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Objective: To pursue the previously long-standing but formally untested clinical view that melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone., Method: We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome., Results: Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 61.1% vs. 34.4%, respectively [Number Needed to Treat (NNT) = 3.7] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 2.8) and remission (66.7% vs. 45.4%, NNT = 4.7) rates., Conclusion: As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study., (© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Melancholia is positioned as either a more severe expression of clinical depression or as a separate entity. Support for the latter view emerges from differential causal factors and treatment responsiveness but has not been convincingly demonstrated in terms of differential clinical features. We pursue its prototypic clinical pattern to determine if this advances its delineation., Methods: We developed a 24-item measure (now termed the Sydney Melancholia Prototype Index or SMPI) comprising 12 melancholic and 12 non-melancholic prototypic features (both symptoms and illness correlates). In this evaluative study, 278 patients referred for tertiary level assessment at a specialized mood disorders clinic completed the self-report SMPI as well as a depression severity measure and a comprehensive assessment schedule before clinical interview, while assessing clinicians completed a clinician version of the SMPI items following their interview. The independent variable (diagnostic gold standard) was the clinician's judgment of a melancholic versus non-melancholic depressive episode. Discriminative performance was evaluated by Receiver Operating Characteristics (ROC) analysis of four strategies for operationalising the SMPI self-report and SMPI clinician measures, and with the former strategies compared to ROC analysis of the depression severity measure. The external validity of the optimally discriminating scores on each measure was tested against a range of clinical variables., Result: Comparison of the two self-report measures established that the SMPI provided greater discrimination than the depression severity measure, while comparison of the self-report and clinician-rated SMPI measures established the latter as more discriminating of clinically diagnosed melancholic or non-melancholic depression. ROC analyses favoured self-report SMPI distinction of melancholic from non-melancholic depression being most optimally calculated by a 'difference' score of at least four or more melancholic than non-melancholic items being affirmed (sensitivity of 0.69, specificity of 0.77). For the clinician-rated SMPI measure, ROC analyses confirmed the same optimal difference score of four or more as highly discriminating of melancholic and non-melancholic depression (sensitivity of 0.84, specificity of 0.92). As the difference score had positive predictive values of 0.90 and 0.70 (for the respective clinician-rated and self-report SMPI forms) and respective negative predictive values of 0.88 and 0.70, we conclude that the clinician-rated version had superior discrimination than the self-report version. External validating data quantified the self-rated and clinician-rated Index-assigned non-melancholic patients having a higher prevalence of anxiety disorders, a higher number of current and lifetime stressors, as well as elevated scores on several personality styles that are viewed as predisposing to and shaping such non-melancholic disorders., Limitations: Assigned melancholic and non-melancholic diagnoses were determined by clinician judgement, risking a circularity bias across diagnostic assignment and clinical weighting of melancholic and non-melancholic features. The robustness of the Index requires testing in primary and secondary levels of care settings., Conclusions: The clinician-rated SMPI differentiated melancholic and non-melancholic depressed subjects at a higher level of confidence than the self-report SMPI, and with a highly acceptable level of discrimination. The measure is recommended for further testing of its intrinsic and applied properties., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: It has been held that if bipolar disorder is categorically distinct, it should differentiate from unipolar depressive disorders by showing bimodality or a 'zone of rarity' in bipolar symptom scores. Two previous studies have failed to demonstrate bimodality. We undertook a third study., Methods: A total of 1106 patients attending the Black Dog Institute Depression Clinic completed the Mood Disorders Questionnaire (MDQ), in addition to undergoing clinical assessment by an Institute psychiatrist., Results: The distributions of scores for the total number of hypomanic symptoms endorsed by unipolar and bipolar patients were both skewed, with the bipolar group endorsing a high number of hypomanic symptoms and the unipolar group endorsing few symptoms--and so giving the impression of an 'even' distribution generated by two quite distinctly differing sub-groups. However, formal statistical analyses involving mixed modelling provided no clear evidence that a bimodal distribution provided a better fit to the data than a unimodal one., Conclusions: Failure to statistically demonstrate a 'point of rarity' did not marry with visual inspection of the plotted data--which clearly suggested two groups putatively capturing those with bipolar and unipolar disorders respectively. The paper considers some limitations to the emphasis on 'bimodality' in differentiating potentially differing conditions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This study aimed to examine the short-term clinical impact of identifying bipolar disorder in patients previously managed as having a unipolar disorder. The study was incorporated within a consecutive sample of 1000 patients attending a specialist depression clinic for diagnostic and management considerations. Of those assessed, 34% were evaluated as having a bipolar disorder, with this condition having been diagnosed for the first time in three-quarters of those patients. We reviewed sample members 12 weeks later and compared the courses of the "newly diagnosed" and "established" bipolar subsets. Some four-fifths of the bipolar patients reported a degree of improvement, whereas there were no clear differences between the two bipolar subsets. The nondifferential outcome of the bipolar (previously and newly diagnosed) subsets could suggest that there were nonspecific benefits of assessment or that the management was optimized for both groups. Future studies examining the impact of diagnosing a bipolar disorder would therefore benefit from the close consideration of the optimal control group or control strategy.

Background: As melancholia has resisted symptom-based definition, this report considers possible explanations and options for moving forward. Clinician-assigned melancholic and non-melancholic groups were initially compared to refine a candidate set of differentiating symptoms alone for examination against a set of non-clinical validators. Analyses then examined the capacity of both the refined symptom and validator sets to discriminate the assigned melancholic and non-melancholic subjects., Methods: Subjects completed measures assessing symptoms and correlates (putative validators) of diagnostic sub-type, and were assessed independently by two psychiatrists., Results: Analyses identified 14 severity-based symptoms as discriminating clinically-diagnosed groups - with melancholic subjects differing significantly from non-melancholic subjects across a number of validators. Such symptom-based discrimination was superior to DSM-IV and Newcastle Index assignment in a study sub-set. While the refined symptom set had an overall accurate classificatory rate of 68%, use of the combined sets of refined symptoms and validators improved classification to 80%., Conclusions: Melancholia definition is improved by the use of correlates in addition to depressive symptoms, suggesting that melancholia may be mapped more precisely by use of multiple co-ordinates or data sources., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Melancholia has long resisted classification, with many of its suggested markers lacking specificity. The imprecision of depressive symptoms, in addition to self-report biases, has limited the capacity of existing measures to delineate melancholic depression as a distinct subtype. Our aim was to develop a self-report measure differentiating melancholic and non-melancholic depression, weighting differentiation by prototypic symptoms and determining its comparative classification success with a severity-based strategy., Method: Consecutively recruited depressed out-patients (n=228) rated 32 symptoms by prototypic or 'characteristic' relevance (using the Q-sort strategy) and severity [using the Severity-based Depression Rating System (SDRS) strategy]. Clinician diagnosis of melancholic/non-melancholic depression was the criterion measure, but two other formal measures of melancholia (Newcastle and DSM-IV criteria) were also tested., Results: The prevalence of 'melancholia' ranged from 20.9% to 54.2% across the subtyping measures. The Q-sort measure had the highest overall correct classification rate in differentiating melancholic and non-melancholic depression (81.6%), with such decisions supported by validation analyses., Conclusions: In differentiating a melancholic subtype or syndrome, prototypic symptoms should be considered as a potential alternative to severity-based ratings.