A cost-utility comparison of four first-line medications in painful diabetic neuropathy.

BACKGROUND: Painful diabetic neuropathy is common and adversely affects patients' quality of life and function. Several treatment options exist, but their relative efficacy and value are unknown. OBJECTIVE: To determine the relative efficacy, costs and cost effectiveness of the first-line treatment options for painful diabetic neuropathy. METHODS: Published and unpublished clinical trial and cross-sectional data were incorporated into a decision analytic model to estimate the net health and cost consequences of treatment for painful diabetic peripheral neuropathy over 3-month (base case), 1-month and 6-month timeframes. Efficacy was measured in QALYs, and costs were measured in $US, year 2006 values, using a US third-party payer perspective. The patients included in the model were outpatients with moderate to severe pain associated with diabetic peripheral neuropathy and no contraindications to treatment with tricyclic antidepressants. Four medications were compared: desipramine 100 mg/day, gabapentin 2400 mg/day, pregabalin 300 mg/day and duloxetine 60 mg/day. RESULTS: Desipramine and duloxetine were both more effective and less expensive than gabapentin and pregabalin in the base-case analysis and through a wide range of sensitivity analyses. Duloxetine offered borderline value compared with desipramine in the base case ($US47,700 per QALY), but not when incorporating baseline-observation-carried-forward analyses of the clinical trial data ($US867,000 per QALY). The results were also sensitive to the probability of obtaining pain relief with duloxetine. CONCLUSIONS: Desipramine (100 mg/day) and duloxetine (60 mg/day) appear to be more cost effective than gabapentin or pregabalin for treating painful diabetic neuropathy. The estimated value of duloxetine relative to desipramine depends on the assumptions made in the statistical analyses of clinical trial data.

An assessment of drug-drug interactions: the effect of desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy subjects.

A number of antidepressants inhibit the activity of the cytochrome P450 2D6 enzyme system, which can lead to drug-drug interactions. Based on its metabolic profile, desvenlafaxine, administered as desvenlafaxine succinate, a new serotonin-norepinephrine reuptake inhibitor, is not expected to have an impact on activity of CYP2D6. This single-center, randomized, open-label, four-period, crossover study was undertaken to evaluate the effect of multiple doses of desvenlafaxine (100 mg/day, twice the recommended therapeutic dose for major depressive disorder in the United States) and duloxetine (30 mg b.i.d.) on the pharmacokinetics (PK) of a single dose of desipramine (50 mg). A single dose of desipramine was given first to assess its PK. Desvenlafaxine or duloxetine was then administered, in a crossover design, so that steady-state levels were achieved; a single dose of desipramine was then coadministered. The geometric least-square mean ratios (coadministration versus desipramine alone) for area under the plasma concentration versus time curve (AUC) and peak plasma concentrations (C(max)) of desipramine and 2-hydroxydesipramine were compared using analysis of variance. Relative to desipramine alone, increases in AUC and C(max) of desipramine associated with duloxetine administration (122 and 63%, respectively) were significantly greater than those associated with desvenlafaxine (22 and 19%, respectively; P < 0.001). Duloxetine coadministered with desipramine was also associated with a decrease in 2-hydroxydesipramine C(max) that was significant compared with the small increase seen with desvenlafaxine and desipramine (-24 versus 9%; P < 0.001); the difference between changes in 2-hydroxydesipramine AUC did not reach statistical significance (P = 0.054). Overall, desvenlafaxine had a minimal impact on the PK of desipramine compared with duloxetine, suggesting a lower risk for CYP2D6-mediated drug interactions.

Comparing the cost effectiveness of psychiatric treatments: bulimia nervosa.

We conducted an exploratory post hoc study that compared the cost effectiveness of five treatments for bulimia nervosa: 15 weeks of cognitive behavioral therapy (CB) followed by three monthly sessions, 16 weeks (Med16) and 24 weeks (Med24) of desipramine (< or = 300 mg/day), and CB combined with desipramine for those durations (Combo16 and Combo24). We illustrate how a treatment's cost effectiveness varies according to when evaluation is done and how effectiveness and cost are defined. At 32 weeks, Med16 appears the most cost-effective treatment, and Combo16 appears the least. At 1 year, Med24 appears the most cost-effective treatment, and Combo16 appears the least. Using this post hoc analysis as an example, we discuss the pitfalls and limitations of cost-effectiveness analysis of psychiatric treatments.

Desipramine-, not tartrazine-, induced drug eruption.

A 46-year-old woman's antidepressant therapy was changed from doxepin to desipramine because of sedative side effects. Within ten days of initiation of desipramine, a pruritic, morbilliform rash developed. The rash extended despite attempts to continue therapy with a tartrazine-free desipramine as well as antihistamines and prednisone. The rash promptly improved when desipramine was discontinued. Classic drug eruptions are quite uncommon with tricyclic antidepressants. Tartrazine, a common additive in the food and drug industry, is implicated in a number of hypersensitivity reactions. Our report presents an apparent case of desipramine-induced drug rash independent of tartrazine, and discusses the nonassociation of tartrazine.