A Study On Clinical Features And Treatment Outcomes Of Anxious Depression

Background and objectives:Co-occurring anxiety symptoms or anxiety disorders among patients with major depressive disorder(MDD) is common. Chanllges in diagnosis and assessment on concurrent anxiety of MDD still exist. The concept of anxious depression has been developed to increase understanding of the relationship between depression and concurrent anxiety.Two approaches in terms of either high degree of anxiety symptom severity(dimensional approach) or anxiety disorder comorbidity(syndromal approach) in MDD are used to define anxious depression. Controversial ideas exist on which assessment approach may be the best on defining anxious depression. Previous studies including our reported findings of specific clinical features and tendency of worse outcomes of dimensional anxious depression suggest its clinical feasibility instead of syndromal assessment. To present no previous studies reported the impact of dimensional anxious depression on treatment outcomes among Chinese population. We also argue that evidence of clinical usefulness of dimensional assessment on anxious depression may be weaken without ruling out potential effects of comorbid anxiety disorders due to a probably substantial overlap between the two forms.We hereby compared acute treatment outcome for anxious depression and nonanxious depression in previous published clinical trials for patients with treatment-resistant depression. Then we conducted a crossetional investigation on clinical features and correlates of dimesional anxious depression(without any comorbid anxiety disorder) and MDD with at least one comorbid anxiety disorder, compared to MDD with neither dimensional anxious depression or comorbid anxiety disorders in a naturalistic clinical population. Acute and longterm treatment outcomes were assessed and compared among groups.Methods: Part I. A total of 375 patients met DSM-IV criteria of MDD and Treatment-Resistant Depression(TRD) criteria were enrolled(dataset 1). Anxious depression was defined as MDD with a HRSD-17 anxiety/somatization factor score ≥ 7. Data were derived from an earlier study, designed to compare efficacy and tolerability of fixed dosage of extended-release venlafaxine, mitazapine, paroxetine, and risperidone,sodium valproate, buspirone, trazodone or thyroid hormone augmenting to paroxetine in those patients. Treatment outcomes were compared between patients with anxious and nonanxious TRD.Part II. Up to 504 patients(dataset 2) met DSM-IV criteria of MDD were enrolled and three groups of participants were defined as follows: those having at least one comorbid anxiety disorder(CAD group), those having dimensional anxious depression(defined as MDD with a 17-HAMD anxiety/somatization factor score ≥ 7, AD group) and those having neither dimensional anxious depression nor any comorbid anxiety disorder(NAD group). Socio-demographics and clinical features were collected and compared among groups. Diagnoses of comorbid anxiety disorders including panic disorder, agoraphobia without panic attack, social anxiety disorder, generalized anxiety disorder were based on the MINI-International Neuropsychiatric Interview. Multinomial logistic regression models were developed to estimate association of independent variables shown to differ among groups with endorsement of dimensional anxious depression or comorbid anxiety disorders.Part III. A total of 257 participants were further followed at week 8, week 24 and week 48 after finishing investigation in Part II. Treatment outcomes of remission defined as QIDS-16 SR total score ≤ 5 at endpoint and self-report adverse events were compared among groups. Binary logistic regression models were developed to estimate association of presence of AD or CAD with remission at the three time points.Results: Part I. Remission rates were significantly lower and ratings of adverse event frequency were significantly greater in patients with anxious TRD than in those with nonanxious TRD. Presence of anxious depression predicted worse outcomes.Part II. There were significant differences among the three tested groups in terms of age, age at onset, illness severity either measured by 17-HAMD total score before(all p < 0.001) and after(p < 0.05) adjusted(anxiety/somatization factor score not included) or by QIDS-16 SR total score(p < 0.001), anxiety measured by HAMA total score, GAF total score(all p < 0.001), as well as comorbid dysthymia, OCD, psychosis(all p < 0.001) and suicidal ideation(p < 0.05). Overall, there was a tendency of escalating complexity of psychopathology beginning with the NAD group and progressing to the AD group and then CAD group. In the CAD group, this trend was highlighted by the group having the most complicated pathology with youngest age and age at onset, lowest level of functioning, as well as the largest proportion of participants with dysthymia, OCD, psychosis and suicidal ideation. While limted idenfiable clinical correlates including highest leval of illness severity(as reflected in QIDS-16 SR total score), oldest age and age at onset as well as lowest proportion of participants with dysthymia of AD group were detected. Multinomial logistic regression analysis(the reference category was NAD) indicated high level of illness severity(OR = 1.054) and anxiety(HAMA total score ≥ 14)(OR = 2.785), and presence of comorbid dysthymia(OR = 0.283) were associated with endorsement of AD. A younger age at onset(OR = 0.971), high level of anxiety(OR = 2.358), comorbid OCD(OR = 3.205) and suicidal ideation(OR = 1.701) were associated with endorsement of CAD.Part III: Compared to NAD group and AD group, least proportion of remitted participants at week 8(?2 = 37.211, p = 0.000), week 24(?2 = 15.537, p = 0.000) and week 48(?2 = 14.239, p = 0.001) were seen in CAD group and highest proportion of participants in CAD group endorsed adverse events at week 8 andweek 48(all p < 0.005). Participants in CAD group intended to have highest level of residual symptoms at each endpoints. Results of Binary logistic analysis indicated, compared to participants of NAD group, those of CAD group were less likely to get remission at week 8(OR = 0.184) and week 24(OR = 0.249).Conclusions: Part I. The findings in dataset 1 support and extend the hypothesis that anxious depression is associated with poorer outcomes. It suggests a dimensional assessment of co-occurring anxious features of MDD patients may be clinically feasible for countries like China where difficulties in making comorbidity diagnosis exist.Part II. Concurrent anxiety at symptom or syndromal level is common in patients with MDD. Compared to dimensional anxious depression without comorbid anxiety disorders, those with at least one comorbid anxiety disorder endorsed more complexed psychopathology and identifiable clinical correlates. Dimensional anxious depression is still clinically identifiable even after ruling out overlapping interaction with comorbid anxiety disorders. The findings indicated a more dimensional assessment capable of addressing co-occurring anxiety from symptom to syndromal level of MDD is needed.Part III. Our findings indicate dimensional anxious depression has no major effects on acute and longterm antidepressant treatment outcomes after ruling out overlapping interactions with comorbid anxiety disorders. Endorsement of comorbid anxiety disorders is stable and robust predictors of worse outcomes of MDD compared to presence of co-occurring anxiety symptoms. Previous evidence of averse outcomes of dimensional anxious depression may be weaken by our findings. The findings of this research do not fully support the notion that dimensional anxious depression may be a valid diagnostic subtype of MDD. There is still an urgent need to develope more specific dimensional assessment on concurrent anxiety of MDD.