Valproic acid treatment

Kastnet, T, and Ftiedman, D.L. (1992) Verapamil and valproic acid treatment of ptolonged mania. / Am Acad Child Adolesc Psychiatry 31 271-275. 

Herman JB, Rosenbaum JE, Brotman AW The alprazolam to clonazepam switch for the treatment of panic disorder. J Clin Psychophamacol 7 175-178, 1987 Herrmann N Valproic acid treatment of agitation in dementia. Can J Psychiatry 43 69-72, 1998... 

Herrmann N. Valproic acid treatment of agitation in dementia. Can J Psychiatry 1998 43 69-72. 

Friedman, S.D., Dager, S.R., Parow, A., Hirashima, F., Demopulos, C., Stoll, A.L., Lyoo, I.K., Dunner, D.L., and Renshaw, P.F., 2004, Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol. Psychiatry 56 340-348. 

TOXICITY The most common side effects are transient GI symptoms, including anorexia, nausea, and vomiting in -16% of patients. CNS effects include sedation, ataxia, and tremor these symptoms occur infrequently and usually respond to a decrease in dosage. Rash, alopecia, and stimulation of appetite have been observed occasionally, and weight gain has been seen with chronic valproic acid treatment. Elevation of hepatic transaminases is observed in up to 40% of patients and often occurs asymptomatically during the first several months of therapy. 

Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity. Eur J Paediatr Neurol 2009 13(5) 439 3. 

Erdogan S, QeUkel FC. Massive creatine kinase and hepatic enzyme elevation due to quetiapine and valproic acid treatment a case report. Arch Neuropsychiatry 2012 49 238-40. 

Temporal Relationships of Adverse Events. The temporal relationship between duration of product exposure and development of an adverse event is important in assessing causality. But how can data on temporal relationships be systematically summarized in a database containing thousands or even hundreds of thousands of subjects Temporal relationships cannot be clearly elicited if only frequencies of adverse events between treatment and control groups are compared. There can be many disparities in the subjects time of exposure or time at risk. Toxic manifestations of drugs may not occur until several months or even years after the initial exposure to the drug. How do we systematically assess delayed toxicity of a previously prescribed drug from the effect of a newly prescribed drug Such a scenario occurred with reported cases of pancreatitis associated with valproic acid therapy, in which some cases appeared several years after therapy [2]. 

Epilepsy is a clinical disorder characterized by spontaneous, recurrent seizures arising from excessive electrical activity in certain parts of the brain [51]. Currently available drugs, such as phenytoin, carbamazepine, valproic acid, lamotrigine, and topiramate (for molecular structures see Fig. 6), provide symptomatic seizure suppression in only 60-70% of those receiving treatment [52-54]. These drugs are also associated with unwanted side... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Valproic acid was determined in plasma by treatment with 2,4-dibromoacetophe-none or 2-bromoacetonapththalone and with dicyclohexano-18-crown-6 and heated at 70 °C for 40 min. The solution was subjected to TLC on C8F octyl plates or to high performance TLC on RP 8 254 S or Kieselgel 60 F254 plates with developing solvents of aq. 63% ethanol, aq. 73% ethanol or CHCl3-cyclohexane (2 1), respectively, with detection at 280 or 254 nm for the naphthoylmethyl or phenacyl derivative, respectively. The limits of detection were 9.7 and 4.9 pg/mL of valproic acid for the TLC RP 8 and HPTLC RP 8 plates, respectively. Recovery was 84-92.74% [28],... 

The answer is b. (Katzung, p 41L) Severe hep at o toxicity of an idiosyncratic nature is associated with valproic acid The risk is very high in the pediatric population, particularly in patients below the age of two. Fatalities generally occur within four months of treatment Hepatotoxicity may be reversed in some individuals. 

The traditional treatment of tonic-clonic seizures is phenytoin or phe-nobarbital, but the use of carbamazepine and valproic acid is increasing, as efficacy is equal and side effects are more favorable. 

Agents that increase GABA activity or decrease glutamate activity are used for the treatment of mania and for mood stabilization (eg, benzodiazepines, lamotrigine, lithiurn, or valproic acid). 

Anticonvulsants. Finally, several antiseizure medications have been tried. These include valproic acid (Depakote, Depakene), carbamazepine (Tegretol), Lamotrig-ine (Lamictal), and gabapentin (Neurontin). The anticonvulsants are effective treatments for bipolar disorder. Their use for major depression needs to be studied further. Please refer to Section 3.4 Bipolar Disorders. 

Anticonvulsants. Scattered case reports suggest that carbamazepine (Tegretol) and valproic acid (Depakote, Depakene) may be helpful in the treatment of panic disorder. This has yet to be verified in systematic studies. Furthermore, because these anticonvulsants are hindered by toxicity and side effect concerns (cf. Chapter 3), they should only be considered if other better studied and more tolerable treatment options have failed. 

Carbamazepine is believed to be effective in BPD, though the data is far less robust than with valproic acid. It is prescribed at doses up to 1200mg/day. Like valproic acid, it can also canse birth defects and requires laboratory monitoring including serum levels. For more information on the use of carbamazepine, please refer to the discussion of bipolar disorder treatment in Chapter 3. 

Valproic acid (dipropylacetic acid) is a single branched chain carboxylic acid that is structurally unlike any of the other drugs used in the treatment of bipolar disorder or epilepsy. The amide derivative, valproamide, is available in Europe as a more potent form of valproate. Valproate was first developed in Erance as an antiepileptic agent in 1963. As an antiepileptic agent, it was shown to be active against a variety of epilepsies without causing marked sedation. 

Whether there is any other connection between anticonvulsant activity and camosine s antiaging actions is obviously highly speculative. It may be relevant to note that epileptic seizures and a shortened life span, together with altered protein accumulation, are consequences of PIMT-deficiency in mice, while treatment with valproic acid, an anticonvulsant, partially suppresses these symptoms including effects on life span (Yamamoto et ah, 1998). Conversely, PIMT overexpression can increase life span of Drosophila (Bennet et ah, 2003). Furthermore, the chemistry of some anticonvulsants (ethosuximide) resembles quite closely the structure of the succinimide intermediate formed during both asparagine deamidation and PIMT-mediated repair of isoaspartate residues. One conjectures whether there are any relationships between these... 

B) The GC trace of an extract of plasma obtained from the same patient after treatment with valproic acid (peak 1) to which caprylic acid (peak 2) has been added as an internal standard. 

Valproic acid has become a major AED against several seizure types. It is highly effective against absence seizures and myoclonic seizures. In addition, valproic acid can be used either alone or in combination with other drugs for the treatment of generalized tonic-clonic epilepsy and for partial seizures with complex symptoms. 

Convulsions associated with fever often occur in children 3 months to 5 years of age. Epilepsy later develops in approximately 2 to 3% of children who exhibit one or more such febrile seizures. Most authorities now recommend prophylactic treatment with anticonvulsant drugs only to patients at highest risk for development of epilepsy and for those who have multiple recurrent febrile seizures. Phenobarbital is the usual drug, although diazepam is also effective. Phenytoin and carba-mazepine are ineffective, and valproic acid may cause hepatotoxicity in very young patients. 

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