Stimulants for adult ADHD have become very popular.  It is keeping adult psychiatry thriving.  Stimulant and Strattera manufacturers are funding a bandwagon campaign.  However, the materials available in physicians' offices from these manufacturers are so broad in the symptoms that they call evidence of ADHD that almost everyone can think of himself as fitting the diagnosis.  

Sure, stimulants help people focus, but anything learned under their influence is forgotten at a higher rate, probably resulting in no net long-term benefit.  Of course, patients love stimulants.  Why do you think cocaine and speed are so popular?  They make people feel energetic and productive, able to focus and have great thoughts.  However, do we really know enough of the long-term effects of a lifetime on stimulant drugs?  Many children are now being started on stimulants with little evidence of long-term benefit and continued on stimulants through high school, college, and into adult life.  

Nortriptyline (Aventyl), clonidine (Catapres), and bupropion (Wellbutrin) are less expensive and more reasonable initial treatments for adult ADHD than stimulants and should help the majority of patients.  Each has been shown in double-blind studies to be helpful.  However, many non-medication interventions should be tried first: a healthy diet, exercise, magnesium, zinc, fish or fish oil, and carnitine.

Atomoxetine (Strattera) Helped Adult ADHD in 2 Large DB: Two large DB PC studies by the Eli Lilly drug company of 280 and 256 adult ADHD patients for 10 weeks each reported that both studies found benefits from atomoxetine 60-120 mg/day with drop-outs from side-effects of 8.5% vs. 3% with placebo. Improvement measured by Connor's Adult ADHD Rating Scale in atomoxetine versus placebo recipients were 28.3% vs. 18.1% and 30.1% vs. 19.6% in the two studies. Benefit continued through a total of 34 weeks in non-controlled follow-up. Adverse events reported significantly more frequently with atomoxetine than placebo included dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems and palpitations. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Michelson D, Adler L, et al. Biol Psychiatry. 2003 Jan 15;53(2):112-20. Ed: This amount of atomoxetine costs $135-$270 per month.  The benefits are significant, but no better than those found with similar anti-depressants, nortriptyline and desipramine, at one-tenth the cost.

Bupropion Did Better than Placebo: In an 8-week DB PC study of 162 adults with ADHD (combined and inattentive types), 53% of those given up to 450 mg/day of bupropion XL had a 30% reduction in the investigator-rated ADHD Rating Scale score vs. 31% for placebo (p =.004) with benefit being significant at 2 weeks. The benefit lasted throughout the day (morning p =.033, afternoon p =.004, evening p = .024). Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Wilens TE, et al. Massachusetts General Hospital, Boston. . Biol Psychiatry 2005 Apr 1;57(7):793-801.

Bupropion May Be Almost as Good as Methylphenidate: In a 7-week DB PC study of 30 ADHD adults randomized to bupropion, methylphenidate, or placebo with methylphenidate titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M., the response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. Because of the small size of the study, the difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Kuperman S, et al. University of Iowa. Ann Clin Psychiatry 2001 Sep;13(3):129-34. 

Bupropion Helped Adult ADHD: In a 6-week DB PC study of 40 adults with ADHD, those receiving bupropion (up to 200 mg b.i.d.) had a significant change in ADHD symptoms (42% vs. 24% for placebo). Using a cutoff of 30% or better reduction to denote response, 76% on bupropion improved vs. 37% on placebo. Clinical Global Impression scale scores of "much improved" to "very improved," were 52% vs. 11% for placebo. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Wilens TE, et al. Harvard. . 2005.

Methadone Adults: Ritalin = Wellbutrin = Placebo: In a 12-week DB PC study of 98 methadone-maintained adult ADHD patients with 53% meeting DSM-IV criteria for cocaine dependence/abuse, there were no differences in retention rate or outcome based on treatment groups of methylphenidate (Ritalin), bupropion (Wellbutrin), or placebo. There was no evidence of misuse of medication or worsening of cocaine use among those randomized to methylphenidate. Treatment of methadone-maintained patients with adult ADHD: Double-blind comparison of methylphenidate, bupropion and placebo. Levin FR, et al. New York State Psychiatric Institute, Columbia University. Drug Alcohol Depend. 2005 Aug 12. Ed: It is possible that the high improvement rate in the placebo group was a fluke.  Even 98 patients is not a large study. 

Methylphenidate (Ritalin) Helped Adult ADHD: In a meta-analysis of six DB PC studies totaling 253 patients, Harvard researchers conclude that there is strong evidence that stimulants help ADHD. In fact, they conclude that higher doses work more often than lower doses and have an effect size of 1.3 vs. 0.9 for the studies overall. Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. Faraone SV, Spencer T, Aleardi M, Pagano C, Biederman J. J Clin Psychopharmacol. 2004 Feb;24(1):24-9. Ed: Adult ADHD is a newer concept. While research shows that stimulants are effective, it also shows that several much less expensive anti-depressants are just as effective. 

Methylphenidate: Harvard Says Ritalin Helped Adult ADHD: In a 6-week DB PC study of 146 adults with DSM-IV ADHD, those given methylphenidate (1.1 mg/kg/day or 77 mg for a 154# male) had a marked reduction in ADHD symptoms of 76% vs. 19% for placebo. A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Spencer T, Biederman J, et al. Massachusetts General-Harvard. Biol Psychiatry. 2005 Mar 1;57(5):456-63. Ed: I disagree with the stampede to prescribe Ritalin to huge numbers of adults. I don't agree with the standard listing of adult ADHD symptoms. Stimulants will make anyone focus and concentrate better while temporarily under the medication effect. However, this doesn't lead to any improvement in learning, since much of the learning is state-dependent and forgotten. Also, a 6-week study for what would be a many-year treatment doesn't make sense.  Child research suggests all of the benefit occurs in the first weeks of treatment and that long-term benefit is minor. Putting 5% of America's adult population on stimulants for a minor benefit seems misguided.  I'd like to see long-term research with randomized control groups.

Lithium as Good as Methylphenidate in Adult ADHD: A Buenos Aires PC DB study of methylphenidate up to 40mg/d vs. lithium up to 1200 mg/d for 8 weeks found both groups improving equal amounts. A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: preliminary findings. Dorrego MF, Canevaro L, Kuzis G, Sabe L, Starkstein SE. J Neuropsychiatry Clin Neurosci. 2002 Summer;14(3):289-95

Adult ADHD Cocaine Addicts in DB with Methylphenidate: A PC DB study of 48 cocaine dependent patients diagnosed as co-morbid ADHD treated with MPH or placebo for 12 weeks.  There was no difference in cocaine use. There were subjective reports of improved ADHD symptoms. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Schubiner H, Saules KK, Arfken CL, Johanson CE, Schuster CR, Lockhart N, Edwards A, Donlin J, Pihlgren E. 2003

Pycnogenol vs. Methylphenidate Studied: A PC DB study of only 24 adult ADHD didn't find any superiority from either med. The lack of benefit may have been due to lower dosages being used. An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Tenenbaum S, Paull JC, Sparrow EP, Dodd DK, Green L. J Atten Disord. 2002 Sep;6(2):49-60

ADHD Medications Increase Blood Pressure in Adults: In a DB PC study of 125 ADHD adults, average age 39, all five ADHD medications used increased blood pressure. Statistically significant changes in systolic blood pressure (bupropion: +5.9 mm Hg, p < .05; amphetamine: +5.4 mm Hg, p < .05), diastolic blood pressure (desipramine: +7.1 mm Hg, p < .05), and heart rate (bupropion: +6.9 mm Hg, p < .05; amphetamine: +7.3 mm Hg, p < .05; methylphenidate: +4.5 mm Hg, p < .05). Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. Wilens TE, Hammerness PG, et al. Massachusetts General Hospital. J Clin Psychiatry. 2005 Feb;66(2):253-9

Adult ADHD Linked to PTSD: In a study of 25 male veterans with PTSD and 22 with panic disorder, 36% with PTSD and 9% with panic disorder met criteria for childhood ADHD, while 28% with PTSD and 5% with panic disorder met criteria for current ADHD. Attention-deficit/hyperactivity disorder in adult patients with posttraumatic stress disorder (PTSD): is ADHD a vulnerability factor? Adler LA, Kunz M, et al. New York University. J Atten Disord. 2004 Aug;8(1):11-6.

Thomas E. Radecki, M.D., J.D.

 modern-psychiatry.com