Pharmacokinetics

• Elimination half-life 3–21 hours

• No active metabolites

Drug Interactions

• Increased depressive effects when taken with other CNS depressants

Other Warnings/Precautions

• Dosage changes should be made in collaboration with prescriber

• Use with caution in patients with pulmonary disease; rare reports of death after initiation of benzodiazepines in patients with severe pulmonary impairment

• History of drug or alcohol abuse often creates greater risk for dependency

• Some depressed patients may experience a worsening of suicidal ideation

• Some patients may exhibit abnormal thinking or behavioral changes similar to those caused by other CNS depressants (i.e., either depressant actions or disinhibiting actions)

Do Not Use

• If patient has angle-closure glaucoma

• If there is a proven allergy to oxazepam or any benzodiazepine

OXAZEPAM: SPECIAL POPULATIONS

Renal Impairment

• Use with caution; oxazepam levels may be increased

Hepatic Impairment

• Use with caution; oxazepam levels may be increased

• Because of its short half-life and inactive metabolites, oxazepam may be a preferred benzodiazepine in some patients with liver disease

Cardiac Impairment

• Benzodiazepines have been used to treat anxiety associated with acute myocardial infarction

Elderly

• Initial 30 mg in 3 divided doses; can be increased to 30–60 mg/day in 3–4 divided doses

Children and Adolescents

• Safety and efficacy not established under age 6

• No clear dosing guidelines for children ages 6–12

• Long-term effects of oxazepam in children/adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Risk Category D [positive evidence of risk to human fetus; potential benefits may still justify its use during pregnancy]

• Possible increased risk of birth defects when benzodiazepines taken during pregnancy

• Because of the potential risks, oxazepam is not generally recommended as treatment for anxiety during pregnancy, especially during the first trimester

• Drug should be tapered if discontinued

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• Effects on infant have been observed and include feeding difficulties, sedation, and weight loss

OXAZEPAM: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Rapid onset of action

Potential Disadvantages

• Euphoria may lead to abuse

• Abuse especially risky in past or present substance abusers

Primary Target Symptoms

• Panic attacks

• Anxiety

• Agitation

Pearls

• Can be a very useful adjunct to SSRIs and SNRIs in the treatment of numerous anxiety disorders

• Not effective for treating psychosis as a monotherapy, but can be used as an adjunct to antipsychotics

• Not effective for treating bipolar disorder as a monotherapy, but can be used as an adjunct to mood stabilizers and antipsychotics

✽ Because of its short half-life and inactive metabolites, oxazepam may be preferred over some benzodiazepines for patients with liver disease

• Oxazepam may be preferred over some other benzodiazepines for the treatment of delirium

• Can both cause and treat depression in different patients

• When using to treat insomnia, remember that insomnia may be a symptom of some other primary disorder itself, and thus warrant evaluation for comorbid psychiatric and/or medical conditions

• Though not systematically studied, benzodiazepines have been used effectively to treat catatonia and are the initial recommended treatment

Suggested Reading

Ayd FJ Jr. Oxazepam: update 1989. Int Clin Psychopharmacol 1990;5:1–15.

Garattini S. Biochemical and pharmacological properties of oxazepam. Acta Psychiatr Scand Suppl 1978;274:9–18.

Greenblatt DJ. Clinical pharmacokinetics of oxazepam and lorazepam. Clin Pharmacokinet 1981;6:89–105.

OXCARBAZEPINE

OXCARBAZEPINE: THERAPEUTICS

Brands

• Trileptal

see index for additional brand names

Generic?

Yes

Class

• Anticonvulsant, voltage-sensitive sodium channel antagonist

Commonly Prescribed for

(bold for FDA approved)

• Partial seizures in adults with epilepsy (monotherapy or adjunctive)

• Partial seizures in children ages 4–16 with epilepsy (monotherapy or adjunctive)

• Bipolar disorder

How the Drug Works

✽ Acts as a use-dependent blocker of voltage-sensitive sodium channels

✽ Interacts with the open channel conformation of voltage-sensitive sodium channels

✽ Interacts at a specific site of the alpha pore-forming subunit of voltage-sensitive sodium channels

• Inhibits release of glutamate

How Long Until It Works

• For acute mania, effects should occur within a few weeks

• May take several weeks to months to optimize an effect on mood stabilization

• Should reduce seizures by 2 weeks

If It Works

• The goal of treatment is complete remission of symptoms (e.g., seizures, mania)

• Continue treatment until all symptoms are gone or until improvement is stable and then continue treating indefinitely as long as improvement persists

• Continue treatment indefinitely to avoid recurrence of mania and seizures

If It Doesn’t Work (for bipolar disorder)

✽ Many patients have only a partial response where some symptoms are improved but others persist or continue to wax and wane without stabilization of mood

• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory

• Consider increasing dose, switching to another agent, or adding an appropriate augmenting agent

• Consider adding psychotherapy

• For bipolar disorder, consider the presence of noncompliance and counsel patient

• Switch to another mood stabilizer with fewer side effects

• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)

Best Augmenting Combos for Partial Response or Treatment Resistance

• Oxcarbazepine is itself a second-line augmenting agent for numerous other anticonvulsants, lithium, and atypical antipsychotics in treating bipolar disorder, although its use in bipolar disorder is not yet well studied

• Oxcarbazepine may be a second- or third-line augmenting agent for antipsychotics in treating schizophrenia, although its use in schizophrenia is also not yet well studied

Tests

• Consider monitoring sodium levels because of possibility of hyponatremia, especially during the first 3 months

OXCARBAZEPINE: SIDE EFFECTS

How Drug Causes Side Effects

• CNS side effects theoretically due to excessive actions at voltage-sensitive sodium channels

Notable Side Effects

✽ Sedation, dizziness, headache, ataxia, nystagmus, abnormal gait, confusion, nervousness, fatigue

✽ Nausea, vomiting, abdominal pain, dyspepsia

• Diplopia, vertigo, abnormal vision

✽ Rash

Life-Threatening or Dangerous Side Effects

• Hyponatremia

• Rare activation of suicidal ideation and behavior (suicidality)

Weight Gain

• Occurs in significant minority

• Some patients experience increased appetite

Sedation

• Occurs in significant minority

• Dose-related

• Less than carbamazepine

• More when combined with other anticonvulsants

• Can wear off with time, but may not wear off at high doses

What to Do About Side Effects

• Wait

• Wait

• Wait

• Switch to another agent

Best Augmenting Agents for Side Effects

• Many side effects cannot be improved with an augmenting agent

OXCARBAZEPINE: DOSING AND USE

Usual Dosage Range

• 1,200–2,400 mg/day

Dosage Forms

• Tablet 150 mg, 300 mg, 600 mg

• Liquid 300 mg/5 mL

How to Dose

• Monotherapy for seizures or bipolar disorder: initial 600 mg/day in 2 doses; increase every 3 days by 300 mg/day; maximum dose generally 2,400 mg/day

• Adjunctive: initial 600 mg/day in 2 doses; each week can increase by 600 mg/day; recommended dose 1,200 mg/day; maximum dose generally 2,400 mg/day

• When converting from adjunctive to monotherapy in the treatment of epilepsy, titrate concomitant drug down over 3–6 weeks while titrating oxcarbazepine up over 2–4 weeks, with an initial daily oxcarbazepine dose of 600 mg divided in 2 doses