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Neuropathic pain is caused by nerve damage, often accompanied by changes in the central nervous sytem, and fibromyalgia is a related complex pain syndrome. Many people with these conditions are disabled with moderate or severe pain for many years. Conventional analgesics are usually not effective treatment options. In light of the fact that there are similarities between the pathophysiologic and biochemical mechanisms observed in epilepsy and in neuropathic pain, it is not surprising that antiepileptic agents can be used to treat neuropathic pain. The aim of this review was to investigate the efficacy and adverse events associated with use of sodium valproate and valproic acid for the treatment of chronic neuropathic pain and fibromyalgia. We identified three relevant studies, two in diabetic neuropathy and a third in post‐herpetic neuralgia. Two of the three studies report significantly greater reduction in pain for valproate than placebo, but studies were small (≤ 45 participants) and provided insufficient data for pooled analysis, and the methods of analysis used may have overestimated treatment effect. Adverse events such as nausea, sedation, drowsiness, vertigo, and abnormal liver function are more common with valproate than placebo, but these studies were unsuitable to allow for a comprehensive assessment of harm.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Epilepsy is a disorder where seizures are caused by abnormal electrical discharges from the brain. Absence epilepsy involves seizures that cause a sudden loss of awareness. It often starts in childhood or adolescence. Three antiepileptic drugs are often used for absence epilepsy: valproate, ethosuximide and lamotrigine.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2017

Various medicines, collectively termed 'antiepileptics', are used to treat epilepsy. For several years, some of these drugs have also been used for preventing migraine attacks. For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of valproate (valproic acid or sodium valproate or a combination of the two) in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013 and found 10 relevant studies. Compared with placebo, valproate reduced the frequency of migraine headaches by approximately four per month (two studies, 63 participants). Patients were also more than twice as likely to reduce the number of their migraine headaches by 50% or more with valproate than with placebo (five studies, 576 participants). Side effects associated with valproate were common but generally mild; valproate can, however, cause birth defects and so should be used with caution in women of childbearing age. Further research is needed comparing valproate with other active drugs used for preventing migraine attacks.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

An updated review (October 2008) of valproate treatment of agitation in demented patients failed to show any improvement in agitation among treated patients compared with those not receiving treatment, and also demonstrated a higher rate of harmful effects, such as falls,infections and gastrointestinal disorders (diarrhoea, nausea) among those receiving valproate preparations. Although further research on the value of valproate preparations is indicated, current evidence does not support use of this drug to control agitation of people with dementia.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Bibliographic details: Ananthavarathan P.  A systematic review and meta-analysis of the efficacy and safety of sodium valproate for "off-label" indications in mental health. Journal of Neurology, Neurosurgery and Psychiatry 2014; 85(8): e3 Available from: http://jnnp.bmj.com/content/85/8/e3.9

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

OBJECTIVE: To review the evidence supporting the efficacy and safety of l-carnitine in the management of acute valproic acid overdose.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

PURPOSE: Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, and patients that undergo the maximum tumor resection that is safely possible and standard radiochemotherapy only achieve a median survival time of 14.6 months. Several clinical studies have reported that valproic acid could prolong survival of GBM patients. However, the results of these studies are inconsistent. We examined relevant studies and conducted a meta-analysis to assess the effects of VPA on survival times and recurrence.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

We performed this systematic review to determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus (SE). A literature search was performed using Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). From 544 articles screened, 5 were identified as randomized controlled trials and were included for data extraction. The main outcomes were SE controlled and risk of seizure continuation. The meta-analysis was performed with the Random-effect model. The quality of the included studies was evaluated by GRADE (Grading of Recommendations Assessment, Development, and Evaluation). There was no significant statistics in SE controlled between intravenous sodium valproate and phenytoin. Compared with diazepam, sodium valproate had a statistically significant lower risk of time interval for control of refractory SE (RSE) after having drugs; however, there was no statistically significant difference in SE controlled within 30 min between the two groups. There was no statistically significant difference in cessation from status between intravenous sodium valproate and levetiracetam. Intravenous sodium valprate was as effective as intravenous phenytoin for SE controlled and risk of seizure continuation.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

BACKGROUND: Numerous studies have shown that long term treatment with anticonvulsants may be an important risk factor for the onset of atherosclerosis, or worsening of its symptoms. There are many contradictory reports regarding these effects.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Worldwide, phenobarbitone and phenytoin are commonly used antiepileptic drugs. This review found no evidence to suggest a difference between phenobarbitone and phenytoin for the control of the seizure types investigated. Phenobarbitone was more likely to be withdrawn than phenytoin, presumably due to adverse effects, however other factors may have influenced the rate of withdrawal of phenobarbitone in this review.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

This systematic review investigated the efficacy and acceptability of valproate compared to that of placebo, lithium, carbamazepine, olanzapine and haloperidol in the treatment of acute episodes of bipolar disorder. Ten randomised studies were included in the review: all examined patients with mania. Valproate was more effective than placebo in the treatment of mania. There was no significant difference between efficacy in valproate and lithium or between valproate and carbamazepine, but there were fewer data on these comparisons and so these questions remain unanswered. The evidence suggests that valproate may be less effective in reducing manic symptoms than olanzapine but may cause less sedation and weight gain. There remains a need for more trials comparing medicines in treating all affective episodes.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Fifteen trials met the inclusion criteria and are included in the review. Interpretation of the results was hindered by the small total sample size and by the low quality of reporting of the included trials. There was some evidence that haloperidol was more efficacious than placebo in terms of reduction of manic and psychotic symptom scores, when used both as monotherapy and as add‐on treatment to lithium or valproate. There is no evidence of difference in efficacy between haloperidol and risperidone, olanzapine, valproate, carbamazepine, sultopride and zuclopentixol. There was a statistically significant difference with haloperidol being probably less effective than aripiprazole. No comparative efficacy data with quetiapine, lithium or chlorpromazine were reported. Haloperidol caused more extrapyramidal symptoms (EPS) than placebo and more movement disorders and EPS but less weight gain than olanzapine. Haloperidol caused more EPS than valproate but no difference was found between haloperidol and lithium, carbamazepine, sultopride and risperidone in terms of side effects profile.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

People with bipolar disorder suffer from repeated episodes of severe mood disturbance. These can vary from mania to severe depression.  Sometimes manic and depressive symptoms can occur at the same time. Episodes may also fluctuate frequently, so‐called 'rapid‐cycling'. Periods of normal mood and function may occur in between these episodes, but this is not always the case.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Bipolar disorder is a mental disorder that is seen as periods of high mood called mania, or hypomania if less severe, and periods of low mood (depression).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

People with epilepsy are currently treated with antiepileptic drugs but a significant number of people continue to have seizures and many experience adverse effects to the drugs. As a result, there is increasing interest in alternative therapies and acupuncture is one of those. Seventeen randomised controlled trials with 1538 participants were included in the current systematic review (literature search conducted on 3rd June 2013).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Faecal incontinence (inability to control bowel movements or leakage of stool or faeces) is a common healthcare problem, affecting up to one in 10 of adults living at home. This affects daily activities in about one or two in 100 people. It is more common in people living in residential care. Leakage of urine often occurs as well. Faecal incontinence can be debilitating and embarrassing. Treatments include pelvic floor muscle training, electrical stimulation, surgery and drugs. This review looked at drugs for the treatment of faecal incontinence. These included anti‐diarrhoea drugs or laxatives to regulate stools, and drugs to try to enhance the tone of muscle around the anus which help to keep it closed. Sixteen small trials were found, including 558 participants. The review of these trials found some evidence that anti‐diarrhoea drugs may reduce faecal incontinence for people having liquid stools. However, these drugs were associated with some side effects. There was some evidence that drugs to enhance the tone of the muscle around the anus may help, but more research is needed.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2013

No reliable evidence to distinguish between carbamazepine and valproate for partial onset seizures and generalized onset tonic‐clonic seizures.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

No evidence to support routine therapeutic monitoring of antiepileptic drugs in the treatment of epilepsy.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Juvenile myoclonic epilepsy (JME) is characterized by involuntary (uncontrolled) twitching of muscles in shoulders and arms after awakening, often starting in childhood.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2017

Bipolar affective disorder is a severe and common mental illness, characterised by periods of mania, depression and "mixed episodes" (or "dysphoric mania": a mixture of manic and depressed symptoms). Antipsychotic drugs are often used to treat acute manic episodes and one commonly used antipsychotic drug that has recently been approved for use in mania in USA and Europe is olanzapine. This review considered the efficacy, acceptability and adverse effects of olanzapine in long‐term treatment of bipolar disorder in comparison with placebo or other active drug comparisons. Five trials (1165 participants) met the inclusion criteria and are included in the review. Based on a limited amount of information, olanzapine may prevent further mood episodes (especially manic relapse) in patients who responded to olanzapine during an index manic or mixed episode and who have not previously had a satisfactory response to lithium or valproate. The olanzapine group had significantly fewer patients suffering from insomnia than the placebo group, but a significantly larger number of people suffering from weight gain. When compared with lithium, olanzapine caused more weight gain and depressive symptoms but fewer insomnia and nausea symptoms and a lower rate of manic worsening. However, considering the lack of clear findings of this review, conclusions on efficacy and acceptability of olanzapine compared to placebo, lithium or valproate cannot be made with any degree of confidence

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

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