Article

Augmentation and combination strategies for depression

Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA.
Journal of Psychopharmacology (Impact Factor: 2.81). 06/2006; 20(3 Suppl):11-8. DOI: 10.1177/1359786806064310
Source: PubMed

ABSTRACT Treatment-resistant depression represents a common problem, with the vast majority of depressed patients showing incomplete response to antidepressant trials. Augmentation and combination strategies are commonly employed to address this problem, but there are few randomized, controlled studies to guide treatment choice. Indeed, some of the most common augmentation strategies in depression are those with the least controlled evidence. The popularity of bupropion, psychostimulants and atypical antipsychotics as augmentors may not be warranted by existing controlled studies, whereas two less commonly used augmentors-lithium and thyroid hormone- have substantial controlled evidence to support their use. This paper summarizes the state of the evidence for commonly used augmenting strategies and explores preliminary findings for more investigational approaches.

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    • "interventions are being developed. New pharmacologic interventions include NMDA antagonists, as zinc (Nowak et al., 2003a), and the addition of one or more agents to an existing antidepressant regimen (DeBattista, 2006). Our results show, to our knowledge for the first time, that ZnCl 2 given systemically by p.o. route (10 and 30 mg/kg) is effective in reducing the immobility time in the TST, consistent with an antidepressant-like effect in this predictive test of antidepressant action (Steru et al., 1985). "
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    ABSTRACT: The antidepressant-like activity of creatine in the tail suspension test (TST) was demonstrated previously by our group. In this study we investigated the involvement of the noradrenergic system in the antidepressant-like effect of creatine in the mouse TST. In the first set of experiments, creatine administered by i.c.v. route (1 μg/site) decreased the immobility time in the TST, suggesting the central effect of this compound. The anti-immobility effect of peripheral administration of creatine (1 mg/kg, p.o.) was prevented by the pretreatment of mice with α-methyl-p-tyrosine (100 mg/kg, i.p., inhibitor of tyrosine hydroxylase), prazosin (1 mg/kg, i.p., α1-adrenoceptor antagonist), but not by yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist). Creatine (0.01 mg/kg, subeffective dose) in combination with subeffective doses of amitriptyline (1 mg/kg, p.o., tricyclic antidepressant), imipramine (0.1 mg/kg, p.o., tricyclic antidepressant), reboxetine (2 mg/kg, p.o., selective noradrenaline reuptake inhibitor) or phenylephrine (0.4 μg/site, i.c.v., α1-adrenoceptor agonist) reduced the immobility time in the TST as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of α1-adrenoceptor and that creatine produces synergistic effects in the TST with antidepressants that modulate noradrenaline transporter, suggesting that an improvement in the response to the antidepressant therapy may occur when creatine is combined with these antidepressants. Furthermore, the synergistic effect of creatine (0.01 mg/kg, p.o.) and reboxetine (2 mg/kg, p.o.) combination was abolished by the α1-adrenoceptor antagonist prazosin, indicating that the antidepressant-like effect of combined therapy is likely mediated by an activation of α1-adrenoceptor.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2013; DOI:10.1016/j.pnpbp.2013.01.014 · 4.03 Impact Factor
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    • "Pindolol (7.5 mg daily) augmentation of SSRIs is probably not effective in treatment-resistant depression; two small studies were positive (Maes, et al., 1999; Sokolski, et al., 2004) but three, including the two largest were not (Moreno, et al., 1997; Perez, et al., 1999; Perry, et al., 2004). Manipulation of the glucocorticoid system may be of benefit in treatment-resistant depression but somewhat confusingly both antiglucocorticoid treatment and steroid agonists may have some efficacy (DeBattista, 2006). An RCT in nonresistant patients of 3-weeks treatment with the steroid synthesis inhibitor metyrapone added to nefazodone or fluvoxamine found better response at 5 weeks compared with placebo (58% versus 33%, NNT 4) (Jahn, et al., 2004) and a small RCT of predominantly treatment-resistant patients found an advantage over placebo to the addition of dehydroepiandrosterone (DHEA) to ongoing treatment (Wolkowitz, et al., 1999). "
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    ABSTRACT: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.
    Journal of Psychopharmacology 07/2008; 22(4):343-96. DOI:10.1177/0269881107088441 · 2.81 Impact Factor
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    ABSTRACT: Lithium augmentation, first described in 1981, is considered one of the best-supported strategies for treating refractory depression. However, clinical use of this approach has fallen dramatically in recent years, and some recent studies have cast doubt over its efficacy. This article reviews published findings in order to clarify the current role of lithium augmenta-tion in treating refractory depression. Ten placebo-controlled studies, eight comparator-controlled studies, and 13 uncontrolled large-scale prospec-tive studies of acute efficacy were reviewed in addition to six studies of effects on long-term outcome. Detailed examination found that controlled studies of lithium augmentation suffer from inadequate criteria for refractoriness, marked variability in duration of augmentation, variability in lithium levels, inadequate criteria for evaluating response, and idiosyn-cratic designs. Even more recent studies, while methodologically superior to earlier trials, have significant limitations, especially with respect to vari-ability in lithium levels. "True" response rates to lithium augmentation are likely between 30% to 40%, rather than the 50% assumed by clinicians. A more balanced appraisal of the benefits and risks of this underutilized approach might encourage its wider use by clinicians.
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