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: 5.5). 02/1998; 59 Suppl 6:28-33; discussion 34.
Source: PubMed


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.

Download full-text


Available from: Charles B Nemeroff,
  • Source
    • "It is the standard treatment for bipolar depression and is also effective against recurrent unipolar depression. It can be used in conjunction with antidepressants (Heit and Nemeroff, 1998) or as a temporary mood stabilizer between treatments (Lenox et al., 1998). Li ϩ , however, has a small therapeutic index and a number of hazardous side effects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The therapeutic properties of lithium ions (Li+) are well known; however, the mechanism of their action remains unclear. To investigate this problem, we have isolated Li+-resistant mutants from Dictyostelium. Here, we describe the analysis of one of these mutants. This mutant lacks the Dictyostelium prolyl oligopeptidase gene (dpoA). We have examined the relationship between dpoA and the two major biological targets of lithium: glycogen synthase kinase 3 (GSK-3) and signal transduction via inositol (1,4,5) trisphosphate (IP3). We find no evidence for an interaction with GSK-3, but instead find that loss of dpoA causes an increased concentration of IP3. The same increase in IP3 is induced in wild-type cells by a prolyl oligopeptidase (POase) inhibitor. IP3 concentrations increase via an unconventional mechanism that involves enhanced dephosphorylation of inositol (1,3,4,5,6) pentakisphosphate. Loss of DpoA activity therefore counteracts the reduction in IP3 concentration caused by Li+ treatment. Abnormal POase activity is associated with both unipolar and bipolar depression; however, the function of POase in these conditions is unclear. Our results offer a novel mechanism that links POase activity to IP3 signalling and provides further clues for the action of Li+ in the treatment of depression.
    The EMBO Journal 06/1999; 18(10):2734-45. DOI:10.1093/emboj/18.10.2734 · 10.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A substantial part of patients with major depressive episode do not respond to antidepressants. Lithium can presently be considered the best validated augmentation strategy for patients not responding to tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI's), venlafaxine, and mirtazapine. We present a report of successful lithium aug- mentation in a patient not responding to the highly selective noradrenaline reuptake inhibitor reboxetine. Whereas syn- ergistic serotonergic mechanisms have habitually been proposed as the neurobiological basis of lithium augmentation, the presented observation raises the question of other possible rationalizations. Lithium augmentation should be considered as a treatment strategy in case of non response to specific noradrenergic antidepressants, and this strategy merits further investigations (German J Psychiatry 2005; 9: 31-32).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To review the pharmacological treatment of depression and to evaluate current strategies for treatment to maximize the benefits of antidepressant medications. MEDLINE was searched to January 1999, using the headings depression, combination, augmentation, lithium, triiodothyronine, pindolol, buspirone, methylphenidate, and electroconvulsive therapy, for randomized controlled trials, systematic overviews, and consensus reports. Recent high-quality reviews were often found. References from papers retrieved were scrutinized for other relevant reports. Preference was given to more recent articles and well-designed studies. Recommendations from academic groups were analyzed. Optimization of antidepressant therapy is the cornerstone of pharmacological treatment of depression. When symptoms persist despite optimization, further strategies include substitution, combination, augmentation, and reviewing and sometimes referring. Decisions are based on the evidence supporting the various strategies. Antidepressants will work only if prescribed correctly. Awareness of the strategies for using antidepressants and evaluating their effectiveness improves primary care physicians' ability to treat this common disorder.
    Canadian family physician Médecin de famille canadien 12/1999; 45:2663-8. · 1.34 Impact Factor
Show more