Journal of clinical psychopharmacology
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J Clin Psychopharmacol · Aug 2005
Case ReportsAcute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy.
The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). ⋯ All patients showed signs of impaired mitochondrial beta-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.
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J Clin Psychopharmacol · Apr 2005
Randomized Controlled Trial Comparative Study Clinical TrialEfficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing.
Pregabalin is a new anxiolytic that acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha2-delta subunit of voltage-gated calcium channels. The current study evaluated the anxiolytic efficacy of BID versus TID dosing of pregabalin in patients with generalized anxiety disorder. Outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition generalized anxiety disorder and having baseline Hamilton Anxiety (HAM-A) total scores > or =20 were randomized to 6 weeks of double-blind treatment with pregabalin 200 mg/d (BID; N = 78), 400 mg/d (BID; N = 89), or 450 mg/d (TID; N = 88) or placebo (N = 86). ⋯ Improvement on both factors was rapid: significance versus placebo was achieved as early as the first assessment at week 1, with > or =30% reduction in HAM-A severity and equal or greater improvement for every subsequent visit in > or =38% of patients in all 3 pregabalin dosage groups (P < or = 0.001). Pregabalin was well tolerated, and despite the fixed-dose study design, discontinuations caused by adverse events ranged from 9% to 13%--comparable with that observed with placebo (8%). This study demonstrates that pregabalin is an effective treatment of generalized anxiety disorder, with BID dosing showing similar efficacy and comparable tolerability with TID dosing.
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J Clin Psychopharmacol · Feb 2005
Randomized Controlled Trial Multicenter Study Clinical TrialRelapse prevention with gepirone ER in outpatients with major depression.
To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. ⋯ All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache. In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.
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The authors present a case of a patient treated with valproic acid for seizure disorder who presented with acute mental status changes consistent with encephalopathy. Notably, her serum ammonia level was 3 times the upper limit of normal, despite an only mildly elevated aspartate aminotransferase and normal bilirubin. ⋯ Her symptoms resolved with discontinuation of valproic acid and supportive care. The authors review the possible mechanisms of valproic acid-associated hyperammonemia with encephalopathy and propose clinical practice modifications to minimize the incidence of this adverse reaction to this generally well-tolerated and clinically important psychotropic medication.