Treatment of Psychosis and Agitation in Alzheimer's Disease
NCT ID: NCT02129348
Last Updated: 2024-05-02
Study Results
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View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
77 participants
Study Classification
INTERVENTIONAL
Study Start Date
2014-06-30
Study Completion Date
2020-01-31
Brief Summary
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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.
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.
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Detailed Description
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Symptoms of psychosis or agitation are common in Alzheimer's disease. These symptoms are associated with distress for the patient, an increased burden for caregivers, more rapid cognitive decline, greater risk of institutionalization and mortality, and increased health care costs. In a recent meta-analysis, caregiver education and behavior modification studies revealed a small to medium effect size in treating agitation in these patients. However, none of these studies were double-blind (difficult to achieve in such studies) and none had a control group that received the same amount of staff time as the intervention group, thereby biasing the results toward the active intervention.
Among the psychotropic medications that have been studied, only antipsychotics have shown superiority over placebo for the treatment of psychosis and agitation in patients with dementia.
However, most studies show only moderate superiority for antipsychotic over placebo and a few studies have been negative. The side effects of antipsychotic medications include sedation, extrapyramidal signs, tardive dyskinesia, weight gain, and the metabolic syndrome. A pooled analysis from 17 short-term trials showed that the mortality rate in patients with dementia receiving antipsychotic medications was 1.6 to 1.7 times as high (60-70% increase in mortality rate) as the mortality rate in patients receiving placebo. These findings led the FDA to issue a black-box warning for antipsychotic medication use in patients with dementia; a more recent meta-analysis reported a slightly lower odds ratio of 1.54 (54% increase in mortality rate).
Lithium has several different actions from anticonvulsants, though both are effective in bipolar disorder, especially mania. Lithium is not being proposed here to treat mania in AD though the investigators will monitor symptoms on the Young Mania Rating Scale. In patients with AD, lithium has been studied for its putative cognitive enhancing effects. A few reports suggest that chronic lithium use reduces the risk of dementia, but other data show increased dementia risk with lithium use. A placebo-controlled, single-blind lithium trial showed no cognitive effects in patients with AD, but a recent trial of lithium in 45 patients with mild cognitive impairment (MCI, which often leads to clinically diagnosable AD) showed a small advantage for lithium (n=24) over placebo (n=21) in attention and other cognitive domains. None of these studies with lithium were intended to treat psychosis or agitation in AD, and patients with these symptoms typically were excluded in these clinical trials.
There has been no systematic placebo-controlled trial of lithium to treat agitation/aggression with or without psychosis in AD even though lithium is a highly effective treatment for mania with psychosis and symptoms of agitation or aggression. Nonetheless, the published studies of lithium to treat cognitive decline in older patients show that low-dose lithium is safe in patients with MCI or AD.
Specific Aims and Hypotheses Specific Aim 1. To compare changes in agitation/aggression with or without psychosis in patients with AD who receive 12 weeks of randomized, double-blind treatment with lithium or placebo.
Primary Hypothesis. Over these 12 weeks, the agitation/aggression domain score on the Neuropsychiatric Inventory (NPI) will decrease significantly more on lithium than placebo.
Secondary Hypothesis. Over these 12 weeks, the proportion of responders on lithium will be significantly greater than the proportion of responders on placebo. Response is defined as a 30% decrease in NPI core score (defined as the sum of domains for agitation/aggression, delusions and hallucinations) plus a CGI Change score of much improved or very much improved (CGI based on these behavioral symptoms only). Exploratory hypothesis. Over these 12 weeks, the psychosis score, measured by the sum of the NPI domain scores for delusions and hallucinations, will decrease significantly more on lithium than placebo. Specific Aim 2. To evaluate the tolerability of low dose lithium by assessing emergent somatic side effects over the course of the 12-week trial on lithium compared to placebo. Specific Aim 3. To explore associations between improvement on lithium (decrease in agitation/aggression and psychosis scores) and serum brain-derived neurotrophic factor (BDNF) levels (baseline, 12 weeks), a SNP in intron 1 of the ACCN1 gene, and variation at the 7q11.2 gene locus, because these indices are associated with lithium response in bipolar disorder. The investigators do not postulate a specific mechanism of action for lithium in the investigators trial, but will evaluate these three potential predictors of lithium response with the aim of improving patient selection for personalized treatment. The investigators will examine BDNF serum levels as a biomarker correlate of lithium treatment by correlating change in BDNF levels with change in NPI agitation/aggression and psychosis scores.
Among the psychotropic medications that have been studied, only antipsychotics have shown superiority over placebo for the treatment of psychosis and agitation in patients with dementia.
However, most studies show only moderate superiority for antipsychotic over placebo and a few studies have been negative. The side effects of antipsychotic medications include sedation, extrapyramidal signs, tardive dyskinesia, weight gain, and the metabolic syndrome. A pooled analysis from 17 short-term trials showed that the mortality rate in patients with dementia receiving antipsychotic medications was 1.6 to 1.7 times as high (60-70% increase in mortality rate) as the mortality rate in patients receiving placebo. These findings led the FDA to issue a black-box warning for antipsychotic medication use in patients with dementia; a more recent meta-analysis reported a slightly lower odds ratio of 1.54 (54% increase in mortality rate).
Lithium has several different actions from anticonvulsants, though both are effective in bipolar disorder, especially mania. Lithium is not being proposed here to treat mania in AD though the investigators will monitor symptoms on the Young Mania Rating Scale. In patients with AD, lithium has been studied for its putative cognitive enhancing effects. A few reports suggest that chronic lithium use reduces the risk of dementia, but other data show increased dementia risk with lithium use. A placebo-controlled, single-blind lithium trial showed no cognitive effects in patients with AD, but a recent trial of lithium in 45 patients with mild cognitive impairment (MCI, which often leads to clinically diagnosable AD) showed a small advantage for lithium (n=24) over placebo (n=21) in attention and other cognitive domains. None of these studies with lithium were intended to treat psychosis or agitation in AD, and patients with these symptoms typically were excluded in these clinical trials.
There has been no systematic placebo-controlled trial of lithium to treat agitation/aggression with or without psychosis in AD even though lithium is a highly effective treatment for mania with psychosis and symptoms of agitation or aggression. Nonetheless, the published studies of lithium to treat cognitive decline in older patients show that low-dose lithium is safe in patients with MCI or AD.
Specific Aims and Hypotheses Specific Aim 1. To compare changes in agitation/aggression with or without psychosis in patients with AD who receive 12 weeks of randomized, double-blind treatment with lithium or placebo.
Primary Hypothesis. Over these 12 weeks, the agitation/aggression domain score on the Neuropsychiatric Inventory (NPI) will decrease significantly more on lithium than placebo.
Secondary Hypothesis. Over these 12 weeks, the proportion of responders on lithium will be significantly greater than the proportion of responders on placebo. Response is defined as a 30% decrease in NPI core score (defined as the sum of domains for agitation/aggression, delusions and hallucinations) plus a CGI Change score of much improved or very much improved (CGI based on these behavioral symptoms only). Exploratory hypothesis. Over these 12 weeks, the psychosis score, measured by the sum of the NPI domain scores for delusions and hallucinations, will decrease significantly more on lithium than placebo. Specific Aim 2. To evaluate the tolerability of low dose lithium by assessing emergent somatic side effects over the course of the 12-week trial on lithium compared to placebo. Specific Aim 3. To explore associations between improvement on lithium (decrease in agitation/aggression and psychosis scores) and serum brain-derived neurotrophic factor (BDNF) levels (baseline, 12 weeks), a SNP in intron 1 of the ACCN1 gene, and variation at the 7q11.2 gene locus, because these indices are associated with lithium response in bipolar disorder. The investigators do not postulate a specific mechanism of action for lithium in the investigators trial, but will evaluate these three potential predictors of lithium response with the aim of improving patient selection for personalized treatment. The investigators will examine BDNF serum levels as a biomarker correlate of lithium treatment by correlating change in BDNF levels with change in NPI agitation/aggression and psychosis scores.
Conditions
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Alzheimer's Disease
Psychosis
Agitation
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Participants were outpatients and recruited primarily from memory clinics and physician referrals at all four sites. Salient inclusion criteria were a diagnosis of possible or probable Alzheimer's disease by National Institute on Aging (NIA) criteria, score ≥4 on the Neuropsychiatric Inventory (NPI) domain score for agitation/aggression, Folstein Mini Mental State Exam (MMSE) range 5-26, and availability of an informant. Patients with current major depression or suicidality, alcohol/substance dependence in the prior 6 months, bipolar or other psychotic disorder, and specific neurological disorders were excluded.
Primary Study Purpose
TREATMENT
Blinding Strategy
TRIPLE
Participants
Caregivers
Investigators
Patients were randomized to lithium or placebo, 1:1, stratified by site, for 12 weeks. Randomization, developed by the statistician and executed by the NYSPI pharmacy, was stratified within each site by the presence of psychosis (NPI score ≥4 on delusions or hallucinations) with randomization sequences balanced in blocks of four.
All study personnel and patients were masked to treatment assignment. After the final study visit, a psychiatrist independent of the study was unmasked and clinically treated the patient while study personnel remained blind.
All study personnel and patients were masked to treatment assignment. After the final study visit, a psychiatrist independent of the study was unmasked and clinically treated the patient while study personnel remained blind.
Study Groups
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Lithium Treatment Group
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Group Type
ACTIVE_COMPARATOR
Lithium
Intervention Type
DRUG
Placebo Group
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
Interventions
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Lithium
Intervention Type
DRUG
Placebo
Intervention Type
DRUG
Other Intervention Names
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lithium carbonate
Eligibility Criteria
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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.
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 (small infarcts, 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.
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 (small infarcts, 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.
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Institute on Aging (NIA)
NIH
Sponsor Role
collaborator
New York State Psychiatric Institute
OTHER
Sponsor Role
lead
Responsible Party
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Davangere P. Devanand
Professor of Clinical Psychiatry and Neurology
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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DP Devanand, MD
Role: PRINCIPAL_INVESTIGATOR
Columbia University
Locations
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University of Miami Miller School of Medicine
Miami, Florida, United States
Site Status
McLean Hospital
Belmont, Massachusetts, United States
Site Status
New York State Psychiatric Institute
New York, New York, United States
Site Status
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Site Status
Countries
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United States
References
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Devanand DP, Marder K, Michaels KS, Sackeim HA, Bell K, Sullivan MA, Cooper TB, Pelton GH, Mayeux R. A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. Am J Psychiatry. 1998 Nov;155(11):1512-20. doi: 10.1176/ajp.155.11.1512.
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Camins A, Verdaguer E, Junyent F, Yeste-Velasco M, Pelegri C, Vilaplana J, Pallas M. Potential mechanisms involved in the prevention of neurodegenerative diseases by lithium. CNS Neurosci Ther. 2009 Winter;15(4):333-44. doi: 10.1111/j.1755-5949.2009.00086.x.
Reference Type
BACKGROUND
Devanand DP, Mintzer J, Schultz SK, Andrews HF, Sultzer DL, de la Pena D, Gupta S, Colon S, Schimming C, Pelton GH, Levin B. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med. 2012 Oct 18;367(16):1497-507. doi: 10.1056/NEJMoa1114058.
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BACKGROUND
Dunn N, Holmes C, Mullee M. Does lithium therapy protect against the onset of dementia? Alzheimer Dis Assoc Disord. 2005 Jan-Mar;19(1):20-2. doi: 10.1097/01.wad.0000155068.23937.9b.
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Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011 May;198(5):351-6. doi: 10.1192/bjp.bp.110.080044.
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BACKGROUND
Haddad P, Wieck A, Yarrow M, Denham P. 1999. The Lithium Side Effects Rating Scale (LISERS); development of a self-rating instrument. Eur Neuropsychopharmacol 9(s5): 231-232.
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BACKGROUND
Hampel H, Ewers M, Burger K, Annas P, Mortberg A, Bogstedt A, Frolich L, Schroder J, Schonknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Moller HJ, Kurz A, Basun H. Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009 Jun;70(6):922-31.
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BACKGROUND
Janowsky DS, Buneviciute J, Hu Q, Davis JM. Lithium-induced renal insufficiency: a longitudinal study of creatinine increases in intellectually disabled adults. J Clin Psychopharmacol. 2011 Dec;31(6):769-73. doi: 10.1097/JCP.0b013e31823607db.
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BACKGROUND
Jefferson JW. A clinician's guide to monitoring kidney function in lithium-treated patients. J Clin Psychiatry. 2010 Sep;71(9):1153-7. doi: 10.4088/JCP.09m05917yel.
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Katz I, de Deyn PP, Mintzer J, Greenspan A, Zhu Y, Brodaty H. The efficacy and safety of risperidone in the treatment of psychosis of Alzheimer's disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials. Int J Geriatr Psychiatry. 2007 May;22(5):475-84. doi: 10.1002/gps.1792.
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BACKGROUND
Kessing LV, Sondergard L, Forman JL, Andersen PK. Lithium treatment and risk of dementia. Arch Gen Psychiatry. 2008 Nov;65(11):1331-5. doi: 10.1001/archpsyc.65.11.1331.
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BACKGROUND
Macdonald A, Briggs K, Poppe M, Higgins A, Velayudhan L, Lovestone S. A feasibility and tolerability study of lithium in Alzheimer's disease. Int J Geriatr Psychiatry. 2008 Jul;23(7):704-11. doi: 10.1002/gps.1964.
Reference Type
BACKGROUND
McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012 Feb 25;379(9817):721-8. doi: 10.1016/S0140-6736(11)61516-X. Epub 2012 Jan 20.
Reference Type
BACKGROUND
Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder. Br J Psychiatry. 2007 Apr;190:359-60. doi: 10.1192/bjp.bp.106.029868.
Reference Type
BACKGROUND
Rej S, Abitbol R, Looper K, Segal M. Chronic renal failure in lithium-using geriatric patients: effects of lithium continuation versus discontinuation--a 60-month retrospective study. Int J Geriatr Psychiatry. 2013 May;28(5):450-3. doi: 10.1002/gps.3841. Epub 2012 Jun 4.
Reference Type
BACKGROUND
Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210. doi: 10.1097/01.JGP.0000200589.01396.6d.
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BACKGROUND
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934-43. doi: 10.1001/jama.294.15.1934.
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BACKGROUND
Shulman KI, Sykora K, Gill SS, Mamdani M, Anderson G, Marras C, Wodchis WP, Lee PE, Rochon P. New thyroxine treatment in older adults beginning lithium therapy: implications for clinical practice. Am J Geriatr Psychiatry. 2005 Apr;13(4):299-304. doi: 10.1176/appi.ajgp.13.4.299.
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Tariot PN, Schneider LS, Cummings J, Thomas RG, Raman R, Jakimovich LJ, Loy R, Bartocci B, Fleisher A, Ismail MS, Porsteinsson A, Weiner M, Jack CR Jr, Thal L, Aisen PS; Alzheimer's Disease Cooperative Study Group. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry. 2011 Aug;68(8):853-61. doi: 10.1001/archgenpsychiatry.2011.72.
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Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord. 2010 Nov;126(3):436-40. doi: 10.1016/j.jad.2010.04.018. Epub 2010 May 16.
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Wong YW, Tam S, So KF, Chen JY, Cheng WS, Luk KD, Tang SW, Young W. A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury. Spinal Cord. 2011 Jan;49(1):94-8. doi: 10.1038/sc.2010.69. Epub 2010 Jun 8.
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Zhang X, Heng X, Li T, Li L, Yang D, Zhang X, Du Y, Doody RS, Le W. Long-term treatment with lithium alleviates memory deficits and reduces amyloid-beta production in an aged Alzheimer's disease transgenic mouse model. J Alzheimers Dis. 2011;24(4):739-49. doi: 10.3233/JAD-2011-101875.
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BACKGROUND
Deliyannides DA, Graff JA, Nino I, Lee S, Husain MM, Forester BP, Crocco E, Vahia IV, Devanand DP. Effects of lithium on serum Brain-Derived Neurotrophic Factor in Alzheimer's patients with agitation. Int J Geriatr Psychiatry. 2023 Sep;38(9):e6002. doi: 10.1002/gps.6002.
Reference Type
DERIVED
Devanand DP, Crocco E, Forester BP, Husain MM, Lee S, Vahia IV, Andrews H, Simon-Pearson L, Imran N, Luca L, Huey ED, Deliyannides DA, Pelton GH. Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial. Am J Geriatr Psychiatry. 2022 Jan;30(1):32-42. doi: 10.1016/j.jagp.2021.04.014. Epub 2021 May 12.
Reference Type
DERIVED
Devanand DP, Strickler JG, Huey ED, Crocco E, Forester BP, Husain MM, Vahia IV, Andrews H, Wall MM, Pelton GH. Lithium Treatment for Agitation in Alzheimer's disease (Lit-AD): Clinical rationale and study design. Contemp Clin Trials. 2018 Aug;71:33-39. doi: 10.1016/j.cct.2018.05.019. Epub 2018 May 31.
Reference Type
DERIVED
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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https://pubmed.ncbi.nlm.nih.gov/34059401/
Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial
Other Identifiers
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#6915
Identifier Type: -
Identifier Source: org_study_id
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Sub-Lingual Dexmedetomidine in Agitation Associated With Schizophrenia
NCT04010305
COMPLETED
PHASE1
A Study to Test the Effectiveness and Safety of a New Medication in the Treatment of Schizophrenia
NCT00088634
COMPLETED
PHASE2
Patient-Centered Medication Adherence Intervention for Schizophrenia
NCT00144027
COMPLETED
NA
Brief Hospitalization for Schizophrenia: Strategies to Improve Treatment Outcome
NCT00018837
COMPLETED
NA
Safety, Biomarker Study of RL-007 in Subjects With Schizophrenia
NCT04822883
COMPLETED
PHASE2
A Long-Term Study of MP-214 in Patients With Receiving Multiple Drugs Schizophrenia
NCT01626885
COMPLETED
PHASE2/PHASE3
Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia
NCT05184335
RECRUITING
PHASE3
Targeting Emotion Dysregulation to Reduce Suicide in People With Psychosis
NCT05440214
RECRUITING
NA
Long-term Safety and Efficacy of ABT-126 in Subjects With Schizophrenia: An Extension Study for Subjects Completing Study M10-855 (NCT01655680)
NCT01834638
TERMINATED
PHASE2
The MIND Study: Modifying the INcidence of Delirium
NCT00096863
COMPLETED
PHASE2
Nicotinic Enhancement of Cognitive Remediation Training in Schizophrenia
NCT02069392
COMPLETED
NA
Safety and Efficacy Study for Cognitive Deficits in Adult Subjects With Schizophrenia
NCT01095562
COMPLETED
PHASE2
Clinical Trial of AVL-3288 in Schizophrenia Patients
NCT02978599
COMPLETED
PHASE1
A Clinical Trial That Will Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia
NCT04092686
COMPLETED
PHASE3
Study to Demonstrate Cognitive Enhancing Effects of BF2.649
NCT00690274
COMPLETED
PHASE2