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Background: Due to the heterogeneity of depressive symptoms-which can include depressed mood, anhedonia, negative cognitive biases, and altered activity levels-researchers often use a combination of depression rating scales to assess symptoms. This study sought to identify unidimensional constructs measured across rating scales for depression and to evaluate these constructs across clinical trials of a rapid-acting antidepressant (ketamine)., Methods: Exploratory factor analysis (EFA) was conducted on baseline ratings from the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Snaith-Hamilton Pleasure Rating Scale (SHAPS). Inpatients with major depressive disorder (n = 76) or bipolar depression (n = 43) were participating in clinical ketamine trials. The trajectories of the resulting unidimensional scores were evaluated in 41 subjects with bipolar depression who participated in clinical ketamine trials., Results: The best solution, which exhibited excellent fit to the data, comprised eight factors: Depressed Mood, Tension, Negative Cognition, Impaired Sleep, Suicidal Thoughts, Reduced Appetite, Anhedonia, and Amotivation. Various response patterns were observed across the clinical trial data, both in treatment effect (ketamine versus placebo) and in degree of placebo response, suggesting that use of these unidimensional constructs may reveal patterns not observed with traditional scoring of individual instruments., Limitations: Limitations include: 1) small sample (and related inability to confirm measurement invariance); 2) absence of an independent sample for confirmation of factor structure; and 3) the treatment-resistant nature of the population, which may limit generalizability., Conclusions: The empirical identification of unidimensional constructs creates more refined scores that may elucidate the connection between specific symptoms and underlying pathophysiology., (Published by Elsevier B.V.)

Background: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects., Methods: We conducted a randomized, double-blind, placebo-controlled trial of riluzole monotherapy for the treatment of BDep. Nineteen subjects aged 18 to 70 years with bipolar disorder currently experiencing a depressive episode were tapered off of excluded medications and randomized to receive riluzole (50-200 mg/d) or placebo for 8 weeks. Rating scale scores (Montgomery-Åsberg Depression Rating Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Young Mania Rating Scale) were obtained weekly., Results: No significant differences in depressive symptoms were observed between subjects treated with riluzole and those receiving placebo (P = 0.12). Anxiety scores were significantly lower in the placebo group (P = 0.046). An interim analysis was conducted that resulted in stopping the study because of futility; no subjects had achieved treatment response., Conclusions: Although we found no change in severity of depressive symptoms in BDep patients receiving riluzole compared with placebo, this trial was limited by the relatively high number of subject withdrawals and the small sample size. Thus, while riluzole monotherapy did not demonstrate efficacy for BDep, further studies examining riluzole as adjunctive therapy for this disorder may be warranted.Clinical Trials Identifier NCT00054704.

In patients with major depressive disorder or bipolar disorder, abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate and gamma-aminobutyric acid have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic-dose ketamine has led to a collection of studies that have examined neurochemical (e.g., glutamatergic and gamma-aminobutyric acidergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation. [ABSTRACT FROM AUTHOR]