Treatment Overview

The illness is treated with an anticonvulsant, dual antidepressants, and a neuroleptic as needed. The following table is an overview of the medications that are considered to be suitable:

The anticonvulsant acts to suppress the seizure activity. The antidepressants act to reduce the deep depression that is often associated with seizure disorders. The two antidepressants should cover a range of those that increase norepinephrine and serotonin levels in the blood. The psychosis that may accompany the disorder arises from the depression. Antidepressants will help to relieve the depression and in so doing reduce or eliminate the psychosis. Thus, the antidepressants perform a major role in the treatment of the disorder. The neuroleptic is added in modest amounts as necessary to further reduce the psychotic effects.

Various studies in the area of “psychotic depression” indicate that the most effective treatment is the administration of a wide spectrum of antidepressants and neuroleptics. Thus, the literature appears to converge on the best approach to treat the disorder.

The success or failure of treatment methods depends upon the ability to reduce the underlying deep depression. Alternative methods to deal with the deep depression are discussed in a separate section.

Selection of the Anticonvulsant

Tegretol is the usual choice for treatment of the disorder. This medication has a long history for use as an anticonvulsant and as a mood stabilizer. It tends to be used as the drug of choice for partial seizures.

Trileptal is a new medication that is quite similar to Tegretol. It has the same chemistry with an extra oxygen molecule attached to the structure. This change has improved the medication by reducing the tendency of Tegretol to reduce the white blood cells that are used for fighting infection. Trileptal has few side effects except for an occasional problem with hyponatremia (lowering of blood sodium).

Depakote has also been successfully used as an anticonvulsant and mood stabilizer. It is a potent medication that is very effective for mood stabilization and for the control of impulses arising from panic and anxiety. It tends to be used for generalized seizures including grand mal and petit mal. It has more side effects than Tegretol (e.g. weight gain) but is especially useful for the control of impulses.

Lamictal is a newer anticonvulsant that was recently approved by the FDA for the treatment of bipolar disorder. It has a chemical structure that is unrelated to other anticonvulsants or mood stabilizers. The indications are that the medication is effective for those dealing with depression and bipolar disorders. In comparison with Tegretol or Depakote, Lamictal has much more antidepressant potency. It is also effective both for partial and generalized seizure conditions.

Klonepin is an older medication that has sometimes been used for its anticonvulsant properties. It is a benzodiazepine that can be effective for reducing seizures. However, it has more side effects than others and also has addictive properties that make it difficult to stop the medication.

Dr. Blumer (2002) recommends that the highly potent new anticonvulsants not be used. Examples are Topiramate and Gabapentin. These medications are so potent in reducing seizure activity that psychosis can develop. Ethosuximide has also been known to greatly increase psychotic effects in those with a seizure disorder. Various studies over the years indicate that the “forced normalization” of electrical activity increases the depression and the tendencies for psychosis.

In summary, the consensus is that Tegretol, Depakote, and Lamictal are all considered effective as an anticonvulsant and for mood stabilization. Tegretol is a usual starting point based upon its long treatment history. Depakote is a potent medication but with more side effects than Tegretol. Lamictal is a good choice where the depression has not responded to past treatments. Treatment with a single anticonvulsant is the usual recommendation, but a combination treatment may ultimately be required.
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Selection of the Antidepressants

Antidepressants help to correct the chemical imbalances in the brain by affecting the actions of certain neurotransmitters. Neurotransmitters are responsible for sending messages between nerve cells. Serotonin affects functions such as mood, appetite, sleep, memory and sexual behavior. Norepinephrine affects functions such as the fight or flight response, blood pressure, heart rate, and concentration. Dopamine plays a role in emotion, learning, motivation, pleasure, memory, movement and other roles. The following are the two types of antidepressants that are commonly used in the treatment of depression:

Selective Serotonin Reuptake Inhibitors (SSRI) increase the amount of serotonin by hindering the Reuptake process that is involved in the elimination of serotonin. Commonly known SRRIs include Prozac, Paxil, Zoloft, and Lexapro.

Tricyclic antidepressants increase serotonin, norepinephrine, and dopamine by blocking the Reuptake process. Commonly known tricyclics include Imipramine, Nortriptyline, and Elavil.

Special considerations are needed in the selection of antidepressants for use in seizure disorders. The following criteria should be used:

1. Safety profile. Safety of antidepressants has been a subject of great concern for children. Children and adolescents appear to react differently to antidepressants than adults. A number of suicides among young people have been recently attributed to the use of antidepressants. The implication is that young people should take antidepressant medication under the careful guidance of the physician.

2. Dual Acting. The selected antidepressants should increase both the norepinephrine and serotonin activity (SRRI). The antidepressants may be administered by a single medication with dual-acting properties or by two separate antidepressants. Examples of dual acting antidepressants include Effexor, Remeron, and Cymbalta.

3. Seizure induction potential. All antidepressants reduce the seizure threshold. Care should be taken to select those antidepressants with a low seizure threshold.

4. Drug-drug interactions. A number of drug interactions can occur which affect the level of a medication in the blood. For example, a number of the SRRIs interact with Tegretol to produce antidepressant levels that far exceed the prescribed level. These combinations can produce dangerous side-effects if not carefully monitored. Prozac is particularly vulnerable to interactions with Tegretol.

Barry (2005) and Lambert (1999) has evaluated the suitability of various antidepressants for use with epilepsy. Some of their key findings are summarized in the table below. The most suitable antidepressants listed as “good” are those that show no interaction with anticonvulsants and show no potential for increasing seizure activity. These tend to be the newer antidepressants. Other antidepressants listed as “acceptable” or “special precautions” can be used with precautions. Others listed as “unacceptable” should not be used as all.

Suitability of Antidepressants for Patients with Seizure Disorders

Antidepressant	Interaction with Anticonvulsants*	Epileptogenic Potential*	Side Effects	Suitability for Seizure Disorders
Effexor	0	0		Good
Celexa	0	0		Good
Cymbalta	0	0		Good
Lexapro	0	0		Good
Trazadone	0	0	Sedation	Good
Doxepin	+	0	Sedation	Acceptable
Remeron	+	0	Weight gain, sedation	Acceptable
Zoloft	+	0	Anxiety, insomnia	Acceptable
Paxil	0	+		Precautions
Pamelor	+	+		Special precautions
Surmontil	+	+		Special precautions
Imipramine	+	+lose dose ++high dose		Special precautions
Norpramin	+	+		Special precautions
Prozac	++	+		Unacceptable
Luvox	++	+		Unacceptable
Amoxapine	+	++		Unacceptable
Anafranil	+	++		Unacceptable
Amoxapine	+	++		Unacceptable

Dr. Stephen Stahl (2002) a noted psychiatrist dealing with depressive disorders, recommends a blend of Effexor and Remeron for the treatment of deep depression. This blend is sometimes referred to as the “California rocket fuel”. Higher levels of these medications are reported to produce a triple boost to the serotonin system, a double boost to the norepinephrine system, and a single boost to the dopamine system. This antidepressant mixture should not be used for bipolar disorders unless a mood stabilizer is used. Otherwise, the treatment can move the patient into a manic phase or create psychosis.

Our own experience has been the most positive with those that are listed in the “good’ category. Dr. Blumer often recommends Pamelor and Imipramine, but at the lower dosages. He indicates that Imipramine should not be used above 150 mg. Excess agitation was encountered when using Prozac. Trazadone is a safe antidepressant, but has not otherwise been beneficial.

Selection of the Neuroleptic

The psychiatric disturbances associated with seizure disorders are treated principally with anticonvulsants and antidepressants. However, a low to moderate amount of neuroleptics may be required to remove some of the remaining symptoms.

A principal consideration in the selection of a neuroleptic is the degree to which the medication reduces the seizure threshold. The usual recommendation of Dr. Blumer is Risperdal because of its efficacy and relative safety. Other safe medications include Haldol (at low dosages) and Amisulpride, which is available in the UK.

Medications which should not be used include Thorazine and Clozapine. Clozapine should never be used because of the extreme danger of inducing seizures.

Risperdal has proven to be the best neuroleptic for us over the years. Medications that proved to be unsuitable included Thorazine, Abilify, and Geodon.

Generic Drugs

Brand name medications are the safest to use because of the standards used in the manufacturing of the product. However, generic medications are often used after the patent protection on the brand product has expired because of the large cost differences. Most generic medications are suitable. However, there can be significant variability in quality. It is therefore important to know the manufacturers and ratings of individual generic medications.

The U. S. Food and Drug Administration has rated all generic drugs as “A” or “B”. “A” drugs are considered bioequivalent to the brand-name original.

“A” drugs are those that have no known or suspected bioequivalence problems. These are designated as AA, AN, AO, AP, or AT.

“B” drug products are those that the FDA considers not to be therapeutically equivalent to the brand name medication. These are designated as BC, BD, BE, BP, BS, BT, BX or B. Many of these products are in fact suitable. However, there may not yet have been adequate evidence of bioequivalence. Often the problem is with specific dosage rather than the quality of the activity ingredients.

AB products are those medications where actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence.

FDA has rated all generic drugs and is reported in their website located at www.fda.gov/cder/ob/default.htm.

Our experience has favored the use of brand names when available. In particular, Tegretol XR has proven to be superior to the generic carbamazepine.