Venlafaxine design

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

The one study done to date with venlafaxine used a double-blind continuation design rather than a crossover design used with the SSRIs ( Table 7-21). Responders in the double-blind, placebo- and active-controlled acute efficacy phase could elect to remain on double-blind treatment for a 1-year follow-up phase ( 271). The treatment arms in these studies included venlafaxine, trazodone, imipramine, and placebo. At the end of 1 year, 18% of patients on venlafaxine had relapsed versus 32% on placebo. The difference between the venlafaxine and the placebo groups was smaller than that seen between the SSRIs and their respective placebo groups (Table 7-20), consistent with the difference in the design of these studies. 

Given their design differences, no direct comparison can be made between the relative relapse efficacy of SSRIs, venlafaxine, and nefazodone. The bottom line, however, is that both designs demonstrated that maintenance therapy for up to 1 year is important in reducing the risk of a depressive relapse after an initial response. 

The first studies of venlafaxine and nefazodone in both children and adolescents examined pharmacokinetics, safety, and tolerability of these agents ( 35, 36). As expected, the clearance was modestly more rapid in children and adolescents for both of these medications when compared with clearance in adults, but the difference was not sufficient to warrant a significant change in the milligram per kilogram daily dose. These studies should be followed up by appropriately designed efficacy studies. 

Somasekhag V., Gowrisankar, D. and Shivakumar, H. N. Development and validation of a rapid RP-HPLC method for the determination of venlafaxine hydrochloride in pharmaceutical dosage forms using experimental design. E-J. Chem. 6(4) 1091-1102, October 2009. 

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