Lamotrigine Augmentation Research Articles

Rapid Improvement in Bipolar II Depression Induced by Low-Dose Lamotrigine Augmentation: Two Case Reports

Rapid Improvement in Bipolar II Depression Induced by Low-Dose Lamotrigine Augmentation: <i>Two Case Reports</i>

Systematic review of lamotrigine augmentation of treatment resistant unipolar depression (TRD)

Objective: Our aim was to review all the evidence of lamotrigine's effectiveness in treatment resistant depression after at least one failed antidepressant trial.Method: We used a systematic search strategy to identify studies that included adults aged 18–65 years with a diagnosis of unipolar depression who had not responded to at least a 4-week course of a recommended dose of an antidepressant.Results: We found only one randomized, double blind study that has been published, showing its effectiveness for treatment-resistant depression. In this study, lamotrigine was found statistically superior to placebo on the CGI scale for severity and improvement; however, it was not on the HAM-D (primary end point) and MADRS scales. There were a number of smaller non RCT's which are included.Conclusions: There is little evidence to guide the use of lamotrigine for depression that has not responded to a course of antidepressants. Treatment-refractory depression continues to be significant mental health problem and large RCT trials are needed to inform clinical practice.

Lamotrigine augmentation for the treatment-resistant mood disorder

Purpose: A number of depressed patients do not respond adequately to standard antidepressant treatments, and some of them subsequently suffer from treatment-resistant mood disorder (TRMD). Lamotrigine (LTG) is the only mood stabilizer that is effective for preventing depressive episodes of bipolar disorders. This study aimed to evaluate the efficacy of LTG augmentation in Japanese patients with TRMD. Methods: The subjects were 30 patients with refractory depression who had already shown insufficient response to multiple pharmacotherapy including antidepressants, mood stabilizers and atypical antipsychotics. The diagnoses were major depressive disorder (n=16), bipolar disorder (n=10) and dysthymic disorder (n=4). All patients gave written informed consent to receive LTG as an off-label indication in Japan after explanation for possible risks of unwanted skin reactions. The daily dose of LTG was titrated by the clinician's decision (88.0±61.9 mg/day). Treatment response was assessed by Montgomery-Asberg Depression Rating Scale (MADRS) and Global Assessments of Functioning (GAF) before and after the 8-week LTG augmentation. Results: Significant improvements were observed in the scores of MADRS (25.3±10.1 → 14.7±10.5) and GAF (49.2±12.3 → 64.1±11.7) after the 8-week LTG augmentation (p=0.0010). Greater number of the past mood episodes and shorter duration of the present depressive episode are associated with better response to LTG. Mild adverse skin reactions developed in 10 patients although 8 out of them were treatment responders. Discussion: LTG augmentation may be effective for the treatment of TRMD, especially with shorter duration of unremitted depression and more recurrent episodes. However, attention should be paid to the development of adverse skin reactions in LTG responders.

P03-360 - The effect of lamotrigine augmentation to haloperidol deaconate in the treatment of resistant schizophrenia: randomized, double-blind, placebo-controlled, study

ObjectiveThe current paper reports on a double-blind, randomized study of the role of lamotrigine as an augmentation agent to haloperidol deaconate in the treatment of out patient's schizophrenia with verbal resistant hallucinosis.MethodThree hundred fifty patients were studied. The patients were then randomly divided into two groups on 175 subjects in each group. First group patients received either haloperidol deaconate 100 mg in month intramuscular and lamotrigine 150-200 mg in day per so for 12 weeks. Second group patients were given haloperidol deaconate 100 mg in month intramuscular and placebo per os for 12 weeks. The expressiveness of psychopathology was estimated on PANSS.Results75 (44%) of the 168 first group participants responded by 12 weeks, versus one (0.6%) of the 167 second group treated participants.ConclusionsOur data suggest that haloperidol with the combination of lamotrigine was more effective than placebo.

The efficacy of lamotrigine in clozapine-resistant schizophrenia: A systematic review and meta-analysis

Background Clozapine is the drug of choice for patients with unsatisfactory response to routine antipsychotic treatment. Polypharmacy is widely used among patients having clozapine-resistant schizophrenia, although no solid evidence exists for any effective augmentation therapy for this patient population. We aimed to study the efficacy of lamotrigine in the treatment of clozapine-resistant schizophrenia. Method We conducted electronic searches of the Cochrane PsiTri database, the Website of metaRegister of Controlled Trials, including NIH ClinicalTrials.gov, and a clinical trial register by the manufacturer of lamotrigine (GlaxoSmithKline). All randomized placebo-controlled studies on patients receiving clozapine were included in the analysis. The primary outcome measure was a total score for symptoms of psychosis, and the secondary outcome measures were scores for positive and negative symptoms of psychosis. For continuous and binary data, standardized mean differences (SMD), and odds ratios (OR) and the number needed to treat (NNT) were calculated, respectively. Results Five trials with 10 to 24 weeks duration and total of 161 randomized clozapine patients were included in the meta-analysis. Lamotrigine was superior to placebo augmentation in both the primary outcome measure (SMD 0.57, 95%CI 0.25–0.89, p < 0.001; OR 0.19, 95%CI 0.09–0.43, p < 0.001; NNT 4, 95%CI 3–6) and secondary outcome measures (SMD 0.34, 95%CI 0.02–0.65 for positive symptoms, SMD 0.43, 95%CI 0.11–0.75 for negative symptoms). Conclusions This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia. A substantial proportion of these most severely ill patients appeared to obtain clinically meaningful benefit from this combination treatment.

Depression and schizophrenia

Byline: Chittaranjan. Andrade CME Questions A) Schizophrenia and bipolar disorder are both associated with an increased risk of weight gain, incident diabetes mellitus, and the metabolic syndrome; at least a part of the risk is mediated by iatrogenic factors such as atypical antipsychotic medication and mood stabilizers. The relationship between depression and diabetes mellitus has also been studied. With this background, mark True or False against each of the following statements: *Depression is associated with an increased risk of incident diabetes mellitus. *Diabetes mellitus is associated with an increased risk of incident depression. *Depression is associated with superior treatment adherence to antidiabetic measures. *In diabetic samples, inactive persons are less likely to be depressed. *In diabetic samples, depressed persons are more likely to be inactive. *In diabetic samples, long-term glycemic control is no different between depressed and nondepressed patients. B) Just as antidepressant augmentation strategies are employed in antidepressant-refractory depression, so too are antipsychotic augmentation strategies considered in antipsychotic-refractory schizophrenia. Lamotrigine is a broad-spectrum antiepileptic drug which has also demonstrated efficacy in the acute treatment of bipolar depression and in the maintenance therapy of rapid-cycling and nonrapid-cycling bipolar disorder. With this background, mark True or False against each of the following statements: *The rationale for the use of lamotrigine in schizophrenia is that the drug is a partial agonist at dopamine autoreceptors. *Lamotrigine augmentation of antipsychotic medication attenuates positive symptoms of schizophrenia. *Conventional doses of lamotrigine are associated with clinically significant increases in antipsychotic drug levels. *There is weak clinical evidence that lamotrigine augmentation may attenuate obsessive-compulsive disorder symptoms in patients with schizophrenia. CME Answers A) Depression and diabetes mellitus Answers: 1. True; 2. True; 3. False. 4. False; 5. True. 6. False. Mezuk et al.[sup] [1] described a systematic review and meta-analysis of the relationship between depression and Type 2 diabetes. They identified 13 prospective studies of depression which excluded diabetes at baseline, and 7 prospective studies of diabetes which excluded depression at baseline. They found that depression was associated with a 60% increased risk of new-onset diabetes (Relative Risk [RR], 1.60; 95% confidence intervals [CI], 1.37-1.88) and diabetes was associated with a 15% increased risk of new-onset depression (RR, 1.15; 95% CI, 1.02-1.30). Gonzalez et al.[sup] [2] described a systematic review and meta-analysis of the relationship between depression and treatment nonadherence in 47 studies of patients with type 1 and type 2 diabetes mellitus. They found that depression was significantly associated with treatment nonadherence; studies with better methodology demonstrated larger nonadherence effects. Lysy et al.[sup] [3] described a systematic review of the relationship between physical activity and depressed mood in Type 2 diabetes patients. They identified 10 cross-sectional studies and 2 trials. They found that, in adults with Type 2 diabetes, inactive persons were 1.72-1.75 times more likely to be depressed, and depressed persons were 1.22-1.90 times more likely to be inactive. Richardson et al .[sup] [4] examined the longitudinal effects of ICD-9 depression on glycemic control in 11,525 persons with Type 2 diabetes. The mean age of the sample was about 66 years. The sample was 97% male. The sample was followed up for a mean of 4.1 years. Depression was recorded in 6% of the sample. HbA1c values were found to be slightly (by a mean of 0.13%) but significantly higher in depressed persons at all time points during the study. These findings suggest that, in depressed patients who are not diabetic, efforts should be made to modify lifestyle risk factors for diabetes in order to reduce the risk of future diabetes; and these patients should be monitored so that diabetes, if incident, is detected early. …

Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms

Obsessive-compulsive symptoms (OCS) are clinically important phenomena in schizophrenia patients. Lamotrigine has a modulating effect on glutamatergic neurotransmission relevant to pathophysiology of both schizophrenia and OCD. Efficacy and tolerability of lamotrigine in schizophrenia and schizoaffective patients with comorbid OCS were evaluated. In an 8-week, open-label trial, lamotrigine (25 mg/day for 1 week, 50 mg for 2 weeks, 100 mg for 2 weeks, 200 mg for 3 weeks) was added to ongoing psychotropic drug regimens in schizophrenia (N = 5) and schizoaffective disorder (N = 6) patients with clinically significant OCS [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16]. The Y-BOCS score for nine completers decreased significantly from baseline to week 8 (22.9 +/- 6.1 vs 17.4 +/- 3.6; t = 2.33, df = 1, P = 0.033). Five patients, all with schizoaffective disorder, were responders (>or=35% decrease in Y-BOCS score). No significant changes were detected in schizophrenia symptom severity. Depressive symptoms, assessed with the Calgary Depression Rating Scale, improved significantly (6.4 +/- 1.5 vs 4.0 +/- 2.5; t = 3.19, df = 1, P = 0.013); this change positively correlated with OCS improvement (r = 0.69, P = 0.04). Lamotrigine was safe and well tolerated. Explicit evaluation of therapeutic efficacy of adjunctive lamotrigine in schizoaffective disorder patients with comorbid OCS merits further investigation.

Lamotrigine as Add-On Therapy in Schizophrenia

: Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication. : Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12. : Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo. : Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may merit further study.

P.3.c.010 Lamotrigine augmentation of clozapine antiagressive properties in a patient with chronic disorganized schizophrenia

P.3.c.010 Lamotrigine augmentation of clozapine antiagressive properties in a patient with chronic disorganized schizophrenia

Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study

Treatment-resistant depression affects up to 70% of patients. In our 8-week, randomized, open-label, prospective study of 34 treatment-resistant depression patients lamotrigine-add-on was compared with lithium-augmentation. Both treatments resulted in clinically significant reduction in Hamilton rating scale for depression score: mean Hamilton rating scale for depression-score declined from 22.7 (SD 3.9) to 11.7 (SD 4.2) in the lamotrigine group and from 21.5 (SD 3.8) to 13.3 (SD 5.7) in the lithium (Li) group. No significant differences were seen in Hamilton rating scale for depression scores between treatment groups at baseline (P=0.82) and after 8 weeks (P=0.11). Twenty-three percent of the lamotrigine group (n=4) and 18% (n=3) of the Li group achieved remission, 53% of the lamotrigine group (n=9) responded to treatment vs. 41% in the Li group (n=7) and 47% of the lamotrigine group (n=8) vs. 35% of the Li group (n=6) showed at least a partial response. Lamotrigine-augmentation was well tolerated. In conclusion, this study demonstrated that the add-on of lamotrigine to antidepressive medication revealed comparable results in most outcome measures as a lithium augmentation. Owing to small sample size no conclusions regarding similar efficacy can be drawn from our data. Larger trials that should include a placebo arm are needed to further investigate lamotriginés role in treatment-resistant depression.

The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: A double-blind, placebo-controlled study

Based on the evidence that lamotrigine added to clozapine in refractory schizophrenic patients has reported promising results, the present 24-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 200 mg/day of lamotrigine or a placebo. A final sample of fifty-one patients completed the study. The results obtained indicate that lamotrigine added to stable clozapine treatment showed a beneficial effect on the negative, positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients. Regarding cognitive functions, improvement was observed in some explored areas, such as attentional resistance to interference, verbal fluency and executive functioning. The findings provide evidence that lamotrigine augmentation of clozapine treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant schizophrenia.

Lamotrigine Augmentation Strategy for Patients with Treatment-Resistant Depression

To investigate if lamotrigine added to an antidepressant regimen reduces the symptoms of major depression in treatment-resistant patients. Charts were retrospectively reviewed for 34 patients (36-63 years of age) with major depressive disorder who received lamotrigine augmentation to the antidepressant regimen for treatment-resistant depression (TRD). Data collection occurred at baseline and at an average of 30 (Time 2), 78 (Time 3), 167 (Time 6), and 356 days (Time 12), thereafter, using a "Medication Visit by MD" scale for collection of target symptom data at each timepoint. Following the addition of lamotrigine to the antidepressant regimen (mean dose of 43, 63, and 113 mg/day for Time 3, Time 6, and Time 12, respectively), a statistically significant reduction of scores was shown as early as Time 2 for target symptoms of depressed mood, loss of interest, anxiety, irritability, (low) energy, and cognitive impairment. The difference from baseline remained statistically significant at Time 3, Time 6, and Time 12 (with the exception of irritability, which was not statistically significant at Time 6). "Patient's response" also reflected statistically significant improvement at each time period compared with baseline. The most common side effect reported and reason for discontinuation was tiredness. Because TRD is a clinical condition that can present with severe and disabling symptoms, many clinicians are faced with an urgent need to find relief for their patients. Trying to achieve symptom improvement in a timely manner during a medication change can be challenging and difficult. This can be managed by an augmentation strategy using a psychotropic add-on to an existing medication regimen. Our results show the benefits of lamotrigine augmentation to an antidepressant regimen. Prospective, controlled clinical trials with larger sample size are needed to confirm our results. In this retrospective chart review, augmentation with lamotrigine was a tolerable and efficacious strategy for treating patients with TRD.

Sustained remission with lamotrigine augmentation or monotherapy in female resistant depressives with mixed cyclothymic–dysthymic temperament

Background: The treatment of bipolar depression remains problematic. Lamotrigine has been shown in randomized controlled studies to be efficacious in preventing bipolar depression and rapid cycling states. Methods: Twenty-four women with cyclothymic temperament and refractory depression were recruited from four outpatient sites (three primary care and one psychiatric) and treated with lamotrigine in a naturalistic, open-label study. Temperament was determined by responses on the TEMP-A self-rating scale. Eighteen (75%) of these cyclothymic patients also scored high on the depressive temperament. Eighteen (75%) met DSM-IV criteria for bipolar II disorder. In two thirds of the cases, lamotrigine was add-on therapy to an antidepressant. Response to therapy was assessed using the DSM-IV Global Assessment of Functioning (GAF). Limitations: This study was naturalistic in design, without controls or blinds. Results: Of the 23 patients who remained in the study, 16 (70%) had significant, sustained responses. Of these 16, 12 (75% of responders, 52% of the total) had remissions (GAF>80) sustained longer than 12 months. Robust, sustained responses to lamotrigine monotherapy were seen in 4 patients (17%). Seven patients (30%) received no apparent benefit from lamotrigine. Conclusions: Lamotrigine induced prolonged illness remissions in a substantial number of female patients whose symptoms were both complex and refractory. Most manifested high scores on the cyclothymic and depressive temperaments, and prior refractoriness to multiple antidepressant and antidepressant/mood stabilizer combinations, before remitting with lamotrigine augmentation or monotherapy.

Lamotrigine augmentation in unipolar depression.

A significant number of patients with unipolar depression fail to achieve remission after one or a series of antidepressants. We present the results of a retrospective chart review of the efficacy and tolerability of lamotrigine as an augmentation drug in treatment-resistant unipolar depression. A previous absence of a response was defined as the clinically significant presence of depressive symptomatology after 6 weeks of treatment with an antidepressant, with at least 3 weeks at the maximum dose tolerated by the patient. The patients were rated retrospectively using the Clinical Global Impression rating scale. Seventy-six percent of the patients improved. Gender, age, basal severity of the episode and degree of previous non response were not statistically significantly associated with response to lamotrigine augmentation. Comorbidity showed a tendency to be negatively related with response to lamotrigine. Three patients abandoned the treatment with lamotrigine due to side-effects. Complaints were excessive somnolence, headache, dizziness, nausea and malaise. Data suggest that lamotrigine is a promising drug for treatment-refractory unipolar depression. Double-blind studies are necessary to confirm its use as an augmentation agent.

Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder

Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder