2 Study Matches
Treatment of Psychosis and Agitation in Alzheimer's Disease
Clinically, many patients with AD show no response or minimal response to antipsychotics for symptoms of agitation/aggression or psychosis, or they have intolerable side effects on these medications. Antipsychotics have a wide range of side effects, including the risk of increased mortality (60-70% higher rate of death on antipsychotic compared to placebo) that led to an FDA black box warning for patients with dementia; a more recent review and meta-analysis showed a 54% increased risk of mortality. In addition, some patients show only partial response to antipsychotics and symptoms persist. For these reasons, the investigators need to study alternative treatment strategies. Currently, there is no FDA-approved medication for the treatment of psychosis or agitation in AD. The investigators innovative project will examine the efficacy and side effects of low dose lithium treatment of agitation/aggression with or without psychosis in 80 patients with AD in a randomized, doubleblind, placebo-controlled, 12-week trial (essentially a Phase II trial). The results will determine the potential for a large-scale clinical trial (Phase III) to establish the utility of lithium in these patients.
Inclusion Criteria:1. Male and female adults. 2. Diagnosis of possible or probable AD by standard NIA criteria (McKahnn et al, 1984; McKhann et all, 2011) 3. Folstein MMSE 5-26 out of 30 4. Neuropsychiatric Inventory (NPI) agitation/aggression subscale score > 4. On each subscale (frequency X severity), a score higher than 4 represents moderate to severe symptoms. 5. Female patients need to be post-menopausal 6. Availability of informant; patients without an informant will not be recruited. Patients who lack capacity must have a surrogate.
Exclusion Criteria:1. Medical contraindication to lithium treatment or prior history of intolerability to lithium treatment. Contraindications to lithium in this study include: resting tremor causing functional impairment, history of falls in the last month, untreated thyroid disease or any abnormal thyroid function test (T3, T4, or TSH), creatinine level greater than 1.5 mg/100ml or a glomerular filtration rate less than 44ml/min/ 1.73m2; blood pressure > 150/90 mm Hg; heart rate < 50 bpm; unstable cardiac disease based on history, physical examination, and ECG. 2. Medications, in combination with lithium, known to have adverse renal effects, including therapeutic or higher doses of diuretics, i.e. hydrochlorothiazide greater than 25mg daily or furosemide greater than 10mg daily. Whenever feasible, patients receiving concomitant antidepressants or antipsychotics will be washed off these medications for at least 24 hours before starting lithium. Patients who do not wish to discontinue antipsychotics or antidepressants, typically because of family member/caregiver objection, will be allowed to enter the trial provided there is no contraindication to concomitant lithium use with that specific psychotropic medication. During the trial, patients will be permitted to receive lorazepam as needed up to 1 mg/day for anxiety/insomnia, and non-benzodiazepine hypnotics, e.g., zolpidem. 3. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, or bipolar 1 disorder (DSM-IV TR criteria). 4. Current or recent (past 6 months) alcohol or substance dependence (DSM-IV TR criteria). 5. Current major depression or suicidality as assessed by the study psychiatrist. 6. Suicidal behavior or dangerous behavior with serious safety risk or risk of physical harm to self or others. 7. Parkinson's disease, Lewy body disease, multiple sclerosis, CNS infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder. 8. Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (smallinfarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion. 9. Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion. 10. QTc interval > 460 ms at the time of baseline EKG is an exclusion criterion for treatment. 11. Hypernatremia as determined by serum sodium level > 150 meq/L.
Drug: Lithium, Drug: Placebo
Alzheimer's Disease, Psychosis, Agitation
Alzheimer's disease, psychosis, agitation, aggression, Lithium, delusions, hallucinations
Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
This is an extension study of the Phase 3 Studies 15-AVP-786-301 and 15-AVP-786-302, which also allows participants from the Phase 2 Study 12-AVR-131 to be included.
50 Years to 90 Years old
• Participant has successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, or 12-AVR-131
• Participants from Study 12-AVR-131 with a diagnosis of probable AD according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working group criteria
• Either out-patients or residents of an assisted-living facility or a skilled nursing home
• Participants from Study 12-AVR-131 who have clinically significant, moderate/severe agitation at least 2 weeks prior to baseline
• Participants from Study 12-AVR-131 with a diagnosis of agitation that must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
• Participants from Study 12-AVR-131 with a Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation of ≥ 4 (moderately ill) at screening and baseline
• Participants from Study 12-AVR-131 with a Mini-Mental State Examination (MMSE) score between 6 and 26 (inclusive) at screening and baseline
• Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
• Participants determined to have a high imminent risk of falls during the study based on a clinical evaluation by the investigator
• Participants who are currently using or were on NUEDEXTA® in the 2 weeks preceding baseline
Agitation in Patients With Dementia of the Alzheimer's Type