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1.
Recenti Prog Med ; 104(2): 70-2, 2013 Feb.
Artículo en Italiano | MEDLINE | ID: mdl-23535961
2.
Riv Psichiatr ; 47(2): 149-69, 2012.
Artículo en Italiano | MEDLINE | ID: mdl-22622251

RESUMEN

The metabotropic glutamate receptors (mGluRs) are expressed pre- and post synaptically throughout the nervous system where they serve as modulators of synaptic transmission and neuronal excitability. The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. This paper reviews the neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to NMDA receptor neurotransmission, and discusses the relationship between NMDA hypofunction and different domains of symptom in schizophrenia as well as putative treatment modality for the disorder. mGlu receptors have been hypothesizes as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Group II of mGlu receptors are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. The glutamate hypothesis of schizophrenia predicts that agents that restore the balance in glutamatergic neurotransmission will ameliorate the symptomatology associated with this illness. Development of potent, efficacious, systemically active drugs will help to address the antipsychotic potential of these novel therapeutics. This review will discuss recent progress in elucidating the pharmacology and function of group II receptors in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.


Asunto(s)
Antipsicóticos/farmacología , Receptores de Glutamato Metabotrópico/agonistas , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Animales , Antipsicóticos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ensayos Clínicos como Asunto , Medicina Basada en la Evidencia , Humanos , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/fisiopatología , Transmisión Sináptica/efectos de los fármacos
3.
Hum Psychopharmacol ; 26(3): 177-87, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21455971

RESUMEN

OBJECTIVE: Clozapine is the most powerful new­generation antipsychotic. Although this drug leads to great therapeutic benefits, two types of undesirable conditions frequently occur with its use: side effects and resistance to treatment. Therapeutic drug monitoring of clozapine would be very useful to avoid both these situations. The necessity of monitoring the therapy is the result of a wide interindividual variability in the metabolism of clozapine. In this review, we highlight all the conditions underlying this variability, analyzing them one by one. METHODS: Relevant literature was identified through a search of MEDLINE and PubMed. In addition, the case of a treatment­resistant patient with accelerated metabolism of clozapine is reported as representative of utility of therapeutic drug monitoring in terms of clozapine dose adjustment. RESULTS: Genetic polymorphisms of cytochrome P450 enzymes and of neurotransmitter receptors; drug interactions; interactions of clozapine with other substances such as food and drink; smoking; and nonmodifiable variables such as age, ethnicity, and gender have been examined in relation to the existing scientific literature. The laboratory techniques that clinicians could use to identify these variables and adequate therapies are also reviewed.


Asunto(s)
Clozapina/uso terapéutico , Individualidad , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Citocromo P-450 CYP1A2/genética , Humanos , Masculino , Esquizofrenia/enzimología , Resultado del Tratamiento , Adulto Joven
4.
Neuropsychiatr Dis Treat ; 8: 55-64, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22347797

RESUMEN

BACKGROUND: Biological treatments are considered as additional options for the treatment of resistant unipolar depression. Controversial data exist about the efficacy and tolerability of three of the most used somatic treatments: electroconvulsive therapy (ECT), transcranial magnetic stimulation (rTMS), and deep transcranial magnetic stimulation (deepTMS). The aim of this review is to investigate and compare the efficacy and tolerability of these three techniques in drug-free patients with pharmacoresistant unipolar depression. METHODS: Three independent reviewers extracted data and assessed the quality of methodological reporting of selected studies. The first outcome was the clinical response to the three different techniques defined as a percentage improvement of Hamilton Depression Rating Scale (HDRS). The second outcome was the evaluation of their neuropsychological effects. The third outcome was the evaluation of the number of remitted patients; remission was defined as an absolute HDRS-24 score of ≤11 or as an absolute HDRS-17 score of ≤8. Tolerability was the fourth outcome; it was evaluated by examining the number of dropped-out patients. RESULTS: The comparative evaluation of HDRS percentage variations shows ECT as the most effective method after 4 weeks of therapy; on the other hand, a better efficacy is obtainable by deepTMS after 2 weeks of therapy. DeepTMS is the technique that gives the best improvement of cognitive performances. The percentage of remitted patients obtained with ECT treatment is the same obtained in the deepTMS group. Both techniques have a remitted patients percentage two times larger than the rTMS. DeepTMS shows a tolerability, measured by the number of dropped-out patients, worse than ECT. CONCLUSION: Our investigation confirms the great therapeutic power of ECT. DeepTMS seems to be the only therapy that provides a substantial improvement of both depressive symptoms and cognitive performances; nevertheless it is characterized by a poor tolerability. rTMS seems to provide a better tolerability for patients, but its therapeutic efficacy is lower. Considering the small therapeutic efficacy of deepTMS in the last 2 weeks of treatment, it could be reasonable to shorten the standard period of deepTMS treatment from 4 to 2 weeks, expecting a reduction of dropped-out patients and thus optimizing the treatment outcome.

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