Lamotrigine versus lithium augmentation of antidepressant therapy in treatment-resistant depression: efficacy and tolerability.

Institute for psychiatry, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
Psychiatria Danubina (Impact Factor: 0.63). 07/2009; 21(2):187-93.
Source: PubMed

ABSTRACT Mood stabilizer augmentation of standard antidepressant drugs has been shown to be effective in treatment-resistant depression. Despite the reported high overall efficacy, lithium has been relatively underused in recent years. Lamotrigine, a novel anticonvulsant recently recognized as a mood stabilizer, seems to have putative antidepressive properties. The aim of the study was to investigate lamotrigine efficacy and tolerability as antidepressant augmentation for unipolar treatment-resistant depression compared to lithium.
88 patients suffering from treatment-resistant Major depressive disorder, having acute recurrent depressive episodes according to DSM-IV criteria, were enrolled in the study. This was an open-label trial with a flexible dosing regimen. All patients, received antidepressants in full therapeutic doses. They were divided into two augmentation groups: 46 patients received 50-200 mg/day lamotrigine, and 42 patients received 600-1200 mg/day lithium. The Hamilton Rating Scale for Depression (HAM-D) and The Clinical Global Impression scale (CGI) were used to monitor therapeutic efficacy. Patients were evaluated weekly for an 8 week treatment period.
The HAM-D total score was significantly reduced in both treatment groups at the study endpoint, without any difference between the groups. However, significant clinical improvement was reached within the second treatment week in the lamotrigine group compared to the lithium group (p=0.01 vs. lithium). Lamotrigine showed significant efficacy on the HAM-D item 1(depressed mood; p=0.01), item 7 (work and interest; p=0.01) and CGI-Improvement scale (p=0.02). The drop-out rate due to treatment failure was lower in the lamotrigine group (n=1) compared to the lithium (n=4) group. Also, the incidence of side effects did not differ between the groups.
Our results suggest that lamotrigine could be useful as augmentation of antidepressants for treatment-resistant unipolar depression. Also, lamotrigine may accelerate the onset of antidepressant action, and therefore might be useful in treatment of major depression in general.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Depression often coexists with epilepsy. Simultaneous therapy of the two diseases may be associated with pharmacodynamic and/or pharmacokinetic interactions between antiepileptic and antidepressant drugs. The aim of this study was to investigate the influence of acute and chronic treatment with intraperitoneal milnacipran (MLN), a selective serotonin/noradrenaline reuptake inhibitor, on the protective activity of valproate, carbamazepine (CBZ), phenytoin, or phenobarbital (PB) in the maximal electroshock (MES) test in mice. Electroconvulsions were produced by an alternating current (50 Hz, 25 mA) delivered via ear-clip electrodes. Motor coordination and long-term memory were evaluated in the chimney test and passive-avoidance task, respectively. Brain concentrations of antiepileptic drugs (AEDs) were assessed by immunofluorescence. Given acutely, MLN at 10 mg/kg increased the convulsive threshold. Acute MLN applied at the subprotective dose of 5 mg/kg enhanced the anticonvulsant effects of CBZ and PB. Chronic treatment with MLN (5-30 mg/kg once daily for 2 weeks) did not affect either the electroconvulsive threshold or the anticonvulsant action of all studied conventional antiepileptic drugs. Since the antidepressant did not affect brain concentrations of antiepileptics used in the study, the revealed interactions seem to be of pharmacodynamic nature. Moreover, acute and chronic MLN, AEDs, and their combinations did not produce significant motor and long-term memory impairment. Acute, but not chronic, treatment with MLN can increase the effectiveness of some AEDs against MES-induced seizures in mice. It seems that MLN may also be considered as a candidate drug for clinical trials in patients with epilepsy and depressive disorders.
    Psychopharmacology 10/2009; 207(4):661-9. · 4.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reason why depression may respond poorly to treatment with antidepressant drugs may be connected with the features of bipolarity. Evidence to this effect has accumulated in recent studies of various kinds of depression in mood disorders. Additional evidence for such a connection may be the efficacy of mood-stabilizing drugs in the augmentation of antidepressants in treatment-resistant depression. This review is based on clinical and psychopharmacological research performed over the past five years. The clinical investigation was based on the response to antidepressants of bipolar depression or to symptoms of hypomania, assessed mainly by the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32). The psychopharmacological research tested the efficacy of augmentation of antidepressants in treatment-resistant depression by mood-stabilizing drugs of the 1st and 2nd generations. A number of studies have pointed to an association between bipolar depression, or symptoms of hypomania and an inadequate response to antidepressants. Such a connection was also found in the Polish TRES-DEP study which included 1051 depressed patients. Pharmacological studies have demonstrated the efficacy of first generation mood-stabilizing drugs (lithium, carbamazepine) and second generation drugs (quetiapine, olanzapine, risperidone, ziprasidone, lamotrigine) for augmentation of antidepressants in treatment-resistant depression. Some evidence has been presented that mixed depressive episodes may also belong to this category. The results of these clinical and psychopharmacological studies appear to confirm an association between bipolarity and a poor response of depression to treatment with antidepressant drugs.
    Journal of affective disorders 05/2011; 136(1-2):e13-9. · 3.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients. We therefore reviewed the main characteristics of these drugs regarding their efficacy, tolerability, side effects and cost-effectiveness, by accessing all meta-analyses and systematic reviews published from 2004 to 2009. In addition, we reviewed the augmentation strategy of associated antidepressants with neurostimulation therapies (such as transcranial magnetic stimulation [TMS] and transcranial direct current stimulation [tDCS]). A search was undertaken in MEDLINE, Web of Science, Cochrane, and Scielo databases. We included: 21 meta-analyses of antidepressant trials, 15 neurostimulation clinical trials and 8 studies of pharmacoeconomics. We then performed a comprehensive review on these articles. Although recent meta-analyses suggest sertraline and escitalopram might have increased efficacy/tolerability, other studies and large pragmatic trials have not found these to be superior to other antidepressant drugs. Also, we did not identify any superior drug in terms of cost-effectiveness due to the different designs observed among pharmacoecomics studies. Side effects such as sexual dysfunction, gastrointestinal problems and weight gain were common causes of discontinuation. Tolerability was an important issue for novel neurostimulation interventions, such as TMS and tDCS. These therapies might be interesting augmentation strategies, considering their benign profile of side effects, if proper safety parameters are adopted.
    Therapeutics and Clinical Risk Management 01/2009; 5:897-910.

Full-text (2 Sources)

Available from
May 20, 2014