Other Warnings/Precautions

• Patients with history of drug abuse should be monitored closely

• Armodafinil may cause CNS effects similar to those caused by other CNS agents (e.g., changes in mood and, theoretically, activation of psychosis, mania, or suicidal ideation)

• Armodafinil should be used in patients with sleep disorders that have been completely evaluated for narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift work sleep disorder

• In OSAHS patients for whom continuous positive airway pressure (CPAP) is the treatment of choice, a maximal effort to treat first with CPAP should be made prior to initiating armodafinil, and then CPAP should be continued after initiating armodafinil

• The effectiveness of steroidal contraceptives may be reduced when used with armodafinil and for 1 month after discontinuation of armodafinil

• Armodafinil is not a replacement for sleep

Do Not Use

• If there is a proven allergy to armodafinil or modafinil

ARMODAFINIL: SPECIAL POPULATIONS

Renal Impairment

• Use with caution

Hepatic Impairment

• Reduce dose in severely impaired patients

Cardiac Impairment

• Use with caution

• Not recommended for use in patients with a history of left ventricular hypertrophy, ischemic EKG changes, chest pain, arrhythmias, or recent myocardial infarction

Elderly

• Limited experience in patients over 65

• Clearance of armodafinil may be reduced in elderly patients

Children and Adolescents

• Safety and efficacy have not been established

• Can be used cautiously by experts for children and adolescents

Pregnancy

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

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

✽ Generally, armodafinil should be discontinued prior to anticipated pregnancies

Breast Feeding

• Unknown if armodafinil is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

✽ Recommended either to discontinue drug or bottle feed

ARMODAFINIL: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Selective for areas of brain involved in sleep/wake promotion

• Less activating and less abuse potential than stimulants

Potential Disadvantages

• May not work as well as stimulants in some patients

Primary Target Symptoms

• Sleepiness

• Concentration

• Physical and mental fatigue

Pearls

• Armodafinil is the longer-lasting R enantiomer of racemic modafinil

• Armodafinil maintains high plasma concentrations later in the day than does modafinil on a mg to mg basis, which could theoretically result in improved wakefulness throughout the day with armodafinil compared to modafinil

✽ Armodafinil is not a replacement for sleep

✽ The treatment for sleep deprivation is sleep, not armodafinil

• Controlled studies suggest armodafinil improves attention in OSAHS and shift work sleep disorder, but controlled studies of attention have not been performed in attention deficit hyperactivity disorder (ADHD) or major depressive disorder (MDD)

• Controlled studies of racemic modafinil in ADHD suggest improvement in attention

✽ May be useful to treat fatigue in patients with depression as well as other disorders, such as multiple sclerosis, myotonic dystrophy, HIV/AIDS

• May be useful in treating sleepiness associated with opioid analgesia, particularly in end-of-life management

• Subjective sensation associated with armodafinil is usually one of normal wakefulness, not of stimulation, although jitteriness can rarely occur

✽ Compared to traditional stimulants, armodafinil has a novel mechanism of action, novel therapeutic uses, and less abuse potential

• Alpha 1 antagonists such as prazosin may block the therapeutic actions of armodafinil

• Some controlled trials suggest efficacy in bipolar depression as an adjunct to atypical antipsychotics

Suggested Reading

Darwish M, Kirby M, Hellriegel ET, Robertson Jr P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29(9):613–23.

Darwish M, Kirby M, Hellriegel ET, Robertson Jr P. Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4, and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1): 61–74.

Garnock-Jones KP, Dhillon S, Scott LJ. Armodafinil. CNS Drugs. 2009;23(9):793–803.

ASENAPINE

ASENAPINE: THERAPEUTICS

Brands

• SAPHRIS

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, acute and maintenance

• Acute mania/mixed mania (monotherapy and adjunct to lithium or valproate)

• Other psychotic disorders

• Bipolar maintenance

• Bipolar depression

• Treatment-resistant depression

• 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 2C, serotonin 7, and alpha 2 antagonist properties may contribute to antidepressant actions