Other Warnings/Precautions

• Patients with history of drug abuse should be monitored closely

• Modafinil 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)

• Modafinil 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 modafinil, and then CPAP should be continued after initiating modafinil

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

• Modafinil is not a replacement for sleep

Do Not Use

• If patient has severe hypertension

• If patient has cardiac arrhythmias

• If there is a proven allergy to modafinil

MODAFINIL: SPECIAL POPULATIONS

Renal Impairment

• Use with caution; dose reduction is recommended

Hepatic Impairment

• Reduce dose by half 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 modafinil may be reduced in elderly patients

Children and Adolescents

• Safety and efficacy not established under age 16

• 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]

• Animal studies were conducted at doses lower than necessary to elucidate the effects of modafinil on the developing fetus

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

✽ Generally, modafinil should be discontinued prior to anticipated pregnancies

Breast Feeding

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

✽ Recommended either to discontinue drug or bottle feed

MODAFINIL: 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

✽ Anecdotal usefulness for jet lag short-term (off label)

✽ Modafinil is not a replacement for sleep

✽ The treatment for sleep deprivation is sleep, not modafinil

• Controlled studies suggest modafinil improves attention in OSAHS, shift work sleep disorder, and ADHD (both children and adults), but controlled studies of attention have not been performed in major depressive disorder

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

• In depression, modafinil’s actions on fatigue appear to be independent of actions (if any) on mood

• In depression, modafinil’s actions on sleepiness also appear to be independent of actions (if any) on mood but may be linked to actions on fatigue or on global functioning

• Several controlled studies in depression show improvement in sleepiness or global functioning, especially for depressed patients with sleepiness and fatigue

• May be useful adjunct to mood stabilizers for bipolar depression

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

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

• Anecdotally, some patients may experience wearing off of efficacy over time, especially for off-label uses, with restoration of efficacy after a drug holiday; such wearing off is less likely with intermittent dosing

✽ Compared to stimulants, modafinil has a novel mechanism of action, novel therapeutic uses, and less abuse potential, but is often inaccurately classified as a stimulant

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

• The active R-enantiomer of modafinil, called armodafinil, is also available

Suggested Reading

Batejat DM, Lagarde DP. Naps and modafinil as countermeasures for the effects of sleep deprivation on cognitive performance. Aviat Space Environ Med 1999;70:493–8.

Bourdon L, Jacobs I, Bateman WA, Vallerand AL. Effect of modafinil on heat production and regulation of body temperatures in cold-exposed humans. Aviat Space Environ Med 1994;65:999–1004.

Cox JM, Pappagallo M. Modafinil: a gift to portmanteau. Am J Hosp Palliat Care 2001;18:408–10.

Jasinski DR, Koyacevic-Ristanovic. Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy. Clin Neuropharmacol 2000;23:149–56.

Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs 2008;68(13):1803–39.

Wesensten NJ, Belenky G, Kautz MA, Thorne DR, Reichardt RM, Balkin TJ. Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Psychopharmacology (Berl) 2002;159:238–47.

MOLINDONE

MOLINDONE: THERAPEUTICS

Brands

• Moban

see index for additional brand names

Generic?

Yes

Class

• Conventional antipsychotic (neuroleptic, dopamine 2 antagonist)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia (no longer available in the U.S.)

• Other psychotic disorders

• Bipolar disorder

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

How Long Until It Works

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

If It Works

• Most often reduces positive symptoms in schizophrenia but does not eliminate them

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

• Continue treatment in schizophrenia until reaching a plateau of improvement

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

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

• Reduces symptoms of acute psychotic mania but not proven as a mood stabilizer or as an effective maintenance treatment in bipolar disorder

• After reducing acute psychotic symptoms in mania, switch to a mood stabilizer and/or an atypical antipsychotic for mood stabilization and maintenance