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)

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

Gabapentin is a new adjunctive medication to antiseizure therapies. Anecdotal evidence suggests that it may also help to alleviate mood symptoms in patients with bipolar illness. An open-label study examined the effects of adjunctive gabapentin in bipolar patients with mixed symptoms who had previously demonstrated only partial treatment responses. Mood ratings and side-effect profiles were followed weekly in 10 patients for 1 month. Decreases in Hamilton depression (P < 0.05) and Bech mania ratings (P < 0.01) were evident in the first week of treatment and were sustained. Potent early improvements were noted in early, middle, and late insomnia. The results suggest that gabapentin may be of benefit to bipolar patients who only partially respond to other mood stabilizers. A favorable side-effect profile and rapid action make this drug an attractive choice as an adjunctive therapy.
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PMID:Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. 1059 36

Over a 3-yr period, 19 patients who had sustained brain traumas during motor vehicle incidents and who exhibited abnormal scores for a dichotic word-listening task and Roberts' Epileptic Spectrum Disorder Inventory more than one year after the injury were recommended for treatment with carbamazepine (Tegretol). The psychiatric profile of these patients, as defined by the Minnesota Multiphasic Personality Inventory, was similar to the profile of patients from other studies who had displayed more objective improvement following this treatment. Of the 14 patients 12 who followed the recommendation retrospectively reported that within a few weeks after treatment they experienced marked reductions in the incidence of sudden confusion and depression, increased attention and focus, and either elimination or attenuation of an aversive sensed presence. Such results suggest that many of the debilitating symptoms that persist for months to years after a traumatic brain injury may be electrical in nature rather than due to "psychological responses" and might be treatable by appropriate dosages of carbamazepine or other, e.g., Gabapentin (Neurontin) antiepileptic compounds.
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PMID:Subjective improvement following treatment with carbamazepine (Tegretol) for a subpopulation of patients with traumatic brain injuries. 1076 80

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

Of the 9 new anticonvulsants that have been marketed recently in the UK or US, a number appear to have either adverse or beneficial effects on behaviour. There is now a considerable database of information, in terms of the number of patients treated and/or the number of published reports, on vigabatrin, lamotrigine, gabapentin and topiramate. Oxcarbazepine has been available in some centres for several years and there is extensive experience with the drug in Scandinavia. It appears that the profile of adverse and beneficial effects is similar to that of carbamazepine. Behavioural effects have probably been greatest with vigabatrin, with psychosis, depression and other behavioural problems recorded, but the use of this drug has been limited because of the concern about visual field constriction. The cognitive and behavioural effects of topiramate have caused concern, but these may be much less of a problem if lower starting dosages and escalation rates are used. Psychosis and depression have been associated with topiramate, as they have with another carbonic anhydrase inhibiting drug, zonisamide. Although zonisamide has been used for many years in Japan and Korea, experience elsewhere with this drug is currently very limited. Gabapentin seems to be less associated with adverse behavioural effects than some of the other new anticonvulsant drugs. The reports of behavioural disturbance with gabapentin in children may be related to dose escalation. Behavioural disturbance as a direct result of lamotrigine seems to be uncommon, although indirect effects on behaviour, through the so-called 'release phenomenon' from improved seizure control and consequent ability to misbehave, can occur. Positive behavioural effects have been described with several of the new anticonvulsants, particularly gabapentin, lamotrigine and oxcarbazepine; all of these drugs may have mood-levelling effects that could be of value in treating affective disorders. The information on tiagabine and levetiracetam is too limited to allow any firm conclusions to be drawn with regard to positive or negative behavioural effects. When interpreting reports of behavioural changes with anticonvulsants, it is important to avoid attributing the effect to the drug when one or more of the other multiple causes of behavioural disturbance in people with epilepsy may be responsible or when an indirect effect such as 'forced normalisation' may be the cause. Many of the published studies are retrospective and unblinded rather than double-blind, placebo-controlled, prospective trials, implying that much of the data must be interpreted with caution at this stage.
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PMID:Behavioural effects of the new anticonvulsants. 1144 24

Diabetes mellitus is a major health concern that is only expected to become more prevalent over the next few decades. It causes much morbidity and mortality through various macro- and microvascular complications, including diabetic neuropathy. Currently, there is no treatment that directly affects the natural course of diabetic neuropathy except for rigorous glycemic control, a goal that is not always achievable. Despite these therapeutic limitations, the morbidity caused by diabetic neuropathy can be minimized by early and accurate diagnosis. A detailed history and physical examination, along with carefully selected laboratory tests will confirm the presence of diabetic neuropathy while excluding other etiologies that may require alternative management strategies. Treatment is always tailored to the patient's symptoms. In addition to improved glycemic control, health care providers can provide education, support, and symptomatic relief. There are many pain modulating therapies that are effective in diabetic neuropathy as discussed above. Nortriptyline at low doses is an inexpensive well-tolerated medication that is effective. Gabapentin is an excellent choice when nortriptyline is ineffective or not tolerated. Other anticonvulsants, such as lamotrigine, carbamazepine, oxycarbazepine, and topiramate, may also provide benefit. Judicious use of narcotics is appropriate when other treatment modalities fail. The importance of treating underlying depression cannot be overemphasized. When gait becomes impaired as a result of neuropathy, appropriate prescription of assistive devices will prevent injuries from falls. Ankle-foot orthoses and other orthotic devices may allow patients to remain ambulatory and independent for a longer period. Despite the challenges ahead, the future holds the promise of more effective treatments for diabetes mellitus and its complications.
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PMID:Medical evaluation and treatment of diabetic peripheral neuropathy. 1463 32

The negative and positive effects of the nine newer antiepileptic drugs that have received a product licence in the UK or in the US are reviewed. The importance of avoiding misinterpretation of the data because of confounding factors such as alternative psychosis, the release phenomenon or drug interactions is emphasised. Vigabatrin has been associated with both psychosis and depression. Due to the concentric visual field defects that may occur with vigabatrin, its use is now limited, although it remains the drug of choice for infantile spasms. Lamotrigine seems to be largely associated with improvement rather than deterioration of mood and behaviour. It may have a role in treating affective disorder. Gabapentin probably has relatively little effect on behaviour but may exacerbate behavioural problems in some children with pre-existing difficulties. Topiramate may precipitate both psychosis and depression, but these are less likely to occur if the currently recommended lower starting doses, escalation rates and target doses are used. The data for tiagabine are limited, but there is no clear evidence for psychosis or depression being caused by this drug. Oxcarbazepine may be of value in treating mood disorder, but the information is very limited. There are few reports of behavioural disturbances with levetiracetam, but the data suggest that there is no significant increase in psychosis or depression. There are some reports of psychosis and other behavioural disturbances with felbamate, but the use of this drug is limited by the serious adverse effects of hepatotoxicity and aplastic anaemia. There is some evidence for psychosis with zonisamide, but there is also a suggestion that this drug may be of benefit in treating psychiatric disorders. Careful individual assessment of each patient should enable the clinician to determine whether the medication or some other factor is responsible for any behavioural disturbance.
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PMID:Behavioural effects of the newer antiepileptic drugs: an update. 1468 Apr 57

Therapy of bipolar disorders is a rapidly evolving field. Lithium has efficacy in classic bipolar disorders whereas divalproex sodium and carbamazepine may have broader spectrum efficacy that includes non-classic bipolar disorder. In the last 10 years, a series of anticonvulsants have been approved for marketing in the United States. Gabapentin has indirect g-aminobuytric acid-ergic actions, is generally well tolerated, and appears to have anxiolytic, analgesic, and hypnotic effects. Lamotrigine has antiglutamatergic actions and is generally well tolerated (aside from rash in 1 in 10, and serious rash in 1 in 1,000 patients). Lamotrigine is indicated for maintenance treatment in bipolar disorder. Emerging evidence suggests lamotrigine may have utility in bipolar disorder patients with depression and treatment-refractory rapid cycling, as well as analgesic effects. Topiramate and zonisamide may allow both weight loss, while topiramate may have specific efficacy in bulimia, binge eating disorder, and alcohol dependence. Two small studies found oxcarbazepine had similar efficacy to lithium and haloperidol in acute mania. Phenytoin, an older anticonvulsant, may have adjunctive acute mania efficacy. Levetiracetam, a newer anticonvulsant, may be worth exploring and has minimal drug-drug interactions. None of these newer agents has been shown effective in a large placebo controlled trial for acute mania. Although the clinical profiles of these newer anticonvulsants do not appear to overlap markedly with divalproex and carbamazepine (except perhaps for oxcarbazepine), these novel agents may still offer important new options in relieving a variety of specific target symptoms in patients with bipolar disorder.
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PMID:New anticonvulsant medication uses in bipolar disorder. 1497 68

The prevalence, natural course, risk profile, and treatment of anxiety disorders in the elderly are remarkably understudied. Anxiety disorders are less prevalent in the elderly than in younger adults, but rates of subsyndromal anxiety disorders in elderly persons are nearly as high as in their younger cohorts. The most common late-life anxiety disorders are mixed anxiety-depression and generalized anxiety disorder. Though the benzodiazepines are widely used in this population and are considered relatively safe given appropriate dosing and safety monitoring, important liabilities remain with the use of these agents. Antidepressants also are widely used in elderly patients, but there are no randomized controlled anxiety disorder treatment trials in this population. Gabapentin and low-dose atypical antipsychotics are beginning to be used and studies of the atypical antipsychotics are ongoing. Until studies are completed, treatment of late-life anxiety will continue to be guided by extrapolating data from the general adult population. Psychopharmacology Bulletin. 2004;38(Suppl 1): 25-30.
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PMID:Late-life anxiety disorders. 1527 15

Gabapentin is a drug with anticonvulsant and analgesic properties causing the reduction of neurotransmitter release. We show that one of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of rat hippocampal slices. Interestingly, we found that gabapentin-induced depression of FV is mimicked and occluded by NMDA receptor (NMDA-R) antagonists, indicating that these receptors are located presynaptically and are activated by ambient levels of glutamate. Conversely, NMDA application (20 microM, 10 min) elicits a reversible FV potentiation which is reduced by gabapentin. Both NMDA- and gabapentin-induced FV changes are partially explained by modifications in the firing threshold of individual fibres. Increasing [K(+)](o) does not mimic or occlude (at a concentration of 6.5 mM) the effect of NMDA on FV amplitude, which makes it unlikely that a rise in [K(+)](o) induced by NMDA receptor activation could indirectly participate in the potentiation of the FV. The NMDA-induced FV potentiation is independent of extracellular calcium presence but is completely inhibited in a low-Na(+) solution (50% reduction) or under NMDA channel block (high Mg(2+) or MK 801). These findings suggest that sodium entry through presynaptic NMDA-R channels facilitates axon excitability. The interaction of gabapentin with this newly described mechanism might contribute to its therapeutic benefits.
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PMID:Presynaptic NMDA autoreceptors facilitate axon excitability: a new molecular target for the anticonvulsant gabapentin. 1565 57


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