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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms of action, onset and duration of action, and interactions with other medications--all of these pharmacokinetic properties of pharmacologic agents affect the efficacy and safety of therapeutic regimens for bipolar disorder. For example, antiglutamatergic agents such as lamotrigine may relieve depression but have no impact on mania. Atypical antipsychotics with the dual effect of blocking dopamine and serotonin receptors in the brain decrease psychosis, mania, and, according to some preliminary indications, possibly depression. The impact of these properties has been borne out in clinical studies. Mood stabilizers such as lithium and valproate stabilize mood by significantly decreasing the manic and hypomanic symptoms of bipolar disorder, although they can have effects on depressive symptoms too. Lamotrigine stabilizes mood by reducing depression. The atypical anti-psychotics have been shown to be effective either as monotherapy or in combination with mood stabilizers.
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PMID:Employing pharmacologic treatment of bipolar disorder to greatest effect. 1555 91

Bipolar disorder is a psychiatric condition characterised by episodes of mania, depression, and underlying mood instability. Anticonvulsant drugs have an established place in the treatment of the disorder, but identifying novel drugs in this class is complicated by the absence of validated animal models. We have evaluated the efficacy of three anticonvulsant mood stabilising drugs (lamotrigine, valproate, and carbamazepine) in a model of mania, in which hyperactivity is induced by the combination of D-amphetamine and chlordiazepoxide. All three drugs were effective at preventing the hyperactivity. Lower doses of valproate and carbamazepine were required to prevent hyperactivity compared to doses required to block tonic-clonic seizures induced by pentylenetetrazole. Lamotrigine was equipotent in the two models. However, the complex pharmacology of the D-amphetamine/chlordiazepoxide model means that there may be several mechanisms by which hyperactivity can be reduced, and these may have more or less relevance to the treatment of bipolar disorder. To address this issue, we also evaluated effects of the three anticonvulsants on baseline locomotion, on activity in the presence of chlordiazepoxide alone, or on activity induced by D-amphetamine alone. Based on the results, we propose that hyperactivity induced by D-amphetamine/chlordiazepoxide may arise through dopaminergic drive coupled with disinhibition caused by low doses of the benzodiazepine. The efficacy of lamotrigine may then arise through a reduction in neuronal excitability or increased glutamate transmission, these latter a consequence of the disinhibition. Carbamazepine may also reduce excitability and glutamate release, but its broader pharmacology, manifested by sedation at higher doses complicates interpretation of its efficacy and reflects its poorer tolerability in the clinic. Valproate may be effective, at least in part, through an enhancement of GABAergic transmission. The predictive validity of the D-amphetamine/chlordiazepoxide model for efficacy in bipolar disorder remains to be established, and research with a wider range of clinically tested drugs is warranted to help validate the model further. In the meantime, the model may be useful for distinguishing novel anticonvulsant drugs with different mechanisms of action.
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PMID:Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania. 1568 Feb

Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [Cox's F test for comparing survival in two groups: F(6, 18)=3.44, p=0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine and valproate. To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton Depression Scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.
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PMID:Phenytoin: an anti-bipolar anticonvulsant? 1642 79

This study examined the efficacy of lamotrigine in the prevention of migraine aura. Fifty nine patients suffering from migraine with aura received lamotrigine in a controlled three year prospective open study. Treatment response was defined as a reduction of aura frequency each month by at least 50%. Primary endpoint was reached by three quarters of the patients. Lamotrigine significantly reduced both frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7) after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v 8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of those patients with a reduction of aura symptoms experienced a significant reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in reducing migraine aura and migraine attacks. The strong correlation between reduction of aura symptoms and migraine attacks stresses the potential role of aura-like events and possibly cortical spreading depression as a trigger for trigeminal vascular activation, and subsequently the development of migraine headaches.
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PMID:Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. 1629 5

Lamotrigine (LTG) is an anti-epileptic drug that is widely used clinically in various neuropsychiatric disorders. Although consensus is found on the general mode of action by LTG on voltage-gated sodium current, its effect on field potential, neuropropagation, and long-term potentiation, especially in prefrontal cortex (PFC), is still not understood completely. We investigated LTG effects on synaptic response in rat prefrontal cortical slice with the aid of a novel multi-electrode dish (MED64) system. The amplitude and propagation of field excitatory postsynaptic potentials (fEPSP), presynaptic fiber volleys (PrV) were expressed dimensionally in the MED64 system. Lamotrigine (3-100 microM) inhibited the amplitude and propagation of fEPSP and PrV in a concentration dependent manner. It exerted a predominant presynaptic action, as indicated by the increment in paired-pulse facilitation. Stimulating dependency with reduction fEPSP was seen in the presence of LTG at clinically relevant concentrations as well as with PrV, both in amplitude and propagation. In addition, the depression of PrV amplitudes in the presence of LTG showed a use-dependent fashion. As to LTP in PFC, it was not fEPSP amplitude but propagation reduced by LTG. In PFC, LTG exerts its use- and concentration-dependent inhibitory effect on presynaptic action and depresses fEPSP amplitude and propagation in a clinically relevant concentration. LTP was preserved in its fEPSP amplitude but not propagation in PFC in the presence of LTG.
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PMID:Effects of lamotrigine on field potentials, propagation, and long-term potentiation in rat prefrontal cortex in multi-electrode recording. 1649 13

Lamotrigine is an anticonvulsant drug that exhibits a clinical antidepressant effect. However, few studies have been conducted with lamotrigine in animal models of depression and its mechanism of antidepressant action is still unclear. The present study evaluates the effect of lamotrigine (5-20mg/kg, i.p.) in the modified forced swimming test and compare its behavior pattern in the test with those of paroxetine (20mg/kg, i.p.), nortriptyline (20mg/kg, i.p.) and dizolcipine-MK-801 (0.1mg/kg, i.p.). The effect of lamotrigine on locomotor activity and memory was also studied in order to exclude false-positive results. At low doses, lamotrigine (10mg/kg) decreased immobility and increased climbing scores, a similar pattern to nortriptyline. A higher lamotrigine dose (20mg/kg) also increased swimming scores. Lamotrigine neither changed locomotion in the open-field test nor impaired habituation. Paroxetine and dizolcipine decreased immobility and increased swimming. Dizolcipine also decreased climbing. However, although the effects of paroxetine and nortriptyline were seen without effect on locomotor activity, dizolcipine increased locomotor activity. The present study indicates that the antidepressant-like effect of lamotrigine is probably related to noradrenergic/serotonergic systems.
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PMID:Dual monoamine modulation for the antidepressant-like effect of lamotrigine in the modified forced swimming test. 1650 22

This paper reviews the evidence for the efficacy of anticonvulsants in the continuation and maintenance phases of treatment of bipolar disorder, when there has been an episode of mania (Bipolar-I disorder). The evidence to be considered is primarily that arising from randomized controlled trials. A literature search was performed to identify all randomized controlled trials of anticonvulsants used as maintenance treatment for bipolar-I disorder. Placebo-controlled studies were preferred, however there have been relatively few of these and clinical practice must therefore be guided by evidence carrying a lower level of conviction. Valproate monotherapy lacks a convincing evidence base. The view that valproate is more effective than lithium in rapid cycling has not been borne out. Lamotrigine is effective in preventing depression after an episode of mania. As monotherapy, lithium appears superior to carbamazepine in bipolar patients not previously treated with either drug. The combination of lithium and carbamazepine may be superior to either drug alone, in certain treatment-resistant patients, but is associated with increased side effects. Other anticonvulsants lack evidence supporting their use in bipolar disorder except in treating co-morbid alcohol dependence, anxiety and bulimic symptoms. Valproate continues to be recommended by most current guidelines despite the lack of evidence.
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PMID:The use of anticonvulsants in the aftermath of mania. 1655 69

Bipolar disorder affects 1.6% of the population. The majority of the burden of illness for people with bipolar disorder is due to depression. Suicide rates for people with bipolar disorder are 15 times higher than in the general population, and the majority of these deaths occur during depressive episodes. More effective prevention of such depressive episodes is important. Lamotrigine is an anticonvulsant and a mood stabiliser that is more effective at preventing depressive relapses than most other mood stabilising drugs. Its use for this purpose has been recommended by English language treatment guidelines since 2002. Lamotrigine is approved for use in the prophylaxis of depression in bipolar disorder and for epilepsy. PHARMAC subsidises its use in treatment-resistant epilepsy (subject to a 'special authority' application) but not in bipolar disorder. The New Zealand Mental Health Strategy and the imminent New Zealand Suicide Strategy identify reducing suicide as a key goal. Among other initiatives, this requires effective treatment of bipolar depression, yet a treatment likely to support this is not currently subsidised.
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PMID:PHARMAC and treatment of bipolar depression--the limits of utilitarianism. 1658 81

Adjunctive treatment of lamotrigine compared to other antidepressants in the treatment of partially responsive, poorly functioning patients with unipolar depression was assessed. Fourteen consenting patients with confirmed DSM-IV-R diagnosis of unipolar depression were identified as treatment resistant. All patients failed at least two 8-week treatment trials with antidepressants. All were treated with lamotrigine as an adjunct to other antidepressants for at least 6 months. The primary effectiveness measure was the Clinical Global Impression Severity subscale (CGI-S). Other scales included the Montgomery-Asberg Depression Scale (MADRS) and the Global Assessment of Functioning Scale (GAF). Monitoring for skin rashes, headache, dizziness, somnolence, and gastrointestinal disturbances was carried out to assess for adverse events. Baseline measures prior to adding lamotrigine were compared to those at 8 weeks and 6 months with adjunctive treatment. Twelve patients of the total (n=14) completed the trial, and two discontinued treatment. There was significant, rapid, and robust resolution in symptoms in all effectiveness measures, including the core symptoms of depression, as shown by the changes from baseline in CGI-S, and MADRS at 8 weeks. Social and occupational functioning was significantly improved at 6 months. Eight patients returned to gainful employment or started schooling. Patients tolerated the adjunctive lamotrigine treatment well. Lamotrigine may have antidepressant properties in patients with unipolar depression and may have an earlier onset of action when given in combination with antidepressants.
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PMID:Lamotrigine adjunctive treatment in resistant unipolar depression: an open, descriptive study. 1684 46

In this investigation, the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive lamotrigine (n=32) or placebo (n=38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic-clonic (PGTC) seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell Dysthymia Rating Scale-Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score (lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P=0.01) and POMS total score (lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P=0.03) and numerically greater with lamotrigine than placebo for CDRS score (lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P=0.50). Among the subset of patients with at least mild depression (BDI-II score10), mean improvement from baseline was numerically, but not statistically significantly, greater with lamotrigine (11.5, n=13) than placebo (3.1, n=18) (P=0.054). Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood (r=0.1, P=ns). Compared with placebo, lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures. Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms.
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PMID:Effect of lamotrigine on depressive symptoms in adult patients with epilepsy. 1707 Nov 41


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