Sunday, June 21, 2015 12:00 p.m. - 1:15 p.m. Latin American Psychopharmacology Update: INNOVATIVE TREATMENTS IN PSYCHIATRY INNOVATIVE TREATMENTS IN PSYCHIATRY Flavio Kapczinski, The University of Texas Health Science Center at Houston Overall Abstract In this panel, we will propose innovative treatments in psychiatry and recent literature findings will be summarized. The effective pharmacological treatment of psychiatric diseases and development of new therapeutic entities has been a long-standing challenge. Despite the complexity and heterogeneity of psychiatric disorders, basic and clinical research studies and technological advancements in genomics, biomarkers, and imaging have begun to elucidate the pathophysiology of etiological complexity of psychiatric diseases and to identify efficacious new agents (Tcheremissine et al. 2014). Many psychiatric illnesses are associated with neuronal atrophy, characterized by loss of synaptic connections, increase of inflammatory markers like TNF-α and DAMPS (damage-associate molecular patterns,- cell free (ccf) DNA, heat shock proteins HSP70, HSP90, and HSP60, and cytochrome C), decrease of neurotrophic factors, increase of oxidative stress, mitochondrial dysfunction and apoptosis (Fries et al., 2012; Pfaffenseller et al., 2014). Also, neurocognitive impairment and poor psychosocial functioning has been related to a psychiatric disease. Therefore, trying to discover new therapeutic targets that act in these pathways can help to develop new treatment or improve the treatment of these serious diseases. Furthermore, prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity in patients with severe psychiatric disorders. Learning Objectives Describe studies to develop new therapeutic targets to treatment of psychiatric disease. Learning about new strategies to treat psychiatric disease SODIUM NITROPRUSSIDE AS A FAST-ACTING ANTIPSYCHOTIC AGENT Jamie Hallak, University of São Paulo Individual Abstract Despite decades of study, the etiology and physiopathology of schizophrenia remain unknown. Recent evidence suggests that nitric oxide (NO) may be implicated in schizophrenia. NO is a gas that mediates the release of neurotransmitters, learning, memory, and neurodevelopment. Studies investigating the role of NO in patients with schizophrenia found evidence that points to a disruption in NO- mediated neurotransmission. Therefore, we investigated the effects of sodium nitroprusside, an NO donor, as an add-on treatment for patients with schizophrenia. Twenty adult schizophrenia patients treated with stable doses of antipsychotics were randomly assigned to two groups that received an infusion of either sodium nitroprusside or placebo for four hours. Psychiatric symptoms were assessed at baseline and every hour during the infusion with the Brief Psychiatric Rating Scale (BPRS) and the negative subscale of the Positive and Negative Syndromes Scale (PANNS-n). Additional assessments were made 12 hours after the infusion, daily for seven days, and weekly for four weeks. Cognitive tests (Stroop Color Word Test, N-back, and FAS) were administered at baseline and 12 hours after the end of the infusion. No side effects were reported by the participants. All the clinical and demographic characteristics of the sample including age, education, duration of disease, gender, diagnostic subtype, and type of antipsychotic in use were matched across groups. Symptom ratings were significantly reduced in the group treated with sodium nitroprusside, but not in the placebo group. Cognitive performance was also significantly improved in the nitroprusside group compared to placebo. There were no significant differences between the two groups regarding the physiological parameters analyzed (systolic and diastolic blood pressure, cardiac rhythm, and oxygen saturation). The strategy of treating schizophrenia patients for four hours with 0,5 mcg/kg/min sodium nitroprusside improved psychopathology and cognitive function. Our findings support the hypothesis that the NMDA-NO-GMPc pathway is affected in schizophrenia and that nitric oxide donors such as sodium nitroprusside could thus be a promising approach in the management of the disorder. Although exciting, these results are preliminary and must be replicated by future studies. Learning Objectives Role of NO in schizophrenia NO donors as a therapeutical approach in schizophrenia Literature References Hallak JE, Maia-de-Oliveira JP, Abrao J, Evora PR, Zuardi AW, Crippa JA, Belmonte-de-Abreu P, Baker GB, Dursun SM. Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo- controlled trial. JAMA Psychiatry. 2013 Jul;70(7):668-76. Maia-de-Oliveira JP, Abrao J, Evora PR, Zuardi AW, Crippa JA, Belmonte-de-Abreu P, Baker GB, Dursun SM, Hallak JE. The effects of sodium nitroprusside treatment on cognitive deficits in schizophrenia: a pilot study. J Clin Psychopharmacol. 2015 Feb;35(1):83-5. DEEP BRAIN STIMULATION: NEW OPPORTUNITIES IN NEUROPSYCHIATRY Roger Walz, AFSC Individual Abstract Deep brain stimulation (DBS) consists of a neural-network modulation of dysfunctional brain circuits by electric stimulation through steretatically implanted electrodes. The technique has been successfully applied to treat movement disorders. Several reports raise the possible use of DBS to treat pharmacologically refractory neuropsychiatric diseases including: depression, obsessive- compulsive disorder, Gilles de la Tourrete, addictive behavior, obesity, anorexia nervosa, Alzheimer´s, epilepsies and aggressive behavior. The mechanisms of DBS action remain unknown, and understanding the effects of electrical stimulation on brain functions is a fascinating opportunity for basic and clinical research. DBS is an expanding area that offers an endless array for multidisciplinary research involving physicians, engineers and basic neuroscientists. We will discuss some of the promising and challenges aspects related to the clinical applications of DBS in neuropsychiatry. Learning Objectives To present some possible applications of DBS in neuropsychiatry To discuss some challenges related to DBS clinical use in neuropsychiatric diseases Literature References Williams NR and Okun MS. Deep brain stimulation (DBS) at the interface of neurology and psychiatry. J Clin Invest 2013;123: 4546–4556. Krack P, Hariz MI, Baunez C, Guridi J, and Obeso JA. Deep brain stimulation: from neurology to psychiatry? TINS 2010; 33: 474-484. 1:15 p.m. - 2:30 p.m. Latin American Psychopharmacology Update: NEW PHARMACOLOGICAL TARGETS: FROM PRE- CLINICAL MODELS TO PATIENT CARE NEW PHARMACOLOGICAL TARGETS: FROM PRE-CLINICAL MODELS TO PATIENT CARE Marco Romano-Silva, Universidade Federal de Minas Gerais Overall Abstract The number of non-responding patients to current treatments is still unacceptably high, reaching 30% or more in some disorders. Thus, the search for new targets is essential and urgent. Identification of new targets for pharmacological therapy of psychiatric disorders will be presented in this session, with focus on major depression, late life depression and schizophrenia. Learning Objectives To discuss new strategies for the treatment of major depressive disorder and late life depression. To discuss the efficacy of memantine as an adjunctive treatment in schizophrenia. NEUROCHEMICAL MECHANISMS UNDERLYING KETAMINE ANTIDEPRESSANT EFFECT João de Quevedo, The University of Texas Health Science Center at Houston Individual Abstract Major depressive disorder (MDD) affects about 121 million of global population and poses a significant burden to the healthcare sector. Nevertheless, around 50-60% of patients with MDD respond adequately to existing treatments. In addition, the neurobiology of MDD as well as drug action mechanism is not yet fully elucidated. Recently, studies have demonstrated the key role of the glutamatergic system in both pathophysiology and treatment of MDD. Ketamine, an N-methyl-D-asparte (NMDA) receptor antagonist has been proposed as potential revolutionary rapid antidepressant agents for treatment-resistant mood disorders. Preclinical studies have been shown that ketamine stimulate the mammalian target of rapamycin (mTOR), which is involved in neuroplasticity, cell survival and proliferation, including brain-derived neurotrophic factor (BDNF) and MAPK signaling. In addition, ketamine decreases oxidative stress and inflammation in rodents subjected to animal models of depression. Thus, current and future research studies are using ketamine as a promising tool to evaluate the glutamatergic neurotransmitter system to learn more about the pathophysiology of depression and develop more specific rapid-acting antidepressant treatments. Thus, this panel will summarize recent findings from literature. Learning Objectives New strategies to major depressive disorder treatment. Preclinical and clinical studies showing evidences that glutamatergic system is involved with depression. Literature References Lally N, Nugent AC, Luckenbaugh DA, Niciu MJ, Roiser JP, Zarate CA Jr: Neural correlates of change in major depressive disorder anhedonia following open-label ketamine. J Psychopharmacol 2015, in press. Réus GZ, Nacif MP, Abelaira HM, Tomaz DB, dos Santos MA, Carlessi AS, da Luz JR, Gonçalves RC, Vuolo F, Dal-Pizzol F, Carvalho AF, Quevedo J: Ketamine ameliorates depressive-like behaviors and immune alterations in adult rats following maternal deprivation.