Abstract
ObjectiveTreatment-resistant depression (TRD) and treatment-resistant bipolar depression (TRBD) poses a significant clinical and societal burden, relying on different operational definitions and treatment approaches. The detection of clinical predictors of resistance is elusive, soliciting clinical subtyping of the depressive episodes, which represents the goal of the present study.MethodsA hundred and thirty-one depressed outpatients underwent psychopathological evaluation using major rating tools, including the Hamilton Rating Scale for Depression, which served for subsequent principal component analysis, followed-up by cluster analysis, with the ultimate goal to fetch different clinical subtypes of depression.ResultsThe cluster analysis identified two clinically interpretable, yet distinctive, groups among 53 bipolar (resistant cases = 15, or 28.3%) and 78 unipolar (resistant cases = 20, or 25.6%) patients. Among the MDD patients, cluster “1” included the following components: “Psychic symptoms, depressed mood, suicide, guilty, insomnia” and “genitourinary, gastrointestinal, weight loss, insight”. Altogether, with broadly defined “mixed features,” this latter cluster correctly predicted treatment outcome in 80.8% cases of MDD. The same “broadly-defined” mixed features of depression (namely, the standard Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition—DSM-5—specifier plus increased energy, psychomotor activity, irritability) correctly classified 71.7% of BD cases, either as TRBD or not.LimitationsSmall sample size and high rate of comorbidity.ConclusionsAlthough relying on different operational criteria and treatment history, TRD and TRBD seem to be consistently predicted by broadly defined mixed features among different clinical subtypes of depression, either unipolar or bipolar cases. If replicated by upcoming studies to encompass also biological and neuropsychological measures, the present study may aid in precision medicine and informed pharmacotherapy.
Highlights
Almost half of the patients suffering from a major depressive episode (MDE) fail to achieve a response, despite sequential combination or augmentation treatment strategies, irrespective of the operational definition adopted for treatment-resistant depression (TRD) [1, 2]
Among other clinical variables, mixed, anxious, and psychotic features of current MDE were statistically more frequent among bipolar disorder (BD) patients compared to the major depressive disorder (MDD) counterpart
principal component analysis (PCA) was performed on the items of the HAM-D-17 to characterize the sample at the report better, discriminating between unipolar and bipolar cases of depression
Summary
Almost half of the patients suffering from a major depressive episode (MDE) fail to achieve a response, despite sequential combination or augmentation treatment strategies, irrespective of the operational definition adopted for treatment-resistant depression (TRD) [1, 2]. Findings from the Group for the Study of Resistant Depression (GSRD), a multinational European research consortium, pointed toward strong effects of clinical variables on treatment outcome of MDD [21], as well as specific genetic signature [22] This is relevant considering that, when considered separately, the potential predictors of TRD usually showed odd ratios (ORs) around 1.5, and were not applicable as univocal hints in the clinical setting [23, 24]. Four potent clinical predictors of TRD emerged in a validation study that showed a collective predictive accuracy of 87% These latter include symptom severity, suicidal risk, comorbid anxiety disorder, and the lifetime number of MDE episodes [25,26,27]. Symptom severity, suicidal risk, higher number of lifetime of MDEs, and comorbid anxiety disorder were consistently replicated as the most prominent risk factors for different stages of TRD in large-sampled studies [28]
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