Compounds > clobazam
Page last updated: 2024-10-25

clobazam and Deficiency, Mental

clobazam has been researched along with Deficiency, Mental in 17 studies

Clobazam: A benzodiazepine derivative that is a long-acting GABA-A RECEPTOR agonist. It is used as an antiepileptic in the treatment of SEIZURES, including seizures associated with LENNOX-GASTAUT SYNDROME. It is also used as an anxiolytic, for the short-term treatment of acute ANXIETY.
clobazam : 7-Chloro-1H-1,5-benzodiazepine-2,4(3H,5H)-dione in which the hydrogen attached to the nitrogen at position 1 is substituted by a methyl group, whilst that attached to the other nitrogen is substituted by a phenyl group. It is used for the short-term management of acute anxiety and as an adjunct in the treatment of epilepsy in association with other antiepileptics.

Research Excerpts

ExcerptRelevanceReference
"To determine long-term safety and efficacy of adjunctive clobazam for patients with Lennox-Gastaut syndrome (LGS)."9.19Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years. ( Conry, JA; Drummond, R; Isojarvi, J; Kernitsky, L; Lee, D; Mitchell, WG; Ng, YT; Paolicchi, JM; Veidemanis, R, 2014)
"In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2."9.16Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. ( Conry, J; Drummond, R; Isojarvi, J; Kernitsky, L; Lee, D; Mitchell, W; Ng, YT; Owen, R; Paolicchi, J, 2012)
"To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS)."9.15Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. ( Conry, JA; Drummond, R; Ng, YT; Stolle, J; Weinberg, MA, 2011)
"Stiripentol is an antiepileptic drug (AED) approved by the European Medicines Agency for the treatment of Dravet Syndrome (DS) as adjunct treatment with valproate and clobazam."7.81Extending the use of stiripentol to other epileptic syndromes: a case of PCDH19-related epilepsy. ( Specchio, N; Trivisano, M; Vigevano, F, 2015)
"Clobazam is a promising antiepileptic medication, given its effectiveness and relatively low rates of adverse effects."6.48Clobazam for patients with Lennox-Gastaut syndrome and epilepsy. ( Ng, YT; Seif-Eddeine, H, 2012)
"To assess withdrawal-related adverse event (AE) rates following abrupt clobazam discontinuation in Phase I trials and gradual clobazam tapering (2-3 weeks) following discontinuation from III trials met the criteria for potential/III trials, we evaluated AE data from four multiple-dosage Phase I trials (duration: 8-34 days)."5.40Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome. ( Bekersky, I; Harris, SI; Isojarvi, J; Lee, D; Tolbert, D, 2014)
"To determine long-term safety and efficacy of adjunctive clobazam for patients with Lennox-Gastaut syndrome (LGS)."5.19Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years. ( Conry, JA; Drummond, R; Isojarvi, J; Kernitsky, L; Lee, D; Mitchell, WG; Ng, YT; Paolicchi, JM; Veidemanis, R, 2014)
"In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2."5.16Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. ( Conry, J; Drummond, R; Isojarvi, J; Kernitsky, L; Lee, D; Mitchell, W; Ng, YT; Owen, R; Paolicchi, J, 2012)
"To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS)."5.15Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. ( Conry, JA; Drummond, R; Ng, YT; Stolle, J; Weinberg, MA, 2011)
"Clobazam was recently approved for Lennox-Gastaut syndrome in the United States."4.89Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. ( de Leon, J; Diaz, FJ; Spina, E, 2013)
"Stiripentol is an antiepileptic drug (AED) approved by the European Medicines Agency for the treatment of Dravet Syndrome (DS) as adjunct treatment with valproate and clobazam."3.81Extending the use of stiripentol to other epileptic syndromes: a case of PCDH19-related epilepsy. ( Specchio, N; Trivisano, M; Vigevano, F, 2015)
"Clobazam is a promising antiepileptic medication, given its effectiveness and relatively low rates of adverse effects."2.48Clobazam for patients with Lennox-Gastaut syndrome and epilepsy. ( Ng, YT; Seif-Eddeine, H, 2012)
"To assess withdrawal-related adverse event (AE) rates following abrupt clobazam discontinuation in Phase I trials and gradual clobazam tapering (2-3 weeks) following discontinuation from III trials met the criteria for potential/III trials, we evaluated AE data from four multiple-dosage Phase I trials (duration: 8-34 days)."1.40Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome. ( Bekersky, I; Harris, SI; Isojarvi, J; Lee, D; Tolbert, D, 2014)
"Clobazam is a new benzodiazepine recently introduced in Canada on an experimental basis."1.27Clobazam for refractory childhood seizure disorders--a valuable supplementary drug. ( Camfield, C; Camfield, P; Dooley, J; Munn, R, 1988)

Research

Studies (17)

TimeframeStudies, this research(%)All Research%
pre-19902 (11.76)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's14 (82.35)24.3611
2020's1 (5.88)2.80

Authors

AuthorsStudies
Montouris, G1
Aboumatar, S1
Burdette, D1
Kothare, S1
Kuzniecky, R1
Rosenfeld, W1
Chung, S1
Cramer, JA1
Sapin, C1
François, C1
Conry, JA2
Ng, YT4
Kernitsky, L2
Mitchell, WG1
Veidemanis, R1
Drummond, R3
Isojarvi, J4
Lee, D4
Paolicchi, JM1
Tolbert, D1
Harris, SI1
Bekersky, I1
Trivisano, M1
Specchio, N1
Vigevano, F1
Maeda, S1
Tomoyasu, Y1
Higuchi, H1
Ishii-Maruhama, M1
Egusa, M1
Miyawaki, T1
Peng, G1
Sperling, MR1
Stolle, J1
Weinberg, MA1
Traynor, K1
Seif-Eddeine, H1
Yang, LP1
Scott, LJ1
Conry, J1
Paolicchi, J1
Mitchell, W1
Owen, R1
Owen, RT1
de Leon, J1
Spina, E1
Diaz, FJ1
Gyuris, J1
Csémi, K1
Munn, R1
Camfield, P1
Camfield, C1
Dooley, J1

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome[NCT00518713]Phase 3238 participants (Actual)Interventional2007-08-31Completed
Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome[NCT01160770]Phase 3267 participants (Actual)Interventional2005-12-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and 12-week maintenance period

InterventionPercent Reduction (Least Squares Mean)
Clobazam Low Dose41.2
Clobazam Medium Dose49.4
Clobazam High Dose68.3
Placebo12.1

Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose47.8
Clobazam Medium Dose58.9
Clobazam High Dose71.0
Placebo18.6

Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose31.8
Clobazam Medium Dose56.0
Clobazam High Dose68.0
Placebo-0.1

Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose44.1
Clobazam Medium Dose38.8
Clobazam High Dose64.9
Placebo21.1

Percent Reduction in the Number of Non-drop Seizures.

This outcome measure evaluated the percent reduction (average per week) in non-drop Seizures. Non-drop seizures were other seizures not meeting the drop seizure definition. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell. (NCT00518713)
Timeframe: 4-week baseline period and the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose-53.3
Clobazam Medium Dose-3.3
Clobazam High Dose40.0
Placebo-76.3

Percent Reduction of Total (Drop and Non-Drop) Seizures.

This outcome measure evaluated the percent reduction in average weekly rate in total (drop and non-drop) seizures. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell. Non-drop seizures were other seizures not meeting the drop seizure definition. (NCT00518713)
Timeframe: 4-week baseline period and 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose34.8
Clobazam Medium Dose45.3
Clobazam High Dose65.3
Placebo9.3

Investigator Global Evaluations of the Patient's Overall Change in Symptoms.

"The physician was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00518713)
Timeframe: Week 15

,,,
Interventionparticipants (Number)
Very much improvedMuch improvedMinimally improvedNo changeMinimally worseMuch worseVery much worse
Clobazam High Dose82386310
Clobazam Low Dose4201312210
Clobazam Medium Dose102799200
Placebo3101322610

Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.

"The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00518713)
Timeframe: Week 15

,,,
Interventionparticipants (Number)
Very much improvedMuch improvedMinimally improvedNo changeMinimally worseMuch worseVery much worse
Clobazam High Dose1118114320
Clobazam Low Dose814208201
Clobazam Medium Dose1319147220
Placebo4101121630

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the 12-week maintenance period

,,,
InterventionPercent of responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose41383112
Clobazam Low Dose3423154
Clobazam Medium Dose4634227
Placebo281862

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

,,,
InterventionPercent of responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose89.877.663.330.6
Clobazam Low Dose71.747.235.813.2
Clobazam Medium Dose82.872.444.819.0
Placebo52.631.614.03.5

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

,,,
InterventionPercent Responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose71.467.357.120.4
Clobazam Low Dose66.045.328.313.2
Clobazam Medium Dose60.350.036.215.5
Placebo43.929.812.35.3

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

,,,
InterventionPercent Responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose75.571.459.226.5
Clobazam Low Dose64.243.428.39.4
Clobazam Medium Dose65.551.734.515.5
Placebo50.924.612.35.3

Tolerance

Study responders who have ≥50% reduction in their drop seizure rate during the first 4 or first 8 weeks of maintenance compared to the 4 week baseline period. (NCT00518713)
Timeframe: 4-week baseline period and first 4/first 8 weeks of the maintenance period

,,,
InterventionParticipants (Number)
≥ 50% reduction - first 4 weeks of maintenance≥ 50% reduction - first 8 weeks of maintenance
Clobazam High Dose3838
Clobazam Low Dose2523
Clobazam Medium Dose4238
Placebo1820

Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment

Number of drop seizures was obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of drop seizures (Median)
Clobazam92.3

Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment

Number of drop seizures was obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of drop seizures (Median)
Clobazam92.7

Investigator Global Evaluations of the Patient's Overall Change in Symptoms

"The physician was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
VERY MUCH IMPROVEDMUCH IMPROVEDMINIMALLY IMPROVEDNO CHANGEMINIMALLY WORSEMUCH WORSEVERY MUCH WORSE
Clobazam35.045.314.62.20.71.50.7

Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms

"The parent/caregiver was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
VERY MUCH IMPROVEDMUCH IMPROVEDMINIMALLY IMPROVEDNO CHANGEMINIMALLY WORSEMUCH WORSEVERY MUCH WORSE
Clobazam45.335.011.73.61.52.90.0

Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the 7-day Assessment

Number of drop seizures obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
Any reduction≥25% reduction≥50% reduction≥75% reduction100% reduction
Clobazam85.882.377.964.638.1

Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the Last 30-day Assessment

Number of drop seizures obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
Any reduction≥25% reduction≥50% reduction≥75% reduction100% reduction
Clobazam86.083.579.364.531.4

Reviews

7 reviews available for clobazam and Deficiency, Mental

ArticleYear
Expert opinion: Proposed diagnostic and treatment algorithms for Lennox-Gastaut syndrome in adult patients.
    Epilepsy & behavior : E&B, 2020, Volume: 110

    Topics: Algorithms; Anticonvulsants; Clinical Trials as Topic; Clobazam; Electroencephalography; Expert Test

2020
Indirect comparison of clobazam and other therapies for Lennox-Gastaut syndrome.
    Acta neurologica Scandinavica, 2013, Volume: 128, Issue:2

    Topics: Anticonvulsants; Benzodiazepines; Clobazam; Databases, Factual; Dose-Response Relationship, Drug; Eu

2013
Clobazam (Onfi) for Lennox-Gastaut syndrome.
    The Medical letter on drugs and therapeutics, 2012, Mar-05, Volume: 54, Issue:1385

    Topics: Animals; Anticonvulsants; Benzodiazepines; Clobazam; Humans; Intellectual Disability; Lennox Gastaut

2012
Clobazam for patients with Lennox-Gastaut syndrome and epilepsy.
    Expert review of neurotherapeutics, 2012, Volume: 12, Issue:4

    Topics: Anticonvulsants; Benzodiazepines; Clinical Trials as Topic; Clobazam; Drug Interactions; Electroence

2012
Clobazam : in patients with Lennox-Gastaut syndrome.
    CNS drugs, 2012, Volume: 26, Issue:11

    Topics: Administration, Oral; Anticonvulsants; Benzodiazepines; Biological Availability; Clobazam; Humans; I

2012
The use of clobazam as an adjunctive treatment for Lennox-Gastaut syndrome.
    Drugs of today (Barcelona, Spain : 1998), 2012, Volume: 48, Issue:11

    Topics: Anticonvulsants; Benzodiazepines; Clobazam; Drug Interactions; Humans; Intellectual Disability; Lenn

2012
Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies.
    Therapeutic drug monitoring, 2013, Volume: 35, Issue:1

    Topics: Animals; Anticonvulsants; Aryl Hydrocarbon Hydroxylases; Benzodiazepines; Clobazam; Cytochrome P-450

2013

Trials

4 trials available for clobazam and Deficiency, Mental

ArticleYear
Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years.
    Epilepsia, 2014, Volume: 55, Issue:4

    Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Clobazam; Female; Huma

2014
Clobazam-treated patients with Lennox-Gastaut syndrome experienced fewer seizure-related injuries than placebo patients during trial OV-1012.
    Epilepsia, 2016, Volume: 57, Issue:6

    Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Clobazam; Dose-Respons

2016
Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome.
    Neurology, 2011, Oct-11, Volume: 77, Issue:15

    Topics: Adolescent; Adult; Anticonvulsants; Australia; Benzodiazepines; Child; Child, Preschool; Clobazam; D

2011
Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.
    Epilepsy & behavior : E&B, 2012, Volume: 25, Issue:4

    Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Clobazam; Female; Huma

2012

Other Studies

6 other studies available for clobazam and Deficiency, Mental

ArticleYear
Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome.
    Epilepsy & behavior : E&B, 2014, Volume: 37

    Topics: Adult; Aged; Anticonvulsants; Anxiety Disorders; Benzodiazepines; Clobazam; Drug-Related Side Effect

2014
Extending the use of stiripentol to other epileptic syndromes: a case of PCDH19-related epilepsy.
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2015, Volume: 19, Issue:2

    Topics: Age of Onset; Anticonvulsants; Autistic Disorder; Benzodiazepines; Cadherins; Child; Clobazam; Cogni

2015
Independent predictors of delay in emergence from general anesthesia.
    Anesthesia progress, 2015,Spring, Volume: 62, Issue:1

    Topics: Adult; Ambulatory Care; Anesthesia, Dental; Anesthesia, General; Anesthetics, Inhalation; Anesthetic

2015
Clobazam approved for seizure disorder.
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2011, Dec-01, Volume: 68, Issue:23

    Topics: Anticonvulsants; Benzodiazepines; Child, Preschool; Clobazam; Drug Approval; Humans; Intellectual Di

2011
[Eating epilepsy].
    Orvosi hetilap, 1984, Nov-25, Volume: 125, Issue:48

    Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Clobazam; Drug Ther

1984
Clobazam for refractory childhood seizure disorders--a valuable supplementary drug.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1988, Volume: 15, Issue:4

    Topics: Adolescent; Adult; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Child; Child, Preschool;

1988