Predictors of Treatment Resistance Across Different Clinical Subtypes of Depression: Comparison of Unipolar vs. Bipolar Cases

Abstract

Treatment-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. Methods: A 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. Results: The 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. Limitations: Small sample size and high rate of comorbidity. Conclusions: Although 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.

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression

“…Furthermore, in our sample, a more severe suicidal behaviour resulted to be robustly associated with TRD, as showed by the binary logistic regression models. Several authors underlined the association between suicidal behaviour and poor response to treatment in MDD, suggesting that history of self-harm [ 50 , 51 , 52 ] or number of suicidal attempts are strong predictors of TRD [ 53 , 54 , 55 ].…”

Treatment-resistant bipolar depression: concepts and challenges for novel interventions

“…2 Fornaro et al found a similar proportion (28.3%) of patients with TRBD (defined as ''a lack of response to at least two previously established treatments for bipolar depression''), in whom mixed features according to the DSM-5 specifier, in addition to symptoms of irritability, impulsivity, and distractibility, were considered predictors of TRBD. 3 Similarly, cognitive dysfunction has been described as highly frequent in patients with TRBD. Kessler et al reported global cognitive impairment (processing speed, attention/vigilance, working memory, verbal learning, visual learning, and reasoning and problem solving), including clinically significant dysfunction in two or more cognitive domains, in almost 70% of patients with BD type I and 40% of patients with BD type II with TRD.…”

“…2 No interventions have shown clear and established effectiveness for its treatment. [2][3][4] This review will discuss the concept of TRBD, its associated variables and neurobiology, novel strategies for decreasing its burden, and the potential of new paradigms to identify more precise and effective treatments for psychiatric diseases. We performed a narrative review of the medical literature to identify papers discussing treatment-resistant depression (TRD) and novel interventions for bipolar depression that focus on TRBD.…”

Diagnosing and treating major depressive episodes that lie along the mood disorders spectrum: focus on depression with mixed features

“…35,36 Moreover, preliminary data suggest mixed features may be associated with treatment resistance in both bipolar and unipolar disorders. 37 One important unresolved issue, however, is how best to classify mixed depression. Thus, while DSM-5 specifies that mixed depression can be associated with unipolar or bipolar disorders, it might also be possible that unipolar mixed depression sometimes, or even always, reflects a bipolar spectrum disorder.…”