Lena Rane

The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression

BACKGROUND Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). METHODS One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. RESULTS Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). LIMITATIONS The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. CONCLUSIONS Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention.

Prediction of longer-term outcome of treatment-resistant depression in tertiary care

BACKGROUND Systematic studies on the outcome of treatment-resistant depression are scarce. AIMS To describe the longer-term outcome and predictors of outcome in treatment-resistant depression. METHOD Out of 150 patients approached, 118 participants with confirmed treatment-resistant depression (unipolar, n = 77; bipolar, n = 27; secondary, n = 14) treated in a specialist in-patient centre were followed-up for between 8 and 84 months (mean = 39, s.d. = 22). RESULTS The majority of participants attained full remission (60.2%), most of whom (48.3% of total sample) showed sustained recovery (full remission for at least 6 months). A substantial minority had persistent subsyndromal depression (19.5%) or persistent depressive episode (20.3%). Diagnosis of bipolar treatment-resistant depression and poorer social support were associated with early relapse, whereas strong social support, higher educational status and milder level of treatment resistance measured with the Maudsley Staging Method were associated with achieving quicker remission. Exploratory analysis of treatment found positive associations between treatment with a monoamine oxidase inhibitor (MAOI) in unipolar treatment-resistant depression and attaining remission at discharge and at final follow-up, and duloxetine use predicted attainment of remission at final follow-up. CONCLUSIONS Although many patients with treatment-resistant depression experience persistent symptomatology even after intensive, specialist treatment, most can achieve remission. The choice of treatment and presence of good social support may affect remission rates, whereas those with low social support and a bipolar diathesis should be considered at higher risk of early relapse. We suggest that future work to improve the long-term outcome in this disabling form of depression might focus on social interventions to improve support, and the role of neglected pharmacological interventions such as MAOIs.

Discrepancy between subjective and objective severity in treatment-resistant depression: Prediction of treatment outcome

OBJECTIVE Identifying predictors of outcome among patients with treatment-resistant depression (TRD) is challenging. We hypothesised that discrepancy between self-rated and observer-rated scales may be a simple way of making such a prediction. METHOD 102 patients were admitted to a unit specialising in the treatment of resistant depression and underwent fortnightly assessment with clinician-rated (Hamilton Depression Rating Scale-21, HAM-D) and self-rated (Beck Depression Inventory, BDI) measures. All patients had significant depressive symptoms that were treatment resistant, 70% as part of a major depressive disorder and the remainder as part of a bipolar or other disorder. A discrepancy score between the HAM-D and BDI was calculated on admission and its association with patient clinico-demographic factors was determined. A subset of 67 patients remained as inpatients for 40 weeks or until clinical response and were entered into a responder analysis, in which response was defined as ≥50% reduction in admission HAM-D score. The association of the admission BDI-HAM-D discrepancy score with subsequent patient response, was determined. RESULTS The magnitude of BDI-HAM-D discrepancy was higher in those with co-morbid personality disorder, lower in those with psychosis and positively correlated with anxiety. High BDI-HAM-D discrepancy score predicted delayed treatment response (odds ratio 5.40, p = 0.005). CONCLUSION Within TRD, higher discrepancy predicts slower response to treatment independent of objective illness severity; this may be mediated by underlying personality traits and co-morbid anxiety.

Longitudinal course of symptom severity and fluctuation in patients with treatment-resistant unipolar and bipolar depression

Little is currently known about the long-term course of symptom severity and fluctuation in patients with treatment-resistant depression (TRD). We assessed this using the longitudinal interval follow-up evaluation in 115 patients with TRD (84 unipolar, 31 bipolar) with 1-7 years (median 36 months) of follow-up. Of the follow-up months, 39.2% were spent asymptomatic and 21.1% at sub-threshold symptom level, while 15.8% were spent at mild, 13.9% at moderate, and 10.0% at severe depressive episode level. Significantly more unipolar than bipolar patients were continuously symptomatic during follow-up (43% vs. 29%). Patients had a mean of 1.0 (S.D.=1.2) symptom severity level fluctuations per year. High fluctuating patients had significantly poorer global functioning and quality of life. Although most patients with TRD achieve an asymptomatic state, they continue to fluctuate and experience depressive symptoms in the majority of months, mostly at subclinical or mild severity. However, there are important differences between unipolar and bipolar TRD, with unipolar patients more likely to experience an unremitting depressive state. Additionally, a more fluctuating longitudinal illness course is associated with poorer function and quality of life, and with a bipolar diagnosis. We suggest that the longitudinal illness course is an important outcome to be considered in future TRD research.

Psychological and physiological effects of caring for patients with treatment-resistant depression

BACKGROUND Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo-pituitary-adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients. METHOD Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients. RESULTS Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers. CONCLUSIONS Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.

Long-term symptomatic and functional outcome following an intensive inpatient multidisciplinary intervention for treatment-resistant affective disorders

BACKGROUND The natural history of treatment-resistant depression (TRD) is poor, with high rates of chronicity and recurrence. We describe longer-term symptomatic and functional outcome following multimodal intensive inpatient treatment for TRD. METHODS Symptomatic and functional outcomes were assessed in 71 participants (unipolar, n=51; bipolar, n=20) with severe TRD previously treated at a specialist inpatient unit a median of 34 months (IQR 19-52) post discharge. We looked at outcomes in defined subgroups (unipolar, bipolar and psychotic) and at symptom clusters to see whether certain aspects of depression were more resistant to treatment than others. RESULTS Symptomatic improvement during the admission was maintained at follow up: HDRS21 scores fell from admission (median 22; IQR 19-25) to discharge (median 12; IQR 7-16) and follow-up (median 10; IQR 4-18). Overall, two-thirds of patients were judged to have a good long-term outcome, while half remained in full remission at follow-up. Outcomes were more favourable in bipolar patients, patients without a history of psychosis and patients who were discharged in remission, although a minority of responders at discharge no longer met response criteria at follow up, and conversely some patients discharged as non-responders did subsequently respond. Non-remitting depression was characterised by three main factors; anxiety, cognitive difficulties and sleep disturbance. Those who remitted had better functional outcomes as did those who had experienced a more sustained response to treatment whilst inpatients. Quality of life was poor for those who did not respond to the treatment package. LIMITATIONS Variable follow-up length. CONCLUSIONS This difficult-to-treat population gained long-term benefits from multidisciplinary inpatient treatment. Treatment to remission was associated with more favourable outcomes. Non-responsive depression was characterised by specific symptom clusters that might be amenable to more targeted treatments.

Long-Term Impact of Residual Symptoms in Treatment-Resistant Depression

Objective: Although commonly encountered, little work has defined the longitudinal course of treatment-resistant depression (TRD) and the influence of residual posttreatment symptoms on longer-term outcome. The aim of our study was to assess the impact of posttreatment clinical states on longer-term outcome. Method: Patients (n = 118) with TRD received specialist inpatient treatment and were followed-up for a median of 3 years. Longitudinal outcome dichotomized into good and poor outcome was used as the primary outcome and functional measures were used as secondary outcomes. Results: Among 118 treated patients, 40 (34%) entered clinical remission, 36 (31%) entered partial remission, and 42 (37%) remained in episode at discharge. At follow-up, 35% had longitudinally defined poor outcome. Posttreatment clinical status was the main predictor of both poor and good outcome. Nearly 50% of patients achieved postdischarge recovery, and subsequently had longer-term outcome, comparable with patients discharged in remission. Patients who remained in episode posttreatment were more symptomatically and functionally impaired. Conclusion: Posttreatment clinical states are a useful guide to clinicians for projecting the longer-term outcome of patients with TRD. The persistence of residual or syndromal symptoms predicts a poorer longer-term outcome, whereas treatment to remission is associated with better outcomes.