The FDA has approved ganaxolone (Ztalmy – Marinus) for oral treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder in patients ≥2 years old. It is the first drug to be approved in the US for this indication.

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.

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.

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy), which was approved by the FDA in 2021 for chronic weight management in adults, has now been approved for chronic weight management in children ≥12 years old with an initial BMI in the ≥95th percentile for age and sex.Semaglutide is also available as Ozempic and Rybelsus for treatment of type 2 diabetes in adults.

Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. The initial recommendation for any weight loss effort is to achieve a 5-10% reduction in weight, which has been associated with a reduction in the risk of developing type 2 diabetes, hypertension, and dyslipidemia. Diet, exercise, and behavior modification are the preferred methods for losing weight, but long-term weight maintenance can be difficult. Several drugs and devices are FDA-approved for weight reduction and maintenance of weight loss.

View the Comparison Table: Some FDA-Approved Drugs for Weight Management

Consumption of alcohol has increased during the COVID-19 pandemic. The Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) defines alcohol use disorder (AUD; previously called alcohol dependence) as meeting ≥2 of the 11 criteria listed in Table 1 in the past year. The lifetime prevalence of AUD in the US population has been estimated to be about 30%. Despite this high prevalence and the associated morbidity, mortality, and costs, only 3 drugs are FDA-approved for treatment of the disorder.

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).

The FDA has approved fenfluramine oral solution (Fintepla – Zogenix) for treatment of seizures in patients ≥2 years old with Dravet syndrome. It is the third drug to be approved for this indication. Stiripentol (Diacomit) and cannabidiol (Epidiolex), a purified product derived from marijuana, were approved earlier.

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, previously approved by the FDA as Ozempic to treat type 2 diabetes and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, has now been approved in a higher dose as Wegovy (Novo Nordisk) for chronic weight management in adults with or without type 2 diabetes who have a body mass index (BMI) ≥30 kg/m² or a BMI ≥27 kg/m² and ≥1 weight-related comorbidity (e.g., hypertension, dyslipidemia). An oral formulation of semaglutide (Rybelsus) has been available since 2019 for treatment of type 2 diabetes, but it is not approved for weight management. Liraglutide (Saxenda), another subcutaneously injected GLP-1 receptor agonist, was approved for chronic weight management in 2015.

In recently published clinical trials, once-weekly subcutaneous injection of the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Ozempic – Novo Nordisk), which is FDA-approved for treatment of type 2 diabetes and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, has reduced body weight significantly in patients with and without type 2 diabetes when given in addition to lifestyle intervention. Liraglutide (Saxenda), another GLP-1 receptor agonist, has been FDA-approved for chronic weight management since 2015.

The FDA has approved stiripentol (Diacomit – Biocodex) for treatment of seizures in patients ≥2 years old with Dravet syndrome who are also taking clobazam (Onfi). Stiripentol, which has been available in Europe, Canada, and Japan for many years, is the second drug to be approved in the US for this indication; cannabidiol oral solution (Epidiolex), a purified marijuana product, was the first.

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.

The FDA has approved eptinezumab-jjmr (Vyepti – Lundbeck), a calcitonin gene-related peptide (CGRP) antagonist administered IV once every 3 months, for migraine prevention in adults. It is the fourth monoclonal antibody to be approved for this indication; erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), which are all given subcutaneously once monthly (fremanezumab can also be given once every 3 months), were approved earlier.

The FDA has approved two subcutaneously injected calcitonin gene-related peptide (CGRP) antagonists, fremanezumab-vfrm (Ajovy – Teva) and galcanezumab-gnlm (Emgality – Lilly), for migraine prevention in adults. Fremanezumab and galcanezumab are the second and third subcutaneously injected monoclonal antibodies that target the CGRP pathway to be approved by the FDA for this indication; erenumab-aooe (Aimovig), which targets the CGRP receptor, was the first.

The FDA has approved cannabidiol oral solution (Epidiolex – Greenwich Biosciences) for treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome in patients ≥2 years old. Cannabidiol (CBD) is a cannabinoid constituent of the marijuana plant (Cannabis sativa). It is the first natural marijuana product to be approved by the FDA for any indication and the first drug to be approved in the US for treatment of Dravet syndrome. Stiripentol (Diacomit), which is not a marijuana product, was also recently approved by the FDA for treatment of Dravet syndrome in combination with clobazam (Onfi) and will be reviewed in a future issue.

The FDA has approved erenumab-aooe (Aimovig – Amgen/Novartis), a once-monthly, subcutaneously-injected, monoclonal antibody against the calcitonin gene-related peptide receptor, for preventive treatment of migraine in adults. It is the first drug in its class to be approved by the FDA.

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

The FDA has approved use of Exablate Neuro (Insightec) for unilateral thalamotomy to treat medication-refractory essential tremor in patients ≥22 years old. Exablate Neuro uses magnetic resonance-guided focused ultrasound (MRgFUS) to create lesions in the ventral intermediate nucleus of the thalamus. MRgFUS is also approved in the US for treatment of uterine fibroids and for pain palliation of bone metastases.

An oral nonopioid analgesic may be sufficient for treatment of mild to moderate migraine without severe nausea or vomiting. A triptan is the drug of choice for treatment of moderate to severe migraine. Use of a triptan early in an attack when pain is still mild to moderate in intensity improves headache response and reduces recurrence rates.

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

The FDA has approved Lomaira (KVK Tech), an 8-mg tablet formulation of phentermine that can be taken up to three times daily before meals, as an adjunct to lifestyle modifications for weight loss. It is only approved for short-term use (a few weeks) in adults with a body mass index (BMI) ≥30 kg/m², or with a BMI ≥27 kg/m² in addition to a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes. Phentermine has been available alone and in combination with topiramate for years.1

Lomaira was approved by the FDA under an abbreviated new drug application (ANDA) and is considered a generic drug. Its approval was based on the results of earlier phentermine trials. No studies are available comparing the efficacy and safety of Lomaira to standard doses of phentermine or to any other drug approved for weight loss.

Like other sympathomimetic amines approved for weight loss, Lomaira is classified as a schedule IV controlled substance. All sympathomimetics can increase heart rate, raise blood pressure, and cause nervousness and insomnia.2 Phentermine is contraindicated for use in patients with cardiovascular disease, hyperthyroidism, glaucoma, or a history of drug abuse, and in pregnant women. It should not be used while taking, and for 14 days after stopping, a monoamine oxidase (MAO) inhibitor because of the risk of hypertensive crisis.

1. Diet, drugs, and surgery for weight loss. Med Lett Drugs Ther 2015; 57:21.
2. SZ Yanovski and JA Yanovski. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014; 311:74.

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Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight, but long-term failure rates are high. Several drugs have been approved by the FDA for weight reduction, but adherence is poor, adverse effects are common, and patients usually regain the lost weight when the drug is stopped. Bariatric surgery can produce substantial weight loss and significantly reduce obesity-related comorbidities; long-term data on its safety are encouraging, but still limited. Guidelines for the management of overweight or obese adults have recently been published.

The FDA has approved a new extended-release capsule formulation of topiramate (Qudexy XR – Upsher Smith), which can be opened and sprinkled on food for patients who have difficulty swallowing tablets or capsules, for treatment of epilepsy. Qudexy XR was marketed as a branded drug in March 2014 and as a generic drug four months later. An earlier extended-release formulation (Trokendi XR) must be swallowed whole.

Trokendi XR is approved for initial monotherapy in patients ≥10 years old with partial-onset seizures or primary generalized tonic-clonic seizures and for adjunctive therapy in patients ≥6 years old with partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome. Qudexy XR has been approved for the same indications, but the indication for adjunctive therapy has been extended to children ≥2 years old. Topiramate has been available for many years in immediate-release formulations (Topamax, and others) for the same indications for patients ≥2 years old. Trokendi XR and Qudexy XR both appear to be bioequivalent to immediate-release formulations of topiramate; whether they are bioequivalent to one another has not been established.

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The FDA has approved a fixed-dose combination of the opioid receptor antagonist naltrexone (ReVia, and others) and the antidepressant and smoking cessation agent bupropion (Wellbutrin SR, Zyban, and others), as Contrave (Orexigen/Takeda) for weight loss. The combination was approved for use as an adjunct to diet and increased physical activity in patients with a body mass index (BMI) ≥30 kg/m² or a BMI ≥27 kg/m² and one or more weight-related comorbidities such as hypertension, diabetes, or dyslipidemia. Naltrexone/bupropion is not a controlled substance.

Perampanel (per am’ pa nel; Fycompa – Eisai), a first-in-class noncompetitive AMPA receptor antagonist, has been approved by the FDA for adjunctive treatment of partial-onset seizures in patients ≥12 years old. New drugs for epilepsy are often initially approved by the FDA as adjunctive treatment for partial seizures.

Treatment of migraine in the emergency department, which may involve use of intravenous drugs, is not discussed here.

The FDA has approved a once-daily extended-release (ER) formulation of the antiepileptic topiramate (Trokendi XR – Supernus) for initial monotherapy in patients ≥10 years old with partial onset seizures or primary generalized tonic-clonic seizures and for adjunctive therapy in patients ≥6 years old with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome. Topiramate has been available for many years as an immediate-release (IR) formulation (Topamax, and generics) for the same indications in patients ≥2 years old

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.

In 2013 the FDA approved one new drug and a new combination of 2 old drugs as adjuncts to lifestyle changes for chronic weight management. Lorcaserin (lor-ca-SER-in; Belviq – Arena/Esai) is a selective serotonin 2C receptor agonist. Qsymia (Vivus) is a fixed-dose combination of the weight-loss drug phentermine and an extended-release (ER) formulation of topiramate. The new products are approved for use in obese patients (body mass index [BMI] of ≥30 kg/m²) and for patients who are overweight (BMI ≥27 kg/m²) and have one weight-related risk factor such as hypertension, dyslipidemia or type 2 diabetes.

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).

Adults with a body mass index (BMI=kg/m²) of 25-<30 are considered overweight; those with a BMI of ≥30 are considered obese.

Drugs for treatment of migraine are listed in Table 2 on page 9. Drugs for prevention of migraine are listed in Table 3 on page 10. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

The FDA has approved injection of onabotulinumtoxinA (Botox – Allergan) for prevention of headaches in adult patients with chronic migraine (≥15 headache days/month for ≥3 months). It is the first drug approved for treatment of this indication. Botox is also FDA-approved for treatment of upper limb spasticity, axillary hyperhidrosis, cervical dystonia, blepharospasm and strabismus, and for cosmetic reduction of wrinkles.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

The FDA has approved vigabatrin (vye gá ba trin; Sabril – Lundbeck) for oral use as add-on therapy for complex partial seizures in adults who are refractory to several antiepileptic drugs and as monotherapy for infantile spasms. Vigabatrin has been available in other countries for many years. Because of its potential for retinal toxicity, it will be available in the US only through a restricted distribution program called SHARE (Support, Help and Resources for Epilepsy). Prescribers and pharmacists distributing the drug must register, and patients must undergo visual field testing.

The equivalence of generic drugs to their brand-name precursors continues to be controversial. The last Medical Letter review of this subject (2002) concluded that well-documented therapeutic inequivalence between brand-name and FDA-approved generic drugs had not been reported. Is that still true? New data have become available for some drugs.

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

Rufinamide (Banzel - Eisai), a triazole derivative structurally unrelated to other marketed antiepileptic drugs (AEDs), has been approved by the FDA for treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥4 years old.

Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. The greater the number of office visits and the longer the counseling time, the higher the smoking cessation rates have been.

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.

Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight but are associated with high long-term failure rates. Drugs may help some patients, but all currently available drugs for weight reduction have drawbacks. Gastric surgery can produce marked weight loss in the severely obese, but long-term data on safety are limited.

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.

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.

Acamprosate calcium (Campral - Forest) is now being marketed for oral use to maintain abstinence from alcohol. It has been used in France and other countries since 1989.

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.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

The latest definitions of overweight and obesity are based on body mass index (BMI). The BMI is calculated by dividing the weight in kilograms by the square of the height in meters (kg/m²). More than half of American adults are considered overweight with a BMI of ≥25, and about one third are obese with a BMI of ≥30. All ages seem to be affected; the proportion of children and adolescents who are overweight has more than doubled in the past 25 years. There is no lack of effort to treat obesity: drugs, diets and programs to change lifestyle are the basis for a large and flourishing industry. The frequent failure of diet and drug treatment sometimes leads to recommendations for surgery, usually restricted to those with a BMI ≥40.

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.

Zonisamide (Zonegran - Elan Pharma), a sulfonamide chemically unrelated to other antiepileptic drugs, has been approved by the FDA for adjunctive use in adults with partial seizures. Zonisamide has been available in Japan for more than 10 years.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Non-opioids can be given concurrently with opioids for an additive analgesic effect.

Oxcarbazepine, which is chemically similar to carbamazepine, and levetiracetam, a pyrrolidine acetamide chemically unrelated to other antiepileptic drugs, are the sixth and seventh drugs approved by the US Food and Drug Administration in the last five years for oral use in partial seizures.

Topiramate (Topamax - Ortho-McNeil) has been approved by the US Food and Drug Administration (FDA) for oral use as an adjunct to other drugs in adult patients with partial seizures. Since this diagnostic category includes the largest number of patients with refractory epilepsy, new drugs with antiepileptic activity are usually tried first for this indication. Topiramate (toe pyre' a mate) is a structurally unique agent chemically related to the D-enantiomer of fructose.