Page last updated: 2024-10-26

valproic acid and Hypothyroidism

valproic acid has been researched along with Hypothyroidism in 23 studies

Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.
valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Hypothyroidism: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.

Research Excerpts

ExcerptRelevanceReference
"We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions."7.85[Profile of lithium carbonate use in patients with bipolar disorder in Colombia]. ( Alzate-Carvajal, C; Machado-Alba, JE; Machado-Duque, ME; Zapata-Castañeda, K, 2017)
"To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy."7.83Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy. ( Bogićević, D; Ilić, V; Ješić, M; Kovačević, M; Kovačević, SV; Miljković, B; Prostran, M, 2016)
"The aim of this study was to evaluate the incidence of thyroid dysfunction during valproic acid (VPA) therapy in children and adolescents with epilepsy."7.78Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy. ( Chae, JH; Chung, HR; Hwang, H; Hwang, YS; Kim, H; Kim, KJ; Kim, SH; Lim, BC, 2012)
"We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months."7.70Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism. ( Castro-Gago, M; Del Río-Garma, M; Del Río-Garma, MC; Eirís-Puñal, J; Lojo-Rocamonde, S; Novo-Rodríguez, I, 1999)
" The study included a total of 183 pediatric epilepsy patients, aged 15 months-16 years, comprising 114 patients treated with valproic acid, 69 patients treated with phenobarbital, and 151 age-matched healthy volunteers as the control group."5.05The effect of antiepileptic drugs on thyroid hormonal function: valproic acid and phenobarbital. ( Güngör, O; Özkaya, AK; Temiz, F, 2020)
"We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions."3.85[Profile of lithium carbonate use in patients with bipolar disorder in Colombia]. ( Alzate-Carvajal, C; Machado-Alba, JE; Machado-Duque, ME; Zapata-Castañeda, K, 2017)
"To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy."3.83Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy. ( Bogićević, D; Ilić, V; Ješić, M; Kovačević, M; Kovačević, SV; Miljković, B; Prostran, M, 2016)
" In our article, we report two sisters, one of whom was treated with levothyroxine because of hypothyroidism."3.80Transient hypothyroidism induced by anticonvulsant agents. ( Krysiak, R; Stojko, R, 2014)
"The aim of this study was to evaluate the incidence of thyroid dysfunction during valproic acid (VPA) therapy in children and adolescents with epilepsy."3.78Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy. ( Chae, JH; Chung, HR; Hwang, H; Hwang, YS; Kim, H; Kim, KJ; Kim, SH; Lim, BC, 2012)
"Carbamazepine and valproic acid are effective antiepileptic drugs for treating many types of epilepsy."3.71Thyroid hormones in epileptic children receiving carbamazepine and valproic acid. ( Basciani, F; Chiarelli, F; Morgese, G; Morresi, S; Verrotti, A, 2001)
"We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months."3.70Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism. ( Castro-Gago, M; Del Río-Garma, M; Del Río-Garma, MC; Eirís-Puñal, J; Lojo-Rocamonde, S; Novo-Rodríguez, I, 1999)
"The effect of di-n-propylacetic acid (valproic acid), an inhibitor of gamma aminobutyric acid (GABA) transaminase, was studied with reference to its effect on the serum concentration of thyroid hormones, baseline serum TSH concentration and TRH stimulated TSH release, in seven normal controls and six patients with primary hypothyroidism."3.66Effect of di-N-propylacetic acid (valproic acid) on the TSH response to TRH--a presumptive role for gamma aminobutyric acid. ( Elias, AN; Grossman, M; Szekeres, AV; Valenta, LJ, 1981)
"The prevalence of unrecognized primary hypothyroidism and hyperthyroidism was 5·2% and 2·8%, respectively."1.37Thyroid status in a large cohort of patients with mental retardation: the TOP-R (Thyroid Origin of Psychomotor Retardation) study. ( de Rijke, YB; van Toor, H; Visser, TJ; Visser, WE, 2011)

Research

Studies (23)

TimeframeStudies, this research(%)All Research%
pre-19902 (8.70)18.7374
1990's4 (17.39)18.2507
2000's6 (26.09)29.6817
2010's9 (39.13)24.3611
2020's2 (8.70)2.80

Authors

AuthorsStudies
Zhao, Y1
Wen, SW1
Qin, Y1
Liu, Y1
Gao, Y1
Retnakaran, R1
Zhang, R1
Zhai, D1
Machado-Duque, ME1
Alzate-Carvajal, C1
Zapata-Castañeda, K1
Machado-Alba, JE1
Güngör, O1
Özkaya, AK1
Temiz, F1
Turan, MI1
Cayir, A1
Ozden, O1
Tan, H1
Krysiak, R1
Stojko, R1
Barnhorst, A1
Xiong, GL1
Kumar, P1
Mohan, V1
Sinha, RA1
Chagtoo, M1
Godbole, MM1
Ilić, V1
Bogićević, D1
Miljković, B1
Ješić, M1
Kovačević, M1
Prostran, M1
Kovačević, SV1
Visser, WE1
de Rijke, YB1
van Toor, H1
Visser, TJ1
Sahu, JK1
Gulati, S1
Kabra, M1
Arya, R1
Sharma, R1
Gupta, N1
Kaleekal, T1
Reeta, Kh1
Gupta, YK1
Kim, SH2
Chung, HR1
Kim, H1
Lim, BC1
Chae, JH1
Kim, KJ1
Hwang, YS1
Hwang, H1
Gracious, BL1
Findling, RL1
Seman, C1
Youngstrom, EA1
Demeter, CA1
Calabrese, JR1
Shulman, KI1
Sykora, K1
Gill, SS1
Mamdani, M1
Anderson, G1
Marras, C1
Wodchis, WP1
Lee, PE1
Rochon, P1
Mikati, MA1
Tarabay, H1
Khalil, A1
Rahi, AC1
El Banna, D1
Najjar, S1
Hirfanoglu, T1
Serdaroglu, A1
Camurdan, O1
Cansu, A1
Bideci, A1
Cinaz, P1
Gucuyener, K1
Rao, P1
Madhav Natu, S1
Mati Goel, M1
Ali, B1
Salvatoni, A1
Martini, C1
Cammareri, V1
Elias, AN1
Valenta, LJ1
Szekeres, AV1
Grossman, M1
Jefferson, JW1
Sen, D1
Gnam, W1
Flint, AJ1
Gonzalez, IG1
Martin Luquero, M1
Marcos Martinez, L1
Gargallo Fernandez, MA1
Eirís-Puñal, J1
Del Río-Garma, M1
Del Río-Garma, MC1
Lojo-Rocamonde, S1
Novo-Rodríguez, I1
Castro-Gago, M1
Verrotti, A1
Basciani, F1
Morresi, S1
Morgese, G1
Chiarelli, F1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Treatment of Psychosis and Agitation in Alzheimer's Disease[NCT02129348]Phase 277 participants (Actual)Interventional2014-06-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Basic Activities of Daily Living (BADL)

Basic Activities of Daily Living with items for 6 functions: bathing, dressing, toileting, transferring, continence, and feeding. Each item is scored as unimpaired=1, impaired=0. Total score is the measure used, range 0-6; higher scores indicate better functioning. (NCT02129348)
Timeframe: Assessed at Week 0, Week2, Week 4, Week 6, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group0.3
Placebo Group0.1

Change in Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score

Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain is the measure used that combines symptoms of agitation and aggression. Frequency X Severity rating score, range 0-12. Higher score indicates more agitation and aggressive behavior. (NCT02129348)
Timeframe: Assessed at screening, Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group3.2
Placebo Group2.5

Clinical Global Impression (CGI) Behavior Change

Clinical Global Impression (CGI) Behavior Change score is the measure used to assess change in overall behavior; scoring range 1-7 with higher scores indicating worsening over time and lower scores indicating improvement over time. Scores ranging from 1-3 indicate improvement. Only patients that demonstrated improvement at week 12 were reported; scores for earlier weeks were only used to assess progress throughout the study. (NCT02129348)
Timeframe: Week 12

InterventionParticipants (Count of Participants)
Lithium Treatment Group12
Placebo Group8

Clinical Responder Defined as a 30% Decrease in NPI Core Score (Sum Score of NPI Domains of Agitation/Aggression, Delusions and Hallucinations) Together With a Clinical Global Impression (CGI) Behavior Change Score of 1 or 2

The patient is classified as a responder (score=1) if both criteria are met or as a non-responder (score=0) if both criteria are not met. The first criterion to determine responder status, NPI core score, has a scoring range 0-36; each of the three component scores for symptoms of agitation/aggression, delusions and hallucinations has a scoring range 0-12. For each symptom and the total score, higher score indicates more symptoms. The second criterion to determine responder status, Clinical Global Impression (CGI), is used to assess change in overall behavior; scoring range 1-7 with higher scores indicating worsening over time and lower scores indicating improvement over time. Only patients who met both criteria, assessed as change compared to baseline, were counted as responders; all other patients were non-responders. Patients that demonstrated improvement at week 12 were reported; scores for earlier weeks were only used to assess progress throughout the study. (NCT02129348)
Timeframe: Week 12

InterventionParticipants (Count of Participants)
Lithium Treatment Group12
Placebo Group7

Folstein Mini-Mental Status Exam

30 item questionnaire used to assess degree of cognitive impairment. Orientation, registration, attention/calculation, recall, language, repetitions and commands are assessed. Total score is the measure used; range 0-30, higher scores indicate better global cognitive function. (NCT02129348)
Timeframe: Assessed at Screening, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group0.9
Placebo Group0.9

Severe Impairment Battery

Neuropsychological test used to assess a patient's cognitive ability. The patient is asked to complete small tasks such as drawing shapes and printing their name. They are also asked to remember certain names and objects, such as a cup and a spoon, and the evaluator's first name. Total score is the measure used; range 0-100, higher scores indicate better cognition. (NCT02129348)
Timeframe: Assessed at Week 0, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group2.1
Placebo Group-0.0

Simpson-Angus Scale

Simpson Angus Scale for Extrapyramidal Sign requires in-person examination to assess gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Total score is the measure used, range 0-40; higher scores indicate increased severity of signs. (NCT02129348)
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group-0.0
Placebo Group0.0

Treatment Emergent Signs and Symptoms

Treatment Emergent Symptom Scale that covers 26 somatic symptoms, each rated as present (score=1) or absent (score=0). Total score is the measure used with scoring range 0-26; higher scores indicate more somatic symptoms. (NCT02129348)
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group0.6
Placebo Group0.7

Young Mania Rating Scale

Young Mania Rating Scale total score is the measure used to assess symptoms that occur in mania; each item is a symptom that is rated for severity. Scoring range 0-60; higher scores indicate more severe symptoms. (NCT02129348)
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group3.1
Placebo Group1.1

Zarit Caregiver Burden Interview

Zarit Caregiver Burden Interview with the caregiver asked to rank 22 items on a scale with responses for each item from 'never' (score 0) to 'nearly always' (score 4). Total score is the measure used; range 0-88 with higher scores indicating greater caregiver burden. (NCT02129348)
Timeframe: Assessed at Week 0, Week 4, Week 8, Week 10, Week 12

Interventionscore on a scale (Least Squares Mean)
Lithium Treatment Group2.8
Placebo Group-0.4

Reviews

1 review available for valproic acid and Hypothyroidism

ArticleYear
The effect of antiepileptic drugs on thyroid hormonal function: valproic acid and phenobarbital.
    Acta neurologica Belgica, 2020, Volume: 120, Issue:3

    Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Hypothyroidism; Inci

2020

Trials

2 trials available for valproic acid and Hypothyroidism

ArticleYear
Elevated thyrotropin in bipolar youths prescribed both lithium and divalproex sodium.
    Journal of the American Academy of Child and Adolescent Psychiatry, 2004, Volume: 43, Issue:2

    Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Child; Child, Preschool; Female

2004
Thyroid function and volume in epileptic children using carbamazepine, oxcarbazepine and valproate.
    Pediatrics international : official journal of the Japan Pediatric Society, 2007, Volume: 49, Issue:6

    Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Hypot

2007

Other Studies

20 other studies available for valproic acid and Hypothyroidism

ArticleYear
Association between valproate treatment for acute phase schizophrenia and risk of new onset hypothyroidism.
    Schizophrenia research, 2021, Volume: 235

    Topics: Antimanic Agents; Humans; Hypothyroidism; Retrospective Studies; Schizophrenia; Valproic Acid

2021
[Profile of lithium carbonate use in patients with bipolar disorder in Colombia].
    Biomedica : revista del Instituto Nacional de Salud, 2017, Apr-01, Volume: 37, Issue:0

    Topics: Bipolar Disorder; Colombia; Humans; Hypothyroidism; Lithium Carbonate; Retrospective Studies; Valpro

2017
An examination of the mutual effects of valproic acid, carbamazepine, and phenobarbital on 25-hydroxyvitamin D levels and thyroid function tests.
    Neuropediatrics, 2014, Volume: 45, Issue:1

    Topics: Anticonvulsants; Carbamazepine; Child; Female; Humans; Hypothyroidism; Male; Phenobarbital; Thyroid

2014
Transient hypothyroidism induced by anticonvulsant agents.
    Neuro endocrinology letters, 2014, Volume: 35, Issue:3

    Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamm

2014
Pulmonary embolism in a psychiatric patient.
    The American journal of psychiatry, 2014, Nov-01, Volume: 171, Issue:11

    Topics: Adult; Aggression; Antipsychotic Agents; Autopsy; Benzodiazepines; Bipolar Disorder; Catatonia; Deat

2014
Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats.
    The Journal of endocrinology, 2015, Volume: 227, Issue:2

    Topics: Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Cerebellum; Co-Repressor Proteins; Dis

2015
Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy.
    Epileptic disorders : international epilepsy journal with videotape, 2016, Jun-01, Volume: 18, Issue:2

    Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Epilepsy; Female; Hum

2016
Thyroid status in a large cohort of patients with mental retardation: the TOP-R (Thyroid Origin of Psychomotor Retardation) study.
    Clinical endocrinology, 2011, Volume: 75, Issue:3

    Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Cohort Studies; Cross-Sectional Studies; Drug Therapy,

2011
Evaluation of subclinical hypothyroidism in ambulatory children with controlled epilepsy on valproate monotherapy.
    Journal of child neurology, 2012, Volume: 27, Issue:5

    Topics: Adolescent; Ambulatory Care; Antibodies; Anticonvulsants; Case-Control Studies; Child; Child, Presch

2012
Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy.
    Neuropediatrics, 2012, Volume: 43, Issue:3

    Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Humans; Hypothyroidism; Severity of

2012
New thyroxine treatment in older adults beginning lithium therapy: implications for clinical practice.
    The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2005, Volume: 13, Issue:4

    Topics: Aged; Aged, 80 and over; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cohort Studies; Dr

2005
Risk factors for development of subclinical hypothyroidism during valproic acid therapy.
    The Journal of pediatrics, 2007, Volume: 151, Issue:2

    Topics: Adolescent; Age Distribution; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Dose-Re

2007
Valproate-induced subclinical hypothyroidism.
    The Journal of neuropsychiatry and clinical neurosciences, 2008,Winter, Volume: 20, Issue:1

    Topics: Adult; Anticonvulsants; Bipolar Disorder; Humans; Hypothyroidism; Male; Valproic Acid

2008
Hypothyroidism and sodium valproate.
    The Journal of pediatrics, 1983, Volume: 103, Issue:6

    Topics: Child, Preschool; Female; Humans; Hypothyroidism; Valproic Acid

1983
Effect of di-N-propylacetic acid (valproic acid) on the TSH response to TRH--a presumptive role for gamma aminobutyric acid.
    Metabolism: clinical and experimental, 1981, Volume: 30, Issue:10

    Topics: 4-Aminobutyrate Transaminase; Adult; Female; gamma-Aminobutyric Acid; Humans; Hypothyroidism; Male;

1981
Manic depressive disorder and lithium over the decades: the very educational case of Mrs. L.
    The Journal of clinical psychiatry, 1994, Volume: 55, Issue:8

    Topics: Aged; Aged, 80 and over; Bipolar Disorder; Drug Administration Schedule; Electroconvulsive Therapy;

1994
New onset rapid cycling bipolar disorder in an 87 year old woman.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie, 1993, Volume: 38, Issue:5

    Topics: Aged; Aged, 80 and over; Bipolar Disorder; Cerebral Infarction; Female; Humans; Hypothyroidism; Lith

1993
[Study of the influence of anticonvulsant treatment on thyroid function].
    Anales de medicina interna (Madrid, Spain : 1984), 1995, Volume: 12, Issue:12

    Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Child; Enzyme-Linked Immunosorbent Assay; E

1995
Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism.
    Epilepsia, 1999, Volume: 40, Issue:12

    Topics: Adolescent; Age Factors; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Hypothyro

1999
Thyroid hormones in epileptic children receiving carbamazepine and valproic acid.
    Pediatric neurology, 2001, Volume: 25, Issue:1

    Topics: Adolescent; Anticonvulsants; Carbamazepine; Case-Control Studies; Child; Drug Interactions; Drug The

2001