A Double-Blind Comparison of Naltrexone and Placebo in Adults With Attention Deficit Hyperactivity Disorder
Condition: ADHD; Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Naltrexone; Placebo
Intervention description: Up to 100mg of Naltrexone once a day for 6 weeks; Placebo twice a day for 6 weeks
Intervention MeSH terms: Naltrexone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: ADHD; Attention Deficit Hyperactivity Disorder; Psychopharmacology; Psychiatry; Non-stimulant treatment

Summary:

      The primary aim of this study is to assess whether naltrexone as a monotherapy is effective
      in treating ADHD in adults. Medications that increase dopamine are often effective treatments
      for ADHD. Since naltrexone is a kappa opioid receptor antagonist, it increases dopamine in
      the brain. The investigators predict that naltrexone as a monotherapy will be effective for
      ADHD symptoms in adults with ADHD.

      The investigators also plan to assess the effects of naltrexone on dopamine as measured by
      changes in serum prolactin. The investigators predict that naltrexone will increase dopamine
      as indexed by decreases in serum prolactin. This study will be a six-week, double-blind,
      placebo-controlled pilot study with adults 18-55 years of age with ADHD.
    

Eligibility criteria:

        Inclusion Criteria

          1. Male and female outpatients 18-55 years of age.

          2. Diagnosis of ADHD, by Diagnostic and Statistical Manual-IV (DSM-IV) by clinical
             evaluation by an expert clinician.

          3. A CGI of 7 (among the most extremely ill patients) at the pre-baseline visit is
             exclusionary, and any subject who presents a CGI-S of 7 at any point during the study
             will be removed from participation.

          4. Subjects presenting with a CGI-S score of 6 (severely ill) at two consecutive visits
             after week 2 will be dropped from the study (i.e. A subject with a CGI of 6 at his/her
             week 3 visit and at week 4 visit will be dropped from the study at the week 4 visit).
             Subjects who are dropped for severe or worsening symptoms after exposure to the study
             medication will receive free follow up care as described in the detailed protocol and
             protocol summary.

          5. Subjects treated for anxiety disorders and depression who are on a stable medication
             regimen for at least one month, and who have a disorder-specific CGI-Severity score ≤
             3 (mildly ill) and who have a score on the Hamilton-Depression and Hamilton-Anxiety
             rating scales below 15 (mild range).

        Exclusion Criteria

          1. Any clinically unstable psychiatric conditions including any history of psychosis or
             mania, suicidality, sociopathy, criminality, or delinquency.

          2. Current (last 3 months) substance use disorders (alcohol or drugs),

          3. Medical condition or treatment that will either jeopardize subject safety or affect
             the scientific merit of the study including cardiovascular disease, current untreated
             hypertension, or history of renal or hepatic impairment.

          4. A condition that will or may require treatment with opioid analgesics.

          5. Clinically significant abnormal baseline laboratory LFT's, which is defined as LFT's
             greater than the ULN.

          6. Mental retardation (IQ < 80).

          7. Organic brain disorders including delirium, dementia, seizures, stroke, neurosurgery,
             and head trauma with loss of consciousness.

          8. Pregnant or nursing females.

          9. Subjects with current adequate treatment for ADHD.

         10. Any other concomitant medication with primarily central nervous system activity other
             than specified in Concomitant Medication portion of the protocol (a stable and
             effective treatment regimen of an SSRI or benzodiazepine is permitted per clinical
             review).

         11. Non-English speaking subjects will not be allowed into the study for the following
             reasons:

               1. The assessment instruments are unavailable and have not been adequately
                  standardized in other languages;

               2. Even if such translation services were available, the assessments in the English
                  language conducted by English-speaking clinicians and raters with
                  English-speaking subjects are already extremely time-consuming, lasting many
                  hours, making it unfeasible, unrealistic, and of dubious clinical validity to
                  conduct them with a translator with non-English-speaking subjects;

               3. Psychiatric questionnaires and evaluations are taxing, and adding the complexity
                  of a translator has the potential to make the patient experience even more
                  exhausting.