Is Bipolar Disorder Overdiagnosed?

Source: Zimmerman M, et al. Clin Psychiatry. 2008;69(6):935-940.

It has been suggested that bipolar disorder (BPD) is underdiagnosed, and is hence sometimes regrettably discovered subsequent to unmasking with treatment instituted for presumed unipolar depression. The MIDAS project of Rhode Island (Methods to Improve Diagnostic Assessment and Services) has to-date examined psychiatric diagnostic accuracy and recognition in 2500 patients attending an outpatient psychiatric practice affiliated with an academic medical center.

MIDAS has corroborated that utilization of semistructured interviewing using DSM-IV diagnostic criteria coupled with self-administered questionnaires identifies more cases of BPD than simple clinician interview. Zimmerman et al in this communication investigated whether persons who carried a clinical diagnosis of BPD might have been overdiagnosed; ie, how many persons with a clinical diagnosis of BPD might fail to have their diagnosis confirmed using a semistructured interview and questionnaire.

Structured interviews of 145 persons carrying a clinical BPD diagnosis corroborated the diagnosis in only 45%. Although it is certainly possible that DSM-IV criteria for diagnosis of BPD are too narrow, this degree of discrepancy suggests that overdiagnosis of BPD is common—indeed, it may be more commonplace than BPD underdiagnosis.


One out of Three Prescriptions Are Never Filled

Source: Storm A, et al. J Am Acad Dermatol. 2008;59:27-33.

Clinicians would like to think that once a treatment is suggested and prescription written, the prescription will be filled. For a variety of reasons, that is too often not the case. It is not always easy to reliably track prescription filling, but data from the metropolitan area of Copenhagen, Denmark simplify that through the Danish National Electronic Pharmacy Register. Public Health Insurance in Denmark covers 50% of expenses $90-$215, 75% of expenses $215-$510, and 85% of any additional expenses. Private insurance is available to cover the difference.

The Danish Medicines Agency electronically registers all prescriptions from all physicians and pharmacies in the entire nation, all of which are accessible by treating physicians. The population studied in this communication includes only dermatology patients who received a new prescription for a treatment never previously used.

Among 322 evaluable patients, 30.7% had not filled one or more prescriptions 4 weeks later. Patients who did fill prescriptions generally did so promptly (3 days median). No particular demographic distinguished adherence/nonadherence, although geriatric patients were most adherent, and persons with chronic disorders requiring chronic treatment, like psoriasis, were least adherent. The authors remind us in their closing statements that "treatment failure" may sometimes simply represent unrecognized "failure to be treated."


Skin Cancer Screening in the U.S.

Source: LeBlanc WG, et al. J Am Acad Dermatol. 2008;59:55-63.

In the United States, skin cancer (S-CA) is the most common cancer, and although usually curable, is responsible for over 10,000 deaths annually. Major groups that provide clinical guidelines differ in their recommendations: the ACS (2007) suggested that S-CA examination should occur as part of the cancer-related check-up at the periodic health examination, whereas the USPSTF found insufficient evidence to recommend for or against routine screening for S-CA.

The National Center for Health Statistics conducts an annual, in-person survey of almost 20,000 adults. In 2000 and 2005, subjects were queried about having a head- to-toe skin check for cancer. Over 38,000 adults were interviewed, of whom 69% had seen a healthcare provider in the past year, yet only 8% acknowledged having received a skin examination.

Of the cancer screenings reviewed by national organizations, these data on S-CA are the most bleak. However, they may not be perfectly accurate, as no chart assessment was done to corroborate patient report. A patient who has undergone colonoscopy or colposcopy would be anticipated to accurately recollect whether or not such a screening had taken place. It may well be that clinicians are doing a much more frequent job of screening for S-CA, but simply not "announcing" it. These sobering statistics suggest that either clinicians need to increase their frequency of S-CA screening, be more forthright about pointing out to patients that a S-CA screening is being performed, or both.


Androgen Deprivation Therapy for Localized Prostate Cancer

Source: Lu-Yao GL, et al. AMA. 2008;300(2):173-181.

After skin cancer, prostate cancer (P-CA) is the most common cancer among American men. Guidelines suggest that for localized P-CA (stage T1 or T2) surgery, radiation, or conservative management (treatment deferred until demanded by disease progression) is appropriate. Despite the absence of major consensus group endorsement, androgen deprivation therapy (ADT) has been sufficiently popular that in a 2003 report, ADT was employed second only to surgery for localized disease.

When employed as an adjunct to radiation or surgery in high-risk P-CA (poorly differentiated or advanced stage), ADT has been associated with as much as 50% or greater mortality reductions. Whether ADT provides such benefits in earlier or less aggressive disease, and as initial therapy instead of adjunctive, has not been definitively studied.

Lu-Yao et al evaluated data on men aged 66 years or greater (n=19,271) treated with either ADT or conservative management only (ie, no definitive surgical or radiation therapy had been used). The population studied began accruing data in 1992, and men were followed through 2006.

ADT did not show advantage compared to conservative management for either mortality specifically related to P-CA or all-cause mortality. In fact, for the metric of 10-year prostate cancer-specific mortality, ADT was associated with a statistically significant 17% increased hazard ratio. Selecting the subgroup of men with poorly differentiated P-CA did not favorably affect overall mortality either, although in this subgroup there was a favorable impact on P-CA related mortality. Despite its recent popularity, ADT for localized disease has no mortality advantage over conservative management strategies.


Heart Failure Complicated by Atrial Fibrillation: Rate or Rhythm Control?

Source: Roy D, et al. N Engl J Med. 2008;358(25):266-277.

Among patients with atrial fibrillation (AFIB), clinical trial data have confirmed that outcomes using rate control are equally favorable as using rhythm control. Since rate control is usually easier to attain, and medications for rate control are generally both less expensive and better tolerated than agents required for rhythm control, rate control is often the preferred strategy.

Patients with heart failure (CHF) who also have AFIB have a worse prognosis. Whether management of AFIB in heart failure is most advantageous with rate or rhythm has not been fully elucidated, since the trial data upon which rate/rhythm equivalence is based were sparsely populated with heart failure patients.

Roy et al performed a randomized trial of rate vs rhythm control in heart failure patients with AFIB (n=1,376). Patients were followed for approximately 3 years. At the end of this trial, both mortality and all secondary outcomes were essentially equivalent with either intervention, although there was a trend towards greater CV mortality in the rhythm control group. Additionally, rhythm control patients experienced more hospitalizations.

Based upon these results, the authors suggest that rate control is preferred. Because pharmacologic treatments were used rather than radioablation techniques, no conclusions can be drawn about the relative efficacy of the latter.


Efficacy, Safety, and Tolerability of Pregabalin for Diabetic Peripheral Neuropathic Pain

Source: Freeman R, et al. Diabetes Care. 2008;31(7):1448-1454.

Long-standing diabetes is associated with development of diabetic peripheral neuropathy (DPN). As many as 1 out of every 4 patients with diabetes eventually develops diabetic peripheral neuropathic pain (DPNP). In addition to the burden of pain, patients are often much disquieted by the worsening of DPNP symptoms at night which interrupts sleep and produces next-day excessive drowsiness, as well as exacerbation of pain with activity which may compromise well-intended exercise plans.

Pregabalin is one of two agents approved for the treatment of DPNP in the last 2 years. Because our experience with pregabalin is relatively recent, this report which includes data from 7 randomized trials (total n= 1,510) may help bolster our knowledge base.

Daily pregabalin doses ranging from 150 mg-600 mg were all shown to be more effective than placebo when divided t.i.d.; when administered b.i.d., only a 600 mg daily dose was effective.

The literature has shown that patients with chronic pain report that a 30% reduction in pain from baseline is a clinically meaningful improvement. This threshold was achieved for most patients within 4 days (median) at pregabalin doses of 600 mg/d and 5 days at the 300 mg/d dosing, but took over twice as long at the lowest dose (150 mg/d).

Adverse events—most commonly dizziness, edema, weight gain, and somnolence are dose related. Less than 10% of patients discontinue treatment for any of these individual adverse events.