View the Comparison Table: Some Oral Antiseizure Medications

When used for the appropriate seizure type, antiseizure medications (ASMs) are roughly equivalent in efficacy. In addition to the seizure type, the choice of drug is usually based on factors such as ease of use, spectrum of activity, adverse effects, interactions with other drugs, presence of comorbid conditions, suitability for elderly persons and those with childbearing potential, and cost. Treatment should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally try at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time.

Bipolar disorder is characterized by episodes of mania, hypomania, and depression. Recurrences of manic or (more frequently) depressive symptoms are common. About 15-20% of patients with bipolar disorder die by suicide.

View the Comparison Table: Some Drugs for Migraine Prevention in Adults

View the Comparison Table: Some Drugs for Migraine Prevention in Adults

An oral nonopioid analgesic is often sufficient for acute treatment of mild to moderate migraine pain without severe nausea or vomiting. A triptan is the drug of choice for treatment of moderate to severe migraine in most patients without vascular disease. Treatment of pain when it is still mild to moderate in intensity improves headache response and reduces the risk of recurrence.

Atogepant (Qulipta – Abbvie), an oral small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ("gepant"), has been approved by the FDA for prevention of episodic migraine in adults. It is the second oral CGRP receptor antagonist to be approved in the US for this indication; the first was rimegepant (Nurtec ODT), which is also approved for acute treatment of migraine. Parenteral CGRP monoclonal antibodies are approved for prevention of migraine (see Table 3).

An oral nonopioid analgesic is often sufficient for acute treatment of mild to moderate migraine headache without severe nausea or vomiting. A triptan is the drug of choice for treatment of moderate to severe migraine headache pain in most patients without vascular disease. Early treatment of pain when it is still mild to moderate in intensity improves headache response and reduces the risk of recurrence.

Treatment of epilepsy should begin with a single antiepileptic drug (AED), increasing its dosage gradually until seizures are controlled or adverse effects become intolerable. If seizures persist, specialists generally recommend trying at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs concurrently. When used for the appropriate seizure type, AEDs are roughly equivalent in efficacy. Drug choice is usually based on factors such as ease of use, adverse effects, drug interactions, presence of comorbidities, and cost.

View the Comparison Table: Some Oral Antiepileptic Drugs

View the Comparison Table: Some Drugs for Migraine Prevention in Adults

Bipolar disorder is characterized by intermittent episodes of mania and/or depression. Even with maintenance treatment, recurrences of manic or (more frequently) depressive episodes are common. Some of the drugs and dosages recommended here have not been approved by the FDA for use in bipolar disorder.

The FDA is advising health care professionals not to prescribe valproate sodium (Depacon), valproic acid (Depakene, Stavzor, and generics) or divalproex sodium (Depakote, Depakote ER, and generics) for migraine prevention in pregnant women because a recently published study showed that IQ scores are decreased in children of mothers who took these drugs during pregnancy. The FDA recommends avoiding valproate altogether, if possible, in women of childbearing age.1

VALPROATE — Valproic acid and divalproex sodium dissociate to valproate in the GI tract. Valproate is considered the drug of choice for treatment of primary generalized tonic-clonic seizures. It is one of many drugs used for treatment of bipolar disorder and prevention of migraine.2,3

EFFECTS ON CHILDREN — The recent publication is the third in a series comparing IQ scores in a cohort of children exposed to various antiepileptic drugs throughout pregnancy.4 At 3 years of age, 4.5 years, and now 6 years, IQ scores were 6-11 points lower in children exposed to valproate than in those exposed to carbamazepine, lamotrigine or phenytoin. In addition, valproate taken during pregnancy has the highest demonstrated risk, compared to other antiepileptic drugs, of major congenital malformations, including oral cleft, cardiac, urinary tract and neural tube defects, and most recently, it has been associated with an increased risk of autism.5,6

USE IN MIGRAINE — Beta blockers such as propranolol and timolol and the antiepileptics valproate and topiramate are the drugs generally used for prevention of migraine. There is no evidence that any one is more effective than any other. Because of concerns about possible adverse fetal effects with all of these agents, preventive therapy for migraine is generally not recommended during pregnancy.7

CONCLUSION — Taking valproate during pregnancy can lower the IQ of exposed children and possibly could have other devastating effects. Those risks are certainly not worth taking for prevention of migraine.

1. FDA Drug Safety Communication: Valproate anti-seizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. Available at www.fda.gov/Drugs/DrugSafety/ucm350684.htm. Accessed May 28, 2013.

2. Drugs for psychiatric disorders. Treat Guidel Med Lett 2013; 11:53.

3. SD Silverstein et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012; 78:1337.

4. KJ Meador et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12:244.

5. J Christensen et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309:1696.

6. KJ Meador and DW Loring. Risks of in utero exposure to valproate. JAMA 2013; 309:1730.

7. Drugs for migraine. Treat Guidel Med Lett 2011; 9:7.

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Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) can be used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. When used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of drug is usually based on factors such as ease of use, adverse effects, interactions with other drugs, presence of comorbid conditions and cost.

The FDA has approved ezogabine (ee-ZOE-ga-been; Potiga – GSK/Valeant) for oral adjunctive treatment of partial-onset seizures in adults. Ezogabine is available in Europe as retigabine (Trobalt).

Drugs are not the only treatment for mood disorders. Psychotherapy remains an important component in the management of these disorders, and electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective, poorly tolerated or cannot be used. Some drugs are recommended here for indications that have not been approved by the FDA.

The FDA has approved lacosamide (Vimpat - UCB Pharma) for oral or intravenous (IV) use as add-on therapy in adults with partial-onset seizures.

The FDA has approved a delayed-release capsule formulation of valproic acid (VPA; Stavzor - Noven Therapeutics) for all of the indications for which divalproex sodium (Depakote, and others; Depakote ER) is approved: monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures, and adjunctive therapy in patients with multiple seizure types that include absence seizures; acute treatment of manic episodes associated with bipolar disorder; and prophylaxis of migraine headaches. In addition, valproate (valproic acid or divalproex sodium) is considered a drug of choice for treatment of other types of seizures including generalized tonic-clonic, myotonic and atonic seizures.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy. Studies suggest that when used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of a drug is usually based on factors such as ease of use, adverse effects and cost.

Some drugs for treatment of migraine attacks are listed in table 2 on page 18. Drugs for prevention of migraine are listed in table 3 on page 20. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) is used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy.

Patients with frequent, severe or disabling migraine headaches may benefit from taking a drug to prevent the attacks. Beta-blockers traditionally have been the prophylactic treatment of choice, but in recent years some antiepileptic drugs such as valproate (Depakote, and others) and topiramate (Topamax) have also been used for this indication. Valproate was approved by the FDA for such use in 1996. Now topiramate has also been approved.

Drugs for treatment of migraine attacks are listed in the table on page 64. All of the oral drugs are most effective if taken early in an attack when the pain is mild (H Christoph-Diener et al, Neurology 2004; 63:520). Drugs for prevention of migraine are listed in the table on page 65. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

The number of drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only for adjunctive therapy are probably also effective as monotherapy. Many of the drugs used to treat epilepsy interact with each other (see table beginning on page 63) and with other drugs; for interactions with other drugs, see The Medical Letter Handbook of Adverse Drug Interactions, 2003. The treatment of status epilepticus is not included here.

Anticonvulsants are now widely used for treatment of psychiatric illnesses, particularly bipolar disorder. Lithium is the standard drug for treatment of bipolar disorder, but it can cause severe toxicity, serum concentrations must be monitored, and it is not effective in some patients.

Three new 5-HT1 receptors agonissts ('triptans') have been marketed recently for treatment of migraine. Some drugs for prevention of migraine are listed in the table on page 99. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

The number of new drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 1997.