Ask the Experts: Mood Disorders with Andrés Kanner, M.D.

Earlier this year, we asked our epilepsyfoundation.org readers to submit questions to Andrés Kanner, M.D. The questions with his responses appear below:

Epilepsy & Mood Disorders

I was on Depakote for 17 years and then, quite suddenly, my hair began falling out, I gained about 20 pounds and my hands were shaking – all reactions to Depakote. Now I take Keppra, which controls my epilepsy. But now my period is different. Right before my period I get very sad, upset, etc. I also feel a bit more anxious overall. Could this have anything to do with the medication switch? If so, will it stabilize?

Dr. Kanner: Valproic acid (Depakote) is an antiepileptic drug with adverse effects consisting of hair loss, weight gain and tremor, such as the ones you described. Since you were switched to levetiracetam (Keppra), you have become seizure-free, but have noticed peri-menstrual symptoms of dysphoria consisting of sadness, irritability and anxiety.

These symptoms could be the expression of just peri-menstrual dysphoric symptoms frequently referred to as PMS that are commonly seen in women during the days preceding a menstrual period and may persist throughout the period. Women who have a history of predisposition to depressive disorders, or in whom there is family history of depression may exhibit these symptoms with greater frequency and severity. It is possible that you may not have experienced these symptoms while on Depakote, as this medication has mood-stabilizing properties which were protecting you from experiencing symptoms of depression, anxiety and dysphoria. You may want to consider having a psychiatric evaluation to establish this possibility.

Levetiracetam is an antiepileptic drug that can have adverse effects consisting of symptoms of depression, irritability and poor frustration tolerance, but these are not restricted to a peri-menstrual period. Thus, it makes it less likely that these symptoms are, in fact, an expression of an adverse effect of the levetiracetam.

If the symptoms of anxiety, depression and irritability around the menstrual period are disabling enough, you should talk to your doctor and consider the option of taking an antidepressant around the time of your menstrual period. Antidepressants of the family of the selective serotonin reuptake inhibitors such as escitalopram (Lexapro) or citalopram (Celexa) can be safe in women with epilepsy and effective for this type of condition.

My nephew, who was recently diagnosed with epilepsy, gets pretty violent when he comes out of seizures. Should he be placed in a hospital where they can constantly monitor him? He's in temporary foster care now, but the people he’s with don't want to take care of him any more. His mother is bipolar and can't handle him, either. We all just want the best for him.

Dr. Kanner: Violent behavior occurring after a seizure during the postictal period is not unusual and can often occur when the patient has tried to get out of bed, walk around or get out of the house, and he is not allowed to move around through physical means. In patients in whom violent behavior is a reaction to attempts to restrict their ability to move around, the best approach is to walk with them without attempting to stop them, while making sure that they don’t put themselves in a situation of danger (crossing the street by themselves, etc.).

In patients with postictal agitation, the best treatment approach is obviously to achieve optimal seizure control; therefore, it is important that your family discuss with the neurologist taking care of your nephew all the options available to yield better seizure control, and if medication treatments have been exhausted, a consideration for surgery should be entertained if it has not been so far.

I have a 17 year old son who had surgery almost two years ago. He had part of his right-front temporal lobe removed. Since his surgery he’s had fewer seizures, but he’s tried to commit suicide twice. He can’t stand school anymore either. He blames this on severe mood swings which we’ve witnessed an increase in at home. Do mood swings increase and, if so, do they ever stop? He is on Depakote, Lamicital, Lexapro and Tranxene.

Dr. Kanner: In patients who have undergone an anterior temporal lobectomy, depressive disorders can occur during the first twelve months after surgery. Some of the depressive disorders can be severe enough that suicidal thoughts and attempts can also occur. These types of complications are significantly more frequent among patients who have had a history of depression prior to the epilepsy surgery. When these types of psychiatric disorders occur after surgery, pharmacologic treatment with antidepressant medications in combination with psychotherapy should be considered.

On some occasions, a first trial of antidepressant medication may not result in remission of symptoms of depression, in which case additional trials of antidepressant medication should be considered. Patients with these types of psychiatric occurrences after surgery should be under the care of a psychiatrist. In a majority of these patients, these depressive episodes tend to improve significantly and subside after the first year. However, about 10% to 15% of patients may continue to experience depressive episodes after surgery, and these are the patients in whom treatment with antidepressant medication with or without psychotherapy needs to be maintained for longer periods of time.

I take Depakote which controls my seizures, but I’ve recently developed tremors that make my handwriting illegible and cause problems with motor skills. I am currently in school in the Health Information Management Program, which requires a great amount of typing. This, too, is very difficult. Do I have any options, and also, is there financial help for doctor's appointments? I have no income at this time.

Dr. Kanner: The development of tremor can often be an adverse effect of valproic acid (Depakote) and the severity of this tremor may be such that it may interfere with the ability to write or to perform activities that require fine motor coordination, such as yours. You should discuss this side-effect with your neurologist and consider the option of using other antiepileptic medications that are not associated with these types of side-effects.

The choice of the antiepileptic medication depends on the type of epileptic syndrome and seizures. At times, a conversion to the extended-release formulation of Depakote (Depakote ER) may improve the occurrence of tremors, and this may be considered if you are not already taking this formulation.

You can discuss with your local chapter of the Epilepsy Foundation whether you are eligible for a patient assistance program which would allow you to get medication for free. With respect to getting free healthcare, you can seek care at a county hospital clinic.

I care for a developmentally disabled individual who has seizures and a Thyroid disorder. She requests coffee all the time and, unfortunately, isn't able to understand the consequences of drinking coffee late at night. After the coffee she is really excited, happy and talkative. She falls asleep about three hours later and eventually has a seizure. Is there a connection between coffee and seizures? Can excessive talking bring on a seizure?

Dr. Kanner: The vast majority of patients with epilepsy do not experience a worsening of their seizures after drinking coffee. The excessive talking, also, is not a trigger for the development of seizures. Sleep-deprivation, however, can facilitate the occurrence of seizures, especially in patients who have primary generalized epilepsy presenting as generalized tonic-clonic seizures on awakening; although, this can occur also with other types of epileptic seizures. Given the reaction of this patient to the intake of coffee, i.e., becoming excited, happy and talkative, one has to suspect the possibility of coffee facilitating the occurrence of what are known as "hypomanic" symptoms.

This should be investigated by a psychiatrist to determine if it is so. This type of reaction to coffee should be discussed with the patient's physicians to consider the possibility of placing him or her on antiepileptic medication that has mood stabilizing properties and specific antimanic properties, such as valproic acid, carbamazepine, oxcarbazepine or lamotrigine.

Could erratic speech during childhood, such as speaking so fast it's not understandable, hypersensitive hearing and a short temper be signs or symptoms of epilepsy?

Dr. Kanner: Erratic speech during childhood, such as speaking so fast that it is not understandable, hypersensitive hearing and short temper are not signs of epilepsy.

My son was recently diagnosed with simple seizures. His right arm and hand contorts and jerks uncontrollably for 10 to 15 seconds. He was prescribed Depakote, but it’s not working. His mood also changes from yelling one minute, then laughing the next. I notice him having more difficulty retaining school information and focusing, too. What other medications might he be able to try to control his seizures without altering his mood and his focusing ability? What might be causing this seizure what can I do to help him focus more so he doesn't fall behind in school?

Dr. Kanner: This question is very vague. You should ask the treating physician to explain to you: What is the actual nature of the seizure disorder? What are the findings of the neuroimaging studies? You should also ask to discuss the different types of options that are available for the management of your son’s seizures. It is not clear from the information whether the difficulties your son is experiencing in school are the expression of toxicity to high levels of valproic acid (Depakote), the seizure disorder, the cause of the seizure disorder, or a combination of all of the above.

How might parents cope with the anxiety and depression of having a child recently diagnosed with epilepsy?

Dr. Kanner: Feelings of depression and anxiety are common in parents when they are told that their child suffers from epilepsy. The best way that parents can cope with such symptoms is first by learning as much as possible about their child’s epilepsy, the causes, the impact that this type of seizure disorder may have on their child’s present and future life, both professionally and socially, and the available treatments. It is important that parents have an opportunity to discuss these questions openly with the treating physician of their child, and to make sure that all of their questions and concerns are answered.

Often, attending support groups for parents of children with epilepsy can be extremely helpful for parents to learn ways in which they can cope with these feelings of depression and anxiety, how they can help their child lead a normal life despite the occurrence of seizures, and how to best bring up their child. The parents should check with their local chapter of the Epilepsy Foundation to find out where such support groups are taking place. 

My epilepsy seems to have lost me the ability to stay on task and it’s affecting my job. Also, I take Dilantin and Zonegran to control my seizures and one of them has seemingly killed my libido – causing my husband and me to fight. My doctor says I’m "impotent." Are these problems caused by my epilepsy, my medication or both? What do I do?

Dr. Kanner: Problems with concentration can often be seen in people with epilepsy, or they can also be triggered by the use of antiepileptic medications, especially when given at high doses. Certain antiepileptic medications, however, are known to interfere with cognitive functions more than others, and zonisamide (Zonegran) is one with which problems with concentration and memory, as well as finding words, have been identified. It is therefore important that you discuss with your treating physician the presence of these symptoms to determine whether these were caused by the administration of antiepileptic medications, particularly zonisamide (Zonegran) or phenytoin (Dilantin) at high levels, or the combination of the two, or, whether these symptoms were an expression of your epilepsy.

In addition, there's the possibility that a combination of problems with concentration associated with a seizure disorder may have worsened by the use of antiepileptic medications. In this kind of situation, the use of antiepileptic medications that have less impact on the cognitive side-effects, such as lamotrigine (Lamictal), should be considered, if appropriate, for the type of epileptic syndrome and seizure. Alternatively, and especially if a diagnosis of attention deficit disorder can be established, symptomatic treatment can be entertained with the use of medication and behavior therapy.

Likewise, a loss of libido can occur as sequelae of a certain type of epileptic seizure disorder, such as seizures of temporal lobe origin and can also be facilitated by certain antiepileptic medications, such as phenytoin (Dilantin), as this drug decreases the amount of the sexual hormones (estrogen and testosterone) to access the brain. Occasionally, the loss of libido can result from a combined effect of the seizure disorder and the use of antiepileptic medication.

You should consider an open discussion with the treating physicians in order to consider a switch to other antiepileptic medications as well as a referral for sex therapy if the former is not sufficient to cause remission of the problems with libido.

Our son has had myoclonic epilepsy for over four years and has been on the ketogenic diet for over a year. Since the diet acts like an epilepsy medicine, will it create the same mood problems? He can be very emotional and sometimes pinches and bites.

Dr. Kanner: The ketogenic diet is not known to cause psychiatric symptoms. If anything, children treated with a ketogenic diet are less likely to experience the type of psychiatric adverse events seen with antiepileptic medications. The most likely cause of your son's psychiatric symptoms is related to the cause of the epileptic seizure disorder, the epileptic seizure disorder itself, or a combination of the two.

My three-year-old son has been on Trileptal, Keppra and now Carbatrol. When on Trileptal he was mean and hit people. When on Keppra he once woke in the middle of the night screaming, kicking and biting. We eventually had to call an ambulance. The doctor said it was the Keppra. He is now doing better on the Carbatrol, but around 1 p.m. every day he gets very hyper. Why would this happen, and why the same time every day?

Dr. Kanner: Epileptic seizures can often be associated with behavioral problems, as well as impulsivity, poor frustration tolerance, and motor hyperactivity. Certain antiepileptic medications can also result in similar types of symptoms. While oxcarbazepine (Trileptal) is not a drug that is known for causing behavioral adverse events typically, occasionally such adverse events can occur.

Keppra, on the other hand, has been associated with developmental aggressive behavior and impulsivity, and could account for some of the night screaming, kicking and biting reported by the parents. Discontinuation of Keppra apparently resulted in the remission of the symptoms, hence supporting causality of Keppra on this behavior.

The occurrence of motor hyperactivity around the same time of the day is difficult to explain. In a three year-old child, it could be the expression of the fact that the child is getting tired, and as a consequence, becomes more restless, impulsive and hyperactive. Other causes cannot be excluded, but I don't have enough information available to comment on other possible explanations.

My husband will have sudden mood changes prior to a cluster of seizures. Is there anything I can say to him or do that will help us?

Dr. Kanner: You are describing a not infrequent experience known as preictal (before a seizure) dysphoria, which consists of symptoms of depression, anxiety and irritability, and which are well-known to occur up to three days before a seizure or cluster of seizures and increase in severity as the seizure occurrence gets closer. These symptoms disappear following the seizure cluster.

At this point, there is no known treatment of this type of preictal dysphoria, except for trying to get the patient seizure-free, in other words, avoiding the occurrence of these seizures. If the seizures occur with a relatively high frequency and the depressive episodes are frequent enough, your husband can discuss with his treating neurologist the use of antidepressant medication; although, there is no information to date proving that such treatment may prevent the occurrence of these symptoms.

I have had epilepsy since I was pregnant with my second child, 17 years ago. I have kept it mostly under control with a daily regimen of Neurontin, Topamax, Imipramine and Lexapro. But the seizures are now returning. I am very depressed and feel like life is not worth living. I just can't take this anymore and my situation is getting worse as I age. What will happen when I go through menopause? All my problems seem to be connected to my hormones. It started in my first month of pregnancy, and it is worse in the two weeks before my period. Can you help me at all? Is there something better I should be telling my doctor?

Dr. Kanner: Depression is a common psychiatric complication of epilepsy. It can account for one of the causes of poor quality of life in these patients. Therefore, aggressive treatment of comorbid depressive disorders is of the essence.

You appear to have seizures around your menstrual period, which is known as catamenial epilepsy. If regular antiepileptic medications cannot control the seizures, you can discuss with your treating neurologist the use of certain hormone therapies, such as progesterone suppository or injection of Depo Provera in an attempt to cause remission of your seizures. Caution should be exerted, however, with the use of this hormone therapy, as these medications can be associated by themselves with the development of symptoms of depression.

The occurrence of seizures around the menstrual period does not necessarily imply that they may disappear when you enter menopause. One-third of women may experience improvement of seizures with menopause, another third may experience a worsening and another third may not experience any change in seizure frequency.

A reassessment of the treatment of depression is necessary at this point, as it appears that your symptoms of depression have persisted despite the trial with two antidepressants, imipramine and Lexapro. Use of other antidepressant medications should be considered, and at this point, if you have not been seen by a psychiatrist, you should consider doing so.

What can you tell me about vagus nerve stimulation? My neurologist thinks it may be a good option for me because many medications make me dizzy and are no longer options. However, he has not had any patients with the device and that makes me nervous. I have been in touch with Cyberonics, the company that makes the implant, but I would like to know a little bit more. Can you help?

Dr. Kanner: The vagal nerve stimulator is a device that has been approved for the treatment of patients with seizures of focal onset, also known as partial complex seizures or secondarily generalized tonic-clonic seizures. It also has been used quite effectively for the treatment of patients with Lennox-Gastaut syndrome, also known as secondarily generalized epilepsy.

Further, the efficacy of the vagal nerve stimulator in the treatment of partial seizures has been found to yield a greater than 50% reduction in the seizure frequency in 30% to 40% of patients. The probability of being seizure-free with a vagal nerve stimulator is probably 5% or less. When patients are implanted with vagal nerve stimulators, they will continue to take antiepileptic medication, and only rarely is it possible to discontinue the antiepileptic medication.

In general, the vagal nerve stimulator is only considered for patients in whom antiepileptic medication has not rendered them seizure-free and in whom epilepsy surgery is not a viable option for the treatment of their seizures. In other words, you have a seizure disorder that has failed to respond to several antiepileptic drug trials (at least two or three), it would behoove you to discuss with your treating neurologist the possibility to establish whether surgery may be an option for you, as the probabilities of becoming seizure-free with epilepsy surgery are significantly greater (in the order of 50% to 70% depending on where the seizure focus is localized and provided that the patient is found to be a good candidate for epilepsy surgery).

The vagal nerve stimulator should, therefore, only be considered if the patient is not a candidate for epilepsy surgery or is not interested in pursuing that avenue, but needs to consider the fact that she will probably need to continue to take antiepileptic medication after she has been implanted with the vagal nerve stimulator.

The vagal nerve stimulator, in general, is well-tolerated. Patients may experience a tingling sensation in their throats anytime the stimulation goes off, or they may experience a transient hoarseness of their voices associated with the stimulation. For many of these patients, this is a transient phenomenon. Rarely patients may experience pain when swallowing, shortness of breath when running, and as with any surgical procedure, infection is a potential risk of the implantation of the device. Damage to the one of the branches of the vagal nerve known as the recurrent laryngeal nerve can result in permanent hoarseness of the voice, but this is a rare occurrence. I would recommend that you consult with an epileptologist, if you haven’t done so, to discuss the treatment options for your seizure disorder and get an objective idea of the risks and benefits of the different available modalities for your seizure disorder.

I take Zonegran for my seizures. I have a very explosive temper I can't control and it keeps getting worse. I find myself obsessing over things and find myself getting so enraged I make myself sick. I have no control over it. I don't harm myself or anyone else, but it has ruined my relationship. Also, I have a small child and I don’t want to raise her like that. Can you help?

Dr. Kanner: It is not clear from the question whether the explosive temper that you describe has been present since you started on a regimen of Zonegran for the treatment of your seizure disorder. Zonegran is an antiepileptic medication which can occasionally be associated with the development of symptoms of depression, of which increased irritability and poor frustration tolerance can be prominent.

On the other hand, certain types of epileptic seizures, primarily seizures originating in the temporal and frontal lobes, as well as seizures that are part of juvenile myoclonic epilepsy can be associated with increased irritability, impulsive behavior and poor frustration tolerance, as well.

Accordingly, it is important that you discuss with your treating neurologist the presence of the symptoms and that an evaluation be carried out as to the cause of such symptoms. If it is established that problems with temper have preceded the introduction of Zonegran, you should be evaluated for the treatment of these symptoms, which can often respond to lower doses of certain types of antidepressant medications known as selective serotonin reuptake inhibitors. Consultation with a psychiatrist would therefore be indicated.

If, on the other hand, it is found that these symptoms have been present only since the Zonegran was introduced, you need to discuss with your treating neurologist the option of considering alternative medications that may not have this type of adverse events. The choice of the antiepileptic medication will also depend on the type of epileptic seizure and syndrome that you have.

My daughter and I are treated for epilepsy. I’ve heard epilepsy can be genetic. Is this true? A cousin, my sister and her daughters have all been diagnosed, too.

Dr. Kanner: Certain types of epileptic seizure disorders are genetic, these include the primary generalized epilepsies, which can present as absence seizures, generalized tonic-clonic seizures on awakening, juvenile myoclonic epilepsies, juvenile absence seizures, and with a lesser frequency, certain types of frontal lobe and temporal lobe seizure disorders.

In families, such as yours, where there are multiple members with epilepsy, it would be advisable that you contact major epilepsy centers where research on genetics of epilepsy is carried out. You and your family could contribute to a better understanding of the genetic aspects of epilepsy and through the study of the genes of the various family members, they could help to identify the potential gene mediating their seizure disorder.

These studies are done at no cost to you and your family. You should discuss this option with your treating neurologist.

I used to take Topamax but changed to Depakote once I started feeling depressed, had frequent panic attacks and had continuing numbness in my fingers and toes and, occasionally, my scalp. Is this normal? Depakote, however, has made me gain weight. Is there a way to use a combination of Depakote and Topamax together? The Topamax seemed to help me maintain a more normal weight for my body size.

Dr. Kanner: Topiramate (Topamax) is an antiepileptic medication which can potentially cause symptoms of depression as an adverse effect. Other side-effects can include numbness in the fingers and toes, as well as in the scalp. These side-effects are related to the dose, that is, with higher doses the numbness becomes more intense. Panic attacks are less frequently reported as a side-effect of Topamax, but could also be an expression of adverse effects, especially in the setting of depressive symptomatology. Valproic acid (Depakote) is a medication which can cause weight gain as one of its side-effects.

The combination of Depakote and Topamax is not something I usually recommend, because it can enhance other side-effects of Topamax, such as cognitive problems presenting as difficulty finding words, problems with memory and slow thinking. Accordingly, if you are having problems with weight gain on the Depakote, you should discuss with your treating neurologist the option of considering other antiepileptic medications that have positive psychotropic properties (That means having a positive effect on mood and anxiety symptoms.) and that do not cause weight gain. The choice of the antiepileptic medication, obviously, would need to be determined with the type of epileptic seizures and epileptic syndrome that you are suffering from.

My daughter has had epilepsy for almost two years, and she has had trouble with depression and motivation. She tells me that she has a hard time concentrating and remembering what her teacher says. She is also depressed because she has gained weight due to her medication. Do you have any suggestions for dealing with concentration and mood issues?

Dr. Kanner: Depression is a common complication of epilepsy and should be treated aggressively, as it accounts for a poor quality of life for people with this disorder. The symptoms of depression can include problems with memory and concentration, as well as changes in eating habits, including loss of appetite or increasing appetite, which could then result in weight gain. Your daughter should, therefore, undergo a psychiatric evaluation, and treatment for the depressive disorder should be instituted.

Certain antiepileptic medications can cause weight gain, but because changes in eating habits can be symptoms of depression, one cannot attribute the weight gain necessarily to the antiepileptic medication without ruling out that it is the expression of the depressive disorder. If, on the other hand, it is established that the weight gain has been noticed since your daughter started on antiepileptic medication that is known to cause this type of side-effect, such as valproic acid (Depakote), pregabalin (Lyrica), gabapentin (Neurontin), and carbamazepine (Tegretol), she could be considered for alternative antiepileptic medications that are weight-neutral.

Ideally, antiepileptic medications that also have positive psychotropic effects (that is, improved mood of patients) can be considered, such as lamotrigine (Lamictal). These options should be discussed with the treating neurologist, as well as a psychiatrist, and should carry a complete evaluation for the treatment of the depressive disorder of this young patient.

I had my first seizure at age 23 and I was on Dilantin for over a year. I eventually came off it because the Army doctors and I thought it had been a one time occurrence. But I just recently had a second one at age 27. Both were grand mal seizures. I was put on Dilantin again, but switched to Topamax due to side effects. I obviously lead a pretty busy military life, but recently I have been crying a lot, feeling terribly upset about everything – even my own family. I am afraid to discuss this with my bosses and the Army neurologist, though, because I may get medically boarded out of the military. What should I do?

Dr. Kanner: An initial seizure that is followed by a prolonged seizure-free state of two years duration can often allow antiepileptic medication to be discontinued. However, in some patients seizures can recur just as it happened with you… one or two years later. Hence, the use of antiepileptic medications is appropriate. It appears, however, that after you started on topiramate, you developed symptoms of depression.

It is important that you discuss with your treating neurologist whether these symptoms of depression became apparent soon after the topiramate (Topamax) was started, in which case you should inquire about the possibility of being switched to other antiepileptic medications that are not known to cause symptoms of depression as adverse effects. Topiramate (Topamax) is known to cause symptoms of depression as one of its side-effects.

The choice of the antiepileptic medication will depend on the type of epileptic syndrome that you have. Antiepileptic medications with positive psychotropic properties should be considered (that means that they are effective in treating symptoms of depression), and it would be helpful to establish whether your seizure disorder would be appropriate for those antiepileptic drugs which are: lamotrigine (Lamictal), valproic acid (Depakote), and oxcarbazepine (Trileptal).

On the other hand, if no temporal relationship can be established between the onset of symptoms of depression and the introduction of topiramate (Topamax), you are probably suffering from a depressive disorder which should be treated aggressively, and a psychiatric evaluation would be recommended.

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Editor's Note: For more information about the Foundation's Mood Disorders Initiative, contact emabry@efa.org or visit the Mood Disorders section of our website.

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This edition of "Ask the Experts" was made possible in part by an educational grant from Cyberonics, Inc.