Other Warnings/Precautions

• Quinidine can cause immune-mediated thrombocytopenia that can be severe or fatal; dextromethorphan/quinidine should be discontinued immediately if thrombocytopenia occurs unless it is clearly not drug-related, and should not be restarted in sensitized patients

• Quinidine has been associated with a lupus-like syndrome involving polyarthritis

• ECG should be monitored if patient must take an agent that prolongs QT interval or that inhibits CYP450 3A4

• Anticholinergic effects of quinidine may lead to worsening in myasthenia gravis and other sensitive conditions

Do Not Use

• If patient is taking an MAO inhibitor

• If patient is taking another medication containing quinidine, quinine, or mefloquine

• If patient has a history of quinidine, quinine, or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reaction

• If patient has prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure

• If patient has complete atrioventricular block (AV) without implanted pacemaker, or patients at high risk of complete AV block

• If patient is taking a drug that prolongs QT interval and is metabolized by CYP450 2D6 (e.g., thioridazine, pimozide)

• If there is a proven allergy to dextromethorphan or quinidine

DEXTROMETHORPHAN: SPECIAL POPULATIONS

Renal Impairment

• Dose adjustment not necessary in patients with mild to moderate impairment

Hepatic Impairment

• Dose adjustment not necessary in patients with mild to moderate impairment

Cardiac Impairment

• Contraindicated in patients with prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, and heart failure

• Monitor ECG in patients with left ventricular hypertrophy or left ventricular dysfunction

Elderly

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy have not been established

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and strongly consider informing parents or guardian of this risk so they can help observe child or adolescent patients

Pregnancy

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

Breast Feeding

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

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

DEXTROMETHORPHAN: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• No other approved agent for PBA

Potential Disadvantages

• CYP450 2D6 poor metabolizers may require dose reduction

• In patients with past substance abuse, especially of dextromethorphan, ketamine, or PCP

Primary Target Symptoms

• Uncontrollable crying

• Uncontrollable laughter

Pearls

• Quinidine is intended to increase the actions of dextromethorphan by inhibiting its metabolism by CYP450 2D6; therefore, poor metabolizers of CYP450 2D6 may not benefit as much from this treatment while still experiencing adverse effects associated with quinidine

• Affective instability in Alzheimer disease may be treatable with this agent, including agitation, allowing antipsychotics to be avoided in this population

• Some men express emotional lability as laughter and anger rather than laughter and crying

• Affective instability in PTSD and in mild traumatic brain injury may be improved by dextromethorphan/quinidine

• Similar binding properties to ketamine suggest possible efficacy in both treatment-resistant depression and chronic pain

Suggested Reading

Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004;63(8):1364–70.

Garnock-Jones KP. Dextromethorphan/quinidine in pseudobulbar affect. CNS Drugs 2011;25(5):435–45.

The Medical Letter Inc. Dextromethorphan/quinidine (neudexta) for pseudobulbar affect. Med Lett Drugs Ther 2011;53(1366):46–7.

Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol 2010;68(5):693–702.

DIAZEPAM

DIAZEPAM: THERAPEUTICS

Brands

• Valium

• Diastat

see index for additional brand names

Generic?

Yes (not Diastat)

Class

• Benzodiazepine (anxiolytic, muscle relaxant, anticonvulsant)

Commonly Prescribed for

(bold for FDA approved)

• Anxiety disorder

• Symptoms of anxiety (short-term)

• Acute agitation, tremor, impending or acute delirium tremens and hallucinosis in acute alcohol withdrawal

• Skeletal muscle spasm due to reflex spasm to local pathology

• Spasticity caused by upper motor neuron disorder

• Athetosis

• Stiffman syndrome

• Convulsive disorder (adjunctive)

• Anxiety during endoscopic procedures (adjunctive) (injection only)

• Pre-operative anxiety (injection only)

• Anxiety relief prior to cardioversion (intravenous)

• Initial treatment of status epilepticus (injection only)

• Insomnia

• Catatonia