Page last updated: 2024-10-26

donepezil and Depressive Disorder, Major

donepezil has been researched along with Depressive Disorder, Major in 6 studies

Donepezil: An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE.
donepezil : A racemate comprising equimolar amounts of (R)- and (S)-donepezil. A centrally acting reversible acetylcholinesterase inhibitor, its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine.
2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one : A member of the class of indanones that is 5,6-dimethoxyindan-1-one which is substituted at position 2 by an (N-benzylpiperidin-4-yl)methyl group.

Depressive Disorder, Major: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5)

Research Excerpts

ExcerptRelevanceReference
"The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 3."2.76Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. ( Anderson, S; Begley, A; Bensasi, S; Butters, MA; DeKosky, ST; Dew, MA; Gildengers, A; Holm, M; Houck, PR; Kamboh, MI; Karp, JF; Kaufer, DI; Lenze, EJ; Lopez, O; Mazumdar, S; Miller, MD; Mulsant, BH; Pollock, BG; Reynolds, CF; Rogers, JC; Stack, J; Szanto, K; Whyte, EM, 2011)
" These data support a novel antidepressant-like role for donepezil at lower doses as part of an overall u-shaped dose-response curve."1.56The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test. ( Fitzgerald, PJ; Ghimire, A; Hale, PJ; Watson, BO, 2020)

Research

Studies (6)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's1 (16.67)18.2507
2000's2 (33.33)29.6817
2010's2 (33.33)24.3611
2020's1 (16.67)2.80

Authors

AuthorsStudies
Fitzgerald, PJ1
Hale, PJ1
Ghimire, A1
Watson, BO1
Suda, S1
Sugihara, G1
Suyama, R1
Mori, N1
Takei, N1
Reynolds, CF1
Butters, MA1
Lopez, O1
Pollock, BG1
Dew, MA1
Mulsant, BH1
Lenze, EJ1
Holm, M1
Rogers, JC1
Mazumdar, S1
Houck, PR1
Begley, A1
Anderson, S1
Karp, JF1
Miller, MD1
Whyte, EM1
Stack, J1
Gildengers, A1
Szanto, K1
Bensasi, S1
Kaufer, DI1
Kamboh, MI1
DeKosky, ST1
Logan, CJ1
Stewart, JT1
Benazzi, F1
Rossi, E1
Perlis, ML1
Smith, MT1
Orff, HJ1
Andrews, PJ1
Gillin, JC1
Giles, DE1

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Maintenance Therapies in Late-Life Depression: MTLD III[NCT00177671]Phase 4220 participants (Actual)Interventional2003-12-31Completed
Effects of Combined Memantine (Namenda) Plus Escitalopram (Lexapro) Treatment in Elderly Depressed Patients With Cognitive Impairment[NCT01876823]Phase 2/Phase 360 participants (Actual)Interventional2006-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Number of Participants With Recurrence of Major Depression

Recurrence of major depressive episodes as determined by SCID/DSM IV: two weeks of low mood and/or anhedonia, together with at least five of the following symptoms: suicidal ideation, low energy, sleep disturbance, appetite disturbance, psychic anxiety or somatic anxiety. In addition, a diagnosis of major depression requires evidence of distress or impairment. (NCT00177671)
Timeframe: 2 years

Interventionparticipants (Number)
Donepezil19
Placebo11

Percentage of Participants With Mild Cognitive Impairment Converting to Dementia.

Conversion to dementia was ascertained by the University of Pittsburgh Alzheimer Disease Research Center (ADRC), using data on neuropsychological performance and IADL functioning, as well as other relevant clinical data. Diagnoses were made according to National Alzheimer Coordinating Center criteria. (NCT00177671)
Timeframe: 2 year

InterventionPercent of Participants (Number)
Donepezil10
Placebo33

Cognitive Instrumental Activities of Daily Living (IADL)

The PASS (a performance-based assessment of instrumental activities of daily living)generates a composite measure of 13 cognitive IADL items capturing performance on activities such as shopping, bill paying, medication management, and home safety. We report the percentage of subjects at each assessment point adjudged to have independent functioning. This was determined by a clinician rater observing subjects perform each task and rating them according to predetermined criteria on a 4 point scale, ranging from 0 (unable) to 3 (independent). (NCT00177671)
Timeframe: baseline, year 1 and year 2

,
InterventionPercentage of participants (Number)
Baseline (N=33; N=34)Year 1 (N=23; N=25)Year 2 (N=11; N=17)
Donepezil54.1062.1636.67
Placebo61.8254.3547.22

Global Cognitive Performance

Cognitive performance was assessed with 17 well established and validated individual tests measuring multiple domains. We transformed raw scores for individual tests into Z-scores using the baseline distribution of a non-depressed, cognitively normal, older adult comparison group (N=36)of similar age, education, and medical health recruited concurrently with the depressed participants. These Z-scores were averaged within each neuropsychological area to produce domain scores and then averaged over all 17 tests to calculate a global cognition performance score. (NCT00177671)
Timeframe: Measured at baseline and Years 1 and 2 in maintenance

,
InterventionZ-score (Mean)
Baseline (N=67;N=63)Year 1 (N=45; N=57)Year 2 N=42; N=49)
Donepezil-0.47-0.23-0.31
Placebo-0.47-0.65-0.56

Change in 24-item HAMD

Change in 24-item Hamilton Rating Scale for Depression (HAMD) scores from baseline to Week 48: HAMD measures depression severity based on a series of 24 items items. The range of HAMD total score is 0-74; 0 indicates no depressive symptoms and a maximum HAMD score is a 74, where the greater the score indicates more significant psychopathology. In this study, moderate to severe depression is considered a HAMD-24 greater than 14. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionscores on a scale (Mean)
Es-citalopram and Memantine Treatment-15.2

Change in Selective Reminding Test - Delayed Recall (SRT-DR)

Change in Selective Reminding Test-Delayed Recall scores from baseline to Week 48: SRT Delay is administered 15 minutes after the immediate recall portion. Patients are asked to remember as many of the words as they can from the 6 trials. Maximum raw score is a 12 for free recall. If a patient is unable to recall a word, they are given a chance to recognize it among three incorrect word choices. Maximum raw score for recognition is 12. The greater the score on the delayed recall portion, the better the patient does on the assessment. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionunits on a scale (Mean)
Es-citalopram and Memantine Treatment1.2

Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)

Change in Selective Reminding Test-Total Immediate Recall (SRT-IR) scores from baseline to Week 48: Measures word recall (maximum 12 words per trial, across 6 trials). Maximum total recall score across 6 trials is 72; minimum recall is 0 across 6 trials. The higher the raw score, the better the patient did at recalling the target words. The unit of measure is the raw score, or the sum of the number of words recalled across all 6 trials. (NCT01876823)
Timeframe: baseline, 48 weeks

Interventionunits on a scale (Mean)
Es-citalopram and Memantine Treatment7.5

Change in Trails A

Change in Trails A scores from baseline to Week 48: Measures attention and executive function. It asks patients to connect numbers from 1-25 in numerical order as fast as they can. Patients are timed; the longer it takes for the patient to connect the numbers, the worse their score. Unit of measure is in seconds. The amount of errors that the patient makes during trails is also recorded. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionseconds (Mean)
Es-citalopram and Memantine Treatment1.9

Change in Trails B

Change from baseline to Week 48 on Trails B: Measures attention and executive function. It asks patients to connect numbers and letters in numerical to alphabetical order from (1-13 and A-L) as fast as they can. Patients are timed; the longer it takes for the patient to connect the numbers and letters, the worse their score. Unit of measure is in seconds. The amount of errors that the patient makes during trails is also recorded. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionseconds (Mean)
Es-citalopram and Memantine Treatment-36.3

Change in Wechsler Memory Scale-III (WMS-III)

Change in Wechsler Memory Scale-III scores from baseline to Week 48: The WMS-III Visual Reproduction sub-test was used to measure visual working memory and delayed memory. Patients were shown pictures of four drawings and were asked to reproduce them from memory immediately after seeing them, and 25 minutes after seeing them. The four scores are summed and the greater the total raw score, the better the patient did on the assessment. The maximum raw score for this test is a 41 on both the immediate and delayed portions (the overall range is 0-82 points). The change score is calculated using the total scores of both the immediate and delayed portions. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionunits on a scale (Mean)
Es-citalopram and Memantine Treatment9.9

Conversion to Dementia Using Clinical Dementia Rating (CDR)

The CDR is a numeric rating scale that is used to quantify the severity of one's cognitive function. The scale goes from 0=normal; 0.5=mild cognitive impairment; 1 to 3=mild to moderate/severe dementia. CDR was used a dichotomous outcome measure (no=0; yes=1). (NCT01876823)
Timeframe: Baseline, Week 48

Interventionparticipants (Number)
Es-citalopram and Memantine Treatment1

Change in Clinical Global Impression - Cognitive Change

The CGI Cognitive Change follows a seven-point likert scale. Compared to the patient's condition at baseline in the study [prior to medication initiation], the patient's condition is rated as: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. Responses from the entire group were calculated. Mean at final visit and baseline is reported below. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionunits on a scale (Mean)
CGI-Cognitive Change (Baseline)Clinical Global Impression-Cogntive Change (WK 48)
Es-citalopram and Memantine Treatment3.62.7

Change in Clinical Global Impression - Depression Change

The CGI Depression Change follows a seven-point likert scale. Compared to the patient's condition at baseline in the study [prior to medication initiation], the patient's condition is rated as: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. Responses were calculated for the entire group. Mean at final visit has been reported below. Higher mean at baseline indicates a decrease in depression scores. (NCT01876823)
Timeframe: Baseline, Week 48

Interventionunits on a scale (Mean)
Cognitive Global Impression at BaselineCognitive Global Impression at Final Visit (WK 48)
Es-citalopram and Memantine Treatment4.12.1

Change in Treatment Emergent Side Effects (TESS)

"Somatic side effect rating scale which includes 26 common somatic side effects associated with previous medication clinical trials; rated by the study physician. Factors were dichotomized to yes or no responses on this scale, which equated to the symptom being either present or not present. Yes and no responses were given a value of 0 (no) or 1 (yes). Responses from the entire group were calculated and the mean at baseline and the last visit is reported below." (NCT01876823)
Timeframe: Baseline, Week 48

Interventionunits on a scale (Mean)
Treatment Emergent Side Effects (Baseline)Treatment Emergent Side Effects (WK 48)
Es-citalopram and Memantine Treatment6.63.2

Trials

1 trial available for donepezil and Depressive Disorder, Major

ArticleYear
Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy.
    Archives of general psychiatry, 2011, Volume: 68, Issue:1

    Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Antidepressive Agents; Cholinesterase In

2011
Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy.
    Archives of general psychiatry, 2011, Volume: 68, Issue:1

    Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Antidepressive Agents; Cholinesterase In

2011
Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy.
    Archives of general psychiatry, 2011, Volume: 68, Issue:1

    Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Antidepressive Agents; Cholinesterase In

2011
Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy.
    Archives of general psychiatry, 2011, Volume: 68, Issue:1

    Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Antidepressive Agents; Cholinesterase In

2011

Other Studies

5 other studies available for donepezil and Depressive Disorder, Major

ArticleYear
The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.
    Translational psychiatry, 2020, 07-25, Volume: 10, Issue:1

    Topics: Animals; Antidepressive Agents; Cholinesterase Inhibitors; Depressive Disorder, Major; Donepezil; Mi

2020
Donepezil and concurrent sertraline treatment is associated with increased hippocampal volume in a patient with depression.
    The Journal of clinical psychiatry, 2010, Volume: 71, Issue:6

    Topics: Adult; Alzheimer Disease; Atrophy; Cholinesterase Inhibitors; Cognition Disorders; Depressive Disord

2010
Treatment of post-electroconvulsive therapy delirium and agitation with donepezil.
    The journal of ECT, 2007, Volume: 23, Issue:1

    Topics: Aged; Cholinesterase Inhibitors; Delirium; Depressive Disorder, Major; Donepezil; Electroconvulsive

2007
Mania and donepezil.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie, 1999, Volume: 44, Issue:5

    Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Depressive Disorder, Major; Donepezil; Female; Hu

1999
The effects of an orally administered cholinergic agonist on REM sleep in major depression.
    Biological psychiatry, 2002, Mar-15, Volume: 51, Issue:6

    Topics: Administration, Oral; Adult; Cholinergic Agents; Cholinesterase Inhibitors; Depressive Disorder, Maj

2002