The treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. New US guidelines for the management of atrial fibrillation have recently been published.

The majority of patients with insomnia do not have a predisposing psychiatric disease. Rather, untreated insomnia may be a risk factor for development of psychiatric problems such as depression or anxiety.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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A reader expressed disappointment that our recent listing of “Some Warfarin Drug Interactions”1 did not include acetaminophen. Perhaps it should have. Acetaminophen can increase the anticoagulant effect of warfarin, particularly with continued use, but it does so inconsistently. The mechanism of this interaction has not been established, but may be related to an acetaminophen metabolite inhibiting vitamin K-epoxide reductase, the target for warfarin’s anticoagulant effect.2

Patient susceptibility varies, possibly on a genetic basis; occasional use of acetaminophen generally has little or no effect on the international normalized ratio (INR) in patients on chronic warfarin therapy, but in some, even a few grams of the drug may cause a dramatic increase in INR. One study in healthy subjects found no effect of acetaminophen 4 g per day for 2 weeks, while another study in patients with the same acetaminophen dose for the same period of time found a moderate increase in INR.3,4 It might be prudent to monitor INR in patients on chronic warfarin therapy more closely than usual when they take more than 2 g per day of acetaminophen for more than a few days.

1. Pharmacogenetic-based dosing of warfarin. Med Lett Drugs Ther 2008; 50:39.
2. HH Thijssen et al. Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thromb Haemost 2004; 92:797.
3. D Kwan et al. The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999; 39:68.
4. I Mahe et al. Paracetamol: A haemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol 2005; 59:371.

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Warfarin sodium (Coumadin, and others) and other coumarin anticoagulants prevent thrombosis, but patient response is highly variable and overanticoagulation can lead to hemorrhage. Genotyping patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism and sensitivity may help clinicians estimate the therapeutic warfarin dose. The FDA has added a note to warfarin labeling recommending lowrange doses for patients with such genetic variations. Commercial tests for these variants are now available and cost about $500 per test.

Many drugs are used to treat insomnia, but for some patients nonpharmacological treatments such as changing sleep habits, relaxation training and cognitive therapy may be more effective and durable than treatment with drugs. Hypnotic drugs are generally FDA-approved only for short-term use, but in practice they often are taken much longer.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Older patients are especially susceptible to drug-induced cognitive impairment. They are more likely to be taking multiple drugs, to have higher blood levels of those drugs because of renal or hepatic dysfunction, and to have pre-existing cognitive problems that make it difficult to detect the role of drugs causing new symptoms or making old ones worse.

Superseded by Drugs of Choice Handbook
Many drugs are used to treat insomnia, but for some patients nonpharmacological treatments such as changing sleep habits, relaxation training and cognitive therapy may be more effective than drugs.

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

Superseded by Drugs of Choice Handbook
Insomnia is a commom complaint, particularly among the elderly. Many drugs are approved by the US Food and Drug Administration (FDA) for treatment of insomnia, including five benzodiazepines and zolpidem (Ambien), a non-benzodiazepine that binds to benzodiazepine receptors in the brain. Some drugs marketed for other indications, such as antihistamines, antidepressants and antipsychotics, are also used as hypnotics. For many patients, nonpharmacological treatment of insomnia may be more effective than drugs, especially in the long term (CM Morin et al, Am J Psychiatry, 151:1172, 1994).

Three benzodiazepines and 16 other compounds are marketed in the USA for treatment of insomnia. Many authorities believe that insomnia is overdiagnosed and overtreated (MK Erman, ed, Sleep Disorders, Psychiatr Clin North Am, Volume 10, Dec 1987).