Amiloride Hydrochloride as an Effective Treatment for ADHD

Our specific aims and hypotheses are as follows:

Primary Aim: Assess the efficacy and adverse effects of amiloride in medication naive ADHD
adults in a placebo controlled study. Hypothesis 1: Amiloride will reduce scores on our
primary outcome measure, the Adult Attention-Deficit/Hyperactivity Disorder Investigator
Symptom Rating Scale (AISRS) and on our secondary outcome, the ADHD specific Clinical Global
Impressions (CGI) improvement scale. Hypothesis 2: Amiloride will be well tolerated and will
have few side effects in adults with ADHD.

Exploratory Aim 2: Assess effects of amiloride on ADHD-associated clinical features. We will
also assess, in an exploratory manner, the effect of amiloride on two clinical features that
are not well treated by current ADHD medications: deficits in emotional self-regulation
(DESR) and executive function deficit (EFD). Hypothesis 3 predicts that amiloride treatment
will reduce symptoms of DESR and of EFD.

We will recruit 40 adults who are diagnosed with ADHD in a double blind placebo controlled
study. 20 subjects will receive amiloride hydrochloride and 20 subjects will receive placebo
for 8 weeks. Participation in the study requires subjects to meet with the physician for a
screening visit, baseline visit and 8 additional weekly visits.

Inclusion Criteria:

1. Medication naïve male or female adults ages 18-55 years.

2. A diagnosis of DSM-IV ADHD combined type based on clinical assessment by the study
psychiatrist using the Conners Adult ADHD Diagnostic Interview;

3. proficiency in English;

4. A baseline score of 24 or more on the AISRS;

5. ability to swallow pills;

6. ability to report reliably, understand the nature of the study and sign an informed
consent document as determined by the study psychiatrist

Exclusion Criteria:

We will exclude potential participants who:

1. have had pharmacologic treatment for ADHD in the past year;

2. are pregnant or nursing;

3. are Investigators or their immediate family (spouse, parent, child, grandparent, or
grandchild);

4. have any serious, unstable medical illness including hepatic, renal,
gastroenterological, respiratory, cardiovascular (including ischemic heart disease),
endocrinologic, neurologic, immunologic, or hematologic disease;

5. have severe allergies or multiple adverse drug reactions;

6. have a current or past history of seizures;

7. meet current DSM-IV criteria for anxiety or depression or illicit substance abuse in
prior six months (these exclusions are feasible because, although the lifetime
comorbidity of ADHD with these disorders is high, we and others have shown that the
presence of these disorders at the time of ascertainment for adult ADHD studies is
less than 10%);

8. are judged by the study psychiatrist to be at serious suicidal risk.

9. have current or past diagnoses of schizophrenia or bipolar disorder;

10. have a history of hypersensitivity to amiloride or drug class members;

11. have a history of hyperkalemia, diabetes mellitus, renal disease or anuria;

12. have renal impairment Cr > 1.5; or

13. are taking potassium supplements, aldosterone antagonists, tacrolimus or ACE
inhibitors.