Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder

OBJECTIVE: Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life. METHODS: One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, co-existing medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open-label escitalopram and were divided into full (n = 55; 31%), partial (n = 75; 42.9%), and non-responder (n = 45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups. RESULTS: Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self-esteem than full responders. In general partial responders resembled full responders more than they resembled non-responders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self-esteem predicted worse response status at 6 weeks. CONCLUSION: Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment.     

Previous mood state predicts response and switch rates in patients with bipolar depression

OBJECTIVE: The treatment of bipolar depression is a significant clinical problem that remains understudied. The role for antidepressant (AD) agents vs. mood stabilizers has been particularly problematic to ascertain. METHOD: Detailed life charting data from 42 patients with 67 depressive episodes were reviewed. Response rates and rates of switch into mania were compared based on the preceding mood state and on whether an AD or mood stabilizing (MS) agent was added following onset of depression. RESULTS: Patients who became depressed following a period of euthymia were more likely to respond to treatment (62.5%) than patients who became depressed following a period of mania or hypomania (27.9%). The ratio of response to switch for previously euthymic patients was particularly favorable. CONCLUSION: Mood state prior to onset of depression in bipolar disorder appears to be an important clinical variable that may guide both choice of treatment administered and expectation of outcome to treatment.     

Personality disorder diagnoses using DSM-III-R in a Japanese clinical sample with major depression

To investigate the availability of DSM-III-R Axis-II diagnoses in Japan, DSM-III-R personality disorders (PDs) were diagnosed in a large sample of Japanese out-patients with major depression. The SCID-II was administered to 118 consecutive out-patients with major depression. In general, the frequency of PD according to DSM-III-R criteria in this study was within the range of frequencies reported in North American and European studies. However, schizoid and narcissistic PDs were more frequent in this study. DSM-III-R diagnoses of PD would also be potentially useful for assessing personality disturbance in Japan. The DSM-III-R criteria for schizoid and narcissistic PDs may not be suitable for Japanese samples.     

Late-onset major depression: clinical and treatment-response variability

OBJECTIVE: To explore clinical and treatment-response variability in late-onset vs early-onset non-bipolar, non-psychotic major depression. METHODS: We grouped patients from a late-life depression treatment study according to illness-course characteristics: those with early-onset, recurrent depression (n = 59), late-onset, recurrent depression (n = 27), and late-onset, single-episode depression (n = 95). Early-onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late-onset was defined as having a first episode of major depression at age 60 or later. We characterized the three groups of patients with respect to baseline demographic, neuropsychological, and clinical characteristics, use of augmentation pharmacotherapy to achieve response, and treatment outcomes. RESULTS: Rates of response, remission, relapse, and termination were similar in all three groups; however, patients with late-onset, recurrent major depression took longer to respond to treatment than those with late-onset, single-episode depression (12 weeks vs 8 weeks) and had more cognitive and functional impairment. Additionally, patients with recurrent depression (whether early or late) were more likely to require pharmacotherapy augmentation to achieve response than patients with a single lifetime episode. CONCLUSION: Late-onset, recurrent depression takes longer to respond to treatment than late-onset single-episode depression and is more strongly associated with cognitive and functional impairment. Further study of biological, neuropsychologic, and psychosocial correlates of late-onset, recurrent depression is needed.     

Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta‐analysis

Background: A large number of studies have shown that psychological treatments have significant effects on depression. Although several studies have examined the relative effects of psychological and combined treatments, this has not been studied satisfactorily in recent statistical meta‐analyses. Method: We conducted a meta‐analysis of randomized studies in which a psychological treatment was compared to a combined treatment consisting of the same psychological treatment with a pharmacological therapy. For each of these studies we calculated the effect size indicating the difference between the psychological and the combined treatment. Results: All inclusion criteria were met by 18 studies, with a total of 1,838 subjects. The mean effect size indicating the difference between psychological and combined treatment was 0.35 (95% CI: 0.24～0.45; P<0.001), with low heterogeneity. Subgroup analyses indicated that the difference between psychological and combined treatments was significantly smaller in studies in which cognitive behavior therapy was examined. We also found a trend (P<0.1) indicating that the difference between psychological and combined treatment was somewhat larger in studies aimed at specific populations (older adults, chronic depression, HIV patients) than in studies with adults, and in studies in which Trycyclic antidepressants or SSRIs were examined, compared to studies in which a medication protocol or another antidepressant was used. At follow‐up, no difference between psychological and combined treatments was found. Conclusion: We conclude that combined treatment is more effective than psychological treatment alone. However, it is not clear whether this difference is relevant from a clinical perspective. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Personality disorders improve in patients treated for major depression

Mulder RT, Joyce PR, Frampton CMA. Personality disorders improve in patients treated for major depression. Objective: To examine the stability of personality disorders and their change in response to the treatment of major depression. Method: 149 depressed out‐patients taking part in a treatment study were systematically assessed for personality disorders at baseline and after 18 months of treatment using the SCID‐II. Results: Personality disorder diagnoses and symptoms demonstrated low‐to‐moderate stability (overall κ = 0.41). In general, personality disorder diagnoses and symptoms significantly reduced over the 18 months of treatment. There was a trend for the patients who had a better response to treatment to lose more personality disorder symptoms, but even those who never recovered from their depression over the 18 months of treatment lost, on average, nearly three personality disorder symptoms. Conclusion: Personality disorders are neither particularly stable nor treatment resistant. In depressed out‐patients, personality disorder symptoms in general improve significantly even in patients whose response to their treatment for depressive symptoms is modest or poor.     

The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta‐analysis

Cuijpers P, van Straten A, Hollon SD, Andersson G. The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta‐analysis. Objective: Although there is sufficient evidence that combined treatments of psychotherapy and pharmacotherapy are more effective for depression in adults than each of the treatments alone, it remains unclear what the exact contribution of active medication is to the overall effects of combined treatments. This paper examines the contribution of active medication to combined psychotherapy and pharmacotherapy treatments. Method: Meta‐analysis of randomised controlled trials comparing the combination of psychotherapy and pharmacotherapy with the combination of psychotherapy and placebo. Results: Sixteen identified studies involving 852 patients met our inclusion criteria. The standardised mean difference indicating the differences between the combination of psychotherapy and pharmacotherapy and the combination of psychotherapy and placebo was 0.25 (95% CI: 0.03–0.46), which corresponds to a numbers‐needed‐to‐be‐treated of 7.14. No significant differences between subgroups of studies were found. Conclusion: Active medication has a small but significant contribution to the overall efficacy of combined treatments.     

Childhood adversity and vulnerability to mood and anxiety disorders

Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability. Depression and Anxiety 5:66–72, 1997. © 1997 Wiley-Liss, Inc     

Psychosocial and clinical predictors of unipolar depression outcome in older adults

BACKGROUND: This study examined psychosocial and clinical predictors of depression non-remittance among a sample of initially clinically depressed elders. METHODS: Incident and prevalent unipolar depression cases (n = 166) were enrolled into the MHCRC for the Study of Depression in Late Life and followed for 12 months while undergoing treatment using a standardized algorithm. The outcome was remission vs non-remission (<6 vs > 7 on the Montgomery-Asberg Depression Rating Scale (MADRS)) at one-year follow-up. Baseline predictor variables included psychosocial factors, such as four domains of social support, basic and instrumental activities of daily living (ADLs), and clinical factors, which included use of ECT, past history of depression, comorbidities, and antidepressant treatment. RESULTS: At one-year follow-up, 45% of the sample was in remission based upon MADRS scores. In bivariate analyses, non-remitted patients were more likely at baseline to use benzodiazepines, anxiolytic/sedatives, and/or MAO inhibitors than patients in remission, and have more depressive episodes. Among psychosocial factors, non-remitted patients had at baseline, more ADL and IADL problems and decreased subjective social support as compared to patients in remission. In logistic regression analyses more depression episodes, using anxiolytic/sedatives, more IADL problems and decreased subjective social support predicted poor depression outcome after one-year. CONCLUSIONS: While clinical and diagnostic variables were related to improvement, baseline psychosocial factors were also important.     

Personality disorders in dysthymia and major depression.

OBJECTIVE: The purpose of the present study was to investigate the comorbidity of personality disorders in patients with primary dysthymia compared to those with episodic major depression. METHOD: A total of 177 out-patients with primary dysthymia and 187 outpatients with episodic major depression were administered a structured diagnostic interview for DSM-III-R Axis II disorders. In addition, all of these patients completed the BDI, and those with the appropriate level of education also completed the Minnesota Multiphasic Personality Inventory (MMPI). RESULTS: A significantly higher proportion of dysthymic patients than patients with major depression met the criteria for a personality disorder, for borderline, histrionic, avoidant, dependent, self-defeating types and for personality disorders of clusters B and C. Further analysis revealed that the above differences were mainly due to the subgroup of patients with 'early-onset dysthymia'. Finally, patients with a personality disorder, both dysthymics and those with major depression, had significantly higher scores on the BDI and on the majority of the MMPI scales compared to those without a personality disorder. CONCLUSION: The data indicated that (i) dysthymia--mainly that of early onset--is associated with significantly higher personality disorder comorbidity than episodic major depression, and (ii) the presence of a personality disorder is related to more severe overall psychopathology.     

Regional cerebral volume measurements in late-life depression: relationship to clinical correlates, neuropsychological impairment and response to treatment

BACKGROUND: Elderly people who develop depression have demonstrable changes in cerebral structure but little is known of the relationship between regional cerebral volumes, treatment response and cognitive impairment. METHOD: Forty-four patients with major depression diagnosed according to DSM-IIIR criteria underwent magnetic resonance imaging and regional cerebral volumes were quantified using multispectral analysis. Response to antidepressant treatment was assessed prospectively and a neuropsychological test battery was administered. RESULTS: There was a trend for smaller fronto-temporal volumes in the treatment-resistant patients. Impaired immediate working memory was linked with reduced frontal and parietal lobe volume and impaired short-term memory functioning was associated with reduced temporal lobe volume. Ventricular enlargement was associated with prior administration of electro-convulsive therapy, poor physical health and later age at onset of first episode of depression. CONCLUSION: In late-life depression, brain changes should not preclude vigorous antidepressant treatment. Regional cerebral volume changes may be a complication of poor physical health and are associated with memory dysfunction even upon recovery from depression.