Anticonvulsants valproate

Alternative anticonvulsants valproate,0 carbamaze-pine,0 or oxcarbazepine. 

Alternate treatments. Mood-stabilization and control of manic or hy-pomanic episodes in some subtypes of bipolar illness may also be achieved with the anticonvulsants valproate and carbamazepine, as well as with calcium channel blockers (e.g., verapamil, nifedipine, nimodipine). Effects are delayed and apparently unrelated to the mechanisms responsible for anticonvulsant and cardiovascular actions, respectively. 

Alternative anticonvulsants valproate, carbamazte pine, or oxcarbazepine. 

Alternative anticonvulsants valproate, carbte mazepin or oxcarbazepine. 

Although a number of mood-stabilizing drugs are commonly used in the treatment of BAD, lithium and the anticonvulsants valproate (VPA) and carba-mazepine are the only drugs for which long-term efficacy has been established, and are therefore used for maintenance treatment of BAD (Belmaker, 2004). However, these agents are far from the perfect medications, and they are ineffective and not well tolerated by a significant portion of patients. 

Bipolar disorder is characterized by episodes of mania or hypomania, which include hyperactivity, decreased need for sleep, and a euphoric or irritable mood. Additionally, persons with bipolar disorder may have episodes of depression similar to those seen in major depressive disorder. The lifetime prevalence of severe bipolar disorder is about 1% and 3-5% if milder cases are included, afflicting men and women equally. Both bipolar disorder and major depressive disorder tend to be episodic, and in the periods of time between episodes, persons may experience few or no symptoms. The etiology of bipolar disorder is predominately genetic, with a 70% concordance in monozygotic twins. The neurobiology of bipolar disorder is less well understood, and few animal models have been developed. Treatment of bipolar disorder usually involves mood stabilizer medications, including lithium, and the anticonvulsants valproate and carbamazepine. At times, antidepressant and antipsychotic medications are also used. 

Kunig G, Niedermeyer B, Deckert J et al (1998) Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations an autoradiographic investigation in human hippocampus. Epilepsy Res 31 153-157... 

An extremely well documented and well established interaction of clinical importance. The incidence seems to be high. The effects of concurrent use should be well monitored and suitable phenobarbital dosage reductions made as necessary to avoid toxicity. The dosage may need to be reduced by a third to a half. The significance of the modest reduction in valproate levels is not clear, especially as valproate levels do not correlate well with efficacy of treatment. Valproate has been associated with serious hepato-toxicity, especially in children aged less than 3 years, and this has been more common in those receiving other anticonvulsants. Valproate monotherapy is to be preferred in tbis group. 

The oxa2ohdinedione trimethadione [127-48-0] C H NO (50), at one time the dmg of choice for the treatment of absence sei2ures, has been replaced by ethosuximide (41) and valproate (49). (50) has a distinct profile from that of phenytoin but causes photophobia and night blindness in approximately 30% of the patients taking it and has the CNS and sedative properties seen for other anticonvulsants together with moderate neutropenia, hepatitis, and skin rashes (13). Trimethadione does not appear to produce its effects via modulation of GABA-mediated responses. 

Martin, M.L. Regan, C.M. (1988). The anticonvulsant sodium valproate specifically induces the expression of a rat glial heat shock protein which is identified as the collagen type IV receptor. Brain Res. 459, 131-137. 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

First, initiate and/or optimize mood-stabilizing medication lithium3 or lamotrigine6 Alternative anticonvulsants carbamazepine, oxcarbazepine, or valproate... 

The metabolites and metabolic pathway of a new anticonvulsant drug, sodium valproate, in rats were investigated using carbon-14 labeled sodium valproate. Most of the metabolites in urine and bile were a glucuronide conjugate of valproic acid. Free sodium valproate was as little as one-seventh of the total metabolites. In feces, only free sodium valproate was detected, and the possibility of enterohepatic circulation of sodium valproate was presumed. A part of dosed sodium valproate was excreted in expired air in the form of CO2. This degradative reaction took place in liter mitochondria and required CoA and oxygen. It was stimulated by ATP... 

Carbamazepine (Tegretol, Equetro). Carbamazepine is another anticonvulsant with documented efficacy in treating BEAD, and was recently FDA approved for this indication. Like valproate, carbamazepine is usually preferred to lithium in cases of mixed mania or rapid cycling. 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Anticonvulsants. Several antiseizure medicines have been studied in the treatment of PTSD, and some results have been encouraging. Open label studies, first with carbamazepine (800-1200 mg/day) and later with valproate (500-2000 mg/ day), demonstrated overall improvement in PTSD patients, though not for intrusive recollections per se. Recent open label studies of gabapentin, lamotrigine, tiagabine, and topiramate have suggested these anticonvulsants might also be helpful for some PTSD symptoms. 

Valproate, carbamazepine, and other anticonvulsants pose teratogenic risks. Despite this, treatment should continue during pregnancy, as the potential threat to the fetus by a seizure is greater However, it is mandatory to administer the lowest dose affording safe and effective prophylaxis. Concurrent high-dose administration of folate may... 

Drugs acting on GABA/glutamate - hypnotics/anxiolytics barbiturates, benzodiazepines, chlormethiazole, chloral derivatives, baclofen - anticonvulsants phenobarbitone, primidone, phe-nytoin, sodium, valproate, carbamazepine - alcohol, phencyclidine, ketamine... 

Phenobarbital is still used for the management of partial seizures, generalized tonic-clonic seizures and for the control of status epilepticus. However because of its low therapeutic index and the possibility of dependence, phenobarbital has largely been displaced by other anticonvulsants. For newborns phenobarbital is often the drug of first choice. If given together with sodium valproate the metabolism of phenobarbital may be inhibited while in combination with carbamazepine the serum concentrations of carbamazepine will be reduced due to enzyme induction by phenobarbital. 

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