Ritalin vs Adderall for Inattentive ADD, The Medical Literature

Ritalin or Aderall
I have been asked by several of you to post the citations in the medical literature regarding Ritalin vs Adderall for the treatment of Inattentive ADD.  I have included the Weiss study and the Ishimatsu Studies below.  I tried to get a  reprint of the Milich article but they wanted $35.00 and I said, "No Thanks!!"

The Barkley citation below is what Russell Barkely, PhD reported on the Inattentive type of ADD way back when he was still talking about this subtype of ADHD.  I have quoted him on the synopsis of the findings that are available regarding the benefits of Adderall over Ritalin.

Perhaps a much better read, if you are so inclined, is a much more comprehensive review of Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity) by Adele Diamond  from the University of British Columbia.  Her writings are well worth the time to read carefully as they include much of the information that I have reported on and then some.

What Russell Barkley, PhD has said:

Most children with ADHD (perhaps as high as 90%; Barkley, 2001; Barkley et al., 1991; Milich et al., 2001; Weiss et al., 2003) respond positively to methylphenidate (Ritalin) and over two-thirds of such children respond positively to methylphenidate in moderate to high doses (Barkley, 2001; Barkley et al., 1991; Milich et al., 2001; Weiss et al., 2003). In contrast, a significant percentage of children with ADD are not helped by methylphenidate and those who are helped often do best at low doses (Barkley, 2001; Barkley et al., 1991; Milich et al., 2001; Weiss et al., 2003).

Many individuals with ADD are helped by amphetamines, such as Adderall. There is considerable overlap in the mechanisms of action of methylphenidate and amphetamines, but there is a significant difference. Although both methylphenidate and amphetamines inhibit reuptake of dopamine and norepinephrine, only amphetamines also promote release of those neurotransmitters. Recent research also suggests that low doses of methylphenidate (the dosages likely to be efficacious in treating ADD) preferentially release norepinephrine in the rat brain (Ishimatsu, Kidani, Tsuda, & Akasu, 2002). Possible problems with the neural release of norepinephrine in ADD are relevant to motivational issues discussed later.

J Neurophysiol. 2002 Mar;87(3):1206-12.
J Atten Disord. 2003 Sep;7(1):1-9.
A chart review study of the inattentive and combined types of ADHD.
Weiss M, Worling D, Wasdell M.
Department of Psychiatry-C4, University of British Columbia, Children's and Women's Health Centre, Vancouver, Canada. mweiss@cw.bc.ca

Studies of the clinical correlates of the subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD) have identified differences in the representation of age, gender, prevalence, comorbidity, and treatment. We report retrospective chart review data detailing the clinical characteristics of the Inattentive (IA) and Combined (C) subtypes of ADHD in 143 cases of ADHD-IA and 133 cases of ADHD-C. The children with ADHD-IA were older, more likely to be female, and had more comorbid internalizing disorders and learning disabilities. Individuals in the ADHD-IA group were two to five times as likely to have a referral for speech and language problems. The children with ADHD-IA were rated as having less overall functional impairment, but did have difficulty with academic achievement. Children with ADHD-IA were less likely to be treated with stimulants. One eighth of the children with ADHD-IA still had significant symptoms of hyperactivity/impulsivity, but did not meet the DSM-IV threshold for diagnosis of ADHD-Combined Type. The ADHD-IA subtype includes children with no hyperactivity and children who still manifest clinically significant hyperactive symptomatology but do not meet DSM-IV criteria for Combined Type. ADHD-IA children are often seen as having speech and language problems, and are less likely to receive medication treatment, but respond to medical treatment with improvement both in attention and residual hyperactive/impulsive symptoms.

Effects of methylphenidate on the membrane potential and current in neurons of the rat locus coeruleus.
Ishimatsu M, Kidani Y, Tsuda A, Akasu T.
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Effects of methylphenidate (MPH), a therapeutic agent used in children presenting the attention deficit hyperactivity disorder (ADHD), on the membrane potential and current in neurons of the rat locus coeruleus (LC) were examined using intracellular and whole cell patch-clamp recording techniques. Application of MPH (30 microM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response with amplitude of 12 +/- 1 mV (n = 29). Spontaneous firing of LC neurons was blocked during the MPH-induced hyperpolarization. Superfusion of LC neurons with ACSF containing 0 mM Ca(2+) and 11 mM Mg(2+) (Ca(2+)-free ACSF) produced a depolarizing response associated with an increase in spontaneous firing of the action potential. The MPH-induced hyperpolarization was blocked in Ca(2+)-free ACSF. Yohimbine (1 microM) and prazosin (10 microM), antagonists for alpha(2) and alpha(2B/2C) receptors, respectively, blocked the MPH-induced hyperpolarization in LC neurons. Tetrodotoxin (TTX, 1 microM) produced a partial depression of the MPH-induced hyperpolarization in LC neurons. Under the whole cell patch-clamp condition, MPH (30-300 microM) produced an outward current (I(MPH)) with amplitude of 110 +/- 6 pA (n = 17) in LC neurons. The I(MPH) was blocked by Co(2+) (1 mM). During prolonged application of MPH (300 microM for 45 min), the hyperpolarization gradually decreased in the amplitude and eventually disappeared, possibly because of depression of norepinephrine (NE) release from noradrenergic nerve terminals. At a low concentration (1 microM), MPH produced no outward current but consistently enhanced the outward current induced by NE. These results suggest that the MPH-induced response is mediated by NE via alpha(2B/2C)-adrenoceptors in LC neurons. I(MPH) was associated with an increase in the membrane conductance of LC neurons. The I(MPH) reversed its polarity at -102 +/- 6 mV (n = 8) in the ACSF. The reversal potential of I(MPH) was changed by 54 mV per decade change in the external K(+) concentration. Current-voltage relationship showed that the I(MPH) exhibited inward rectification. Ba(2+) (100 microM) suppressed the amplitude and the inward rectification of the I(MPH.) These results suggest that the I(MPH) is produced by activation of inward rectifier K(+) channels in LC neurons


  1. Its all so interesting this research, my son is on Concerta XL, the slow release form of ritalin and it has changed the whole families life, but we found a lower dose suited him better but we had to fight for that dose, his doctor was happy to put him on a higher dose. Our son is inattentive type with lesser hyperactivity, but also has mild aspergers. I am constantly reading new research and looking things up and find posts like this really helpful;

  2. http://www.campusmoviefest.com/movies/7675-drug-of-choice we did a little about the abuse of it

  3. Kayla,

    The video is very interesting. I attended a conference this fall where the CDC reported there was an exponential increase in college age kids using stimulants. One of my first thoughts was that more kids were being treated with ADHD stimulants because it gave them an 'edge' above other students in college. This video seems to indicate that the edge may be a perceived 'edge' rather than a true edge.

    The potential for abuse of these drugs given the competitive environment in colleges is huge. Thanks for sharing this!!

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