-
Tremor and Other Hyperkinetic Movements... 2021There are few medications for the treatment of essential tremor (ET). One of these, primidone, which is one of only two front-line agents, is associated with... (Review)
Review
BACKGROUND
There are few medications for the treatment of essential tremor (ET). One of these, primidone, which is one of only two front-line agents, is associated with considerable adverse drug reactions (ADRs). It is unclear why some primidone-treated ET patients develop ADRs whereas others do not, and why these ADRs seem to be more prevalent in ET patients than primidone-treated patients with epilepsy.
OBJECTIVE
To review several possible explanations underlying the above-referenced differences.
METHODS
A literature search was conducted in PubMed in October 2021. Studies reporting the ADRs of primidone in different neurological conditions were comprehensively reviewed.
DISCUSSION
Although there were no head-to-head data, a review of the previous studies on ET and epilepsy patients indicates that the former is relatively more intolerant to primidone. Moreover, not all ET patients develop ADR of similar nature or severity. We discuss several potential mechanisms for this variability in the intolerance to primidone. These include: (i) older age (ET vs. epilepsy patients), (ii) cross-tolerance to primidone in patients with epilepsy, (iii) neurobiological (GABA-related) abnormalities associated with ET.
CONCLUSION
We speculate that there are several possible explanations for primidone intolerance in ET. These possibilities should be tested in future studies, and we propose the roadmap for designing these studies. It is of value to obtain detailed insight into these complex issues because primidone remains one of the few frontline anti-tremor medications in ET. Answers to issues we have raised in this article could facilitate more customized formulation of primidone in ET patients.
Topics: Aged; Essential Tremor; Humans; Primidone; Tremor
PubMed: 35070493
DOI: 10.5334/tohm.672 -
Lancet (London, England) Jul 1978
Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Amenorrhea; Child; Child, Preschool; Dexamethasone; Drug Interactions; Drug Therapy, Combination; Epilepsy, Absence; Female; Humans; Primidone
PubMed: 78317
DOI: 10.1016/s0140-6736(78)91405-8 -
Epilepsia May 2023Developmental and epileptic encephalopathy with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a...
Developmental and epileptic encephalopathy with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a decline in cognitive abilities. Early successful treatment of CSWS is associated with a better cognitive outcome. We retrospectively analyzed the clinical, electrophysiological, radiological, and genetic data of children with DEE-SWAS associated with melastatin-related transient receptor type 3 gene (TRPM3) missense variants. We report two unrelated children with pharmacoresistant DEE-SWAS and developmental delay/regression and different heterozygous de novo missense variants in the TRPM3 gene (NM_001366145.2; c.3397 T > C/p.Ser1133Pro, c.2004G > A/p.Val1002Met). The variant p.Val1002Met (previously known as p.Val990Met or p.Val837Met) and p.Ser1133Pro were recently shown to result in a gain-of-function effect. Based on this finding, previous drug resistance, and the experimentally demonstrated inhibitory effect of primidone on TRPM3, we initiated an individualized therapy with this drug. In both children, developmental regression was stopped, psychomotor development improved, and CSWS was no longer detectable. To our knowledge, this is the first report of a treatment with primidone in TRPM3-associated CSWS. Our results highlight the importance of early genetic diagnosis in patients with epilepsy and the possibility of precision medicine, which should be considered in the future in individuals with a TRPM3-linked DEE-SWAS.
Topics: Humans; Female; Primidone; Epilepsy; Retrospective Studies; HEK293 Cells; Electroencephalography; Anticonvulsants; Male; Child, Preschool; Child
PubMed: 36929095
DOI: 10.1111/epi.17586 -
Nihon Rinsho. Japanese Journal of... Feb 1995
Review
Topics: Adult; Anticonvulsants; Child, Preschool; Drug Monitoring; Humans; Primidone
PubMed: 8753590
DOI: No ID Found -
Medical Toxicology and Adverse Drug... 1987Seven cases of crystalluria following primidone overdose have been reported since the 1950s. An eighth case of primidone crystalluria following overdose is presented.... (Review)
Review
Seven cases of crystalluria following primidone overdose have been reported since the 1950s. An eighth case of primidone crystalluria following overdose is presented. Because of low aqueous solubility (600 mg/L at 37 degrees C) which is directly proportional to temperature, any factor increasing renal excretion of unchanged primidone predisposes to crystal formation. Renal clearance is dependent on dosage because of negligible protein binding, zero-order conversion to phenobarbitone (phenobarbital) and first-order conversion to phenylethylmalonamide. Therapy with other anticonvulsants known to induce the metabolism to phenobarbitone does not appear to be protective against crystalluria in overdose situations. The critical serum primidone concentration for crystalluria presence seems to be 80 mg/L. There is evidence for nephrotoxicity of the crystals themselves if formed in vivo (actual crystal presence during voiding). The chemical phenomenon of supersaturation of a solution is protective against in vivo crystal formation with subsequent nephrotoxicity. Vigorous hydration to augment elimination and to lessen the propensity for renal toxicity is recommended.
Topics: Adult; Crystallization; Female; Humans; Kidney; Primidone; Urologic Diseases
PubMed: 3312932
DOI: 10.1007/BF03259955 -
Drug Intelligence & Clinical Pharmacy 1983The authors report the case of a severely retarded, 19-year-old female (treated with primidone 250 mg tid since age 12) who was admitted with visual and auditory...
The authors report the case of a severely retarded, 19-year-old female (treated with primidone 250 mg tid since age 12) who was admitted with visual and auditory hallucinations. After four days of continuing hallucinations, she went into classic catatonic schizophrenia. Upon examination, her primidone serum level was found to be well above the normal therapeutic range. The primidone dosage was decreased, and symptoms subsided as serum levels returned to normal.
Topics: Adult; Female; Humans; Primidone; Schizophrenia, Catatonic
PubMed: 6872851
DOI: 10.1177/106002808301700715 -
Therapeutic Drug Monitoring Apr 2013A 7.5-year-old girl who was treated with phenobarbital (PHB) for epilepsy was admitted with decreased levels of consciousness. She had been known to have high PHB levels... (Review)
Review
A 7.5-year-old girl who was treated with phenobarbital (PHB) for epilepsy was admitted with decreased levels of consciousness. She had been known to have high PHB levels of unknown cause, without symptoms. Her PHB levels were very high, as expected, but primidone levels were also detected although she and her parents denied history of primidone administration. We wished to rule out intentional unprescribed use of primidone. Our retrospective review showed 3 other children with high PHB concentrations where primidone was also detected when PHB levels were over 130 μmol/L. Complementary studies confirmed that high-dose PHB can convert to its prodrug primidone, which has not been reported previously.
Topics: Animals; Anticonvulsants; Child; Epilepsy; Female; Gastrointestinal Diseases; Humans; Phenobarbital; Primidone; Prohibitins; Rats; Rats, Sprague-Dawley; Retrospective Studies
PubMed: 23503440
DOI: 10.1097/FTD.0b013e3182843206 -
Seizure Jan 2006Sudden unexplained/unexpected death (SUDEP) in epilepsy is a major cause of death accounting for 7-17% of the mortality among epileptic patients. Prolongation of... (Review)
Review
Sudden unexplained/unexpected death (SUDEP) in epilepsy is a major cause of death accounting for 7-17% of the mortality among epileptic patients. Prolongation of QT-interval has been issued as a major mechanism in SUDEP since it is associated with fatal cardiac arrhythmias. This condition may be further precipitated by anti-epileptic treatment. Despite thorough literature research, we did not find any reports suggesting that primidone is responsible for QT-prolongation. On the contrary, all the retrieved reports addressed that the drug shortened QT-interval and corrected signs and symptoms of the underlying disease.
Topics: Anticonvulsants; Death, Sudden; Electrocardiography; Epilepsy; Humans; Long QT Syndrome; Primidone
PubMed: 16309926
DOI: 10.1016/j.seizure.2005.10.002 -
British Medical Journal (Clinical... Nov 1982
Topics: Humans; Primidone; Tremor
PubMed: 6814586
DOI: 10.1136/bmj.285.6352.1424 -
Annals of Internal Medicine Oct 1974
Topics: Adult; Female; Humans; Phenobarbital; Primidone; Seizures; Thrombocytopenia
PubMed: 4414356
DOI: 10.7326/0003-4819-81-4-559