Differential Diagnosis

The characterization of the predominant symptoms of ADHD is described in my book (Wender 1995). Because ADHD individuals may exhibit depression, affective lability and irritability, ADHD may sometimes be confused with cyclothymic disorder and with borderline personality disorder (BPD). With regard to the former, the shifts of mood seen in cyclothymic disorder are of weeks' or months' duration and not from hour-to-hour or day-to-day as seen in ADHD. Anhedonia and physiological concomitants are absent in ADHD as are the depressive personality traits which Akiskal describes as characterizing "subaffective dysthymia." The ADHD and BPD patients seemingly share symptoms of impulsivity, affective instability, angry outbursts and feelings of boredom. These symptoms, however, differ both quantitatively and qualitatively between the two diagnostic groups. The ADHD patient's impulsivity is short-lived and is thoughtless rather than "driven." The ADHD patient's anger is episodic and also short-lived compared to the brooding anger of the BPD patient. The major differences between ADHD and BPD patients is that the former do not have the intense conflicted relationships, suicidal preoccupations, self-mutilation, identity disturbances or feelings of abandonment seen in BPD. However, these differences are not clear-cut in all instances and the medications that are useful in the treatment of ADHD might be of value in such individuals' symptoms when the latter are like those seen in ADHD. From a practical standpoint, the diagnosis of ADHD requires the presence of an "other." We have employed spouses, significant others, adult children and parents of adults. Without their observations, critical symptoms are underestimated or not disclosed. The same, as said earlier, is true in regard to estimating the response of symptom treatment.

Treatment

We have conducted placebo-controlled and open-label drug trials in more than 300 patients. These include four double-blind placebo-controlled trials: three of methylphenidate(Drug information on methylphenidate) (Ritalin) [Wood and others 1976 (n=15); Wender and others 1985 (n=37); Wender and others 1996 (n=124)]; and one of pemoline(Drug information on pemoline) (Cyclert) [Wender and others 1981 (n=48)]; a total of 224 ADHD patients treated with stimulants. In addition, we have treated 79 patients in open label trials: pargyline, Wender and others, 1983 (n=16); l-deprenyl (selegiline), Wood and others 1983 (n=11); bupropion (Wellbutrin), Wender and Reimherr (n=19); levodopa(Drug information on levodopa), Wood and others 1982 (n=8); dl-phenylalanine, Wood and others 1985 (n=13); and l-tyrosine, Reimherr and others 1987 (n=12). We have found in crossover and parallel design studies that about 60 percent of patients receiving stimulant medication manifest moderate-to-marked improvement, as compared with 10 percent of those receiving placebo. These degrees of responsivity are reflected in Global Assessment of Functioning (GAF) scores in patients with moderate-to-marked improvement. The average pretreatment GAF scores in the studies are about 55 (moderate symptoms) and posttreatment scores of about 75 (slight symptoms present only in reaction to stress). As mentioned, we have also conducted open studies of pargyline and selegiline(Drug information on selegiline) in 27 patients and have found, again, that about 60 percent exhibited moderate-to-marked improvement to treatment with an MAO inhibitor. Lastly, we have conducted a therapeutic trial of bupropion in 19 patients who had previously responded to stimulants or MAO inhibitors and found that approximately half responded to bupropion, and they decided to remain on that drug. Turning to other drugs, in general, as with children, the tricyclic antidepressants have not been useful. Patients manifest an immediate response and after six to eight weeks become tolerant to the drug despite an increased dose. They seem less tolerant of the side effects of these drugs than are depressed patients and complain of the anticholinergic effects, weight gain and impaired sexual functioning. SSRIs appear to be of no value in ADHD patients who are not concordant for major depressive disorder or dysthymia, but may be of considerable benefit for patients with these disorders and ADHD. There have been two attempts to replicate our treatment studies. Mattes and others conducted a placebo-controlled trial of methylphenidate in 26 patients with evidence of residual ADD with hyperactivity and 35 patients with similar adult symptoms but no childhood history of ADD-H. No overall benefit from methylphenidate was evident, regardless of childhood history of ADD-H. There are several reasons why this may have occurred, foremost of which was the nature of the sample: 60 percent did not meet our criteria of childhood "hyperactivity" and many of the patients were comorbid for substance abuse and BPD, patients we have excluded in our treatment. Spencer and colleagues replicated our findings in a randomized, seven-week, placebo-controlled, crossover study of methylphenidate in 23 adults patients with ADHD. Our studies, taken together, have demonstrated the efficacy of methylphenidate, pemoline and MAO-B inhibitors in the treatment of adults with ADHD by producing a robust response in at least 60 percent of patients. The most effective treatment of the ADHD adult involves education about the disorder, drug treatment and psychotherapy focused on ADHD concomitants. Although medication is the main factor in my treatment of adults with ADHD, education and psychological management play important roles. After evaluation and a discussion of ADHD symptoms, I present the patient with the therapeutic pay-off matrix, i.e., the benefits and liabilities of offering or not offering a therapeutic trial of medication when he or she does or does not have the disorder. A consideration of the four possibilities reveals that the risks of treating when the patient does not have the disorder are minimal while the disadvantage of not offering a trial of treatment when the patient does have ADHD is most unfortunate. The above holds with the proviso that the use of stimulant drugs does not lead to abuse. We do not know whether ADHD individuals will experience "highs" if they take large or intravenous doses of methylphenidate or amphetamines. A few clinical cases suggest that they can produce euphoric "highs." For this reason, they should be used very cautiously or not at all in persons with a history of drug abuse. In general, therapeutic trials are warranted whenever the diagnosis seems probable because the benefits can be assessed rapidly. Here is a list of the changes in symptoms seen when treatment is effective.

1. Hyperactivity- Fidgeting and restlessness decrease; patients are able to relax; then are able to stay at their desks or at the dinner table or at a movie or in church.
2. Inattention- Concentration is greatly improved. It is not only that patients can concentrate better, they can concentrate when they want to. Distractibility diminishes or disappears. Attention to spousal conversation improves and frequently is quickly manifested in better marital relations.
3. Mood lability- Both highs and lows decrease as do feelings of boredom; mood is described as "level" or "stable."
4. Temper- The threshold for outbursts is raised. Patients are less irascible and their angry outbursts are less frequent, less extreme, and frequently disappear altogether.
5. Disorganization- Organizational activities become manifest. This is evident at school, in running a household, in vocational function. Patients may spontaneously establish orderly strategies.
6. Stress sensitivity- Patients describe themselves as having their thin skin thickened, able to take life problems in stride, feeling less "hassled" about daily existence.
7. Impulsivity- Patients report that they do not interrupt others while listening to them (another feature that improves conversations and relationships), that they think before they speak, that they have become tolerant drivers and that they stop impulse buying.

We have used a structured rating scale to assess these symptoms and their changes in our treatment studies (Wender 1995, Appendix E).