Pregnancy

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

• Infants whose mothers take d,l-amphetamine during pregnancy may experience withdrawal symptoms

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

✽ For ADHD patients, d,l-amphetamine should generally be discontinued before anticipated pregnancies

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

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

AMPHETAMINE (D,L): THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• May work in ADHD patients unresponsive to other stimulants, including pure d-amphetamine sulfate

• New sustained-release option

Potential Disadvantages

• Patients with current or past substance abuse

• Patients with current or past bipolar disorder or psychosis

Primary Target Symptoms

• Concentration, attention span

• Motor hyperactivity

• Impulsiveness

• Physical and mental fatigue

• Daytime sleepiness

• Depression

Pearls

✽ May be useful for treatment of depressive symptoms in medically ill elderly patients

✽ May be useful for treatment of post-stroke depression

✽ A classical augmentation strategy for treatment-refractory depression

✽ Specifically, may be useful for treatment of cognitive dysfunction and fatigue as residual symptoms of major depressive disorder unresponsive to multiple prior treatments

✽ May also be useful for the treatment of cognitive impairment, depressive symptoms, and severe fatigue in patients with HIV infection and in cancer patients

• Can be used to potentiate opioid analgesia and reduce sedation, particularly in end-of-life management

✽ Despite warnings, can be a useful adjunct to MAOIs for heroic treatment of highly refractory mood disorders when monitored with vigilance

✽ Can reverse sexual dysfunction caused by psychiatric illness and by some drugs such as SSRIs, including decreased libido, erectile dysfunction, delayed ejaculation, and anorgasmia

• Atypical antipsychotics may be useful in treating stimulant or psychotic consequences of overdose

• Taking with food may delay peak actions for 2–3 hours

• Half-life and duration of clinical action tend to be shorter in younger children

• Drug abuse may actually be lower in ADHD adolescents treated with stimulants than in ADHD adolescents who are not treated

• Some patients respond to or tolerate d,l-amphetamine better than methylphenidate and vice versa

✽ Adderall and Adderall XR are a mixture of d-amphetamine and l-amphetamine salts in the ratio of 3:1

✽ Specifically, Adderall and Adderall XR combine 1 part dextro-amphetamine saccharate, 1 part dextro-amphetamine sulfate, 1 part d,l-amphetamine aspartate, and 1 part d,l-amphetamine sulfate

✽ This mixture of salts may have a different pharmacologic profile, including mechanism of therapeutic action and duration of action, compared to pure dextro-amphetamine, which is given as the sulfate salt

✽ Specifically, d-amphetamine may have more profound action on dopamine than norepinephrine whereas l-amphetamine may have a more balanced action on both dopamine and norepinephrine

✽ Theoretically, this could lead to relatively more noradrenergic actions of the Adderall mixture of amphetamine salts than that of pure dextro-amphetamine sulfate, but this is unproven and of no clear clinical significance

• Nevertheless, some patients may respond to or tolerate Adderall/Adderall XR differently than they do pure dextro-amphetamine sulfate

• Adderall XR capsules also contain 2 types of drug-containing beads designed to give a double-pulsed delivery of amphetamines to prolong their release

Suggested Reading

Fry JM. Treatment modalities for narcolepsy. Neurology 1998;50(2 Suppl 1):S43–8.

Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002;41 (2 Suppl):S26–49.

Jadad AR, Boyle M, Cunningham C, Kim M, Schachar R. Treatment of attention-deficit/hyperactivity disorder. Evid Rep Technol Assess (Summ) 1999;(11):i–viii,1–341.

Stiefel G, Besag FM. Cardiovascular effects of methylphenidate, amphetamines, and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf 2010;33(10):821–42.

Vinson DC. Therapy for attention-deficit hyperactivity disorder. Arch Fam Med 1994;3:445–51.

Wender PH, Wolf LE, Wasserstein J. Adults with ADHD. An overview. Ann NY Acad Sci 2001;931:1–16.

ARIPIPRAZOLE

ARIPIPRAZOLE: THERAPEUTICS

Brands

• Abilify

• Abilify Maintena

see index for additional brand names

Generic?

Not in U.S., Europe, or Japan

Class

• Dopamine partial agonist (dopamine stabilizer, atypical antipsychotic, third generation antipsychotic; sometimes included as a second generation antipsychotic; also a mood stabilizer)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia (ages 13 and older) (Abilify, Abilify Maintena)

• Maintaining stability in schizophrenia

• Acute mania/mixed mania (ages 10 and older; monotherapy and adjunct)

• Bipolar maintenance (monotherapy and adjunct)

• Depression (adjunct)

• Autism-related irritability in children ages 6 to 17

• Acute agitation associated with schizophrenia or bipolar disorder (IM)

• Bipolar depression

• Other psychotic disorders

• Behavioral disturbances in dementias

• Behavioral disturbances in children and adolescents

• Disorders associated with problems with impulse control