Recent advances in the pharmacotherapy of psychiatric disorders

Psychopharmacology has developed over approximately the past five decades. The remarkable proliferation of information in this area has made it difficult for clinicians to understand the characteristics of various psychotropic agents. Atypical antipsychotics including amisulpride, asenapine, aripiprazole, blonanserin, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and zotepine cause fewer extrapyramidal problems and have many clinical applications, but they can cause metabolic disturbances. Mood stabilizers and lamotrigine are widely used for bipolar disorder. Other novel anticonvulsants such as topiramate, oxcarbazepine, gabapentin, tiagabine, pregabalin, vigabatrin, levetiracetam, and riulzole have also been tested with diverging or inconclusive results. Antidepressants are commonly used in the clinical treatment of depression and anxiety disorder. However, the mechanism of action of medications used in the treatment of psychiatric disorders remains unclear. Understanding the mechanisms of action and clarifying the diagnosis may enhance the treatment outcome in psychiatry. In this review, we analyzed clinical pharmacology data for each drug within a class and discussed clinical strategies for administering currently available antipsychotics, mood stabilizer/anticonvulsants, and antidepressants widely used for various psychiatric indications.

New Antiepileptic Drugs in Childhood Epilepsy

Many new antiepileptic drugs (AEDs) have been developed in the last two decades, contributing to the optimal treatment for childhood epilepsy. The goal of the treatment is to achieve seizure-free without any side effects, that deteriorates the quality of life by causing negative consequences. The new AEDs have not shown better efficacy, but generally seem to be better tolerated, having fewer systemic reactions and better pharmacokinetics than the established AEDs. The new AEDs have a broad spectrum of activities, which offer new opportunities to patients who have not shown any favorable responses to the established ones. There are more choices when trying to select AEDs for epileptic seizures and syndromes. Majority of the new AEDs have more than one action mechanism. AEDs acting selectively through the GABAergic system are tiagabine and vigabatrin; acting by inhibition of voltagedependent Na+ and Ca2+ channels are lamotirigine, oxcabarbazepine and topiramate; and acting by inhibition of glutamate-mediated excitation are felbamate, topiramate. The pharmacokinetic parameters of the new AEDs compared to the established AEDs, new AEDs have improved in terms of longer half-lives, permitting less frequent daily dosing, reduced potential for drug interactions. Considerations in selecting an AEDs are not only dependent on seizure types or syndromes, side effect profile, action mechanism, drug interaction, pharmacokinetic profile, facility of drug initiation, but also on age and sex of patients. Patients with worsened seizurefrequency or development of new types of seizure after the introduction of AEDs, should be questioned on the previously diagnosed seizure types or syndromes.

Tiagabine induced non-convulsive status epilepticus in a patient without history of epilepsy

Cases of non-convulsive status epilepticus [NCSE] induced by tiagabine [TGB] were occasionally reported. Almost all had a prior history of epilepsy. We describe here, the clinical and EEG findings in a patient, without history of seizures, who after the start of TGB developed NCSE. A 53-year-old man with history of paranoid schizophrenia, presented with "alteration of his mental state". Three weeks early, TGB was added to his psychiatric regimen. On the second day of admission, he became unresponsive with a blank stare. Concomitant EEG showed abundant sharp and slow wave complexes. The episode lasted for 4 hours and was aborted by the intravenous administration of lorazepam. The TGB was discontinued without recurrence of subsequent seizure activity. This case supports the contention that TGB can induce NCSE in subjects not previously known to have seizures

clinical overview of the new antiepileptic drugs

Over the past decade, several new antiepileptic drugs [AEDs] have become available including Gabapentin, Lamotrigine, Topiramate, Tiagabine, Oxcarbazepine, Levetiracetam, Zonisamide, Vigabatrin and Felbamate. These drugs had proved their efficacy in various types of seizures. Lamotrigine and Topiramate were suggeseted as effective for use as monotherapy for generalized seizures, and Topiramate, Lamotrigine, Oxcarbazepine and Gabapentin for partial onset seizures, and Vigabatrin for infantile spasms. All the new anti-epileptic drugs are also effective as add-on therapy for partial seizures without or with secondary generalization. This article briefly reviews the pharmacodynamics of the new antiepileptic drugs to provide information that physicians in the Kingdom particularly non-epileptologists for rational choice and judicious use of these agents

Inhibition of thermal hyperalgesia and tactile allodynia by intrathecal administration of gamma-aminobutyric acid transporter-1 inhibitor NO-711 in rats with chronic constriction injury / 生理学报

The present study was undertaken to explore the role of gamma-aminobutyric acid transporters in the neuropathic pain. On the chronic constriction injury (CCI) rats 4 doses (5, 10, 20, 40 microg in group N5, N10, N20, N40, respectively) of specific gamma-aminobutyric acid transporter-1 inhibitor NO-711 or normal saline (in group NS) were intrathecally administered before sciatic nerve ligation (pre-treatment) or at the third day after ligation (post-treatment). The paw withdrawl latency (PWL) from a noxious thermal stimulus and paw withdrawl mechanical threshold (PWMT) of von Frey filament was used as measure of thermal hyperalgesia and tactile allodynia respectively. The results demonstrated that post-treatment of NO-711 significantly suppressed thermal hyperalgesia and allodynia in CCI rats (P<0.05, P<0.01), the inhibitory effect lasted for 2 h (N40 group) and 4 h (N20 group) respectively. NO-711 inhibited thermal hyperalgesia induced by CCI in a dose-dependent manner. Intrathecal pretreatment with different doses of NO-711 delayed the occurrence of thermal hyperalgesia, but could not delay the emergence of allodynia induced by CCI. This study indicates that gamma-aminobutyric acid transporter inhibitor has anti-thermal hyperalgesia and anti-tactile allodynia effects in neuropathic rats.