In prescribing treatments for a variety of ailments, it sometimes seems as if no good deed goes unpunished. The September, 2009 issue of the journal Postgraduate Medicine, presents us with a number of excellent papers that show that some remedies for one illness, have potential for causing others, or at least, for requiring more vigilance for co-morbidity, the presence of two diseases in the same patient at once.
Indeed, paradoxes abound, and those physicians and pharmacological researchers who try to navigate between the “rock and the hard place” are to be credited as often as they succeed, because the path is by no means clear for all the affected patients.
Is There A Relationship Between Adult ADHD And Adult Substance Use Disorders?
There has been a longstanding supposition that a link exists between the onset of Attention Deficit Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD usually involving generally street drug addiction).
Demographic studies of adults based on interviews of individuals living in the community (or on the streets), have usually been conducted by walk-in or outpatient clinics. Their results in reporting their rates for separate and simultaneous incidence of both conditions have fluctuated, in part because it is hard to follow up on patients or to retest them to assure reliability.
This uncertainty of a connection, or of the frequency of having both conditions at the same time, has been considerably reduced via a study at Odyssey House, an in-patient, residential treatment facility in New York City (See Adler et al, 2009 below).
It involved a very large group ( 1064) of in-patients, where no subjects had to be excluded for lack of reliability of background information or unwillingness or unavailability to take a series of diagnostic tests, and no patients dropped out, conditions almost never attainable in community-based studies.
The end result is that patients with drug abuse problems had reliably diagnosed ADHD at twice the rate (~7+%) of the “normal” population (~4%), but not necessarily the 25%+ rates seen in other studies.
The paradox in treating the ADHD of these patients who also had drug abuse problems will crop up shortly in this essay.
Is There A Relationship Between ADHD and Patients with Major Mood Disorders Including Bipolar?
Of course, drug abuse is not the only co-morbidity associated with adult ADHD.
Mood disorders, particularly major depression and bipolar disease, also have a connection .
A paper By Goodman & Thase (2009, cited below) reports that 13% of patients presenting primarily for treatment for mood disorders also turn out to have ADHD, and 38% of patients presenting primarily for treatment of ADHD turn out to have major depression or bipolar disorder.
While a wide variety of treatment strategies are suggested to attack this problem, one of them, and quite frankly, the first line of defense, are prescription medications, and these two present prescribers with a paradox.
First Paradox: The Overall Drug of Choice for Primary ADHD is Not Likely to Be the Safest Drug of Choice for Substance Abuse Disorder or BiPolar Patients With Co-morbid ADHD. It’s Enough To Give Some Patients Heartburn
This is where the first in a string of paradoxes comes in.
One salient problem in the case of both studies is that the drug of choice for treating ADHD is “speed”, more technically, amphetamines.
It is not clear that one wishes to give drug addicts a drug, which if they take in doses beyond the prescribed low levels ( a common behavior among addicts, and also among many ADHD patients) will lead to yet another addiction.
It may also be very unwise to use amphetamines, which do have the potential for causing over-excited behavior and a general feeling of edginess to bipolar patients who are entering their manic phase.
In a further complication, some controlled release versions of mixed amphetamine salts, developed in part because their more gradual pharmacokinetics make them less likely to cause a “speed buzz”, are rendered less predictable in their ability to gradually enter the body.
This is due to certain prescribed and over the counter medications (the best-selling of which is omeprazole, brand name Prilosec) designed to control acid reflux (also a common condition shared by both adult ADHD and bipolar patients).
Omeprazole changes the chemical environment of the gut in a manner that has the potential in some patients to subvert the designed rate of release of the mixed amphetamine salts. (See Haffey et al., cited below.)
In about half the cases in this study, the mixed amphetamine salts in controlled released, reached peak saturation significantly sooner, with the dosage tailing off towards the end of the individual dose.
This may leave some patients with the choice to stick with their controlled-release mixedamphetamine salts medication for ADHD and to try and ignore the heartburn, or perhaps switch to the fast-acting amphetamines, without the risk of heart burn because the omeprazole could still be taken, but with the risk of abuse of the fast-acting variety.
(Fortunately lisdexanfetamine, an alternative for some ADHD patients, seems unaffected by omeprazole, but it is not clear whether this drug will work as well for all patients well-controlled with mixed amphetamine salts.)
Second Paradox: The Drugs of Choice for Adult BiPolar Disorder Patients May Predispose them to Weight Gain, Metabolic Syndrome, and Adult Onset Diabetes
If the drug of choice for treating mixed bipolar disorder and ADHD is yet to be identified (with or without acid reflux or heartburn) there is no lack of choice in treating the more severe forms of primary bipolar disorder.
Clozapine (brand name Clozaril), Olanzapine (brand name Zyprexa), Risperidone(brand name Risperdal), Quetiapine (brand name Seroquel), Aripiprazole (brand name Abilify) and Ziprasidone (brand name Geodon) have all been used with significant success in literally millions of patients.
What’s the catch?
According to a paper by Bell, McKenna & Roscoe (2009, cited below) the first four of these are associated with patient weight gain and adverse blood lipid profiles (too much of the wrong kinds of cholesterol, less of the good kind, and overall, higher triglyceride levels.)
All six are associated with increased diabetes risk.
Most psychiatric providers do not, however, suggest that these drugs be discontinued, but rather, they recommend trying to change the patient’s health affecting behaviors in a positive way.
Having said this, they also warn that this is extremely difficult with many bipolar patients, many of whom will go off on their anti-bipolar drugs because, like many “normal people,” they too disdain getting fat (sadly, more so than they fear severe mood swings).
Third Paradox: Many of the Drugs Designed to Stave Off Adult Onset Diabetes Have An Ironic Propensity to Promote Weight Gain
A review by Pi-Sunyer (2009, cited below) of 15 major agents to control the early stages of adult onset diabetes, discloses that most of them paradoxically promote weight gain and sometimes adverse blood profiles, independent factors in increasing the propensity for diabetes and heart disease.
Nonetheless, very few physicians recommend forgoing the glucose control drugs despite this paradox .
The trick, according to the author is to find out which drugs (or injections) account for the least amount of weight gain, because his research shows once again, that many patients will stop taking the prescribed drugs or injecting themselves, if they find themselves gaining weight.
A Fourth & Final Paradox: Taking Capsules Filled with Oil Every Day, Without Otherwise Adjusting Your Diet, Does Not Gain You 4-5 Extra Pounds a Year, If those Oils are Omega-3 Fatty Acids (Or Maybe Even Just Corn Oil)
Finally, not all paradoxes work against the prescribing physician and his or her patient. In a study by Bays et al (2009, cited below) patients with dangerously high triglycerides, a category of fatty substances in the blood associated in many cases with patients who have high intakes of calories and especially of fats and oils, were prescribed Lovaza capsules, the brand name for a highly concentrated form of omega-3 fatty acids in oil form.
While a wide variety of health claims have been made for omega-3 fatty acids over the last few decades, there is somewhat greater certainty that these can help control high triglyceride levels.
They took these capsules in conjunction with fenofibrate (brand name Antara) another agent proposed to help reduce high triglyceride levels.
They compared the “fat-adding” potential of the Lovaza capsule with a capsule containing the caloric equivalent in corn oil.
The results contained two surprises, one of them more surprising than the other.
It was really no surprise that the levels of triglycerides decreased more significantly with the Lovaza+fenofibrate than it did with the corn oil +fenofibrate.
The real surprise is that neither oil-containing capsule, taken in the amounts prescribed, caused significant weight gain!
Tony Stankus, FSLA, [email protected], Life Sciences Librarian, Science Coordinator & Professor
University of Arkansas Libraries MULN 223 –E
365 North McIlroy Avenue
Fayetteville AR 72701-4002
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Fax: 479-575-4592
Adler, L.A., Guida, F., Rotrosen, J. & O’Donneel, M.A. (2009). Screening and imputed prevalence of ADHD in adult patients with comorbid substance use disorder at a residential treatment facility. Postgraduate Medicine, 121(5),7-10.
Bays, H.E., Maki, K.C., Doyle, R.T. & Stein, E. (2009). The effect of prescription omega-3 fatty acids on body weight after 8 to 16 weeks of treatment for very high triglyceride levels. Postgraduate Medicine, 121(5), 145-150.
Bell, P. F., McKenna, J. P., & Roscoe, B. M. (2009). Treatment of bipolar disorders and metabolic syndrome: Implications for primary care. Postgraduate Medicine, 121(5), 140-144.
Brunton, S. (2009). Beyond glycemic control: Treating the entire type 2 diabetes disorder. Postgraduate Medicine, 121(5), 68-81.
Haffey MB, R., Buckwalter, M., Zhang, P., Homolka, R., Martin, P., Lasseter, K. C., et al. (2009). Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults. Postgraduate Medicine, 121(5), 11-19.
Pi-Sunyer, F. X. (2009). The impact of weight gain on motivation, compliance, and metabolic control in patients with type 2 diabetes mellitus. Postgraduate Medicine, 121(5), 94-107.
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