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ADHD |
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Treatment Alternatives for Attention Deficit Hyperactivity Disorder
Alternate treatments (Tx) are defined for this conference as any treatment other than prescription drugs or standard behavioral treatments. In contrast with those two established general treatments, many alternate treatments are etiologically targeted (see Table 1) and consequently applicable to a smaller subpopulation of patients with attention deficit hyperactivity disorder (ADHD). Therefore, scientific evaluation and clinical use of such treatments require a deeper level of diagnosis than the phenomenological criteria of DSM-IV.**
Elimination Diets (Oligoantigenic or Few-Food Diets)
The 1982 consensus development conference on defined diets in hyperactivity (NIH, 1982) called for more controlled research. Since then, at least seven controlled studies (Breakey, 1997) have demonstrated either significant improvement compared with a placebo condition (disguised full diet) (Kaplan, McNicol, Conte, et al., 1989) or deterioration on a placebo-controlled challenge of offending substances after an open diet trial and open challenge to identify the substance (Egger, Carter, Graham, et al., 1985; Pollock, Warner, 1990; Carter, Urbanowicz, Hemsley, et al., 1993; Rowe, Rowe, 1994; Boris, Mandel, 1994; Schmidt, Mocks, Lay, et al., 1997). The finding of scientifically acceptable documentation of efficacy since 1982 appears associated with broadening the range of suspected food items, selecting subjects more carefully (e.g., for allergic diathesis), and allowing for the timing peculiarities of food sensitivities. A related Tx possibility arises from the documentation of successful desensitization to the offending food by enzyme-potentiated desensitization (Egger, Stolla, McEwen, 1992). The main scientific task is to refine the diagnostic characteristics of diet responders and delineate what percentage they constitute of the ADHD population. Preliminary evidence suggests that the profile of a probable responder is a middle- or upper-class preschooler with atopy and prominent irritability and sleep disturbance, with physical as well as behavioral symptoms.
A related dietary strategy, simple elimination of sugar or candy, has not garnered convincing scientific support from repeated placebo-controlled challenge studies (Krummel, Seligson, Guthrie, 1996) despite a few encouraging reports (e.g., Goldman, Lerman, Contois, et al., 1986). return to ADHD home page return to previous page
Nutritional Supplements. Both macronutrients (amino acids, lipids, carbohydrates) and micronutrients (vitamins and minerals) have been proposed as Tx for ADHD.
Table 1. Scientific status of alternate treatments for ADHD
| Treatment | Etiology or Mechanism | Type of Data | ES or p | Rating* (0-6); Recommendation | Risks | |
| Few-foods diet (oligoantigenic) | Food or additive sensitivity | Controlled trial; placebo challenges | ES 0.5-1.5 p,.05-.001 | 5; Define subgroup (profile; % ADHD) | Nuisance, expense, nutrition | |
| Enzyme-potentiated desensitization | Food or additive sensitivity | Controlled comparison with placebo injections | p,.001 | 4; Replication Define subgroup | Injection | |
| Sugar elimination | Sugar malaise | Placebo-controlled challenges | p>.1 | 0 for acute; Take FH of DM | Delay std Tx | |
| Amino acid supplementation | Precursors of catecholamines | Placebo-controlled comparisons | ES up to 0.6, p,.01 | 0 despite short- lived effect of little utility | Eosinophilia, neurotoxicity | |
| Essential fatty acid supplementation | Prostaglandins neur. membrane | Serum level cf. cntrl plac-contr. trials | ES 0.5 .1>p>.05 | 3; trials of n-3 | Upsetting balance | |
| Glyconutritional supplementation | Need for glycoconjugates | Open trials, SNAP-IV, blind teachers | p,.05-.002 | 3; placebo trials | Upsetting balance | |
| Vitamins | Deficiency vs. Idiopathic need for higher dose | Placebo-controlled trials megavitamin cocktails, not RDA | Megadose cocktail no benefit | 0 for megacocktail; 1 for RDA, specific megavit; pilot trials | Hepatotoxicity, neuropathy in megadose | |
| Iron supplementation | Co-factor make catecholamines | Open trial supplementation | ES 1.0 p<.05 | 3 † ; controlled trials | Hemochroma- tosis | |
| Zinc supplementation | Co-factor for many enzymes | Comparison Zn lvl of ADHD with control | ES 2.4 p<.001 | 2 † ; controlled trials | Excess | |
| Magnesium supplementation | Deficiency cf. to controls | Open trial with control group | ES 1.2-1.4 p<.05 | 3 † ; placebo trials | Aggression from excess | |
| Chinese herbals | Clinical exper. | Open trials, one with MPH control | p<.05; no diff. MPH | 3; placebo trials | Delay of other Tx | |
| Other herbals | Clinical exper. | No data | N.A. | 1; pilot trials | Delay Tx | |
| Homeopathic prep | Clinical exper. | No data | N.A. | 1; pilot trials | Delay Tx | |
| Laser acupuncture | Stimulate foci for calming | Open trial | ES 1.0 | 2; controlled trial | Delay other Tx, burn | |
| EEG biofeedback | Suppress theta, increase beta | Open & randomized wait list ctrl trials | p<0.05 | 3; sham-controlled trial | Expense, time | |
| EMG biofeedbck, relaxatn, hypnosis | Lower arousal, muscle tone | Randomized trials with controls | ES 1.0-1.3 p<0.01 | 0 for hypnosis; 4 for EMG/relaxn; cf. med | Delay other Tx | |
| Meditation | Autonomic effect focused attn | Cf. relaxation, wait list ctrl, med | p<.05 | 3; rigorous replication, sham ctrl | Delay other Tx | |
| Channel-specific perceptual training | Basic readiness skills, focus | Randmzd prev trial with 2 control grps | ES 0.9 p<0.01 | 3; controlled Tx trials | Delay other Tx | |
| Vestibular stimulation | Modulate behav attn, perception | Open and single- blind trials | ES 0.4-1.2 p ns-0.001 | 3; randomized sham-controlled trials | Nausea, accident | |
| Antifungal Tx | GI yeast | No systematic data | N.A. | 1; pilot trials | Med risk | |
| Thyroid Tx | Thyroid Fx affects AD Sx | Placebo trial: 5/8 GRTH, 1/9 other | ns if thyr not abnrml | 0 if thyroid nl; 6 if thyroid abnl | Thyroid toxicity | |
| Deleading | Lead toxicity causes AD Sx | Placebo-ctrl trial of chelation (=MPH) | ES 0.7-1.6 p,.05-.001 | 4 if blood Pb>20; 2 if Pb<20; ctrl trial | Toxicity of chelator |
† The rating would be 6 for patients showing frank deficiency of vitamins, iron, zinc, or other nutrients.
Amino Acid Supplementation. Amino acid supplementation is theoretically supported by reports of low levels of amino acids in ADHD, including the precursors of catecholamines and serotonin (Bornstein, Baker, Carroll, et al., 1990; Baker, Bornstein, Rouget, et al., 1991). Several open and controlled studies reported a short-term benefit from tryptophan, tyrosine, or phenylalanine supplementation (Nemzer, Arnold, Votolato, et al., 1986; Reimherr, Wender, Wood, et al., 1987; Wood, Reimherr, Wender, et al., 1985a). However, no lasting benefit beyond 2 to 3 months has been demonstrated (tolerance develops) (Wood, Reimherr, Wender, et al., 1985b), and even short-term benefit was not found in some studies (Eisenberg, Asnis, van Praag, et al., 1988; Zametkin, Karoum, Rapoport, 1987; Ghose, 1983). Further, such supplementation, while originally considered benign, may carry real dangers beyond that of eosinophilia. Therefore, amino acid supplementation does not appear a promising area to explore further.
Essential Fatty Acid Supplementation. Neuronal membranes are composed of phospholipids containing large amounts of polyunsaturated fatty acids, especially the n-3 and n-6 acids, which humans cannot manufacture de novo and hence are essential in the diet. Essential fatty acids (EFA) are also metabolized to prostaglandins, which modify many metabolic processes. Both the n-3 series (progenitor alpha-linolenic acid) and the n-6 series (progenitor linoleic acid) have been reported to be significantly lower in children with ADHD than in comparison controls (Mitchell, Lewis, Cutler, 1983; Mitchell, Aman, Turbott, et al., 1987; Stevens, Zentall, Deck, et al., 1995). Even total serum-free fatty acids were lower in ADHD, with ES = 2.4; p<.001 (Bekaroglu, Yakup, Yusof, et al., 1996). Aggression has been significantly inhibited in young adults by docosohexaenoic acid of the n-3 series (Hamazaki, Sawazaki, Itomura, et al., 1996). Two double-blind placebo-controlled trials of gamma-linolenic acid (n-6 series) supplementation yielded equivocal results from ADHD subjects not selected for low n-6 acids (Aman, Mitchell, Turbott, 1987; Arnold, Kleykamp, Votolato, et al., 1989); in one, the serum triglyceride gamma-linolenic acid correlated inversely with Conners scale scores (Arnold, Kleykamp, Votolato, et al., 1994). A controlled pilot trial of n-3 supplementation in ADHD subjects selected for symptoms of EFA deficiency showed a trend of advantage for the supplement despite a huge placebo effect (pre-post ES 1.8 vs. 1.4), and changes in serum phospholipid n-3 acids correlated negatively with changes in Conners scores (Burgess, Stevens, 1998). The data suggest further controlled trials in subjects selected for low serum levels.
Glyconutritional Supplements. Glyconutritional supplement contains basic saccharides necessary for cell communication and formation of glycoproteins and glycolipids: glucose, galactose, mannose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, and xylose. Only the first two are abundant in the ordinary diet. Dykman and Dykman (1998) found in an open trial of glyconutritional and phytonutritional (flash freeze-dried fruits and vegetables) supplements with 17 ADHD subjects a significant (p<.01) reduction in parent and teacher SNAP-IV ratings. Dykman and McKinley (1997) found in a second open trial with the same supplements in 18 children reductions in parent inattention ratings from 2.47 to 2.05 (p<.05) and hyperactivity-impulsivity ratings from 2.23 to 1.54 (p<.002), sustained for 6 weeks. Placebo-controlled trials are needed.
Vitamin Supplementation. Three strategies for vitamin supplementation are (1) RDA multivitamin preparations, (2) megavitamin cocktails, and (3) megadoses of specific vitamins. The first is noncontroversial, but no research has been done on its effects in diagnosed ADHD, even though some reports suggest mild deficiencies in diet and blood levels that might be addressed. However, in a randomly assigned double-blind placebo-controlled trial of RDA vitamin and mineral supplementation in 47 6-year-old children not selected for ADHD, Benton and Cook (1991) found an 8.3 point IQ advantage (p<.001), mainly in nonverbal ability, an increase in concentration and decreased fidgeting on a frustrating task (p<.05), and advantage on a reaction time task assessing sustained attention (ES = 1.3; p<.05). The second strategy has been found ineffective in double-blind placebo-controlled short (2 weeks) and longer (up to 6 months) trials in ADHD and the related comorbidity of learning disorder (Arnold, 1978; Haslam, Dalby, Rademaker, 1984; Kershner, Hawke, 1979). Further, megadosage carries risks, including hepatotoxicity (Haslam, Dalby, Rademaker, 1984; Shaywitz, Siegel, Pearson, 1977). Therefore, megavitamin cocktails are not worth pursuing. The third possibility, judicious use of single vitamins in megadosage to alter neural metabolism in specific ways, is actually more like psychopharmacology and has not been adequately explored despite some encouraging early reports (e.g., Coleman, Steinberg, Tippett, et al., 1979; Brenner, 1982).
Mineral Supplements. The main mineral candidates for supplementation are iron, zinc, magnesium, and calcium, all of which have been reported deficient in ADHD compared with matched controls (e.g., Kozielec, Starobrat-Hermelin, Kotkowiak, 1994).
1. Iron Supplementation. Iron is a co-enzyme in anabolism of catecholamines. In an open 30-day supplementation trial with 17 nonanemic boys ages 7 to 11 with ADHD, Sever and colleagues (1997) found improvement in Conners parents’ scores from 17.6 to 12.7 (ES = 1.0), but not in teacher ratings. In a double-blind placebo-controlled trial in 73 teenage nonanemic but iron-deficient girls, Bruner and colleagues (1996) found improvements in verbal learning and memory. In a trial of gastroprotected ferritin in 33 iron-deficient children, Burattini and colleagues (1990) reported a decrease of hyperactivity. Iron supplementation merits further study, with focus on whether any benefit found is confined to those with laboratory evidence of iron deficiency and with due concern for possibly toxicity of excess iron.
2. Zinc Supplementation. Animal data suggest involvement of zinc deficiency in hyperactivity (e.g., Halas, Sandstead, 1975; Sandstead, Fosmire, Halas, et al., 1977), and human deficiency syndrome includes impairment of concentration and jitters (Aggett, Harries, 1979). Zinc has been reported deficient in ADHD compared with controls, with ES up to 2.4 (p<.001) (Bekaroglu, Yakup, Yusof, et al., 1996; Toren, Sofia, Sela, et al., 1996). However, McGee and colleagues (1990) did not find a significant correlation of parent and teacher hyperactivity ratings with hair or serum zinc in the epidemiologic Dunedin sample. Arnold and colleagues (1990) reported data suggesting that stimulant response may depend on adequate zinc nutriture. Despite clinical advocacy of zinc supplementation, no systematic prospective trials could be found. The obvious need is a placebo-controlled double-blind trial of RDA zinc supplementation with pretreatment assessment of zinc status to determine whether zinc deficiency is a prerequisite for any benefit found.
3. Magnesium Supplementation. Kozielec and Starobrat-Hermelin (1997) found 95 percent of 116 children ages 9 to 12 with ADHD deficient in magnesium (34 percent by serum alone). They assigned 50 children ages 7 to 12 with DSM-IV ADHD and magnesium deficiency to 6 months open supplementation with 200 mg/day and 30 similar controls to usual treatment without magnesium; the supplemented group significantly decreased their Conners ratings compared with the control group (Starobrat-Hermelin, Kozielec, 1997). Thus, magnesium supplementation merits a placebo-controlled double-blind trial and replication by other investigators. Dosage of supplementation may be important, because animal work suggests a U-shaped behavioral dose-response curve (Izenwasser, Garcia-Valdez, Kantak, 1986).
Herbal and Homeopathic Treatments.In a randomly assigned open trial, Zhang and Huang (1990) compared a Chinese herbal cocktail (80 Ss) with methylphenidate 5-15 mg b.i.d. (20 Ss) for 1 to 3 months; 23 of 80 herbal cocktail cases were “cured” (disappearance of all clinical symptoms and no recurrence for 6 months) compared with 6 of 20 taking methylphenidate. Including improved cases, the effectiveness rates were 86 percent versus 90 percent; the groups did not differ except for lower side effects and greater IQ rise in the herbal group. In an open trial with 100 hyperkinetic children, Wang and colleagues (1995) found an effectiveness rate of 94 percent, including reduction of hyperactivity, improved attention, and improved academics from the herbal Tiaoshen Liquor. In another open trial in 66 hyperkinetic children, Sun and colleagues (1994) found an effectiveness rate of 85 percent with Yizhi wit-increasing syrup, including significant improvement in behavior, school records, and soft neurological signs. Thus the open pilot data warrant placebo-controlled double-blind trials of Chinese herbals. No systematic data in ADHD could be found for Calmplex, Defendol, Gingko biloba, hypericum, or pycnogenol, but the first few listed may be worth pilot trials based on clinical experience.
Acupuncture. Despite the popularity of acupuncture, no published systematic data in ADHD could be found. Loo (1998), in unpublished preliminary pre-post single-blind data from students in grades K to 3, found improvements in Conners 10-item scores by teachers (n = 7) from 17.0 to 12.0 and in analogous parent scores (n = 6) from 23.1 to 15.5. She noted that children with the most severe ADHD could not cooperate with the Tx.
EEG Biofeedback. Electroencephalographic (EEG) biofeedback involves induction of sensorimotor or higher beta band EEG rhythms (12-18 Hertz) and suppression of theta rhythms by visual and auditory feedback. It arose from the observation that some children with ADHD have more theta and less beta rhythm than controls and animal work demonstrating reduction of motor activity associated with sensorimotor rhythm (Shouse, Lubar, 1978; Mann, Lubar, Zimmerman, 1992). There are several promising pilot trials. Lubar (1991) and Lubar and Shouse (1977) reported that in a single-subject ABA design four hyperactive children selected for low arousal showed better behavior and work habits without stimulant at the end of all treatment (ABA) than at the beginning with or without stimulant, and their unmedicated level of undesirable behaviors dropped by over half to the level of the normal controls; three of them showed synchrony of behavior with the ABA shifts. An uncontrolled open trial with 37 hyperactive children yielded significant grade point and achievement score improvements (Lubar, 1991). In an intensive summer treatment regimen, 12 children who showed EEG changes also improved on significantly more TOVA scales than did 7 who failed to show EEG changes (Lubar, Swartwood, Swartwood, et al., 1995). Linden and colleagues (1996) randomly assigned 18 children with DSM-III-R ADD/ADHD to either a wait list (n = 9) or 40 EEG biofeedback sessions over a 40-week period. The treated group showed a 9 point IQ rise compared with the wait list rise of less than 1 point (p<.05) and a 28 percent reduction in the SNAP inattention score compared with a 4 percent increase in the wait list group (p<.05). Thus, this treatment merits a sham-controlled randomized trial.
EMG Biofeedback, Relaxation Training, and Hypnosis. These three related Tx modalities are typically used in some combination. The few published data on hypnotherapy or breathing control alone for ADHD are discouraging (e.g., Calhoun, Bolton, 1986; Simpson, Nelson, 1974). However, the hypnotic techniques of imagery and progressive relaxation have often been incorporated into successful EMG biofeedback protocols. There are more literature citations for EMG than for EEG biofeedback (Lee, 1991). Denkowski and colleagues (1983) randomly assigned hyperactive junior high boys to six 25-minute EMG-assisted relaxation training sessions (n = 24) or a control condition (n = 24); the treated group attained significantly higher reading and language performance and made a significant internal shift in locus of control. In 10 hyperactive boys ages 6 to 12, Dunn and Howell (1982) found significant improvement in behavior observations, parent ratings, and psychological tests after 10 relaxation training sessions but none after 10 neutral sessions. Omizo and Michael (1982) randomly assigned hyperactive boys ages 10 to 12 to either four sessions of EMG biofeedback-induced relaxation (n = 16) or sham treatment of equal length; compared with the sham, the relaxation induced significant improvements in attention and impulsivity on the Matching Familiar Figures test (ES = 1.0 to 1.3; p<.01). Krieger (1985) found in 27 children ages 7 to 11 with DSM-III ADHD significant improvement on Conners parent and teacher scales compared with an equal-n matched wait list control group. Success is largely moderated by baseline locus of control (Denkowski, Denkowski, Omizo, 1984). Despite recent neglect, the data suggest that EMG biofeedback-facilitated relaxation training merits further study.
Meditation. Meditation, though resulting in relaxation, is different from the preceding treatments in not directly targeting relaxation but achieving it indirectly. Kratter (1983) randomly assigned 24 children ages 7 to 12 with DSM-III ADD-H to either meditation training, progressive relaxation, or wait-list control, with 4 weeks of twice-weekly sessions; both active treatments, but not wait list, reduced impulsivity and improved scores on parent behavior scales but not teacher scales; only meditation training showed significant improvement on a test assessing selective attention. Moretti-Altuna (1987) randomly assigned 23 boys ages 6 to 12 with ADD-H to meditation training, medication, or standard therapy; meditation showed significant advantage in classroom behavior but not in parent ratings or psychological tests.
Perceptual Stimulation/Training. Perceptual and sensory stimulation and training include a wide variety of modalities, some with few or no data. The literature search found no systematic data on sensorimotor integration or optometric training for ADHD despite their widespread use. Neither were studies in ADHD found for massage, which has documented efficacy in other applications. The Interactive Metronome provides perceptual-motor concentration training with biofeedback about accuracy from motion sensors as the child taps to the beat provided by the program; open trials show improvements in timing that correlate at 0.2-0.4 with teacher ratings of attention, but there are no controlled data (Synaptec, 1998). In a single-blind prevention paradigm, Arnold and colleagues (1977) randomly assigned matched triplets and quads of first-graders selected for vulnerability on a perceptual screening battery to either 6 months of channel-specific perceptual training (n = 23), the same length of regular academic tutoring (n = 23), or no-contact control (n = 40); at 1-year followup, the trained group surpassed both control groups in blind teacher Conners ratings (p<.01), WRAT reading achievement, and Wechsler IQ (p<.05), although baseline measures were not different.
Mulligan (1996) reported significant impairment of vestibular processing in 309 children with ADHD compared with 309 matched children without ADHD (p<.01). In a single-blind crossover in 18 children with DSM-II hyperkinetic reaction, Bhatara and colleagues (1981) found improvement in Conners teacher ratings from rotational vestibular stimulation compared with a sham condition (p<.05), with benefit mainly confined to the 14 children younger than age 10 and those without comorbid conduct disorder. In another single-blind crossover with 12 children identified through teacher scale screening, Arnold and colleagues (1985) found an ES of 0.5 between vestibular rotational stimulation alone and two control conditions (missing significance at the sample size), compared with an ES of 0.2 between visual rotational stimulation alone and the same control conditions in a similar group of 18 children. The Comprehensive Motion Apparatus provides vestibular stimulation in all vectors through complex motion; an open trial in 14 dyslexic children (mean age, 12 ± 2.6 years) showed pre-post improvement in parent rating of attention (ES = 1.5; p<.003) and objective cognitive/achievement tests (ES = 0.4-1.2; p = .05-.001) (Stillman, 1998). Thus, stimulation and/or training of specific perceptual channels merit further research in controlled trials, especially targeting subgroups that test deficient in the particular perceptual modality.
Antifungal Treatment. Treatment with antifungal agents such as nystatin (in combination with sugar restriction and other measures) is advocated by Crook (1985, 1989, 1991) and others on the hypothesis that repeated antibiotic use for otitis media changes intestinal flora, allowing yeast overgrowth, which compromises immune function and changes the gut mucosal barrier to allow absorption of food antigens. Several components of this hypothesis are supported by collateral documentation from other fields, and the hypothesis would make sense of the reported association of chronic high sugar intake with ADHD symptoms (e.g., Prinz, Riddle, 1986) without acute effects, in that sugar could promote yeast overgrowth chronically without showing acute effects on behavior. However, this hypothesis is not supported by any systematic prospective trial data in ADHD, and a trial of nystatin alone for another syndrome (fatigue, premenstrual tension, gastrointestinal symptoms, and depression) was negative (Dismukes, Wade, Lee, et al., 1990). A systematic randomly assigned trial in ADHD should be carried out, preferably double-blind placebo-controlled and accompanied by the sugar restriction and other supportive measures recommended by the advocates of this treatment.
Thyroid Treatment. Despite initial enthusiasm about resistance to thyroid hormone as a key to a large proportion of ADHD, this genetic syndrome appears extremely rare in ADHD samples. The same studies, however, reveal a rate of other thyroid dysfunction ranging from 2 percent to 5 percent (e.g., Weiss, Stein, Trommer, et al., 1993; Valentine, Rossi, O’Leary, et al., 1997), and the rate may be higher in those with comorbid mood disorder (West, Sax, Stanton, et al., 1996). In children with thyroid dysfunction, it seems related to attentional and hyperactive-impulsive symptoms (Rovet, Alvarez, 1996; Hauser, Soler, Brucker-Davis, et al., 1997). In a double-blind placebo crossover trial of thyroid supplementation, only one of nine children with ADHD and normal thyroid function improved compared with five of eight with ADHD and resistance to thyroid hormone (Weiss, Stein, Refetoff, 1997). Thus, thyroid treatment does not seem promising in children with ADHD with normal thyroid function but would seem the treatment of choice for those with thyroid dysfunction. Therefore, all children with ADHD should be screened for historical and physical exam signs of possible thyroid dysfunction (Weiss, Stein, in press).
Deleading. Animal data (e.g., Silbergeld, Goldberg, 1975) document
hyperactivity as one symptom of chronic lead poisoning and suggest that
lead-induced hyperactivity depends on blood lead levels and can be reversed by
chelation (Gong, Evans, 1997). In humans, the level considered toxic for subtle
neuropsychiatric symptoms has declined with increasing knowledge, with some
authors placing it as low as single digits (Kahn, Kelly, Walker, 1995) and many
recommending 10 mcg/dL as the threshold. Whether such lead levels correlate with
behavioral and cognitive measures is the subject of some controversy, partly
depending on the sample size and consequent power. David and colleagues (1976)
openly treated 13 children who had hyperkinetic (HK) reaction and blood lead
levels greater than 25mcg/dL with penicillamine (CaEDTA if allergic to
penicillin); the 7 with no other probable medical cause of their HK reaction
improved in teacher hyperactivity rating (ES = 1.4; p<.01) and parent
hyperactive-impulsive rating (ES = 2.2; p<.05) but not significantly in
teacher inattention rating (ES = 0.6), whereas the 6 with another probable
medical cause did not improve. In a double-blind placebo-controlled 12-week
trial, David and colleagues (1983) randomly assigned hyperactive children with
“minimally elevated lead levels” (mean, 28 ± 6 mcg/dL) to either
penicillamine plus methylphenidate placebo (n = 22), methylphenidate (5-40
mg/day) plus penicillamine placebo (n = 11), or double placebo (n = 11);
compared with placebo, penicillamine improved Conners teacher hyperactivity
scores (ES = 1.6; p<.001), parent Werry-Weiss-Peters hyperactivity scores (ES
= 0.7; p<.05), and CGI (ES = 1.4; p<.01); across measures the
penicillamine group did nonsignificantly better than the methylphenidate group.
Thus, it appears that deleading would be the treatment of choice for children
with ADHD who have blood lead elevations in the range treated by Oliver and
associates. To how low a blood lead level this treatment should extend is a
research question of high priority.
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