Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.
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PMID:Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. 913 45

Anticonvulsants are used extensively in the treatment of bipolar disorder. Treating depression in bipolar disorder can be difficult because of the limited antidepressant effects of the standard mood stabilizers and the tendency of antidepressants to induce mania or decrease cycle length. Lamotrigine is a new anticonvulsant with few side effects that may have mood-stabilizing and elevating effects. Its mechanism of action probably involves the inhibition of excessive release of excitatory amino acids such as glutamate. Antiglutamatergic agents may be antidepressant and mood stabilizing. A case series of 16 patients treated with lamotrigine (dose range 50 mg to 250 mg, mean dose of responders = 141 mg) is presented along with two case reports. All patients were considered treatment-resistant bipolar type I or II. Patients were rated on average 5 weeks after starting lamotrigine using a semistructured follow-up form that included symptom rating, Clinical Global Impressions (CGI), and Global Assessment of Functioning (GAF) scores. Eight of 16 patients were rated as "responders" (CGI < or = 2) and had a mean increase of 16 in their GAF scores. Lamotrigine seems to have antidepressant and mood-stabilizing effects, but this requires confirmation in randomized, controlled trials.
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PMID:The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness. 916 63

Several case reports and open studies have reported the efficacy of lamotrigine in bipolar depression. A randomised placebo-controlled 7-week study comparing two doses of lamotrigine with placebo in 195 patients with moderate to severe bipolar depression has now been completed. Lamotrigine was superior to placebo after 3 weeks as assessed by changes in the Montgomery-Asberg Depression Rating Scale (MADRS). A response, defined as more than 50% improvement on the MADRS occurred in 56 and 48% of the lamotrigine 200 and 50 mg/day groups, respectively, compared with 29% for placebo (P<0.05). There was no evidence that lamotrigine destabilised mood or precipitated mania. Tolerability was good and there were no cases of serious rashes. Preliminary results from an ongoing study also indicate that lamotrigine is more effective than gabapentin in bipolar depression. In conclusion, lamotrigine is effective in alleviating bipolar depression, without causing mood destabilisation. Slow dosage escalation yields good tolerability.
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PMID:Lamotrigine in the treatment of bipolar depression. 1052 37

The utility of gabapentin and lamotrigine for the treatment of bipolar disorder is reviewed. Bipolar disorder is characterized by extreme mood fluctuations, including mania, hypomania, depression, and mixed episodes. Extrapolation of postulated mechanisms of anticonvulsant activity in bipolar disorder has led to the use of the newer anticonvulsants gabapentin and lamotrigine for therapy. Both agents appear promising on the basis of limited (often anecdotal) evidence. They may prove effective in patients with difficult cases of bipolar disorder, such as patients with rapid cycling, mixed episodes, and illness refractory to other treatments. Lamotrigine may offer a much-needed treatment alternative for bipolar depression and could be found effective for acute mania, but the need for slow dosage adjustment and the risk of rash may limit overall clinical utility. Gabapentin may offer significant advantages for acute mania: The dosage can be adjusted rapidly, adverse effects are generally minimal, the therapeutic index is high, there is no required laboratory monitoring, and there is minimal potential for interactions with other psychotropics. Until the results of randomized controlled trials are known, however, these two agents should be reserved for patients with bipolar disorder unresponsive to traditional therapies and for patients who cannot tolerate traditional agents. Preliminary evidence indicates that gabapentin and lamotrigine may be useful for the treatment of bipolar disorder.
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PMID:Gabapentin and lamotrigine in bipolar disorder. 1055 11

Accumulating evidence suggests that at least some novel anticonvulsants may have mood-stabilizing properties. This paper reviews the literature for empirical studies of this topic. Lamotrigine has the most evidence in favor of its efficacy, with two double-blind studies in which it was more efficacious than placebo in the treatment of bipolar depression. However, it is associated with a 1/1000 risk of potentially fatal Stevens-Johnson syndrome. Gabapentin, although safe and well-tolerated, has been found in two double-blind studies not to be efficacious in treatment-refractory mania or refractory bipolar depression. Topiramate is currently supported only by naturalistic evidence of mild to moderate mood-stabilizing efficacy, but it has the advantage of often producing weight loss. Based on these data, lamotrigine may be effective, in monotherapy or as an adjunct, for treating depression in type I bipolar disorder, but suggestions regarding gabapentin and topiramate await further efficacy data. Most of the current findings derive from small, non-double-blind studies, and further research is required before clinicians can consider any of these agents to be mood stabilizers.
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PMID:Novel anticonvulsants: a new generation of mood stabilizers? 1082 92

Treatments other than lithium have recently emerged as equally important in the management of bipolar disorder. The spectrum of efficacy of newer treatments differs from lithium and among the novel drug treatments valproate, generally used as the better tolerated divalproex form, principally benefits manic symptomatology both acutely and in prophylaxis. Atypical antipsychotic drugs have demonstrated efficacy in reducing acute manic symptoms. No controlled evidence of efficacy in prophylaxis has been published. Lamotrigine has demonstrated efficacy in both acute bipolar depression and maintenance efficacy in rapid cycling bipolar patients, especially those patients with bipolar II disorder, which is principally manifested as depression. Randomised, double-blind, placebo- controlled studies provide good evidence that regimens of risperidone or olanzapine in combination with lithium or valproate provide greater improvement in acute mania than the mood stabilisers alone. Similarly, valproate combined with antipsychotics provided greater improvement in mania than antipsychotic medication alone and resulted in lower dosage of the antipsychotic medication. A positive but unclear placebo-controlled study of omega-3 fatty acids added to lithium in bipolar disorder needs confirmation in standard clinical trial paradigms. Several other drugs that were reported as beneficial in various facets of bipolar disorder in open trials have not differed from placebo when studied in randomised, placebo-controlled trials.
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PMID:Novel treatments for bipolar disorder. 1128 16

Anticonvulsants are frequently used in the treatment of affective illnesses, especially for patients refractory to or intolerant of other treatments. The differential therapeutic roles of anticonvulsants, however, remain largely undetermined. The author reviews the available efficacy data for carbamazepine, oxcarbazepine, valproate, lamotrigine, gabapentin and topiramate. Valproate is efficacious in the monotherapy of acute manic presentations but confirmatory evidence of the efficacy of valproate in long-term maintenance has been elusive. Valproate and possibly carbamazepine, may provide a therapeutic advantage over lithium in non-classic bipolar conditions such as mixed mood states and rapid cycling conditions. Lamotrigine is unique among the anticonvulsants in its monotherapy efficacy for bipolar I depression. Emerging data also suggest a role for lamotrigine in the adjunctive treatment of depressive mixed states and rapid cycling conditions in the absence of prominent manic symptoms. Controlled trials have found gabapentin ineffective for acute mania and refractory bipolar conditions. The role of gabapentin in the treatment of other aspects of affective illness remains uncertain. Definitive statements regarding the differential psychotropic use of topiramate and oxcarbazepine are not possible, though active investigation is underway to better characterise the utility of topiramate. The author suggests that current diagnostic models utilised in controlled trials may limit identification of differential therapeutic benefits. Caution is advised in generalising from the ability or inability of an agent to demonstrate antimanic activity. Future studies of newer anticonvulsants should include dimensional perspectives and soft bipolar presentations, as the greatest contribution of the newer anticonvulsants may be in treatment of mood conditions other than acute mania.
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PMID:Anticonvulsants in the treatment of mood disorders: assessing current and future roles. 1182 2

Lamotrigine has undergone a remarkable series of systematic studies since 1994 that now establish it as an efficacious, well-tolerated treatment in bipolar disorder. Its efficacy principally addresses both acute and maintenance phase benefits on depressive symptomatology. These benefits have been demonstrated in placebo-controlled studies, rapid cycling patients, bipolar I and II patients and monotherapy as well as in combination therapy, although this has been less well studied. The drug is exceptionally well-tolerated in long-term treatment, although initial dosing requires gradual dosage escalation to avoid the risk of inducing serious rashes with features within the spectrum of Stevens-Johnson syndrome. Administration with valproate requires a slower dosage titration, whereas, as with many drugs, administration with carbamazepine requires a more rapid dosage increase. In contrast to marketed antidepressants, lamotrigine appears not to induce manic or hypo-manic episodes, nor to increase cycling frequency. This combination of properties makes it a first-choice treatment for acute bipolar depression and continuation treatment, especially, but not limited to, prophylaxis against recurrent depression and depressive symptoms. Lamotrigine appears not to have acute antimanic properties. A small number of studies suggest a broader spectrum of efficacy, including in some axis I disorders that are comorbidly associated with bipolar disorder.
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PMID:Lamotrigine in the treatment of bipolar disorder. 1238 97

Depressive symptoms are highly prevalent in patients with epilepsy. The antiepileptic drug lamotrigine has been shown to be an effective treatment for the depressive phase of bipolar disorder and to enhance mood and well-being in epilepsy patients. The effects of lamotrigine monotherapy on depressive symptoms in epilepsy have not been evaluated to date in a controlled clinical trial. A recently completed double-blind epilepsy trial comparing the effects of lamotrigine monotherapy and valproate monotherapy on weight change incorporated a battery of standard mood assessments. Mean screening Beck Depression Inventory scores showed that both lamotrigine and valproate groups suffered from mild depression at baseline. Lamotrigine monotherapy was reliably associated with earlier and larger improvements than valproate in mood assessed with the Beck Depression Inventory, the Cornell Dysthymia Rating Scale, and the Profile of Mood States. Considered in the context of other data showing lamotrigine's antidepressant efficacy in bipolar depression, these results suggest that lamotrigine improves mood in mildly depressed patients with epilepsy. Lamotrigine may be particularly useful in treating epilepsy patients with comorbid depression, the most common psychiatric illness in epilepsy.
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PMID:Lamotrigine Monotherapy Improves Depressive Symptoms in Epilepsy: A Double-Blind Comparison with Valproate. 1260 79

Lamotrigine is an anticonvulsant drug with good efficacy and safety in the treatment of epilepsy. There is now substantial evidence that lamotrigine is also useful in treating resistant depression, rapid cycling bipolar affective disorder, depressive episodes in bipolar affective disorder and in the maintenance phase or prophylaxis of bipolar affective disorder. There are possible roles in managing mood changes in borderline personality disorder, reducing chronic pain and treating schizoaffective disorder. The general range of doses found effective in affective disorders is from 50 to 300 mg daily. Clinical use seems to involve a titration of dose upwards over several weeks until the desired effect is obtained. However, further definitive double-blind, randomised controlled trials against gold standard treatments are required. Lamotrigine has a preferable side-effect profile compared to standard agents for bipolar affective disorder such as lithium or carbamazepine. Further research is certainly warranted and, given its tolerability, could point to lamotrigine as the treatment of choice for some affective disorders.
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PMID:Lamotrigine in mood disorders. 1284 19


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