Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

✽ Oxcarbazepine is structurally similar to carbamazepine, which is thought to be teratogenic in humans

✽ Use during first trimester may raise risk of neural tube defects (e.g., spina bifida) or other congenital anomalies

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

✽ If drug is continued, perform tests to detect birth defects

✽ If drug is continued, start on folate 1 mg/day to reduce risk of neural tube defects

• Antiepileptic Drug Pregnancy Registry: (888) 233–2334

• Taper drug if discontinuing

✽ For bipolar patients, oxcarbazepine should generally be discontinued before anticipated pregnancies

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

• Recurrent bipolar illness during pregnancy can be quite disruptive

✽ For bipolar patients, given the risk of relapse in the postpartum period, some form of mood stabilizer treatment may need to be restarted immediately after delivery if patient is unmedicated during pregnancy

✽ Atypical antipsychotics may be preferable to lithium or anticonvulsants such as oxcarbazepine if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant shows signs of irritability or sedation, drug may need to be discontinued

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

✽ Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer than oxcarbazepine during the postpartum period when breast feeding

OXCARBAZEPINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Treatment-resistant bipolar and psychotic disorders

• Those unable to tolerate carbamazepine but who respond to carbamazepine

Potential Disadvantages

• Patients at risk for hyponatremia

Primary Target Symptoms

• Incidence of seizures

• Severity of seizures

• Unstable mood, especially mania

Pearls

✽ Some evidence of effectiveness in treating acute mania; included in American Psychiatric Association’s bipolar treatment guidelines as an option for acute treatment and maintenance treatment of bipolar disorder

• Some evidence of effectiveness as adjunctive treatment in schizophrenia and schizoaffective disorders

• Oxcarbazepine is the 10-keto analog of carbamazepine, but not a metabolite of carbamazepine

• Less well investigated in bipolar disorder than carbamazepine

✽ Oxcarbazepine seems to have the same mechanism of therapeutic action as carbamazepine but with fewer side effects

✽ Specifically, risk of leukopenia, aplastic anemia, agranulocytosis, elevated liver enzymes, or Stevens-Johnson syndrome and serious rash associated with carbamazepine does not seem to be associated with oxcarbazepine

• Skin rash reactions to carbamazepine may resolve in 75% of patients with epilepsy when switched to oxcarbazepine; thus, 25% of patients who experience rash with carbamazepine may also experience it with oxcarbazepine

• Oxcarbazepine has much less prominent actions on CYP 450 enzyme systems than carbamazepine, and thus fewer drug-drug interactions

• Specifically, oxcarbazepine and its active metabolite, the monohydroxy derivative (MHD), cause less enzyme induction of CYP450 3A4 than the structurally related carbamazepine

• The active metabolite MHD, also called licarbazepine, is a racemic mixture of 80% S-MHD (active) and 20% R-MHD (inactive)

• R, S-licarbazepine is also in clinical development as a novel mood stabilizer

• The active S enantiomer of licarbazepine is another related compound in development as yet another novel mood stabilizer

✽ Most significant risk of oxcarbazepine may be clinically significant hyponatremia (sodium level <125 m mol/L), most likely occurring within the first 3 months of treatment, and occurring in 2–3% of patients

• Unknown if this risk is higher than for carbamazepine

✽ Since SSRIs can sometimes also reduce sodium due to SIADH (syndrome of inappropriate antidiuretic hormone production), patients treated with combinations of oxcarbazepine and SSRIs should be carefully monitored, especially in the early stages of treatment

• By analogy with carbamazepine, could theoretically be useful in chronic neuropathic pain

Suggested Reading

Beydoun A. Safety and efficacy of oxcarbazepine: results of randomized, double-blind trials. Pharmacotherapy 2000;20(8 Pt 2):152S–158S.

Centorrino F, Albert MJ, Berry JM, Kelleher JP, Fellman V, Line G, Koukopoulos AE, Kidwell JE, Fogarty KV, Baldessarini RJ. Oxcarbazepine: clinical experience with hospitalized psychiatric patients. Bipolar Disord 2003;5:370–4.

Dietrich DE, Kropp S, Emrich HM. Oxcarbazepine in affective and schizoaffective disorders. Pharmacopsychiatry 2001;34:242–50.

Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy 2001;21:904–19.

Vasudev A, Macritchie K, Vasudev K, et al. Oxcarbazepine for acute affective episodes in bipolar disorder. Cochrane Database Syst Rev 2011;7(12):CD004857.

PALIPERIDONE

PALIPERIDONE: THERAPEUTICS

Brands

• INVEGA

• INVEGA SUSTENNA

see index for additional brand names

Generic?

No

Class

• Atypical antipsychotic (serotonin-dopamine antagonist; second generation antipsychotics; also a mood stabilizer)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia (ages 12 and older)

• Maintaining response in schizophrenia

• Schizoaffective disorder (INVEGA)

• Other psychotic disorders

• Bipolar disorder

• Behavioral disturbances in dementia

• Behavioral disturbances in children and adolescents

• Disorders associated with problems with impulse control

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

✽ Serotonin 7 antagonist properties may contribute to antidepressant actions

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients may require up to 16–20 weeks to show a good response, especially on cognitive symptoms

If It Works

• Most often reduces positive symptoms but does not eliminate them

• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia

• Most schizophrenia patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third

• Perhaps 5–15% of schizophrenia patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year

• Such patients are considered superresponders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships

• Continue treatment until reaching a plateau of improvement

• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis

• For second and subsequent episodes of psychosis, treatment may need to be indefinite

• Even for first episodes of psychosis, it may be preferable to continue treatment