In the September 2007 issue of TCPR, we reviewed the very mixed literatureon whether it makes sense to increase the dose of an antidepressant to achieve a response. We concluded that there is insufficient evidence, but that as long as you can avoid side effects, there is no compelling reason not to try dose escalation. A recent trial examined the effects of increasing the dosage of duloxetine (Cymbalta) for patients who did not achieve remission of depressive symptoms during acute treatment. After six weeks of treatment with Cymbalta 60 mg/day, non-remitted patients were randomly assigned to double blind treatment with either their original 60 mg dose plus placebo or an increase to 120 mg daily. At the end of eight weeks, there was no significant difference between the two groups in terms of efficacy, with 30% of participants in both groups achieving remission. Patients who exhibited a treat- ment response in the initial phase were more likely to show complete remission in the follow-up phase. The discontinuation rate due to adverse events was slightly, but not significantly, higher in the dose escalation group; however, sweating, chest pain, and tremor were significantly more common in patients whose dose was increased (Kornstein et al., J Clin Psychiatry 2008;69:1383-1392).