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| |  Mecamylamine Shows Promise in Treating Major Depression: Presented at ECNP By Joanna Lyford VIENNA, AUSTRIA -- October 18, 2007 -- Mecamylamine, a drug approved for treating hypertension, may be an effective augmentation therapy in patients with major depressive disorder (MDD), according to a study presented at the 20th European College of Neuropsychopharmacology (ECNP) Congress. The multicentre, phase 2 study found that add-on mecamylamine therapy in patients who had responded poorly to citalopram was associated with an improvement in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions - Severity of Illness (CGI-S) scale. The improvements were statistically significant versus placebo, and treatment was well tolerated, suggesting that mecamylamine, a nicotinic neuronal receptor (NNR) antagonist, might be a new approach to the treatment of depression, according to Geoffrey Dunbar, MD, Vice President of Clinical Development and Regulatory Affairs, Targacept Inc., Winston Salem, North Carolina, United States. Four hundred fifty adults with MDD were recruited at nine sites in the US and India for this study. At baseline, all patients had a Hamilton Depression Rating Scale (HAMD-17) score >21 and a CGI-S score >=4. All patients were initially treated for 6 weeks with open-label citalopram 20 to 40 mg/day. Subjects with a HAMD-17 score >=14 and a CGI-S score >=4 at the end of treatment were considered citalopram nonresponders or partial responders, and were entered into the double-blind phase of the study. This 8-week phase entailed randomisation to mecamylamine 5 to 10 mg/day (n = 78) or placebo (n = 77), in addition to citalopram. The study's primary endpoint -- change in HAMD-17 scores between week 6 and week 14 -- showed a trend favouring mecamylamine over placebo, although it just missed statistical significance (P =.059). The changes in both MADRS and CGI-S scores were significantly greater, however, in mecamylamine-treated patients versus patients receiving placebo, as was the change in Clinical Global Impressions total score (all P <.05). With respect to tolerability, 54% of mecamylamine-treated subjects experienced at least one adverse event compared with 37% of those on placebo. The most frequent adverse events in the mecamylamine group were constipation and dizziness, which occurred in 27% and 15% of patients, respectively. In a prespecified analysis, the investigators examined levels of irritability, which is commonly associated with depression and which can also occur in MDD during recovery. In this study, irritability, assessed with the Sheehan Irritability Scale, decreased significantly more in the mecamylamine group than in the placebo group (P <.001). "A strong effect on symptoms of irritability may have a particularly therapeutic benefit," Dr. Dunbar commented. "This study provides the first evidence that compounds that antagonise NNRs [neuronal nicotinic receptors] have antidepressant properties," Dr. Dunbar concluded. This study was funded by Targacept Inc.
[Presentation title: Mecamylamine in the Treatment of Depressed Patients Who Were Inadequate Responders to Citalopram First-line Therapy. Breaking News]
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