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Recent research: six studies on depression - adolescents, heart disease, telephone management, memories, & primary care

Here are half a dozen recent research papers on depression (all details & abstracts to these studies are listed further down this blog post).  The first two are about the well-known Treatment for Adolescents with Depression Study (TADS).  There have been a whole series of research papers published on this large multisite US National Institute of Mental Health funded study.  For more information click on the TADS home page.  The study compared CBT, fluoxetine, or their combination in treating moderate to severe depression in teenagers.  As March & Vitiello state in their overview "Findings revealed that 6 to 9 months of combined fluoxetine plus CBT should be the modal treatment from a public health perspective as well as to maximize benefits and minimize harms for individual patients ... The combination of fluoxetine and CBT appears to be superior to both CBT monotherapy and fluoxetine monotherapy as a treatment for moderate to severe major depressive disorder in adolescents."  The trial ran in four phases which - for those receiving CBT - involved an initial 2 to 3 assessment sessions, and then a 9 month treatment sequence consisting of 12 to 14 treatment sessions over the first 12 week acute treatment stage, 2 to 6 treatments over the next 6 week consolidation stage, and then 3 treatment sessions over the 18 week continuation stage.  Finally there were 4 assessment (not treatment) visits over a further one year naturalistic follow-up.  The second paper quote below reports on the results of the naturalistic follow-up.  Encouragingly the researchers were able to report "The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality ... In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up."

Changing focus, the commentary by Hatcher reports on research looking at "Association between depressive symptoms and cardiovascular events in people with coronary heart disease largely due to physical inactivity."  It was found that in a follow up of " ... 1017 outpatients with stable coronary heart disease ... followed them up for nearly 5 years ... The 20% of people identified as depressed in this group had 50% more cardiac events than those who were not depressed. Most of this increased risk was associated with physical inactivity."  The understandable conclusion is that " ... for people with heart disease, interventions for low mood, which focus on increasing activity, may lead to treatments which decrease the rate of subsequent cardiovascular events as well as improving depression."

Simon, Ludman & colleagues looked at "Incremental Benefit and Cost of Telephone Care Management and Telephone Psychotherapy for Depression in Primary Care."  They found that "Compared with current primary care practice, a structured telephone program including care management and cognitive behavioral psychotherapy has significant clinical benefit with only a modest increase in health services cost."  Kuyken & Moulds reported on "Remembering as an observer: how is autobiographical memory retrieval vantage perspective linked to depression?"  Interestingly they found that "The tendency to retrieve observer perspective memories was associated with greater negative self-evaluation, lower dispositional mindfulness, and greater use of avoidance. Furthermore, participants who recalled more field perspective memories at pre-treatment had lower levels of post-treatment depression, controlling for pre-treatment levels of depression and trait rumination."

Finally Vuorilehto et al published on "Course and outcome of depressive disorders in primary care: a prospective 18-month study."  They followed up a group of 137 people diagnosed as suffering from a variety of depressive disorders in primary care to see how they did.  "Altogether 123 patients (90%) completed the 18-month follow-up, including 79 with major depressive disorder (MDD) and 44 with subsyndromal disorders ... Of the patients with MDD, only a quarter [25% (20/79)] achieved and remained in full remission, while another quarter [25% (20/79)] persisted in major depressive episode for 18 months. The remaining 49% (39/79) suffered from residual symptoms or recurrences ... Of the subsyndromal patients, 25% (11/44) proceeded to MDD.  Conclusions  This prospective medium-term study verified the high rate of recurrences and chronicity of depression also in primary care. Severity of depressive symptoms and co-morbidity are important predictors of outcome. Development of chronic disease management for depression is warranted in primary care."  Sobering findings.

March, J. S. and B. Vitiello (2009). "Clinical Messages From the Treatment for Adolescents With Depression Study (TADS)." Am J Psychiatry 166(10): 1118-1123.   [Abstract/Full Text] 
OBJECTIVE: The purpose of this report was to summarize the key clinical messages from the Treatment for Adolescents with Depression Study (TADS). METHODS: TADS is a National Institute of Mental Health (NIMH)-funded randomized controlled trial designed to evaluate the relative effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and the combination of fluoxetine plus CBT across acute treatment, maintenance treatment, and naturalistic follow-up periods among adolescents with major depressive disorder. RESULTS: Findings revealed that 6 to 9 months of combined fluoxetine plus CBT should be the modal treatment from a public health perspective as well as to maximize benefits and minimize harms for individual patients. CONCLUSION: The combination of fluoxetine and CBT appears to be superior to both CBT monotherapy and fluoxetine monotherapy as a treatment for moderate to severe major depressive disorder in adolescents.

Treatment for Adolescents With Depression Study, T. (2009). "The Treatment for Adolescents With Depression Study (TADS): Outcomes Over 1 Year of Naturalistic Follow-Up." Am J Psychiatry 166(10): 1141-1149.   [Abstract/Full Text]
OBJECTIVE: The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period. METHOD: The randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Children's Depression Rating Scale--Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure. RESULTS: Sixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality. CONCLUSIONS: In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up.

Hatcher, S. (2009). "Association between depressive symptoms and cardiovascular events in people with coronary heart disease largely due to physical inactivity." Evid Based Ment Health 12(3): 75-. [Extract/Full Text] 
The depression and cardiac disease story is a puzzle for two reasons. Firstly, people who have had a recent heart attack are at a considerably higher risk of having another heart attack if they are depressed. However, treatment of the depression seems to make little difference to this risk. Secondly, it is not clear why people who are depressed are at higher risk of heart disease. This paper addresses the second question. Several mechanisms have been proposed, including lifestyle factors such as smoking associated with both depression and heart disease; the effects of antidepressants on the heart; and decreased heart rate variability. The hope is that if we are clearer about why there is a link between depression and heart disease we may be able to design more effective treatments.  This paper (Whooley MA, de Jonge P, Vittinghoff E, et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 2008;300:2379-88) identified 1017 outpatients with stable coronary heart disease from San Francisco and followed them up for nearly 5 years. The 20% of people identified as depressed in this group had 50% more cardiac events than those who were not depressed. Most of this increased risk was associated with physical inactivity. It is worth noting that in this study the definition of activity was fairly modest with someone who did 15 min of brisk walking once a week defined as "quite active" (sic). The impact of physical inactivity on subsequent cardiovascular events was about the same as having a past history of a stroke or currently smoking.  The significance of this paper is that it is one of the first to publish the results of a comprehensive follow-up of a well described cohort of people with established heart disease. What is needed are similar studies in people who have had acute cardiac events, rather than people with stable heart disease, to investigate whether the link between depression and subsequent cardiovascular disease is still accounted for by physical inactivity. In the meantime, for people with heart disease, interventions for low mood, which focus on increasing activity, may lead to treatments which decrease the rate of subsequent cardiovascular events as well as improving depression.

Simon, G. E., E. J. Ludman, et al. (2009). "Incremental Benefit and Cost of Telephone Care Management and Telephone Psychotherapy for Depression in Primary Care." Arch Gen Psychiatry 66(10): 1081-1089.  [Abstract/Full Text] 
Context Effectiveness of organized depression care programs is well established, but dissemination will depend on the balance of benefits and costs. Objectives To estimate the incremental benefit, incremental cost, and net benefit of 2 depression care programs. Design Randomized trial comparing 2 interventions with continued usual care, conducted between November 2000 and June 2004. Setting Seven primary care clinics of a prepaid health care plan in Washington. Participants Consecutive primary care patients starting antidepressant treatment were invited to a telephone assessment 2 weeks later. Of 634 patients with significant depressive symptoms, 600 consented and were randomized. Interventions The telephone care management intervention included up to 5 outreach calls for monitoring and support, feedback to treating physicians, and care coordination. The care management plus telephone psychotherapy intervention added an 8-session structured cognitive behavioral therapy program with up to 4 additional calls for reinforcement. Main Outcome Measures Independent, blinded telephone assessments at 1, 3, 6, 9, 12, and 18 months included the Symptom Checklist 90 depression scale. Health services costs were measured using health care plan accounting records. Results Over 24 months, telephone care management led to a gain of 29 depression-free days (95% confidence interval, -6 to +63) and a $676 increase in outpatient health care costs (95% confidence interval, $596 lower to $1974 higher). The incremental net benefit was negative even if a day free of depression was valued up to $20. Care management plus psychotherapy led to a gain of 46 depression-free days (95% confidence interval, +12 to +80) and a $397 increase in outpatient costs (95% confidence interval, $882 lower to $1725 higher). The incremental net benefit was positive if a day free of depression was valued at $9 or greater. Conclusion Compared with current primary care practice, a structured telephone program including care management and cognitive behavioral psychotherapy has significant clinical benefit with only a modest increase in health services cost.

Kuyken, W. and M. L. Moulds (2009). "Remembering as an observer: how is autobiographical memory retrieval vantage perspective linked to depression?" Memory 17(6): 624-34.  [Abstract/Full Text] 
It has long been noted that the emotional impact of an autobiographical memory is associated with the vantage perspective from which it is recalled (Freud, 1950). Memories recalled from a first-person "field" perspective are phenomenologically rich, while third-person "observer" perspective memories contain more descriptive but less affective detail (Nigro & Neisser, 1983). Although there is some evidence that depressed individuals retrieve more observer memories than non-depressed individuals (e.g., Kuyken & Howell, 2006), little is known of the cognitive mechanisms associated with observer memories in depression. At pre- and post-treatment, 123 patients with a history of recurrent depression completed self-report measures and the autobiographical memory task (AMT). Participants also indicated the vantage perspective of the memories recalled on the AMT. Observer memories were less vivid, older, and more frequently rehearsed. The tendency to retrieve observer perspective memories was associated with greater negative self-evaluation, lower dispositional mindfulness, and greater use of avoidance. Furthermore, participants who recalled more field perspective memories at pre-treatment had lower levels of post-treatment depression, controlling for pre-treatment levels of depression and trait rumination. We apply contemporary accounts from social and cognitive psychology, and propose potential mechanisms that link the tendency to retrieve observer perspective memories to depression.

Vuorilehto, M. S., T. K. Melartin, et al. (2009). "Course and outcome of depressive disorders in primary care: a prospective 18-month study." Psychological Medicine 39(10): 1697-1707.  [Abstract/Full Text] 
Background  Depressive disorders are known to often be chronic and recurrent both in the general population and in psychiatric settings. However, despite its importance for public health and services, the outcome of depression in primary care is not well known.  Method  In The Vantaa Primary Care Depression Study (PC-VDS), 1111 consecutive primary-care patients were screened for depression with the Prime-MD screen, and 137 diagnosed with DSM-IV depressive disorders by interviewing with the Structured Clinical Interview for DSM-IV (SCID)-I/P and SCID-II. This cohort was prospectively followed-up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the 18-month follow-up, including 79 with major depressive disorder (MDD) and 44 with subsyndromal disorders. Duration of the index episode and the timing of relapses/recurrences were examined using a life-chart.  Results  Of the patients with MDD, only a quarter [25% (20/79)] achieved and remained in full remission, while another quarter [25% (20/79)] persisted in major depressive episode for 18 months. The remaining 49% (39/79) suffered from residual symptoms or recurrences. In Cox regression models, time to remission and recurrences were robustly predicted by severity of depression, and less consistently by co-morbid substance-use disorder, chronic medical illness or cluster C personality disorder. Of the subsyndromal patients, 25% (11/44) proceeded to MDD.  Conclusions  This prospective medium-term study verified the high rate of recurrences and chronicity of depression also in primary care. Severity of depressive symptoms and co-morbidity are important predictors of outcome. Development of chronic disease management for depression is warranted in primary care.

 

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