Having trouble distinguishing one erectile dysfunction drug from another? So are researchers at the Agency for Healthcare Research and Quality. A new AHRQ technology assessment and meta-analysis of randomized controlled trials concluded that there is not enough evidence to determine which ED drugs are more effective or which may cause fewer and less serious adverse events.

"Data from multiple randomized controlled trials show that the phosphodiesterase type 5 (PDE-5) inhibitors do have an effect," said AHRQ project officer Steven Fox, MD, who supervised the report. "But there are hardly any long-term evaluations of side effects or outcomes after continued use. Short-term studies find few apparent differences among the three PDE-5 inhibitors except duration of activity."

Pharmacists are reading the same message from "Diagnosis and Treatment of Erectile Dysfunction," which was published by AHRQ in May. "The PDE-5 inhibitors are all effective, just not one over any of the others," said Matthew Cantrell, assistant clinical professor at the University of Iowa College of Pharmacy and clinical pharmacy specialist at the Iowa City VA Medical Center. "This pretty much represents maintenance of the status quo in ED treatment. Product selection is still up to the prescriber and patient and specific factors such as price and formulary status."

The report was prepared by the University of Ottawa Evidence-based Practice Center in Ottawa, Ontario. Researchers compared the three PDE-5 inhibitors on the market, sildenafil (Generic Viagra, Pfizer), vardenafil (Levitra, GlaxoSmithKline), and tadalafil (Cialis, Lilly) as well as topical, intracavernosal, and subcutaneous treatments used to improve ED.

Researchers also looked at the utility of routine serum tests for testosterone, prolactin, and luteinizing hormone/follicle-stimulating hormone (LH/FSC) as a means of identifying and treating hormonal disorders and improving therapeutic outcomes in ED patients.

The report noted that the data supporting the routine use of hormonal blood tests are limited in terms of quantity, quality, and interpretability. Published studies are broadly heterogeneous and contain wide variations in the prevalence of hypogonadism, hyperprolactinemia, and LH/FSC measurements in patients with ED.

The broad range of serum hormone levels and the general lack of comparable patient selection make it impossible to draw useful conclusions about serum hormone levels as diagnostic tools or therapeutic goals. Data are stronger when it comes to pharmacologic ED treatments. Patients in clinical trials who took any of the three PDE-5 inhibitors showed fewer ED symptoms than patients who received placebo.

Patients in the treatment arms of drug trials also showed higher rates of adverse events with all three agents. The overall adverse event rates were similar in trials of the three PDE-5 inhibitors against placebo, but the specific side effects were somewhat different with each agent. The most common side effects from Viagra were headache, flushing, and dyspepsia. For Levitra, the most common side effects were headache, flushing, rhinitis, and dyspepsia.

Among patients who took Cialis, the most common side effects were headache, back pain, dyspepsia, dizziness, nasal congestion, flushing, and myalgia. Researchers found few head-to-head trials of PDE-5 inhibitors, but the few direct comparisons showed similar outcomes. The rates and severity of adverse events were also similar.

"Having three agents on the market raises a lot of options for patients," Cantrell said. "Pharmacists need to be ready to counsel patients on all three of these products as first-line agents. The class as a whole has revolutionized the treatment of ED."

Prescribing practices are often driven by regional preferences or formulary status, he noted. Because there are few dramatic differences in therapeutic effects or adverse events between the three agents, drug selection is often a matter of prescriber preference and familiarity.

One of the most obvious differences between the three PDE-5 inhibitors is duration of action, he said. The effects of tadalafil typically persist longer than 24 hours, compared to a few hours for sildenafil and vardenafil. That makes tadalafil more convenient for some patients, though not for all. Differences in side effects may also affect patient preference. While each of the three agents inhibits PDE-5, each also inhibits a slightly different spectrum of other phosphodiesterase types. Patients may tolerate one agent better than another or may see greater effects with one agent over another. Dose responses are just as individual.