Antidepressants for people with epilepsy and depression | Figure 1

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Antidepressants for people with epilepsy and depression

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Background

Depressive disorders occur in approximately one‐third of people with epilepsy, often requiring antidepressant treatment. However, depression often goes untreated in people with epilepsy, partly due to fear that antidepressants might cause seizures. There are different classes of antidepressants, however they all aim to increase key nerve chemicals in the brain, thereby alleviating depressive symptoms.

Characteristics of studies

We found ten studies that included 626 patients with epilepsy and depression treated with an antidepressant. Four were randomised controlled trials, and six were non‐randomised prospective cohort studies. The studies observed the effect of different antidepressants, mainly a class of antidepressant called a selective serotonin reuptake inhibitor (SSRI). One randomised controlled trial and one prospective study also observed the effect of cognitive behavioural therapy on depression.

Results

Taking all the evidence into account, the review found that there is very limited evidence that antidepressants decrease depressive symptoms more than other treatments, placebo, or no treatment in epilepsy. There was limited information on the effect of antidepressants on seizure control, however in the studies reporting this outcome there did not appear to be any significant worsening of seizures. The evidence is current to February 2021.

Quality of the studies

We assessed the studies with regard to bias and quality. Overall, the quality of the evidence was rated as moderate to low for the clinical trials and low to very low for the non‐randomised prospective cohort studies. Large, high quality trials of antidepressants are needed to examine how different classes of antidepressant compare, and what impact they are likely to have on seizure control.

Read the full Cochrane Review here

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\ \ Background\ Alzheimer's disease is a risk factor for increased seizures in older people. Seizures of any type can be observed in Alzheimer's disease and are probably underestimated.\ Study characteristics\ We searched scientific databases for clinical trials comparing medication and non‐medication‐based treatments for epilepsy in people with Alzheimer's disease. We wanted to evaluate how well the treatment worked and if it had any side effects.\ Key results\ We included and analyzed one randomized controlled trial (a clinical study where people are randomly put into one or two (or more) treatment groups) with 95 participants. Concerning the proportion of participants with freedom from seizures, no significant differences were found between the antiepileptic drugs (levetiracetam versus lamotrigine, levetiracetam versus phenobarbital, and lamotrigine versus phenobarbital). It seemed that levetiracetam could improve cognition (thinking) and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood.\ Certainty of the evidence\ The certainty of the evidence for all the outcomes from the study were very low. This means that we are very uncertain about the results and they should be interpreted with caution. Large randomized controlled trials are required to determine how effective and well tolerated treatments are for epilepsy in people with Alzheimer's disease.\ The evidence is current to August 2020.](https://app.figure1.com/case-detail/0039a19c-bb6c-4f62-8f53-4f5e7f9dd565)

\ \ Why is this question important?\ Epilepsy is a very common condition that affects the brain. People with epilepsy experience seizures ‐ or fits ‐ that can affect their daily lives. They are often prescribed medicines to control or prevent seizures. People with epilepsy can find it difficult to take their medicines as prescribed, and this is thought to be a reason for poor control of seizures. This review of studies reports on ways of improving how they take their antiepileptic medication.\ What we did\ We searched medical databases for clinical studies looking at ways of improving adherence to medication in people with epilepsy. We limited our search to randomised controlled trials (RCTs) involving people with a clinical diagnosis of epilepsy of any age and treated with antiepileptic drugs in a primary care (for example, doctor's surgery), outpatient or other community setting. RCTs are medical studies where people are chosen at random to receive a treatment (called the intervention group) or to receive a different treatment or no treatment (called the control group). This type of study provides the most reliable evidence about whether different approaches to health care make a difference.\ The results are up to date to February 2020.\ What we found\ We identified 20 studies (2832 participants). The studies were conducted in different countries with the majority from the USA. The studies examined three main types of interventions:\ \

  1. education and counselling of participants about topics such as epilepsy and medication used to control epilepsy (4 studies);\
  2. behavioural interventions, such as asking people with epilepsy to link the intention of taking their medication with a particular time, place and other routine activity (13 studies); and\
  3. mixed interventions, which is the use of more than one intervention (4 studies).\ One study is counted twice because it compared a behavioural intervention with a mixed intervention.\ Studies measured adherence to medication in various ways, for example, with questionnaires, blood samples or electronic bottle tops. Studies also measured reduction in frequency or severity of seizures to see if taking medication as prescribed made a difference. The studies were all very different from each other, so we could not combine their results.\ Key results and reliability of the evidence\ Education and counselling interventions may improve medication adherence. Two studies showed improvement, one study showed a small improvement and one no improvement.\ Behavioural and mixed interventions probably improve adherence to medication. People in the intervention groups showed improved adherence compared to the control groups.\ Four studies showed that when adherence improved in the intervention groups, seizure frequency or seizure severity was decreased.\ We were unable to draw firm conclusions about the results because the studies were very different from each other and did not always use the best methods. This means we are not certain about their evidence.\ What should happen next?\ We need carefully‐designed randomised controlled studies involving more people with longer follow‐up periods to identify the best intervention to improve adherence to antiepileptic medication.](https://app.figure1.com/case-detail/0f26a73e-0775-4c78-8599-c5c439a6a1bb)

\ \ Catamenial (menstrual) epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy.\ Current treatment of catamenial epilepsy depends on whether a woman has regular or irregular menstrual periods.\ Catamenial epilepsy is common in women with epilepsy, and may have a significant negative impact on quality of life. There is uncertainty regarding which treatment works best and when in the menstrual cycle treatments should be taken. There are also concerns about the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research.\ The aim of this review was to examine the effectiveness of hormonal and non‐hormonal treatments in stopping seizures in women with catamenial epilepsy.\ Results\ We included four randomised controlled trials of hormonal treatments in the review, two trials evaluating progesterone and two evaluating norethisterone. The treatment was compared to a placebo. We did not find any studies testing non‐hormonal treatments or any studies in women with irregular periods. The four included studies involved a total of 192 women aged 13-45 years experiencing catamenial epilepsy. The included studies did not demonstrate any significant differences between groups when comparing progesterone or norethisterone to placebo for seizure outcomes. The included studies reported limited information on side effects, but women taking progesterone were no more likely to withdraw from the study due to side effects than those receiving placebo.\ The evidence is current to July 2021.\ Certainty of the evidence\ We judged the certainty of the evidence to be very low to moderate, as the included studies provided unclear information on methods of blinding, recruited small numbers of participants, and were inconsistent in reporting treatment outcomes.\ Conclusions\ We found very limited, mostly low‐certainty evidence, of no difference in seizure outcomes for norethisterone and progesterone versus placebo in women with catamenial epilepsy. Our review highlights an overall lack of information on the effectiveness of a wide range of other hormonal and non‐hormonal treatments currently being used. Further studies in women with catamenial epilepsy are needed in this area.](https://app.figure1.com/case-detail/13b8ba36-8abb-467a-b1ff-8073222d746d)

\ \ Background\ Epilepsy is a common neurological disorder that appears in various forms. Many individuals with epilepsy have satisfactory seizure control with the use of antiepileptic medications. Yet, nearly a third of people with epilepsy suffer from frequent and uncontrolled seizures despite the use of medication, or are unable to tolerate the side effects of those medications. Surgery is an option for some people with uncontrolled seizures, but it is invasive and not suitable for all individuals. As a result, there remains a substantial unmet need for safe, effective therapies for these harder‐to‐treat epilepsies.\ Transcranial magnetic stimulation (TMS) is one of several newer treatments that can potentially offer people with epilepsy a safe and non‐invasive alternative to surgery. Long used as a research tool to study brain function, TMS has also been studied as a possible treatment for a number of nervous system conditions, including epilepsy. This non‐surgical and painless treatment uses induced magnetic currents to regulate brain function in order to reduce the tendency to have seizures.\ Objective\ We aimed in this review to evaluate the evidence for the use of repetitive transcranial magnetic stimulation (rTMS) in individuals with epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges (abnormalities on brain electrographic testing that suggest underlying brain disturbance or seizure tendency), antiepileptic medication use, and side effects.\ Methods\ The latest search for trials was 2 June 2020. We assessed the evidence from eight randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) involving a total of 241 participants comparing rTMS to control treatments (sham treatment, antiepileptic medication, or low‐frequency rTMS).\ Results\ Some of the included trials showed that rTMS reduces the number of seizures individuals had compared to before the therapy, but other trials did not show any significant differences in seizure frequency. Four trials showed a reduction in epileptiform discharges following rTMS treatment. One study measured changes in quality of life in seven participants; although not statistically analysed they found that a greater proportion of study participants reported increased quality of life scores with active treatments compared to the sham treatment. One trial reported an increase in antiepileptic medication in a single individual but they had received the control treatment. Side effects were uncommon; the most frequently reported side effect was headache (and the majority of individuals completed the treatment with rTMS). However, one study showed an increase in seizure frequency in two individuals: one during the rTMS treatment (who discontinued the treatment early), and one weeks after the treatment.\ Certainty of the evidence\ Overall, we judged the certainty of the evidence for the main outcome of reduction in seizure frequency to be low due to unclear information in the published papers about study design and the unclear presentation of results. One included study commented on quality of life, but involved only seven participants.\ The evidence is current to June 2020.](https://app.figure1.com/case-detail/240e785d-a0ce-4655-8f0b-0afbd254319d)

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