Lithium augmentation of antidepressants in treatment-refractory depression.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.81). 02/1998; 59 Suppl 6:28-33; discussion 34.
Source: PubMed

ABSTRACT The use of lithium to convert antidepressant nonresponders to responders is reviewed. Although there is little doubt that lithium is effective in a sizable percentage of patients who do not respond to tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs), much remains obscure about this effect. Does it work preferentially on antidepressants that act primarily on serotonergic neurons, or is it equally effective with agents that act upon other neurotransmitter systems? When should lithium, compared with other strategies, be utilized in antidepressant nonresponders? Are certain subtypes of depression more likely than others to respond to lithium augmentation? The available literature highlights the efficacy of lithium as an augmenting agent in refractory depression and serves as an impetus for additional neurobiological and clinical studies of this phenomenon.

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    ABSTRACT: Bipolar depression is one of the most serious psychiatric conditions. In addition, sleep disturbance in bipolar disorder is common, and therapeutic agents restoring sleep disturbances in bipolar disorder patients will be clinically beneficial. In the current study, we compared the effect of quetiapine XR with lithium on depressive symptoms and sleep in bipolar depression patients during 8 weeks of trial. An open-label, randomized comparison of sleep-activity and depressive symptoms between 8-week quetiapine XR monotherapy and lithium monotherapy for bipolar depression was conducted. Each assessment consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self-reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep parameters were assessed. A total of 42 patients (35.7±10.9 years; gender: male 15, female 27) with bipolar depression were screened out. Out of 42 patients, six patients were excluded before randomization. After randomization, seven patients were withdrawn. Twenty-nine patients with more than two visits after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1±10.4, gender: male 13, female 16) were included in the final analysis. In both groups, Hamilton Depression Rating Scale (HDRS) scores were significantly decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate (HDRS≤7) in the quetiapine XR was significantly higher than that of the lithium group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8 was significantly increased. WASO at week 8 was significantly decreased. First, the present study was conducted with the relatively small number of study subjects. Second, bias could have affected the study results due to its open-label design. Third, study subjects were made up of high proportion of bipolar II disorder patients. Quetiapine XR monotherapy was more effective in treating bipolar depression than lithium. In particular, quetiapine XR treatment improved both subjective and objective sleep quality in patients with bipolar depression. However, relationship between favorable sleep quality and depressive symptom improvement were limited.
    Journal of affective disorders 03/2014; 157:33-40. · 3.76 Impact Factor
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    ABSTRACT: For over half a century, lithium has been the gold standard amongst the pharmacological armamentarium used to treat bipolar disorder. Its ascendancy in this regard has been attributed partly to its primacy of discovery and clinical implementation; however, it is important to consider how it has achieved success and retained its prominence and whether this is because of its unique profile and specificity of actions. In this paper, we briefly discuss the clinical evidence in support of lithium specificity and argue for its continuing use in those patients most likely to benefit, namely, patients with 'classic' bipolar disorder. Further, we suggest that accurate characterization of 'lithium responders' through focused research is likely to yield novel treatments and assist in better understanding of the pathophysiology of the illness. In addition, the unique antisuicidal actions of lithium warrant further examination, as do its impressive properties as a prophylactic agent. This is particularly so given the high morbidity associated with bipolar disorder and its potential for suicide. Hence, in this paper, after describing the changing diagnostic backdrop against which much of the research to date has been conducted, we discuss the clinical therapeutic profile of lithium in both the acute and long-term management of bipolar disorder and its phenotypic specificity of action. We demonstrate that lithium possesses significant clinical and therapeutic efficacy that is very individual and thus remains the treatment of choice for bipolar disorder when used specifically in select patients.
    Bipolar Disorders 07/2009; 11 Suppl 2:34-44. · 4.62 Impact Factor
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    ABSTRACT: Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and other mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and mania specifically, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifest beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context, including a discussion of the evidence implicating the glutamate decarboxylase-like protein 1 (GADL1) gene. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.
    Pharmacology Biochemistry and Behavior 01/2014; · 2.61 Impact Factor


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May 31, 2014