Medication Nonadherence, "Professional Subjects," and Apparent Placebo Responders: Overlapping Challenges for Medications Development.

Nonadherence is a major problem in clinical trials of new medications. To evaluate the extent of nonadherence, this study evaluated pharmacokinetic sampling from 1765 subjects receiving active therapy across 8 psychiatric trials conducted between 2001 and 2011. With nonadherence defined as greater than 50% of plasma samples below the limit of quantification for study drug, the percentage of nonadherent subjects ranged from 12.

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

Objectives: To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment.

Methods: Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.

Safety and tolerability of dexmecamylamine (TC-5214) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to antidepressant therapy: results of a long-term study.

Safety and tolerability are important considerations when selecting patients' treatment for major depressive disorder. We report the long-term safety and tolerability of the nicotinic channel modulator dexmecamylamine (TC-5214), adjunct to selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder and who had an inadequate response to antidepressants. This 52-week, double-blind, placebo-controlled study explored the long-term safety and tolerability of dexmecamylamine.

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant.

This paper reports the efficacy and tolerability of the nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy for patients with major depressive disorder who have an inadequate response to initial antidepressant treatment in 2 Phase III studies. These double-blind, placebo-controlled studies (NCT01157078, D4130C00002 [Study 002] conducted in the US and India; NCT01180400, D4130C00003 [Study 003] conducted in Europe) comprised 8 weeks of open-label antidepressant treatment followed by 8 weeks of active treatment during which patients were randomized to flexibly-dosed TC-5214 1-4 mg twice daily (BID) or placebo as an adjunct to ongoing therapy with SSRI/SNRI. The primary efficacy endpoint in both studies was change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomization (week 8) to treatment end (week 16).

A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression.

Objective: There is a major unmet need for effective options in the treatment of bipolar depression.

Method: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score.