Among

individual items, the core “depressed mood” item on either the HAMD-17 or the MADRS was more sensitive to drug-placebo separation and to establishing optimal dosing, compared with the full scales in several controlled trials.13,14 The sensitivity of some items to differentiate between active drug and placebo can be compromised when a drug has an unfavorable effect on certain items. For example, increased anxiety may occur during the early weeks of SSRI therapy, and activating antidepressants may disrupt some aspects of sleep.15 The net result is that, prevalent items may not. emerge on rating scales that are designed to detect improvements during antidepressant, Inhibitors,research,lifescience,medical therapy. Inhibitors,research,lifescience,medical When symptom prevalence and sensitivity to change have been evaluated in large data sets using item analysis or factor analysis, several core symptoms emerge with greater sensitivity to change and less distortion by treatment emergent side effects than with the full versions of the scale. Three such scales derived from the HAMD-17 are the “Been 6,”16 “Maier subscale,”17 and “HAMD-7”18 (Table II). Four items are common to each of these scales: mood, guilt, anhedonia, and psychic anxiety. In HAMD-7 and Bech 6, loss of energy (fatigue)

was also present, as was psychomotor retardation in Bech 6 and Maier 6, while the HAMD-7 included somatic anxiety and suicidal ideation. All Inhibitors,research,lifescience,medical three scales include anxiety symptoms, Inhibitors,research,lifescience,medical in contrast to current diagnostic systems. Table II Core symptoms from three scales derived from the Hamilton Depression Rating Scale. The prominence of anxiety symptoms and syndromes Surprisingly, anxiety is not considered as a core or associated symptom of depression according

to either DSM-IV or ICD-10 criteria. Neither is “with anxious features” a specifier within DSM-IV, yet. up to 90% of patients have co-occurring anxiety symptoms, and approximately 50% of depressed patients meet, NVP-AEW541 order criteria for a comorbid anxiety Inhibitors,research,lifescience,medical disorder.19,20 This lack of syndrome independence on Axis 1 is a major limitation to the current concept, of comorbidity. Comorbid disorders should only exist, at a level second expected by chance, yet. in the case of M’DD, comorbidity is the rule and not the exception.21. A recent proposal for mood and anxiety spectrum disorders, to be considered in DSM-V, has been advanced by Watson22 who proposes three subclasses of emotional disorders: “bipolar disorders,” “distress disorders,” (MDD, dysthymic disorder, generalized anxiety disorder, and post-traumatic stress disorder) and “fear disorders” (panic disorder, agoraphobia, social phobia and specific phobia). This reflects a pendulum swing to the unitary position of Mapother23 and Lewis24 who viewed states of anxiety along a continuum with depressive disorders, in contrast. to the progressive separation of mood and anxiety disorders initiated more than three decades ago.