Diagnosis Drift and Its Contribution to Polypharmacy.

Diagnoses of drug-treatable illnesses has drifted to include milder conditions than in the past. Treating them increases the number of drugs given a person, risking polypharmacy, especially in elderly people with multiple conditions. The adverse consequences of polypharmacy are increased costs, confusion when taking drugs, adverse drug events, intermittent adherence with adverse drug discontinuation effects, and unrecognized delayed adverse effects. Deciding what not to treat helps minimize polypharmacy and its consequences.

Approaches to Gradual Dose Reduction of Chronic Off-Label Antipsychotics Used for Behavioral and Psychological Symptoms of Dementia.

OBJECTIVE: Little is known about how to best taper antipsychotics used in patients with dementia. To address this gap, we reviewed published antipsychotic discontinuation trials to summarize what is known about tapering strategies for antipsychotics used with older adults with dementia. We further developed pharmacokinetic-based gradual dose reduction (GDR) protocols based on antipsychotic half-lives. DATA SOURCES: MEDLINE, EMBASE, and International Pharmaceutical Abstracts were searched up to October 2014 to identify intervention studies reporting the behavioral and psychological symptoms of dementia outcomes resulting from discontinued off-label use of antipsychotics in nursing facility populations. Recently published pharmacokinetic reviews and standard pharmacology texts were used to determine antipsychotic drug half-lives for the pharmacokinetic-based GDR protocols. STUDY SELECTION: For the review, studies with an intervention resulting in antipsychotic medication discontinuation or tapering were eligible, including randomized controlled trials and pre- and post-intervention studies. DATA EXTRACTION: When available, we extracted the protocols used for antipsychotic GDR from each study included in the review. DATA SYNTHESIS: We found that clinical trials used different approaches to antipsychotic discontinuation, including abrupt discontinuation, slow tapers (more than two weeks), and mixed strategies based on drug dosage. None of the published trials described an approach based on pharmacokinetic principles. We developed a two-stage GDR protocol for tapering antipsychotic medications based on the log dose-response relationship; each stage was designed to result in a 50% dose reduction prior to discontinuation. This pharmacologically based strategy for patients chronically prescribed antipsychotics resulted in recommendations for slow tapers. CONCLUSION: Our theoretically derived GDR recommendations suggest a different approach than previously published in clinical trials. Further study is needed to evaluate the effect of this approach on patients.

Alzheimer's disease and Down's syndrome: treating two paths to dementia.

Successful therapy of dementia, like any disease, depends upon understanding its pathogenesis. This review contrasts the dominant pathways to dementia which differ in Alzheimer's disease (AD) and in Down's syndrome (DS). Impaired clearance of neurotoxic amyloid beta peptides (Abeta) leads to dementia in AD. In DS over-production of Abeta plays the dominant role in the development of dementia. It follows, therefore, that the therapy of AD and DS should reflect a different balance between the dominant agent that inhibits the synthesis of Abeta in the brain in AD and increase the clearance of Abeta from the cerebrospinal DS.

Early research on renal function and drug action.

Since the 1960s, systematic studies of drug action in renal failure have found many differences between patients with renal failure and those without. Impaired excretion of drugs was known much earlier and was related to glomerular filtration rate. Kunin first tabulated the pharmacokinetics of antimicrobials and dosage recommendations for azotemic patients in 1967. Other effects of renal failure on drug action include increases in some pathways of drug metabolism with decreases in others and no change in the rest. Some changes in specific drug distribution, drug-protein binding, and drug sensitivity have been demonstrated. This knowledge makes the response of an azotemic patient to a specific dose of a specific drug more predictable than before. This predictability makes drug therapy both safer and more effective for azotemic patients.

Drug discontinuation effects are part of the pharmacology of a drug.

Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include ß-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation.

Physicians being deceived.

OBJECTIVE: In several high profile prosecutions of physicians for prescribing opioids, prosecutors claimed that the doctors should have known the individuals were feigning pain solely to obtain the prescriptions. This study was to determine how readily physicians can tell that patients lie. METHODS: A literature search was done for studies of standardized patients used to evaluate physicians' practices. Standardized patients are actors taught to mimic a patient with a specific illness. The papers were then reviewed for the frequency with which the physician correctly identified which office visits were by the standardized (lying) patients. RESULTS: Six studies of practicing physicians using standardized patients reported the frequency with which these actors were identified as the standardized patients. This occurred around 10% of the time. Some real patients were erroneously identified as the actors. CONCLUSION: Deception is difficult to detect. In the current legal climate surrounding prescribing opioids, accepting patients' reports of pain at face value can have significant legal consequences for the doctor. While doctors must make every reasonable effort to confirm the diagnosis and need for opioid therapy, allowance must be made for the fact that conscientious doctors can be deceived.

The risk of action by the Drug Enforcement Administration against physicians prescribing opioids for pain.

OBJECTIVE: Fear of government actions against physicians for prescribing opioids for their chronic pain patients is a cause for undertreatment of pain. This study was conducted to assess the risk of action by the federal Drug Enforcement Administration (DEA). METHODS: The DEA responded to a written request with a list of all DEA arrests in fiscal 2003. The Federal Register was reviewed for all revocations of DEA registrations for 2003 and 2004. RESULTS: There were 47 arrests in 2003 from among 963,385 doctors registered with the DEA and 56 revocations of registration seen in the 2003 and 2004 period. The reasons for these actions included loss of medical license, fraud, substance abuse by prescriber, sex in exchange for prescriptions, and prescribing without seeing patient. For the majority of cases, there was information to believe that a documented doctor-patient relationship with a chronic pain patient did not exist. CONCLUSION: When adequate documentation exists in the medical record, the risk of civil, criminal, or administrative action being taken by the DEA against a physician for prescribing opioids for a chronic pain patient is small.