Outcome in refractory depression (original) (raw)
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Journal of Clinical Psychopharmacology, 2002
There is compelling evidence from placebocontrolled studies that lithium augmentation is an effective strategy in the acute and continuation treatment of refractory unipolar major depression. Authors prospectively investigated the 1-year outcome of 22 subjects diagnosed with unipolar major depression who had participated in a 4-month placebo-controlled, double-blind continuation study of lithium augmentation without relapse. At the end of the double-blind phase, the blinded medication (lithium in 14 patients, placebo in 8 patients) was tapered off over a 1-week period, while the antidepressant was continued at the same dosage for another 4 weeks. Subsequently, the antidepressant was gradually discontinued over a 4-week period. Clinical status was assessed at regular follow-up visits. During the open 6-month follow-up period, seven subjects suffered an affective recurrence, five of whom had received lithium during the placebo-controlled, double-blind phase of the study. Study data suggest that active medication should be maintained for at least 1 year after successful lithium augmentation in patients with unipolar major depressive disorder.
Predictors of efficacy in lithium augmentation for treatment-resistant depression
Journal of Affective Disorders, 2010
Background: Lithium augmentation is widely applied for treatment-resistant depression, however, the clinical predictors of its efficacy regarding polarity and bipolarity are unknown. Methods: We retrospectively examined the predictive value of clinical variables in 79 depressed patients who underwent lithium augmentation after failure to respond to antidepressant monotherapy. Lithium augmentation efficacy was evaluated by Clinical Global Impression Improvement assessment 4 to 8 weeks after initiating lithium administration; subjects with scores of 1 and 2 were defined as responders, and those with scores of 3 to 7 as non-responders. Clinical variables, including demographic and diagnostic variables, psychiatric medication, and clinical variables, were compared between groups. The bipolarity of patients with major depressive disorder as a final diagnosis was evaluated in association with the lithium augmentation efficacy. Data were analyzed using a chi-square test or Fisher's test. Results: The lithium augmentation efficacy rate was 41% among 79 enrolled patients (14 dropped out, 32 responders, and 33 non-responders). Lithium augmentation was significantly more effective for patients with a final diagnosis of bipolar disorder than with major depressive disorder (p = 0.03). Subjects with more than three major depressive episodes showed a significant response to lithium augmentation (p = 0.004). The rate of a family history of major depressive disorder/bipolar disorder in a first-degree relative was significantly higher in responders (34%) than in non-responders (7%, p = 0.01), consistent with the association between the efficacy of lithium augmentation and bipolarity in major depressive disorder (responders = 27% vs. non-responders = 3%, p = 0.03). Limitation: The study was retrospective and severity was not analyzed. Conclusion: Bipolar disorder, frequency of major depressive episodes, and family history of major depressive disorder/bipolar disorder in a first-degree relative were detected as predictors of lithium augmentation efficacy. Among them, family history of major depressive disorder/bipolar disorder in a first-degree relative was the most reliable predictor of lithium augmentation efficacy for bipolar disorder and major depressive disorder.
Systematic Review of Lithium Augmentation in Depression Resistant to at Least 2 Antidepressants
The Primary Care Companion to The Journal of Clinical Psychiatry, 2009
To the Editor: Refractory depression is common in clinical practice. At least 30% of patients fail to respond to initial antidepressant therapy. 1 In patients who have failed 1 course of antidepressants, there is evidence from 9 randomized controlled trials suggesting that approximately 50% of treatment-refractory patients do respond to lithium augmentation compared with placebo (p < .001). 2 The British Association for Psychopharmacology guidelines recommend that patients be treated with 2 antidepressants before an augmentation strategy is used. 3 Our aim was to review the evidence for use of lithium in those patients who are resistant to treatment with 2 or more antidepressants at recognized therapeutic doses. Method. A systematic review was undertaken of placebo-controlled, double-blind, randomized trials of lithium that assess its effectiveness in treatment-resistant depression. English-language studies of adults (aged 18 years or older; both sexes), suffering from major depressive disorder diagnosed by the International Classification of Diseases, Tenth Revision (ICD-10), the Diagnostic Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or Research Diagnostic Criteria (RDC) were included. The following keywords were used:
Pharmacopsychiatry, 2001
This communication reviews current literature on lithium augmentation in patients not responding to SSRIs, giving some recommendations at the end. A significant proportion of depressive patients do not respond to a first antidepressive treatment independently of the class of drugs used. During the last 10 years, there have been several case reports published about open and controlled studies on the use of lithium augmentation in patients who were non-responders to SSRIs, including citalopram, fluoxetine, paroxetine and sertraline. The main underlying hypothesis is a synergistic effect between SSRIs and lithium, which both act on serotonergic neurotransmission. The available studies vary considerably in methodology. There are insufficient results available to confirm a rapid improvement (within 24 ± 48 h) after introduction of lithium, but most studies show substantial effects after 1 ± 2 weeks, and some after 6 weeks. There is as yet no more clear evidence for a pharmacokinetic interaction between lithium and SSRIs with pharmacodynamic consequences. In conclusion, present evidence suggests that a lithium augmentation in depressive patients who do not respond to SSRIs may be an efficacious and generally well tolerated treatment, with a response rate of at least 50 % after a period lasting 1 ± 2 weeks. However, special care is indicated when treating elderly patients, where the risk of adverse effects is higher.
Long-term naturalistic follow-up of lithium augmentation: Relevance to bipolarity
Journal of Affective Disorders, 2011
Background: Whether bipolarity (unrecognized bipolar disorder) is related to the treatment response to lithium augmentation in antidepressant-refractory depression remains unclear. This study of responders and non-responders to lithium augmentation of 29 antidepressantrefractory patients with major depression, whom we had studied during 1995-1997, compared the bipolar diagnosis at the follow-up based on diagnostic confirmation after longterm follow-up.
2003
Objective: This systematic review examines the evidence and discusses the clinical relevance of lith- ium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. Method: We searched the Medline computer database and
2020
Background: Depressive disorder is the main cause associated with recurrent morbidity which is often associated with suicides. Treatment of depression with antidepressant and electroconvulsive therapy is commonly used and proven effective. Based on previous study, administration of lithium as an augmentation therapy showed efficacy in suicidal behavior. The role of lithium as first line for bipolar disorder in manic episodes, also be an option in unipolar depression with some conditions such as antidepressant resistence, recurrent depression, maintenance therapy which is respond to electroconvulsive therapy and suicide behavioral. Method: The authors conducted an extensive search of the published literature using several terms, including major depressive, lithium, antidepressant and antisuicidal effects. Relevant article were retrieved from PubMed, Cochrane, Springer, ScienceDirect. Conclusion: Lithium given along antidepressants has proven effective in treatment of unipolar depression, preventing relaps and also has anti-suicide effect
Journal of Clinical Psychopharmacology, 2013
Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants. The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place). Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks. Response rates (decrease in Hamilton Depression Rating Scale score 950%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects. Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.