Archive for category Pharmacological

[WEB SITE] List of Seizures (Convulsions) Medications (60 Compared) – Drugs.com

Medications for Seizures (Convulsions)

Other names: Absence Seizure; Complex Partial Seizure; Fits

About Seizures:  A seizure or convulsion can be a sudden, violent, uncontrollable contraction of a group of muscles. A seizure can also be more subtle, consisting of only a brief “loss of contact” or a few moments of what appears to be daydreaming.

 

Drugs Used to Treat Seizures

The following list of medications are in some way related to, or used in the treatment of this condition.[…]

For the list of medications, Visit Site —> List of Seizures (Convulsions) Medications (60 Compared) – Drugs.com

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[Slideshow] Epilepsy & CBD

H Andre, O Danna, W Emma
… Scharfman and MacLusky, 2006 Page 34. Inhibition – Ledgerwood et al., 2010 ● CBD
is shown to inhibit synaptic transmission in hippocampal slices ○ In many forms of epilepsyseizures originate in the medial temporal lobe, an area that includes the hippocampus …

 

The Epilepsy & CBD Slideshow PDF file

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[Abstract] Pharmacotherapy of epilepsy

Pharmacotherapy of epilepsy is usually initiated after two or more unprovoked seizures, a decision that should be made after assessment of the individual risk of further seizures. Antiepileptic drugs (AEDs) are selected based on documented efficacy for the type of seizures, the epilepsy and possible epilepsy syndrome of the patient, taking potential adverse effects and comorbidity into account. For many AEDs, the mechanisms of action are incompletely understood. More than half of patients with newly diagnosed epilepsy achieve sustained seizure freedom with their first or second drug trials. After a prolonged time of seizure freedom discontinuation of therapy may be considered; the risk of relapse after drug withdrawal can be estimated on the basis of a number of clinical factors. The informed patient’s attitude is essential in all therapy decisions. Treatment is still largely symptomatic, but the future may involve a greater degree of disease-modifying precision medicine.

via [Pharmacotherapy of epilepsy]. – Abstract – Europe PMC

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[REVIEW] Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence – Full Text

Abstract

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.

Background

The International League Against Epilepsy (ILAE) defines epilepsy as a disease of the brain,  diagnosis of which requires: (a) at least two unprovoked seizures occurring >24 hours apart; (b) one unprovoked seizure and a probability for further seizures of at least 60%, occurring over the next 10 years or (c) the diagnosis of an epilepsy syndrome.1 Between 70% and 80% of patients with new-onset epilepsy achieve complete seizure control using antiepileptic drugs such as valproate or carbamazepine.2 In 20%–30% who are drug-resistant,3 4 there is great interest in investigating novel agents to reduce seizure frequency and severity. For the purposes of this review, the ILAE’s definition of drug-resistant epilepsy—the failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs (AEDs) schedules (as either monotherapies or in combination) to achieve seizure freedom5—is used. For the 30% of patients who experience drug-resistant epilepsy, the efficacy of alternative and adjunctive therapies is likely to be of great interest.

Preclinical studies suggest that naturally occurring cannabinoids (phytocannabinoids) have anticonvulsant effects which are mediated by the endocannabinoid system.6 Cannabidiol (CBD) and cannabidivarin have shown antiseizure effects in both in vivo and in vitro models. In contrast to tetrahydrocannabinol (THC), CBD does not produce euphoric or intrusive psychoactive side effects when used to treat seizures.7 Cannabinoids have been proposed as an adjunctive treatment for epilepsy7 and parents of children with epilepsy report using CBD products.8–10 There are a number of phase III human trials underway of CBD as an adjunctive therapy for treatment resistant paediatric and adult epilepsies.11 12

Recently Israel, the Netherlands, Germany and Canada have legislated to allow the use of cannabinoids for medicinal purposes. In Australia, Federal and state legislation that allows doctors to prescribe cannabinoids is being implemented. Systematic reviews are required to synthesise the evidence for individual conditions for which cannabinoids may be used to inform clinical practice and patient guidance.

This review considers evidence on the safety and efficacy of cannabinoids as adjunctive treatments for drug-resistant epilepsy. As previous reviews noted a lack of controlled studies,13 14 we synthesised evidence from randomised controlled trials (RCTs) and observational studies.[…]

Continue —> Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence | Journal of Neurology, Neurosurgery & Psychiatry

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[NEWS] Effective epilepsy medication without the side effects? | Epilepsy Research UK

Posted Mar 9 2018 in Anti-epileptic drugs

 

Approximately 60-70% of people with epilepsy will have their seizures controlled with medication. But even when epileptic seizures are controlled with medication the drugs used may have unpleasant, unwanted side effects. Ideally what patients and clinicians are looking for is a drug which works effectively and has no down side. Now new research from the Australian National University aims to look at the molecular level to find a way of reducing negative side effects without reducing the drug’s efficacy.  If you would like to read more about this study please click on the link here:

 

via Effective epilepsy medication without the side effects? | Epilepsy Research UK

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[WEB SITE] Epilepsy Drug With Marijuana-Based Ingredient Could Be Available In The US This Year

 By Allan Adamson Tech Times

A new class of epilepsy drugs based on a marijuana ingredient could be become available in the United States as early as the second half of 2018 pending approval from the Food and Drug Administration.

Epidiolex

GW Pharmaceuticals, the maker of the drug called Epidiolex, announced on Wednesday the promising results of a clinical study of the drug.

A group of 171 individuals were randomly assigned to either receive Epidiolex treatment or placebo. The participants were between 2 and 55 years old with a condition called Lennox-Gastaut syndrome. They were also suffering from seizures existing drugs cannot efficiently control.

The participants on average had tried and discontinued use of six anti-seizure treatments and were experiencing 74 “drop” seizures per month. This particular seizure involves the entire body, head and trunk, and often leads to fall and other injuries.

LGS Patients Taking Epidiolex Sees Significant Reduction Seizures

Results of the study, which was reported in the journal Lancet,  showed that over a period of 14 weeks, 44 percent of the patients taking the drug saw significant reduction in seizures. The rate is significantly higher compared with the 22 percent in the placebo group. More of those who were given the experimental drug also experienced a 50 percent or greater reduction in drop seizures.

“LGS is one of the most difficult types of epilepsy to treat and the majority of patients do not have an adequate response to existing therapies,” said Elizabeth Thiele, from Harvard Medical School. “These results show that Epidiolex may provide clinically meaningful benefits for patients with LGS.”

Epidiolex is based on pure marijuana-derived cannabidiol or CBD. The cannabis compound has been known for its medical benefits sans making people feeling “stoned.”

Adverse Events Linked To Use Of Epidiolex

Adverse events associated with use of the drug include diarrhea, decreased appetite, sleepiness, vomiting, and fever. Once given the go-signal to be marketed in the United States, the drug is intended to be used as a prescription drug to be dispensed by doctors.

“Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated. The long-term efficacy and safety of cannabidiol is currently being assessed in the open-label extension of this trial,” investigators wrote in their report.

GW Pharmaceuticals has not yet disclosed the pricing of the drug, but Justin Gover, GW’s chief executive officer, said that the company is already in talks with health insurers about coverage.

via Epilepsy Drug With Marijuana-Based Ingredient Could Be Available In The US This Year : Health : Tech Times

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[ARTICLE] Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last? – Full Text PDF

The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) –tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability. Over the years, this has led to an increasing use of CBD-enriched extracts in seizure disorders, particularly in children. Although improvement in seizure control and other benefits on sleep and behavior have been often reported, interpretation of the data is made difficult by the uncontrolled nature of these observations. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes. Based on currently available information, however, it is unclear whether the improved seizure control described in these trials was related to a direct action of CBD, or was mediated by drug interactions with concomitant medications, particularly a marked increased in plasma levels of N-desmethylclobazam, the active metabolite of clobazam. Clarification of the relative contribution of CBD to improved seizure outcome requires re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies controlling for the confounding effect of this interaction. (2017;7:61-76) […]

Full Text PDF 

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[WEB SITE] AEDs: Which Work Best as Monotherapy in Epilepsy? – Neurology Times

Which antiepileptic drugs (AEDs) are best as monotherapy? Before the updated Cochrane review, first-line therapy in adults and children with partial onset seizures was with carbamazepine or lamotrigine. And first-line therapy for generalized seizure onset was with sodium valproate.

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  • 60%-70% of people with epilepsy reach remission from seizures shortly after starting AED treatment. Most are treated with AED monotherapy. The National Institute for Health and Care Excellence (NICE) guidelines in the UK recommend carbamazepine or lamotrigine as first-line-therapy in adults and children with partial onset seizures and sodium valproate as first-line for generalized onset seizures. A 2007 network meta-analysis of AED monotherapy generally agreed with these recommendations.[1]

     

  • The Cochrane Review of AED monotherapy, which updates previous meta-analysis with studies published since 2007, adds levetiracetam and zonisamide.[2]

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  • Individual participant data (IPD) approach were used; considered gold standard for time-to-event pooled network meta-analysis. Combined IPD data from 12,391 people in 36 studies and compared 10 AEDS: carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide. ooled data from trials that did head-to-head comparisons were analyzed; a second analysis combined all data from trials to compare drugs that had not been previously compared.

  • For partial seizures, levetiracetam was found to be significantly better than carbamazepine and lamotrigine. Lamotrigine was significantly better than all other AEDs (except levetiracetam). And carbamazepine was significantly better than gabapentin and phenobarbitone. For generalized onset seizures, valproate was significantly better than carbamazepine, topiramate and phenobarbitone. For both partial and generalized onset seizures: phenobarbitone, the earliest licensed treatment, performed worse in terms of treatment failure than all other treatments.

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  • There were few notable differences for partial or generalized seizure types, except fpr 12-month remission: Carbamazepine was significantly better than levetiracetam for partial seizures; and 6-month remission: Sodium valproate was significantly better than lamotrigine for generalized seizures. Regarding time to bot partial and generalized seizures: the oldest AEDs (phenytoin and phenobarbitone) were generally better than newer AEDs. The most commonly reported adverse events across all drugs: drowsiness/fatigue, headache/migraine, GI disturbances, dizziness/faintness, rash/skin disorders.

  • IPD data were available for just 69% of total participants from 47% of eligible trials, leaving out 31% of eligible participants. Methodological inadequacies in some trials could have biased results

  • 1. Phenobarbitone and phenytoin are better for seizure control, but at the expense of earlier treatment failure. 2. Carbamazepine and lamotrigine are suitable as first-line monotherapy for partial onset seizures; levetiracetam may be a suitable alternative. 3. Sodium valproate is suitable as first-line monotherapy for generalized seizures; lamotrigine and levetiracetam may be suitable alternatives, especially for women of child-bearing age given the potential teratogenicity of sodium valproate 4. Zonisamide may effective in partial onset seizures: evidence is limited and more research is needed.

1. Tudur Smith C, Marson AG, Chadwick DW, Williamson PR. Multiple treatment comparisons in epilepsy monotherapy trials. Trials. 2007;5(8):34
2. Nevitt SJ, Sudell M, Weston J, Tudur Smith C, Marson AG. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database of Systematic Reviews. 2017, Issue 6. Art. No. CD011412.

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Which AEDs work best as monotherapy?

A new Cochrane review scrutinizes the efficacy and tolerability of various agents.

 

via AEDs: Which Work Best as Monotherapy in Epilepsy? | Neurology Times

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[WEB SITE] Dopamine deficiency: Symptoms, causes, and treatment

    1. Symptoms
    2. Causes
    3. Diagnosis
    4. Treatment
    5. Dopamine vs. serotonin
    6. Outlook

 

 

Dopamine is a chemical found naturally in the human body. It is a neurotransmitter, meaning it sends signals from the body to the brain.

Dopamine plays a part in controlling the movements a person makes, as well as their emotional responses. The right balance of dopamine is vital for both physical and mental wellbeing.

Vital brain functions that affect mood, sleep, memory, learning, concentration, and motor control are influenced by the levels of dopamine in a person’s body. A dopamine deficiency may be related to certain medical conditions, including depression and Parkinson’s disease.

A dopamine deficiency can be due to a drop in the amount of dopamine made by the body or a problem with the receptors in the brain.

Symptoms

 

Sad and depressed woman with low dopamine levels. alone in thought.

A dopamine deficiency is associated with depression, but researchers are still investigating this complex link.

 

The symptoms of a dopamine deficiency depend on the underlying cause. For example, a person with Parkinson’s disease will experience very different symptoms from someone with low dopamine levels due to drug use.

Some signs and symptoms of conditions related to a dopamine deficiency include:

  • muscle cramps, spasms, or tremors
  • aches and pains
  • stiffness in the muscles
  • loss of balance
  • constipation
  • difficulty eating and swallowing
  • weight loss or weight gain
  • gastroesophageal reflux disease (GERD)
  • frequent pneumonia
  • trouble sleeping or disturbed sleep
  • low energy
  • an inability to focus
  • moving or speaking more slowly than usual
  • feeling fatigued
  • feeling demotivated
  • feeling inexplicably sad or tearful
  • mood swings
  • feeling hopeless
  • having low self-esteem
  • feeling guilt-ridden
  • feeling anxious
  • suicidal thoughts or thoughts of self-harm
  • low sex drive
  • hallucinations
  • delusions
  • lack of insight or self-awareness

Causes

 

Dopamine model 3D render.

 Dopamine deficiency may be influenced by a number of factors. Existing conditions, drug abuse, and an unhealthy diet may all be factors.

 

Low dopamine is linked to numerous mental health disorders but does not directly cause these conditions.

The most common conditions linked to a dopamine deficiency include:

In Parkinson’s disease, there is a loss of the nerve cells in a specific part of the brain and loss of dopamine in the same area.

It is also thought that drug abuse can affect dopamine levels. Studies have shown that repeated drug use could alter the thresholds required for dopamine cell activation and signaling.

Damage caused by drug abuse means these thresholds are higher and therefore it is more difficult for a person to experience the positive effects of dopamine. Drug abusers have also been shown to have significant decreases in dopamine D2 receptors and dopamine release.

Diets high in sugar and saturated fats can suppress dopamine, and a lack of protein in a person’s diet could mean they do not have enough l-tyrosine, which is an amino acid that helps to build dopamine in the body.

Some studies have found that people who are obese are more likely to be dopamine deficient too.

Diagnosis

There is no reliable way to measure levels of dopamine in a person. However, a doctor may look at a person’s symptoms, lifestyle factors, and medical history to determine if they have a condition related to low levels of dopamine.

Treatment

 

Omega-3 fatty acid supplements.

Omega-3 fatty acid supplements may help to boost dopamine levels naturally.

 

 Treatment of dopamine deficiency depends on whether an underlying cause can be found.

If a person is diagnosed with a mental health condition, such as depression or schizophrenia, a doctor may prescribe medications to help with the symptoms. These drugs may include anti-depressants and mood stabilizers.

Ropinirole and pramipexole can boost dopamine levels and are often prescribed to treat Parkinson’s disease. Levodopa is usually prescribed when Parkinson’s is first diagnosed.

Other treatments for a dopamine deficiency may include:

  • counseling
  • changes in diet and lifestyle
  • physical therapy for muscle stiffness and movement problems

Supplements to boost levels of vitamin Dmagnesium, and omega-3 essential fatty acids may also help to raise dopamine levels, but there needs to be more research into whether this is effective.

Activities that make a person feel happy and relaxed are also thought to increase dopamine levels. These may include exercise, therapeutic massage, and meditation.

Dopamine vs. serotonin

Dopamine and serotonin are both naturally occurring chemicals in the body that have roles in a person’s mood and wellbeing.

Serotonin influences a person’s mood and emotions, as well as sleep patterns, appetite, body temperature, and hormonal activity, such as the menstrual cycle.

Some researchers believe that low levels of serotonin contribute to depression. The relationship between serotonin and depression and other mood disorders is complex and unlikely to be caused by a serotonin imbalance alone.

Additionally, dopamine affects how a person’s moves, but there is no clear link to the role of serotonin in movement.

Outlook

Dopamine deficiency can have a significant impact on a person’s quality of life, affecting them both physically and mentally. Many mental health disorders are linked to low levels of dopamine. Other medical conditions, including Parkinson’s disease, have also been linked to low dopamine.

There is limited evidence that diet and lifestyle can affect the levels of dopamine a person creates and transmits in their body. Certain medications and some therapies may help relieve symptoms, but a person should always speak to a doctor first if they are concerned about their dopamine levels.

 

via Dopamine deficiency: Symptoms, causes, and treatment

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[ARTICLE] Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events – Full Text

Abstract

Background

Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety.

Aim

The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV.

Methods

A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher’s exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha = 0.05).

Results

The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p = 0.28).

Conclusion

The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.


1. Background

Epilepsy is a neurological condition with an enduring predisposition to generate seizures and is associated with cognitive, psychological, and social issues [1]. Neuropsychiatric disorders are also more prevalent in people with epilepsy than in the general population [2] ;  [3]. There is, however, still ambiguity as to whether these comorbidities are the result of a direct link such as a genetic predisposition or structural cause leading to seizures and psychiatric problems or if seizures over time lead to psychiatric symptoms [4].

Treatment strategies in epilepsy need to be tailored to the individual and in particular, clinicians when choosing the appropriate antiepileptic drug (AED) medication need to pay attention not only to seizure patterns but also to a number of different parameters such as age, gender, comorbidities, and cognitive state.

Up to 75% of people with epilepsy may at some point have mental health issues. Antiepileptic drugs also have the potential to impact on mental health and cognition [5] ;  [6], and treatment with some AEDs is associated with the occurrence of psychiatric and behavioral side effects (PBSEs) while other may have beneficial psychotropic effects [7][8][9] ;  [10]. The PBSEs are often overlooked in epilepsy management and, withdrawal of an AED occurs only if the impact of these symptoms is significant and usually a risk to self or others.

Understanding psychotropic effects of (AEDs) is crucial but knowledge is limited. Carbamazepine (CBZ)-purported mode of action is via the modulation of voltage-sensitive sodium channels. Apart from antiepileptic action, CBZ is also used as a mood stabilizer and has proven efficacy in affective disorders. Oxcarbazepine (OXB) is structurally related to CBZ and is a prodrug that is converted into licarbazepine. The active form licarbazepine is the S enantiomer, known as eslicarbazepine (ESL). The presumed mechanism of action is as for CBZ. Conversely, OXB has never been proven to work as a mood stabilizer. In view of similarities of the postulated mechanism of action but a better tolerability profile, OXB has been used “off label” in mood management.

Levetiracetam (LEV), a commonly prescribed AED in the UK, is associated with PBSEs including irritability, depression, and anxiety [9] ;  [11]. A study suggested that PBSEs occurred in around 17% of people exposed to commonly used AEDs. Nearly 1 in 5 study participants on LEV reported PBSEs to LEV. However for CBZ the reported PBSEs were significantly lower [11]. The ESL did not figure in this study. Another study suggested that PBSEs with ESL were < 2.5%. While side effects such as irritability, anxiety, and aggressive behavior have been associated with other AEDs, rates of aggression and agitation were comparable between ESL and placebo [12]. […]

Continue —> Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events

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