Delusional depression responds poorly to acute antidepressant monotherapy but appears to respond to intensive combination pharmacotherapy, however with poor short-term outcomes after initial improvement, particularly in later life. The authors compared the efficacy and safety of continuation combination therapy to monotherapy among older patients after remission from a delusional depression. Twenty-nine older adults with SCID-diagnosed major depression with delusions received continuation treatment with nortriptyline-plus-perphenazine or nortriptyline-plus-placebo under randomized double-blind conditions after achieving remission after ECT. Of the 28 subjects included in efficacy analyses, 25% suffered relapses. The relapse frequency was nonsignificantly greater in combination therapy than in monotherapy subjects. However, combination subjects had significantly more extrapyramidal symptoms, an increased incidence of tardive dyskinesia, and a greater number of falls. Continuation treatment with a conventional antipsychotic does not decrease relapse rates but is associated with significant untoward adverse events in older persons after recovery from a delusional depression.
"A 20% difference would mean that 5 patients would need to be treated with olanzapine to prevent 1 case of relapse. Based on the review of literature
[14-16,65] and STOP-PD stabilization data, we estimate that 15% of participants who are maintained on sertraline plus olanzapine will have a relapse in the RCT. A relapse rate of 35% in the sertraline plus placebo group would therefore be consistent with the hypothesized 20% difference between treatment groups. "
[Show abstract][Hide abstract] ABSTRACT: Background:
Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.
The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.
This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.
"They were younger, with earlier onset longer duration of current episode and history of previous episodes. Finally , in the only randomized controlled trial the effect of continuation treatment comparing a combination with monotherapy (nortritpyline plus perphenazine versus nortriptyline plus placebo) was examined in older adults with PMD for 26 weeks . No difference was found between the two treatment regimens. "
[Show abstract][Hide abstract] ABSTRACT: In 1992, a comprehensive review of all previous studies comparing patients suffering from psychotic major de-pression (PMD) to non-PMD patients was published. In this review we present data of all studies comparing PMD pa-tients to non-PMD published in the English language after 1992. The research papers reviewed have shown the following general profile of PMD: the point prevalence of PMD is about 0.4% and 19% of patients with a major depressive episode had psychotic symptoms as well. PMD was found to be a more severe form of depression with more feelings of guilt and more pronounced psychomotor disturbance. Additionally, PMD patients compared to non-PMD were found to be more severely impaired in the cognitive domains of attention, psychomotor speed, executive function and memory, regardless of depression's severity. As regards to the prognosis of the disorder, PMD is associated with poorer short-term outcome; nevertheless, in the long-term period (> 2-5 years) the prognostic significance of delusions in major depression tends to become weaker. However, the recurrence of psychotic episodes in PMD patients suggests that PMD runs "true to form". Of note, young PMD patients with acute onset of the disorder are at greater risk to develop bipolar disorder. Furthermore, PMD was associated with greater HPA abnormalities, higher plasma cortizol levels during the afternoon, lower serum DH activity than age-matched non-PMD patients and healthy controls. In addition, more brain atrophy and paralimbic abnormalities may play a crucial role in the delusion formation. With respect to management of PMD, starting with a combination of AD plus AP or AD as monotherapy may be preferred. Nevertheless, methodological problems in studies on SSRIs as monotherapy and according to recent data -favoring the combination over AD monotherapy-the AP plus AD treatment regime takes precedence.
Current Psychiatry Reviews 02/2009; 5(1). DOI:10.2174/157340009787315271
[Show abstract][Hide abstract] ABSTRACT: One of the common mental disorders seen in elderly population is depression.Though the incidence of depression is similar to that seen in younger adults; when it occurs it is more likely to be severe with higher risk of suicide and frequently requires hospital admission. It leads to more number of consultations with the treating agencies. It also leads to significant burden on families. Early recognition, diagnosis, and initiation of treatment for depression in older people present opportunities for improving their quality of life, preventing suffering or premature death, and maintaining optimal levels of function and independence. Earlier diagnosis and effective treatment of depression in old age can lead to significant reduction in morbidity, mortality due to suicide and medical illnesses and health care costs. The purpose of these guidelines is to present a framework for the evaluation, treatment, and follow- up of geriatric patient, who present with depression. To a large extent these guidelines are evidence based. Most of the data presented in these guidelines is from the western countries, as there is only meager research from India and other developing countries. For the purpose of review of literature, the studies which have been reviewed have been limited to the population aged 60 or more. We hope that these guidelines would help in facilitating proper management and avoiding unnecessary expense and inconvenience. However it is to be remembered that these guidelines are not a substitute for professional knowledge and clinical judgement.
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