Zonisamide in the treatment of binge eating disorder with obesity: A randomized controlled trial
ABSTRACT Binge eating disorder (BED) is associated with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to evaluate zonisa-mide in the treatment of BED associated with obesity.
In this 16-week, single-center, randomized, double-blind, placebo-controlled, flexible-dose (100-600 mg/day) trial, 60 outpatients with DSM-IV-TR BED received zonisamide (N = 30) or placebo (N = 30). The primary outcome measure was weekly frequency of binge eating episodes. The primary analysis of efficacy was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the effect measure. Patients were enrolled from September 5, 2003, through October 1, 2004.
Compared with placebo, zonisamide was associated with a significantly greater rate of reduction in binge eating episode frequency (p = .021), body weight (p < .001), BMI (p = .001), and scores on the Clinical Global Impressions-Severity scale (p < .001), Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (p < .001), and Three Factor Eating Questionnaire disinhibition scales (p < .001). Plasma ghrelin concentrations increased with zonisamide but decreased with placebo (p = .001). The mean (SD) zonisamide daily dose at endpoint evaluation was 436 (159) mg/day. Twelve patients (N = 8 receiving zonisamide, N = 4 receiving placebo) discontinued because of adverse events. The most common reasons for discontinuing zonisamide were accidental injury with bone fracture (N = 2), psychological complaints (N = 2), and cognitive complaints (N = 2).
Zonisamide was efficacious, but not well tolerated, in the short-term treatment of BED associated with obesity.
ClinicalTrials.gov identifier NCT00221442.
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- "No effects in a phase II clinical trial (Murata et al., 2007) ▼ ICD in a pilot study (Bermejo et al., 2010) ▼ binge eating (Marazziti et al., 2012; McElroy et al., 2006, 2012) M a n u s c r i p t 93 GABA receptors Valproate Unknown: may inhibit GABA transaminase ▼ ICD in pilot studies (Hicks et al., 2011; Sriram et al., 2013) ▼ internet addiction (Przepiorka et al., 2014) "
ABSTRACT: Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor symptoms of the disease. However, its chronic use is associated with disabling motor and behavioural side effects, among which levodopa-induced dyskinesias (LID) and impulse control disorders (ICD) are the most common. The underlying mechanisms and pathological substrate of these dopaminergic complications are not fully understood. Recently, the refinement of imaging techniques and the study of the genetics and molecular bases of LID and ICD indicate that, although different, they could share some features. In addition, animal models of parkinsonism with LID have provided important knowledge about mechanisms underlying such complications. In contrast, animal models of parkinsonism and abnormal impulsivity, although useful regarding some aspects of human ICD, do not fully resemble the clinical phenotype of ICD in patients with PD, and until now have provided limited information. Studies on animal models of addiction could complement the previous models and provide some insights into the background of these behavioural complications given that ICD are regarded as behavioural addictions. Here we review the most relevant advances in relation to imaging, genetics, biochemistry and pharmacological interventions to treat LID and ICD in patients with PD and in animal models with a view to better understand the overlapping and unique maladaptations to dopaminergic therapy that are associated with LID and ICD. Copyright © 2015. Published by Elsevier Ltd.Neuroscience & Biobehavioral Reviews 07/2015; DOI:10.1016/j.neubiorev.2015.07.010 · 10.28 Impact Factor
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- "The broad pharmacodynamic properties of zonisamide suggest that they have potential effects on other neuropsychiatric disorders. Several clinical trials have investigated the effectiveness of zonisamide on migraines (Ashkenazi et al., 2006; Drake et al., 2004), chronic pain (Krusz, 2003), bipolar affective disorder (Berigan, 2002; Ghaemi et al., 2008; McElroy et al., 2005; Wang et al., 2008), binge eating disorder (McElroy et al., 2006), and obesity(Gadde et al., 2003; McElroy et al., 2006; Wang et al., 2008; Yang et al., 2010). "
ABSTRACT: This study examined the long-term effectiveness and tolerability of zonisamide for weight control in psychiatric outpatients using various psychotropic medications. We conducted a systematic chart review of 82 psychiatric outpatients with unwanted weight gain after the introduction of psychotropic drugs between January 2008 and September 2009 at Korea University Ansan Hospital. The primary outcome measure was the effect of zonisamide on body mass index (BMI). Additional outcome measures included safety and tolerability as assessed by the clinical global impression-severity of illness scale (CGI-S) and discontinuation rate. The mean final dose of zonisamide was 124.6±53.4 mg/day and ranged from 50mg/day to 300 mg/day. The mean BMI reduction was 0.8±1.7 kg/m(2) and ranged from -2.9 kg/m(2) to 4.7 kg/m(2) (p<0.001). We also observed a significant reduction in CGI-S scores from the baseline (3.8±0.9) to the endpoint (3.3±0.8; p<0.001). Twelve patients (14.6%) discontinued their zonisamide treatment due to its side effects. Patients treated with zonisamide showed significant weight loss. Furthermore, its treatment was generally safe and well tolerated with few negative effects on patients' overall psychiatric symptoms. Additional research is required to confirm these results and to investigate whether patients have rebound weight gains after discontinuing zonisamide.Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2011; 35(8):1918-21. DOI:10.1016/j.pnpbp.2011.07.007 · 4.03 Impact Factor
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- "After extensive studies it became available in 1989 for the treatment of intractable epilepsy in Japan and received over 10 years later approval in the USA and Europe for adjunctive treatment of partial seizures in adults (Murata, 2004). Besides treatment of epilepsy, there has been a growing interest in the therapeutic potential of zonisamide for treating non-seizure conditions, such as intractable neuropathic pain (Atli and Dogra, 2005), headache (Drake et al., 2004), obesity and binge eating disorder (McElroy et al., 2006) and Parkinson's disease (PD) (Murata et al., 2001). Particular in PD, studies reporting positive effects of zonisamide have become more frequent. "
ABSTRACT: Zonisamide is widely used as an antiepileptic drug. Two studies published recently in Experimental Neurology focus on the drug's neuroprotective effect. In the present commentary, we discuss the significance of their findings and aspects of zonisamide in neuroprotection.Experimental Neurology 05/2010; 224(2):336-9. DOI:10.1016/j.expneurol.2010.04.017 · 4.62 Impact Factor