Efficacy Of Lamotrigine Research Articles

Comparative Pre-Emptive Analgesic Efficacy Study of Novel Antiepileptic Agents Lamotrigine and Topiramate in Patients Undergoing Major Surgeries at a Tertiary Care Hospital: A Randomized Double Blind Clinical Trial

Background: Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy. Purpose: This study is designed to study and compare the pre-emptive analgesic efficacy of Lamotrigine, Topiramate, and Diclofenac sodium in postoperative pain control. Methods: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated to control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's and pain scores were recorded using the Visual Analog Scale, Facial and Behavioral Rating Scale at awakening and at 1, 2, 4, 6, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Results: Significantly higher pain scores were observed in the Topiramate group postoperatively for 2 h on all pain scales (p < 0.05), whereas in the control group it was significantly higher at 1 h (p < 0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p < 0.05) postoperative analgesic requirement. Conclusions: Study results strongly suggest the pre-emptive analgesic efficacy of a single oral dose of Lamotrigine over Diclofenac and Topiramate in postoperative pain control.

A.05 Ten years of experience with lamotrigine for the treatment of neonatal and infantile seizures

Background: The therapeutic value of second-generation anticonvulsants such as lamotrigine has not been clearly established in neonates and infants with seizures. To address this issue, we assessed the efficacy of lamotrigine for treating neonatal and infantile seizures, detailed the dosing regimens used, and described its tolerability and safety profile. Methods: This retrospective study included patients (age 0-12 months) diagnosed with seizures and treated with lamotrigine, as monotherapy or adjunctive therapy, by pediatric neurologists at Centre mère-enfant Soleil du CHUQ from 2004 to 2014. The frequency of seizures and EEG patterns were compared before and after introduction of lamotrigine during the first months of life. Data on initial and maintenance doses, rate and magnitude of dosing increments, and adverse effects were collected. Results: Treatment with lamotrigine was initiated in 32 neonates and 13 infants. At first follow-up (mean duration 3 months), 76 % (n = 34) showed a significant (≥50%) reduction of seizures and 64% (n= 29) improvement of EEG pattern compared to baseline. The efficacy in monotherapy and adjunctive therapy was similar. A single case of cutaneous hypersensitivity reaction requiring cessation of treatment was reported. Conclusions: This study suggests that lamotrigine is a useful, safe, and well-tolerated anticonvulsant alternative for the treatment of seizures in neonates and infants.

A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients Undergoing Major Surgeries.

Background:If postoperative acute pain remains unrelieved, it may result in significant morbidity and mortality. Preemptive analgesic initiated before surgery offers premature analgesia even before exposure to an initial noxious stimulus bestowing effective postoperative analgesia. In developed countries, it is regularly practiced as a part of well-defined protocol. In our country however, only a few centers practice it and that too irregularly and with undefined protocol. Few studies support preemptive analgesic efficacy of novel antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in animal models of chronic pain and clinical studies of gabapentin-resistant neuropathic pain, a literature search revealed scarce data on its preemptive analgesic efficacy.Aims:The present study is designed to study the preemptive analgesic efficacy of lamotrigine in comparison with diclofenac sodium in postoperative pain control.Materials and Methods:This randomized clinical trial included 90 patients of both sexes, between 18 years and 70 years undergoing major surgeries. Patients were randomly allocated into placebo, control, and test groups and received the respective treatment 30 min before the induction of anesthesia. Aldrete score and pain score were recorded using visual analog scale (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded.Results:Significantly higher pain scores were observed in the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas in the control group it was significantly higher at 1 h (P < 0.05). The test group patients were more comfortable throughout the study and postoperative analgesic requirement was significantly less (P < 0.05).Conclusions:The study recommends the use of single oral dose lamotrigine as preemptive analgesic for effective postoperative pain control.

The efficacy of lamotrigine for atypical absence status epilepticus in a case of perioral myoclonia with absence

The efficacy of lamotrigine for atypical absence status epilepticus in a case of perioral myoclonia with absence

Comparative animal study of the antinociceptive efficacy of lamotrigine and gabapentin for the management of pain

Pain relief using drugs with high efficacy provides significant improvement in the patients' lives. Drugs like lamotrigine (LTG) and gabapentin (GBP) have the ability to overcome the symptoms of neuropathic pain. The present study offers a comparative analysis of LTG and GBP efficacy in a rat model of nociceptive pain after single administration. Sixty-three Wistar-Bratislava rats randomized into 7 groups were included: a control group treated with saline solution and 6 groups treated with different doses of LTG and GBP. Nociceptive responses to thermal and mechanical stimulations were evaluated before and after drug administration, at different time intervals, using paw pressure and hot plate tests. The obtained data were statistically analyzed, with significance at p value < 0.05. LTG 100 mg/kg and 50 mg/kg presented a significant analgesic effect in both mechanical and thermal tests, 1 and 2 hours after administration. GBP 100 mg/kg increased latency time in hot plate test. The effect of both anticonvulsant drugs occurred rapidly after administration, but had a short duration. LTG and GBP had an analgesic effect in a single dose administration. The effect of LTG was more evident since it was observed in both tests. Their effect was dose dependent.

重度精神遅滞児 (者) の行動障害に対するlamotrigineの効果の検討

重度精神遅滞児 (者) の行動障害に対するlamotrigineの効果の検討

Management of bipolar depression with lamotrigine: an antiepileptic mood stabilizer.

The efficacy of lamotrigine in the treatment of focal epilepsies have already been reported in several case reports and open studies, which is thought to act by inhibiting glutamate release through voltage-sensitive sodium channels blockade and neuronal membrane stabilization. However, recent findings have also illustrated the importance of lamotrigine in alleviating the depressive symptoms of bipolar disorder, without causing mood destabilization or precipitating mania. Currently, no mood stabilizers are available having equal efficacy in the treatment of both mania and depression, two of which forms the extreme sides of the bipolar disorder. Lamotrigine, a well established anticonvulsant has received regulatory approval for the treatment and prevention of bipolar depression in more than 30 countries worldwide. Lamotrigine, acts through several molecular targets and overcomes the major limitation of other conventional antidepressants by stabilizing mood from “below baseline” thereby preventing switches to mania or episode acceleration, thus being effective for bipolar I disorder. Recent studies have also suggested that these observations could also be extended to patients with bipolar II disorder. Thus, lamotrigine may supposedly fulfill the unmet requirement for an effective depression mood stabilizer.

Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study

This study aimed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with bipolar I disorder (BP-I) who were receiving conventional bipolar disorder treatment. In this randomized withdrawal trial, patients with BP-I of at least moderate severity received lamotrigine during an≤18-week open-label phase. Patients who maintained a stable lamotrigine dose for≥2 weeks and Clinical Global Impression-Bipolar Severity of Illness (CGI-BP[S]) score of≤3 for≥6 consecutive weeks were randomized to double-blind lamotrigine or placebo for≤36 weeks. Of 301 patients enrolled, 298 comprised the open-label intention-to-treat population, with 173 (58%) randomized. Of these patients, 41 (24%) completed the study. In the open-label phase, the mean (SD) baseline CGI-BP(S) rating was 4.4 (0.57), and the mean (standard error [SE]) time to stabilization was 101 (1.6) days. During the randomized phase, mean (SE) time to occurrence of a bipolar event (TOBE) for lamotrigine versus placebo (primary endpoint) was 155 (14.7) versus 50 (3.8), 163 (12.2) versus 120 (12.2), and 136 (15.4) versus 107 (13.8) days for the 3 index mood states (depressed, manic/hypomanic, mixed). The primary stratified log-rank analysis of TOBE was not statistically significant (hazard ratio [HR]=0.63; p= .072); however, the prespecified Cox regression analysis favored lamotrigine (p= .047). In 13-to 17-year-olds, log-rank analysis of TOBE significantly favored lamotrigine (HR= 0.46; p= .015), but not in 10- to 12-year-olds (HR= 0.93; p= .877). Dermatologic events were reported in 4% (open-label phase) and 2%(randomized phase) of patients receiving lamotrigine. Suicidality-related adverse events were reported in 7%(open-label phase) and 7% (randomized phase) of patients receiving lamotrigine. Although the primary analysis failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds, lamotrigine may be effective in a subset of older adolescents. Clinical trial registration information-Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients; http://clinicaltrials.gov/; NCT00723450.

The 'disconnect' between initial judgments of lamotrigine vs. its real-world effectiveness in managing bipolar disorder. A tale with wider ramifications.

To detail the disconnect between the quantified efficacy of the mood stabilizer lamotrigine in its registration controlled trials and its later judged clinical effectiveness and consider some determinants of disconnects between some efficacy trial findings and 'real-world' clinical effectiveness judgments. Published articles considering lamotrigine as a treatment for the bipolar I or II disorders were selected for review. While randomized controlled trials were weighted, we also consider open trials and effectiveness observations from clinician researchers and demonstrate that lamotrigine has been quite variably judged over time. We suggest that the early trials evaluating lamotrigine for acute bipolar disorder depression focused on a suboptimal clinical target, and in so doing, ensured less lamotrigine efficacy compared with trials of bipolar disorder preventative treatment. Moreover, a number of additional methodological limitations compromised analyses. We also detail variable reporting of actual study results. The initial sharp disconnect (between efficacy and effectiveness judgments) has narrowed as lamotrigine has been evaluated and progressively taken up as a maintenance mood stabilizer. The lamotrigine disconnect story provides a number of salutary lessons that are salient to evaluating the effectiveness and ecological niche of any psychotropic medication. The lamotrigine story presented here argues strongly for the wisdom of encouraging an iterative process between efficacy studies and clinical observation.

Efficacy of Lamotrigine in the Treatment of Bipolar Depression

Introduction Depressive episodes are common in bipolar illness. Treatment of bipolar depression is often problematic because standard antidepressants carry a number of disadvantages: apparent lower efficacy than in unipolar depression; risk of inducing mania; risk of inducing rapid cycling. Anticonvulsants such as carbamazepine, valproate and lamotrigine are useful in the management of bipolar disorder and they can prevent episodes of depression. There is less evidence that they have antidepressant efficacy but lamotrigine was shown to produce antidepressant effects in a placebo-controlled trial in bipolar depressed patients. Lamotrigine has a role in acute management of bipolar depression and is probably free of a risk of inducing mania or rapid cycling. Objectives To determine the efficacy of lamotrigine in treatment of patients with bipolar depression. Aims Investigation of lamotrigine efficacy with bipolar depression in 3 month-follow-up and 6 months follow-up treatment with lamotrigine. Methods The sample consisted of 30 patients with bipolar depression, age range between 26 and 58. All subjects received monotherapy with lamotrigine in the period of six months. Subjects were assessed prior to therapy and in 3 and 6 months follow-up using the following instruments: The Clinical Global Impressions scale (CGI), and Hamilton Depression Rating Scale (HAM-D-21). Results The difference between three assessments on CGI was statistically significant. The results indicate statistically significant reduction of depression on HAMD-21 following six months treatment with lamotrigine. Conclusions Lamotrigine proved to be efficient in the treatment of patients with bipolar depression for the subjects in this study.

A COMPARATIVE STUDY OF EFFICACY OF LAMOTRIGINE AND LEVETIRACETAM IN THE CONTINUOUS MAINTENANCE PHASE OF PATIENTS WITH BIPOLAR DEPRESSIVE DISORDER

Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mental illnesses. Bipolar disorder is a serious lifelong struggle and challenge The objective of this study is to evaluate the spectrum of efficacy of Lamotrigine versus Levetiracetam as add on therapy comparatively in patient with bipolar depressive disorder who are inadequately responsive to or intolerant of pharmacotherapy with conventional drugs at Jabalpur and adjoining area. In this 60 days open label, randomized comparative study 60 patients were enrolled, out of which 53 patients were evaluated at the end of the study. Two parallel groups were differentiated by the study medication-Lamotrigine or Levetiracetam-that was administered as an adjunct to existing medications for bipolar depressive disorder (N=60). At baseline and every 15th days Mood symptoms were rated using the Hamilton depression scale. Total 61% patients in Lamotrigine group had shown marked improvement on HAM-D (>50% reduction on day 60) while 33% patients in Levetiracetam group showed this level of improvement. On comparison between these two drugs on the basis of HAM-D the difference was statistically significant (P value for HAM-D < 0.05). The addition of either Lamotrigine or levetiracetam to patients preexisting mood stabilizing regimen was associated with a reduction in the frequency of mood fluctuation. Evidence from this preliminary open-label study suggests that Lamotrigine was more efficacious than Levetiracetam in reducing depressive symptoms in patients presenting with depressive phases of bipolar I and bipolar II disorder.

Antiepileptic efficacy of lamotrigine in phenobarbital-resistant and -responsive epileptic rats: A pilot study

About 25% of patients with epilepsy are refractory to treatment, so that new, more effective antiepileptic drugs (AEDs) are urgently needed. Animal models that simulate the clinical situation with individuals responding and not responding to treatment are important to determine mechanisms of AED resistance and develop novel more effective treatments. We have previously developed and characterized such a model in which spontaneous recurrent seizures (SRS) develop after a status epilepticus induced by sustained electrical stimulation of the basolateral amygdala. In this model, prolonged treatment of epileptic rats with phenobarbital (PB) results in two subgroups, PB responders and PB nonresponders. When PB nonresponders were treated in previous experiments with phenytoin (PHT), 83% of the PB-resistant rats were also resistant to PHT. In the present study we examined if rats with PB resistant seizures are also resistant to lamotrigine (LTG), using continuous EEG/video recording of spontaneous seizures over 10 consecutive weeks. For this purpose, a new group of epileptic rats was produced and selected by treatment with PB into responders and nonresponders. As in previous studies, PB nonresponders had a significantly higher seizure frequency before onset of treatment. During subsequent treatment with LTG, all PB nonresponders and 60% of the PB responders exhibited >75% reduction of seizure frequency and were therefore considered as LTG responders. Plasma levels of LTG did not differ significantly between responders and nonresponders. The data of this pilot study indicate that LTG is more effective than PHT to suppress seizures in PB nonresponders in this model, but that not all PB responders also respond to LTG. Overall, our data provide further evidence that AED studies in post-SE TLE models are useful in determining and comparing AED efficacy and investigating predictors and mechanisms of pharmacoresistance.

EPA-0569 – Lamotrigine in patients with recurrent depression, which is resistant to antidepressive pharmacotherapy.

Objective To estimate the efficacy of lamotrigine as add-on therapy in patients with recurrent depression resistant to antidepressive pharmacotherapy. Object The study included 55 patients of both sexes aged 18-65 years with recurrent depressive disorder. At the time of inclusion in the study, patients received antidepressive pharmacotherapy for 2 months with a reduction in depressive symptoms less than 25%. Results According to the results of clinical observations, patients with atypical variants of depressive symptoms have been isolated - Anxious or agitated depression with dominance or significant share of anxiety affect, ideational and motor excitation, high suicide risk; - Apathetic depression - lack of desire and motivation to work, intolerance to intellectual and physical activities; - Adynamic or anergic depression dominated by slackness, weakness in the presence of the desire for activity; - Dysphoric depression with an angry, irritable background mood, a tendency to auto-and getero-agressive actions. In patients with atypical depression and (anxious and dysphoric), lamotrigine adjunctive therapy, a significantly more positive dynamic state was observed than in patients with classical clinical picture of depression. On the Hamilton depression scale decreased to 13 points or less (no anxiety-depressive symptoms) with 25 points or more (clinical symptoms of anxiety depression) at the beginning of the research; Conclusion The efficacy of lamotrigine to overcome treatment resistance in recurrent depression. The most expedient is to use it for additional therapy in combination with antidepressants in recurrent depression with atypical clinical picture of depression - anxious and dysphoric.

Lamotrigine for chronic neuropathic pain and fibromyalgia in adults.

This is an update of the original Cochrane review entitled Lamotrigine for acute and chronic pain published in Issue 2, 2007, and updated in Issue 2, 2011. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds no new additional studies looking at evidence for lamotrigine as an effective treatment for chronic neuropathic pain or fibromyalgia. The update uses higher standards of evidence than previously. To assess the analgesic efficacy of lamotrigine in the treatment of chronic neuropathic pain and fibromyalgia, and to evaluate adverse effects reported in the studies. We identified randomised controlled trials (RCTs) of lamotrigine for chronic neuropathic pain and fibromyalgia (including cancer pain) from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). We ran searches for the original review in 2006, in 2011 for the first update, and subsequent searches in August 2013 for this update. We sought additional studies from the reference lists of the retrieved papers. The original review and first update included acute pain, but no acute pain studies were identified. RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of chronic neuropathic pain or fibromyalgia. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. We included only full journal publication articles. Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. The first tier used data where studies reported the outcome of at least 50% pain reduction from baseline, lasted at least eight weeks, had a parallel group design, included 200 or more participants in the comparison, and reported an intention-to-treat analysis. First-tier studies did not use last observation carried forward (LOCF) or other imputational methods for dropouts. The second tier used data that failed to meet this standard and second-tier results were therefore subject to potential bias. Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post-stroke pain (1), chemotherapy-induced neuropathic pain (1), diabetic neuropathy (4), HIV-related neuropathy (2), mixed neuropathic pain (2), spinal cord injury-related pain (1), and trigeminal neuralgia (1). We did not identify any additional studies. Participants were aged between 26 and 77 years. Study duration was two weeks in one study and at least six weeks in the remainder; eight were of eight-week duration or longer.No study provided first-tier evidence for an efficacy outcome. There was no convincing evidence that lamotrigine is effective in treating neuropathic pain and fibromyalgia at doses of 200 mg to 400 mg daily. Almost 10% of participants taking lamotrigine reported a skin rash. Large, high-quality, long-duration studies reporting clinically useful levels of pain relief for individual participants provided no convincing evidence that lamotrigine is effective in treating neuropathic pain and fibromyalgia at doses of about 200 to 400 mg daily. Given the availability of more effective treatments including antiepileptics and antidepressant medicines, lamotrigine does not have a significant place in therapy based on the available evidence. The adverse effect profile of lamotrigine is also of concern.

Evidence-based treatment for Depersonalisation-derealisation Disorder (DPRD).

BackgroundDepersonalisation-derealisation disorder (DPRD) is a distressing and impairing condition with a pathophysiology that is not well understood. Nevertheless, given the growing interest in its pathogenesis, and the publication of a number of treatment trials, a systematic review of randomised controlled pharmacotherapy and psychotherapy trials is timely.MethodsA systematic search of articles on DPRD published from January 1980 to August 2012, using Cochrane methods, was conducted. All randomised controlled trials (RCTs) of pharmacotherapy, psychotherapy, somatic interventions and a blend of these modalities for the treatment of depersonalisation disorder were included in the review. Searches were carried out on multiple databases. The bibliographies of all identified trials were checked for additional studies and authors were contacted for published trials. No unpublished trials were found and no restrictions were placed on language and setting. Data extraction sheets were further designed to enter specified data from each trial and risk of bias information was identified. PRISMA guidelines were also followed to ensure that our methodology and reporting were comprehensive. Of the unique 1296 papers that were retrieved, four studies met the inclusion criteria and were reviewed.ResultsFour RCTs (all within the duration of 12 weeks or less) met study criteria and were included (180 participants; age range 18–65 years). The four RCTs included two lamotrigine studies, one fluoxetine study and one biofeedback study. Evidence for the treatment efficacy of lamotrigine was found in one study (Cambridge Dissociation Scale, CDC: p < 0.001) with no evidence of effect for lamotrigine in the second study (CDS: p = 0.61 or Present State Examination: p = 0.17). Fluoxetine and biofeedback were not more efficacious than the control condition, although there was a trend for fluoxetine to demonstrate greater efficacy in those with comorbid anxiety disorder. The four studies had 'low' or 'unclear' risk of bias.ConclusionThe limited data from randomised controlled trials on the pharmacotherapy and psychotherapy of DPRD demonstrates inconsistent evidence for the efficacy of lamotrigine, and no efficacy for other interventions. Additional research on this disorder is needed.

A STUDY ON EVALUATION OF THE EFFICACY OF LAMOTRIGINE AS ADD-ON TREATMENT IN RESISTANT TYPE OF PRIMARILY GENERALIZED TONIC-CLONIC EPILEPSY IN BURDWAN MEDICAL COLLEGE, WEST BENGAL, INDIA

Background: Treatment of resistant type of Primarily Generalized Tonic-Clonic (PGTC) Epilepsy is a difficult area. In different parts of the world lots of studies conducted on this area with varying results. In this perspective, there was need of this study, especially in this part of the country, Burdwan Medical College, West Bengal, India, where previously there was no such study. Objective: The objective of my study was to evaluate the efficacy of Lamotrigine as Add-On Treatment in Primarily Generalized Tonic-Clonic Epilepsy. Materials and Methods: 46 resistant type of Primarily Generalized Tonic-Clonic Epileptic patients were randomly recruited from the Out Patient Department (OPD), Burdwan Medical College& Hospital, West Bengal. The patients were taking either Valproic acid or Carbamazepine or combination of Valproic acid & Carbamazepine. All were placed on oral Lamotrigine in addition to their exiting antiepileptic drugs. Efficacy was measured subsequently by efficacy measuring scale. Results: After add-on Lamotrigine 50% responder rate was 39.129%. 5 patients (10.869%) rendered seizure free. The reduction of mean seizure frequency was 47.129% and response ratio was -0.32 ± 0.249 (mean ± SD). Add-on lamotrigine cause significant reduction (p < 0.05) of seizure frequency from the baseline value and desirable effects were seen irrespective of patients whether taking valproic acid or carbamazepine or combination of valproic acid& carbamazepine. CONCLUSION: Add-on lamotrigine was efficacious in resistant type of Primarily Generalized Tonic- Clonic Epilepsy, in this tertiary care teaching hospital. Key Words: Epilepsy, Primarily, Generalized, Tonic-Clonic, Resistant

Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo‐controlled maintenance treatment for bipolar depression

To compare the maintenance efficacy of lamotrigine (Lam) to combination therapy of Lam+divalproex ER (Div) in recently depressed patients with bipolar disorder (BD). We randomized 86 BD I or II patients in a major depressive episode to 8 months of double-blind treatment with Lam+placebo or Lam+Div. To be eligible for randomization, patients had to achieve control of both depressive and manic symptoms during an open phase that included both Lam and Div. Time to depressive episode did not differ significantly by Kaplan-Maier survival analysis (χ2=1.82, df=1, P=0.18). However, several secondary outcomes did show significant differences. The proportion of Lam+placebo patients who had at least one Montgomery-Asberg Depression Rating Scale (MADRS) score≥15 during the maintenance phase was 67% (30/45) compared with 44% (18/41) for the Lam+Div group (χ2=4.51, P=0.03). Among BD I patients assigned to Lam+placebo, 71.4% (25/35) had at least one visit with MADRS score≥15 compared with 36.7% (11/30) among Lam+Div patients (χ2=7.89, df=1, P=0.005). Lam+Div generally provided greater maintenance efficacy than Lam alone for depressive indices in recently depressed BD patients.

Maintenance therapies in bipolar disorders

Bipolar disorder is an inherently recurrent disorder, requiring maintenance preventive treatments in the vast majority of patients. The authors review the data on maintenance treatments in bipolar disorder, highlighting the controlled trial literature. Literature review using PubMed, Medline, and a hand search of relevant literature. Over the last decade, a number of effective maintenance treatments for bipolar disorder have been developed with an evidence base for second-generation antipsychotics and some anticonvulsants. Increasing numbers of patients, therefore, are appropriately treated with multiple medications as a maintenance regimen. For some medications, maintenance treatment has been demonstrated in randomized controlled trials for both monotherapy and in combination with other mood stabilizers. Lithium continues as our oldest well-established maintenance treatment in bipolar disorder with somewhat better efficacy in preventing mania than depression. Lamotrigine, olanzapine, and quetiapine have bimodal efficacy in preventing both mania and depression, although lamotrigine's efficacy is more robust in preventing depression and olanzapine's efficacy is greater in preventing mania. Aripiprazole, ziprasidone, and risperidone long-acting injection all prevent mania, but not depression. Less controlled investigations have suggested some evidence of maintenance mood stabilization with carbamazepine, oxcarbazepine, and adjunctive psychotherapy. Despite the number of agents with demonstrated efficacy as maintenance treatments in bipolar disorder, optimal treatment regimens are still a combination of evidence-based therapy in combination with individualized creative treatment algorithms.

Lamotrigine is a substrate for OCT1 in brain endothelial cells

The mechanisms that underpin the passage of lamotrigine at the blood–brain barrier to its site of action in the brain is poorly understood. Lamotrigine has been postulated to be delivered to its site of action in the brain favourably despite its physicochemical properties. The aim of this study was to investigate the transport of lamotrigine in an in-vitro model of the BBB. In this study, lamotrigine was found to have a distribution coefficient of 0 at pH 7.4 indicating that it was not highly lipophilic. Human brain endothelial cells (hCMEC/D3) were used to probe the interaction of lamotrigine with drug transporters. The uptake of lamotrigine into hCMEC/D3 cells was found to be an active process (Km=62±14μM; Vmax=385±30pmol/min/million cells). Furthermore, use of a panel of transporter inhibitors indicated that this active uptake was mediated by organic cation transporter 1 (OCT1). OCT1 mRNA and protein were shown to be expressed in hCMEC/D3 cells. KCL22 cells overexpressing OCT1 were then used to validate these findings. Lamotrigine was confirmed to be a substrate and inhibitor in OCT1-transfected KCL22 cells. A putative pharmacokinetic drug–drug interaction (DDI) between quetiapine and lamotrigine was recently reported in patients and we show here that quetiapine is a potent inhibitor of the OCT1-mediated transport of lamotrigine. This is the first time that a specific influx transporter has been shown to transport lamotrigine. The clinical implications of these findings with respect to the efficacy of lamotrigine and its potential for DDI require further investigation.

Efficacy of Lamotrigine in Children with Epilepsies of Various Etiology

Purpose: We analyzed seizure frequencies before and during Lamotrigine (LTG) treatment of children with special focus on the etiology of their epilepsy syndrome.