The investigational agent mecamylamine shows promise when used to augment antidepressant therapy with citalopram, according to recently released results from the phase II TRIDMAC trial.

In the first phase, 450 patients with major depression were given open-label citalopram for six weeks and evaluated with two scales -- the Hamilton Depression Rating Scale (HAM-D) and the Clinical Global Impression subscale for severity of illness (CGI-SI).

Partial and non-responders based on scores at the end of the six-week dosing period (HAM-D greater than or equal to 14 and CGI-SI greater than or equal to 4) were enrolled in the second phase. The 184 patients were randomized to mecamylamine or placebo as augmentation for continued citalopram therapy for an additional eight weeks.

Patients in the mecamylamine dose group initially received 5mg daily, titrating up to 10 mg over the dosing period at clinician's discretion. The primary endpoints of the trial were group mean change from baseline and achievement of remission, in each case as measured by HAM-D and compared to continued citalopram therapy plus placebo.

The secondary outcome measures for the trial included rating scales to assess symptoms of depression and anxiety, disability, irritability, global improvement or severity of illness. Data from the trial were evaluated on both an intent to treat and per protocol basis. The intent to treat data set (160 patients) included all participants who received at least one dose of blinded study medication and were assessed using HAM-D at least once after baseline. The per protocol data set (151 patients) included participants who were at least 80 percent compliant with the dosing regimen called for by protocol and were assessed using HAM-D at the end of the dosing period.

In the first primary endpoint, mecamylamine (TRIDMAC) produced greater improvement in symptoms as measured by group mean change from baseline on the Hamilton Depression Rating Scale (HAM-D) than placebo as the augmentation agent. This result was statistically significant on an intent to treat basis and showed a strong trend on a per protocol basis. HAM-D is a commonly used 17-item scale that evaluates depressed mood and other symptoms of depression and anxiety.

The other primary endpoint, achievement of remission, favored the TRIDMAC group over the placebo group, although the result did not reach statistical significance. In addition, the trial included five other rating scales as secondary measures. The results on all five rating scales favored TRIDMAC group over placebo with statistical significance on a per protocol basis. On an intent to treat basis, the results on three of the five rating scales were statistically significant.

"The TRIDMAC study indicates the potential for a new treatment option for the millions of patients suffering from major depression for whom current treatment modalities are inadequate. The large-scale STAR*D trial funded by The National Institute of Mental Health has clearly demonstrated both this significant societal need and the value of combining treatments," commented Ranga Krishnan MD, Chairman of Department of Psychiatry, Duke University Medical Center.

TRIDMAC was generally well tolerated, with one serious adverse event reported in each study arm. In the TRIDMAC group, a patient experienced an upper respiratory tract infection and irregular heartbeat and discontinued participation in the trial.
The manufacturer plans to make a full presentation of data at an upcoming meeting.