Risk factors of treatment resistance in major depression: Association with bipolarity

Subclinical psychotic experiences and bipolar spectrum features in depression: association with outcome of psychotherapy

“…This finding is similar to the results reported by Perlis et al (2011), who also found that psychotic rather than bipolar symptoms have a negative impact on treatment response in MDD. Taken together, these findings contradict the results from some other reports and question the hypothesis that many individuals with treatment-resistant MDD in fact have unrecognized bipolar (spectrum) disorder (Manning, 2003;Parker et al 2005;Sharma et al 2005;Smith et al 2009;Dudek et al 2010). One of the explanations of these diverging results, as suggested by Perlis et al (2011), may be differences in the operationalization of bipolar spectrum disorder, which sometimes includes psychotic symptoms (Smith et al 2009).…”

“…Clinically, disregard of subclinical co-expression of psychotic and bipolar symptoms may contribute to treatment resistance in MDD, as suggested by a number of lines of evidence. First, some but not all studies suggest poorer response to antidepressants in individuals screening positive for subclinical bipolar illness features (Sharma et al 2005;Smith et al 2009;Dudek et al 2010;Perlis et al 2011). Second, the presence of subclinical psychotic features during an episode of MDD (not fulfilling criteria for a formal diagnosis of psychotic depression) predicts poor response to multiple antidepressants (Perlis et al 2011).…”

Non-Response to Initial Antidepressant Therapy

“…Disease severity has been thoroughly associated with TRD (Souery et al, 2007;Dudek et al, 2010) and patients with greater symptom severity were approximately 3 times less likely to remit than those with mild or moderate depression in the STAR*D study . Severe depression is usually associated with lower spontaneous remission rate, greater risk of recurrence and higher chronicity of the disease (Thase et al, 2000).…”

“…Indeed, early onset of depression has been associated with a chronic course of the illness (Akiskal et al, 1981), and often results in higher severity of the disease as well as higher rates of comorbidity (Klein et al, 1999). Furthermore, early onset of first depressive episode has been considered as a risk factor in recent studies including large sample of patients (Dudek et al, 2010;Souery et al, 2007). Onset of depression in patients >60 years has been associated with a greater likelihood of psychotic symptoms and vascular brain changes that may increase the risk to develop to resistance (Kornstein et Schneider, 2001) Similar efficacy rates for antidepressant and psychological therapies have been reported in older adults and those under the age of 60 (Goldberg et al, 1998).…”

Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

“…However, this more inclusively defined mixed-depression subgroup had many of the same clinical characteristics as the restrictive DSM-5 subgroup, including higher rates of comorbid anxiety and apparent reduced response to standard antidepressants. [55][56][57] The larger effect sizes observed in the moderate-to-severe anxiety subgroup in the current analysis of an MDD with mixed features population, and similarly larger effect sizes in a separate analysis of a subgroup of patients with irritability in this MDD/mixed population (see Swann et al in the current issue), provide support for the hypothesis that anxiety/irritability symptoms may be clinical biomarkers of treatment responsivity, and thus are best viewed as core components of the MDD with mixed features presentation.…”