levetiracetam and Schizophrenia

Abnormal involuntary dyskinetic movements in schizophrenia patients have been documented for more than 140 years. Clinicians should distinguish between two kinds of disturbances-spontaneous dyskinetic movements and movements induced by psychotropic medications-which may look familiar clinically. As a modern term, tardive dyskinesia (TD) is a potentially permanent neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. Several distinct forms of TD exist, specifically tardive akathisia, tardive blepharospasm, tardive dystonia, tardive gait, tardive myoclonus, tardive tremor, and tardive tics, and they have different pathophysiologies and treatment. The pathogenesis of TD remains unclear, and the pathophysiology is complex and multifactorial. Moreover, there is solid evidence of a genetic predisposition to TD. This article summarizes recent relevant publications concerning TD and the most recent studies regarding treatment of this disorder with antioxidative agents.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Fatty Acids, Omega-3; Ginkgo biloba; Humans; Levetiracetam; Melatonin; Movement Disorders; Neuroprotective Agents; Phytotherapy; Piracetam; Schizophrenia; Vitamin B 6; Vitamin E

Schizophrenia is associated with persistent cognitive deficits, which worsen treatment outcomes despite increasing antipsychotic doses. This study aimed to assess the effect of levetiracetam on the severity of schizophrenia symptoms and cognitive deficits in these patients.. In this randomized, controlled, three-blind randomized clinical trial approved by Mashhad University of Medical Sciences, Iran (IRCT20101130005280N31), forty chronic schizophrenic patients aged 18-60 years were randomly divided into two groups of levetiracetam and placebo. The levetiracetam group received levetiracetam for 8 weeks. The symptoms were evaluated by Positive and Negative Symptoms Scale (PANSS), Stroop test, Digit Span test and Wisconsin Test at baseline, 4th week, and 8th week. Data were analyzed through SPSS V. 23 software, descriptive tests and inferential statistics.. At the end of the study, all subscales of the PANSS questionnaire reduced significantly (P < 0.05). Also, all subscales of the cognitive tests had significant changes. The trends of digit span tests, correct number of consonants and inconsonant were increasing. While the trends related to consonant errors, inconsistent errors, consistent reaction time and nonconsistent reaction time were decreasing. The changes in the number of classes were increased while changes in preservation error were decreased.. The results showed that levetiracetam has significant effects on clinical symptoms, especially negative symptoms. Also, it impacts significantly on cognitive functions. It is recommended that it be added to the pharmacological regimen of these patients to improve their clinical symptoms, quality of life and treatment outcomes.

Topics: Antipsychotic Agents; Double-Blind Method; Drug Therapy, Combination; Humans; Levetiracetam; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Treatment Outcome

Stress during adolescence is a major risk factor for schizophrenia. We have found previously in rats that adolescent stress caused, in adulthood, behavioral changes and enhanced ventral tegmental area (VTA) dopamine system activity, which were associated with dysregulation of the excitatory-inhibitory (E/I) balance in the ventral hippocampus (vHip). Levetiracetam, an anticonvulsant drug, regulates the release of neurotransmitters, including glutamate, via SV2A inhibition. It also modulates parvalbumin interneuron activity via Kv3.1 channels. Therefore, levetiracetam could ameliorate deficits in the E/I balance. We tested whether levetiracetam attenuate the adolescent stress-induced behavioral changes, vHip hyperactivity, and enhanced VTA dopamine system activity in adult rats.. Male Sprague-Dawley rats were subjected to a combination of daily footshock (postnatal day [PD] 31-40), and three 1 h-restraint stress sessions (at PD31, 32, and 40). In adulthood (PD62), animals were tested for anxiety responses (elevated plus-maze and light-dark box), social interaction, and cognitive function (novel object recognition test). The activity of vHip pyramidal neurons and VTA dopamine neurons was also recorded.. Adolescent stress produced anxiety-like responses and impaired sociability and cognitive function. Levetiracetam (10 mg/kg) reversed these changes. Levetiracetam also reversed the increased VTA dopamine neuron population activity and the enhanced firing rate of vHip pyramidal neurons induced by adolescent stress.. These findings suggest that levetiracetam attenuates the adverse outcomes associated with schizophrenia caused by stress during adolescence.

Topics: Action Potentials; Animals; Dopamine; Dopaminergic Neurons; Levetiracetam; Male; Rats; Rats, Sprague-Dawley; Schizophrenia; Ventral Tegmental Area

Topics: Hemodynamics; Hippocampus; Humans; Levetiracetam; Psychotic Disorders; Schizophrenia

Topics: Epilepsy; Female; Humans; Levetiracetam; Middle Aged; Psychoses, Substance-Induced; Schizophrenia

Imbalance in neural excitation and inhibition is associated with behavioral dysfunction in individuals with schizophrenia and at risk for this illness. We examined whether targeting increased neural activity with the antiepileptic agent, levetiracetam, would benefit memory performance in a preclinical model of schizophrenia that has been shown to exhibit hyperactivity in the hippocampus. Adult rats exposed to ketamine subchronically during late adolescence showed impaired hippocampal-dependent memory performance. Treatment with levetiracetam dose-dependently improved memory performance of the ketamine-exposed rats. In contrast, the antipsychotic medication risperidone was not effective in this assessment. Levetiracetam remained effective when administered concurrently with risperidone, supporting potential viability of adjunctive therapy with levetiracetam to treat cognitive deficits in schizophrenia patients under concurrent antipsychotic therapy. In addition to its pro-cognitive effect, levetiracetam was also effective in attenuating amphetamine-induced augmentation of locomotor activity, compatible with the need for therapeutic treatment of positive symptoms in schizophrenia.

Topics: Amphetamine; Animals; Central Nervous System Stimulants; Cognition Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Ketamine; Levetiracetam; Locomotion; Male; Maze Learning; Memory Disorders; Nootropic Agents; Piracetam; Rats; Rats, Long-Evans; Schizophrenia