Treatment of Psychological Disorders
Mohamed Ahmed Abd El-Hay in Understanding Psychology for Medicine and Nursing, 2019
The effectiveness of valproate in bipolar disorder was first reported in the 1960s. The proposed mechanism of action of valproate includes increasing GABA activity in the brain, neuroplastic effects, as well as blocking sodium channels. Its antikindling and neuroprotective properties may also be relevant to its mood-stabilizing effects. Therapeutic drug concentrations range from 50–125 μg/mL for acute manic/mixed episodes, although lower levels are sometimes employed during maintenance treatment. Valproate metabolism occurs via the cytochrome P-450 system, glucuronidation and beta-oxidation, and valproate has the ability to inhibit the breakdown of other hepatically metabolized medications. Valproate levels may be affected by concomitant use of drugs that induce or inhibit microsomal enzymes.
Pharmacological treatment of bipolar affective disorder in old age
Stephen Curran, John P Wattis in Practical Management of Affective Disorders in Older People, 2018
Lamotrigine, a phenyltriazine derivative, is an anticonvulsant with efficacy in the prevention of mood disorders in adult patients with bipolar I disorder.29 The mechanism of action may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine is metabolised in the liver and primarily eliminated via hepatic glucoronide conjugation. In elderly patients the clearance is reported to decrease by 37% and the volume of distribution by 12%.30 It is generally well tolerated and, unlike lithium, does not appear to cause body weight increase, nor does it require monitoring of serum levels.29 In retrospective case studies lamotrigine showed reasonable tolerability and modest clinical improvement in 19 out of 20 nursing home patients who were treated with it for agitated and aggressive behaviour in a range of medical and psychiatric diagnoses.31 The starting dose is 25 mg (half if the patient is taking valproate) for two weeks, increasing over weeks three and four by 50 mg with further 50 mg increments as needed.
Epilepsy and Sleep Disorders
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
Recent evidence indicates that valproate has among the highest associated fetal malformation rates, and may be associated with an increase in learning difficulties and an average decrease in IQ of approximately nine points. For these reasons, use of valproate is not recommended during pregnancy unless there is no suitable alternative. Some new AEDs appear free from teratogenic effects in animals, but it is not certain that these data can be extrapolated to humans. Indeed, trials of new AEDs are not carried out on pregnant patients, and patients of child-bearing potential involved in drug trials have to be on adequate contraception. There are thus scarce data on the teratogenic potential of new AEDs, and caution is needed when new AEDs are used in women likely to fall pregnant.
Comparing the efficacy of aripiprazole as an add-on to valproate with other second-generation antipsychotics in acute mania symptoms in manic patients in Iran
Published in International Journal of Psychiatry in Clinical Practice, 2022
Zeinab Sadat Ayatollahi, Mehran Shayganfard, Hamidreza Jamilian, Anita Alaghmand
In the intervention group, patients treated with aripiprazole received a basal dose of 5–15 mg per day, which was increased by 5 mg at weeks 2, 4 and 6 (maximum dose at the end of the 6th week: 30 mg per day) (Arnold et al. 2021). Risperidone treatment was initiated with 2–3 mg per day increased to the maximum dose of 6 mg per day (the dose elevation was not more than 1 mg per day). Firstly, olanzapine treatment was administered in 10–15 mg daily maximised to 20–25 mg daily at the end. 100 mg quetiapine was prescribed for the first day which was increased 100 mg per day until the fourth day (400 mg on the fourth day). Then, it was increased on days 5th and 6th (200 mg daily) reached 800 mg on the sixth day. Treatment with sodium valproate was started orally at a dose of 250 mg which was eventually increased to 1200–1500 mg daily in divided doses. To perform an equal treatment plan in both groups, the only mood stabiliser which was added over Aripiprazole or other second-generation antipsychotics was sodium valproate.
Long-term safety, tolerability, and efficacy of magnesium valproate versus sodium valproate in acute seizures
Published in Current Medical Research and Opinion, 2020
Xiaoyan Peng, Yin Yan, Rui Chen, Xuefeng Wang, Xin Xu
The demographic, electroencephalographic (EEG), and neuroimaging information and biomedical records were collected for each patient. Information on seizure onsets, adverse events and dosage adjustments were recorded at every follow-up visit. Patients were followed up every two weeks for the first two months and monthly thereafter. All patients were followed up for at least 12 months. Sodium valproate or magnesium valproate was prescribed according to the order in which they were recruited to the study. Starting daily doses of magnesium valproate and sodium valproate were 10–15 mg/kg for adults. Then, the doses was gradually increased (100 mg increments biweekly for magnesium valproate and 250 mg increments biweekly for sodium valproate) until the seizures was well controlled or the daily doses were 30 mg/kg (or the maximum tolerated dose). Patients remained in the study unless they withdrew due to adverse events, patient choice, inadequate therapeutic effect or loss to follow up.
Moving beyond sodium valproate: choosing the right anti-epileptic drug in children
Published in Expert Opinion on Pharmacotherapy, 2019
Ganna Balagura, Giulia Iapadre, Alberto Verrotti, Pasquale Striano
Sodium Valproate was first synthesized in 1882 as a derivative of valeric acid, extracted from Valeriana officinalis; however, its anticonvulsive activity was a serendipitous discovery in 1963 [4]. VPA is a widely used AED because of its broad-spectrum mechanism of action and anti-seizure activity. Valproate pharmacological effects include potentiation of gamma-aminobutyric acid (GABA)-ergic transmission, reduced effect of excitatory amino acids, blockade of voltage-gated sodium channels, and regulation of dopaminergic and serotoninergic transmission [4]. Acting by altering the balance of inhibition and excitation through multiple mechanisms, this drug has a wide range of clinical effects. Even if the balance between GABAergic potentiation and glutamate/NMDA inhibition is the most likely explanation for the anticonvulsant action of valproate, the role of the drug at therapeutically relevant concentrations in some forms of epilepsies is far to be fully elucidated, as in the case of non-convulsive seizures, such as absences. Furthermore, an important advantage of valproate is that it is available in different dosage forms for either parenteral or oral use. All oral formulations are largely bioavailable and sustained-release formulations are excellent to minimise serum drug fluctuations and can be given once or twice daily. VPA is still the first option in almost every generalized seizure type [5].
Related Knowledge Centers
- Absence Seizure
- Hepatotoxicity
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- Bipolar Disorder
- Epilepsy
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- Focal Seizure
- Generalized Epilepsy
- Intravenous Therapy
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