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Re: AAPs as mood stabilizers/failed traditional Sheilac

Posted by phidippus on September 5, 2015, at 14:44:34

In reply to Re: AAPs as mood stabilizers/failed traditional phidippus, posted by Sheilac on September 5, 2015, at 7:18:31

Mood and Bipolar Disorders. Levetiracetam (Keppra)affects different parts of the brain, including the hippocampus and the amygdala, which are involved in mood disorders.[9,10,94-96] Studies have shown that increased levels of hippocampal Y-1- and Y-5-like receptors might be responsible for mood-stabilizing properties of levetiracetam.[10] Levetiracetam, both as add-on and as monotherapy, has shown its efficacy in a broad spectrum of bipolar disorders.

Bersani[97] investigated the potential efficacy of levetiracetam in outpatients affected by bipolar spectrum disorders as an add-on therapy to previous pharmacologic treatments. Twenty patients, 13 men and 7 women, were enrolled in this pilot study. These patients received oral levetiracetam 500 mg twice daily for 60 days. Fifteen patients completed the study, and for all of these patients the BPRS and the Bech-Raphaelsen scale of mania scores showed a rapid decrease following levetiracetam add-on therapy; this effect was significant at day 60. The tolerability of levtiracetam was assessed by the dosage record and treatment-emergent symptom scale. Five patients dropped out during the study, one because his symptoms worsened and the others for reasons independent of treatment response. The rest of the patients tolerated levetiracetam therapy without significant adverse effects. This study was the first to show the positive effect of levetiracetam in manic syndrome, including mood and behavioral symptoms.[97]

In an open-label trial, 34 patients with treatment-refractory bipolar I disorder (13 depressed, 7 manic, and 14 cycling) were enrolled.[92] These patients received 500-1000 mg of levetiracetam titrated to a target dosage of 2000 mg/day. The dosage was increased to 3000 mg/day as needed. Levetiracetam was an add-on therapy for eight weeks. The patients were rated weekly or once every other week with the Young Mania Rating Scale (YMRS), the Inventory for Depressive SymptomatologyClinical version, and the Clinical Global Impressions scale for use in bipolar illness for severity of mania, depression, and overall illness. A 31% remission rate was reported in patients who were depressed at baseline and who received levetiracetam as an add-on therapy. A 44% remission rate was noted in patients with mania at baseline. Four patients dropped out within the first week of treatment for administrative reasons, drug intolerance, or mood worsening. Another eight patients dropped out before week 3 because of lack of efficacy. Only 1 patient experienced psychosis. This was a high early-withdrawal rate for this open-label study. Moreover, severely depressed patients did not show any good response ( Table 4 ).

Grunze et al.[93] conducted an open-label study in 10 patients with a history of bipolar I disorder who were in an acute manic state. Levetiracetam was used as an add-on therapy with off-and-on design. All patients were treated with haloperidol 5-10 mg/ day. Levetiracetam was added until day 14, then discontinued, and reintroduced at day 21. The maximum dosage of levetiracetam used was 4000 mg/day. The mean dosage of levetiracetam was 3125 mg/day. The YMRS was used to assess the psychopathologic changes. After a mean decrease of the YMRS scores from 29.6 to 17.2 during the first on phase, manic symptoms worsened during the off period and ameliorated again during the second on phase, with a decrease of the mean YMRS score to 14.7 at the end of the study. At day 14, only 2 patients responded compared with 7 at the end of the study at day 28. Levetiracetam showed some additional antimanic effects in this study. The important adverse effects noted in this study were sedation (3 patients), dizziness (1 patient), and asthenia (1 patient). The abrupt discontinuation of drug caused no withdrawal effects except worsening of manic symptoms ( Table 4 ).[93]

Levetiracetam has a potential role in treating refractory bipolar patients with different comorbidities that are difficult to manage even with multiple medications. Kaufman[98] described a 21-year-old white woman with treatment-resistant, rapid-cycling, bipolar disorder who did not respond to 15 different psychotropics. She responded well to levetiracetam monotherapy, which was started at 1000 mg at bedtime and then increased to 2500 mg at bedtime. She remained without bipolar features during 1 year of maintenance treatment, except for one week during which she was noncompliant.[98]

The results of these studies suggest the need for further controlled trials to see the efficacy and tolerability of levetiracetam in patients with different mood and bipolar disorders. It is premature to recommend the use of levetiracetam in patients with these mood disorders in routine clinical practice.





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