Pregnancy

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

• Infants whose mothers took methylphenidate 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, methylphenidate should generally be discontinued before anticipated pregnancies

Breast Feeding

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

✽ Recommended either to discontinue drug or bottle feed

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

METHYLPHENIDATE (D,L): THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Established long-term efficacy as a first-line treatment for ADHD

• Multiple options for drug delivery, peak actions, and duration of action

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

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

• Some patients respond to or tolerate methylphenidate better than amphetamine and vice versa

• Taking with food may delay peak actions of oral formulations 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

• Older sustained-release technologies for methylphenidate were not significant advances over immediate-release methylphenidate because they did not eliminate the need for lunchtime dosing or allow once daily administration

✽ Newer sustained-release technologies are truly once a day dosing systems

✽ Metadate CD and Ritalin LA are somewhat similar to each other, both with an early peak and duration of action of about 8 hours

✽ Concerta has less of an early peak but a longer duration of action (up to 12 hours)

✽ Concerta trilayer tablet consists of 3 compartments (2 containing drug, 1 a “push” compartment) and an orifice at the head of the first drug compartment; water fills the push compartment and gradually pushes drug up and out of the tablet through the orifice

✽ Concerta may be preferable for those ADHD patients who work in the evening or do homework up to 12 hours after morning dosing

✽ Metadate CD and Ritalin LA may be preferable for those ADHD patients who lose their appetite for dinner or have insomnia with Concerta

• Some patients may benefit from an occasional addition of 5–10 mg of immediate-release methylphenidate to their daily base of sustained-release methylphenidate

• Transdermal formulation may confer lower abuse potential than oral formulations

• Transdermal formulation may enhance adherence to treatment compared to some oral formulations because it allows once daily application with all day efficacy, has a smoother absorption curve, and allows for daily customization of treatment (i.e., it can be removed early if desired)

• On the other hand, transdermal formulation has slower onset than oral formulations, requires a specific removal time, can cause skin sensitization, can be large depending on dose, and may lead to reduced efficacy if removed prematurely

Suggested Reading

Challman TD, Lipsky JJ. Methylphenidate: its pharmacology and uses. Mayo Clin Proc 2000;75:711–21.

Kimko HC, Cross JT, Abemethy DR. Pharmacokinetics and clinical effectiveness of methylphenidate. Clin Pharmacokinet 1999;37:457–70.

Wolraich ML, Greenhill LL, Pelham W, Swanson J, Wilens T, Palumbo D, Atkins M, McBurnett K, Bukstein O, August G. Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics 2001;108:883–92.

MIANSERIN

MIANSERIN: THERAPEUTICS

Brands

• Lerivon

see index for additional brand names

Generic?

Yes

Class

• Tetracyclic antidepressant

• Noradrenergic agent

Commonly Prescribed for

(bold for FDA approved)

• Depression

• Anxiety

• Insomnia

• Treatment-resistant depression

How the Drug Works

• Blocks alpha 2 adrenergic presynaptic receptor, thereby increasing norepinephrine neurotransmission

• This is a novel mechanism independent of norepinephrine reuptake blockade

• Blocks alpha 2 adrenergic presynaptic receptors but also alpha 1 adrenergic receptors on serotonin neurons, thereby causing little increase in serotonin neurotransmission

• Blocks 5HT2A, 5HT2C, and 5HT3 serotonin receptors

• Blocks H1 histamine receptors