic brain disorders and non-drug treatments always fail.

Quite the opposite, actually. As any psychologist or psychiatrist will tell you, the best results are always obtained by using a combination of drugs and therapy. However, therapy alone has been shown to have better long term results than medication alone. So if you had to choose, I'd opt for therapy.

Getting back to the ADHD topic, I think that it's fairly apparent to anyone who had friends taking this stuff illegally in college that there is a big performance enhancement aspect to it. Whether some kids are naturally disadvantaged and need this at a young age or whether parents are just taking an easy out with the meds is the real question, I feel. The theory seems to be that those diagnosed with ADHD respond to the meds differently, but I don't know the studies so I can't say if that's been clearly observed.

 

[wphurley]

Wow. IN the age when Google Scholar is free, I stumble across this:

The theory seems to be that those diagnosed with ADHD respond to the meds differently, but I don't know the studies so I can't say if that's been clearly observed.​

Hundreds of studies conducted in the US and beyond have conclusively proven that stimulant medications aid those afflicted with ADHD, period. ADHD is not a disorder effecting merely task performance. It is a developmental disorder that, as developmental disorders do, effects all aspects of an ADHD sufferer's life. Everything from small decisions to large, actual physical well-being and long-term mental health - the latter evidenced by the 5x increase over the norm of ADHD diagnosees suffering dementia later in life.

People with ADHD respond differently than those without to stimulants. Whether in prescription form or in legal alternatives such as caffeine, people with ADHD become less distracted, calmer and more "attuned" to their physical and social context. Conversely, people not suffering from ADHD become increasingly irritable, disconnected and hyper from the use of stimulants. In extreme cases, the latter class (non-ADHD) can be represented by the stereo-type of a "meth-head" or "tweeker" - the archetype of a scattered, mono-focused, dysfunctional individual.

Now, some data.
http://www.springerlink.com/content/12l4816226v44386/
http://www.drthomasebrown.com/pdfs/HighIQAdults.JADonlineversion.pdf

and this one in particular:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=5880004

Is adult attention deficit hyperactivity disorder a valid diagnosis in the presence of high IQ?

Background: Because the diagnosis of attention deficit hyperactivity disorder (ADHD) in higher education settings is rapidly becoming a contentious issue, particularly among patients with high IQs, we sought to assess the validity of diagnosing ADHD in high-IQ adults and to further characterize the clinical features associated with their ADHD.

Method: We operationalized high IQ as having a full-scale IQ [equal to or greater than] 120. We identified 53 adults with a high IQ who did not have ADHD and 64 adults with a high IQ who met diagnostic criteria for ADHD. Groups did not differ on IQ, socio-economic status or gender.

Results: High-IQ adults with ADHD reported a lower quality of life, had poorer familial and occupational functioning, and had more functional impairments, including more speeding tickets, accidents and arrests. Major depressive disorder, obsessive-compulsive disorder and generalized anxiety disorder diagnoses were higher in high-IQ adults with ADHD. All other psychiatric co-morbidities, including antisocial personality disorder and substance abuse, did not differ between the two high-IQ groups. ADHD was more prevalent in first-degree relatives of adults with ADHD relative to controls.

Conclusions: Our data suggest that adults with ADHD and a high IQ display patterns of functional impairments, familiality and psychiatric co-morbidities that parallel those found in the average-IQ adult ADHD population.​

In short, even those who have ADHD and also a high IQ perform, academically speaking, at levels below their non-ADHD/high-IQ peers. I can't speak for this study, but others have arrived at the same findings, having tested the ADHD subjects with and without the aid of medication. In instances when ADHD/hi-IQ subjects are tested without medication, academic performance declines even further.

 

[Mkorr]

In general, whenever you hear sweeping claims about how "psychiatric medications are ineffective" (despite being well-tested in clinical trials), you are dealing with anti-psychiatry. This talk about long-term effects are also usually an attempt at shifting the goal posts, increasing the burden of evidence for the science-based psychiatry side, although the discussion of long-term effects are of course scientifically relevant.

Anyways, here is one interesting abstract:

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [(11)C]raclopride (D(2)/D(3) receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners' Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D(2)/D(3) receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

Volkow ND, Wang GJ, Tomasi D, Kollins SH, Wigal TL, Newcorn JH, Telang FW, Fowler JS, Logan J, Wong CT, Swanson JM. (2012). Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder. J Neurosci. 32(3):841-849.

and another..

OBJECTIVE: The purpose of this study was to describe the significance of potential modifiers of long-term school outcomes among children with attention-deficit/hyperactivity disorder (AD/HD), including treatment with stimulant medication.

METHODS: Subjects included 370 children with research-identified AD/HD from a 1976-1982 population-based birth cohort (N = 5718). In a companion study, the complete school record for each subject was reviewed to obtain information on reading achievement, absenteeism, grade retention, and school dropout. Data on type of stimulant, dose, age at initiation of treatment, and start/stop dates were collected from medical and school records, available for all subjects.

RESULTS: Treatment with stimulants was associated with decreased rates of absenteeism; longer duration of treatment was also associated with decreased absenteeism rates. There was a modest positive correlation (r = .15, p = .012) between average daily stimulant dose and last reading score. Cases treated with stimulants were 1.8 times less likely to subsequently be retained a grade (95% confidence interval: 1.01-3.2; p = .047). The proportion of school dropout was similar between treated and not treated cases (22.2% vs 25.8%, p = .54). Other potential modifiers of school outcomes (sociodemographic risk factors, presence of comorbid learning or psychiatric disorders, and receipt of special educational services) were also examined and found to be associated with poorer outcomes.

CONCLUSIONS: In this birth cohort, stimulant treatment of children with AD/HD was associated with improved reading achievement, decreased school absenteeism, and decreased grade retention. This study provides support for efforts to ensure that children with AD/HD receive appropriate long-term medical treatment.

Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. Modifiers of long-term school outcomes for children with attention-deficit/hyperactivity disorder: does treatment with stimulant medication make a difference? Results from a population-based study. J Dev Behav Pediatr. 2007 Aug;28(4):274-87.