Em conjunto, os resultados do presente estudo revelam a incapacidade do aripirazol, em monoterapia, de reverter diversas alterações provocadas pelo modelo animal de depressão induzido por corticosterona, incluindo menor ganho de peso, comportamento depressivo-símile, memória de trabalho prejudicada e interação social diminuída. Além disso, o aumento dos níveis de BDNF desassociado da reversão do comportamento depressivo- símile, ao contrário do observado com a desvenlafaxina, reforça o caráter multifatorial da depressão.
Os resultados do presente estudo também revelaram um efeito variado da administração de aripiprazol em relação aos parâmetros oxidativos investigados, o que, somado a escassez de estudos a respeito da atividade do aripiprazol em pacientes com depressão ou animais submetidos a modelos de depressão resistente, evidencia a necessidade de estudos que avaliem o efeito do aripiprazol sobre outros parâmetros de estresse oxidativo. Por fim, dentre as limitações do presente estudo, destaca-se a ausência de grupos com associações entre os fármacos utilizados, o que possibilitaria a identificação da capacidade do aripiprazol de potencializar a atividade dos antidepressivos, relatada na literatura, e a compreensão dos mecanismos envolvidos nesse efeito a fim de dar subsídios para o aprimoramento do tratamento da depressão.
REFERÊNCIAS
AFRIDI, M. I. et al. Cognitive disturbance comparison among drug-naïve depressed cases and healthy controls. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, v. 21, n. 6, p. 351–5, jun. 2011.
AGO, Y. et al. Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice. Neuropharmacology, v. 65, p. 29–38, fev. 2013.
ALMEIDA-SANTOS, A. F. et al. The antipsychotic aripiprazole selectively prevents the stimulant and rewarding effects of morphine in mice. European Journal of Pharmacology, v. 742, p. 139–144, nov. 2014.
AMERICAN PSYCHIATRIC ASSOCIATION. What is Depression? Disponível em:
<https://www.psychiatry.org/patients-families/depression/what-is-depression>. Acesso em: 12 jul. 2019.
ANTKIEWICZ-MICHALUK, L. et al. Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat. Neurotoxicity
research, v. 26, n. 1, p. 85–98, jul. 2014.
ARAKAWA, R. et al. Quantitative Analysis of Norepinephrine Transporter in the Human Brain Using PET with (S,S)-18F-FMeNER-D2. Journal of Nuclear Medicine, v. 49, n. 8, p. 1270–1276, 16 jul. 2008.
ARAKAWA, R. et al. Time-course of serotonin transporter occupancy by single dose of three SSRIs in human brain: A positron emission tomography study with [(11)C]DASB.
Psychiatry research, v. 251, p. 1–6, 30 maio 2016.
ARCHER, J. Tests for emotionality in rats and mice: A reviewAnimal Behaviour, 1973. BASTOS, J. R. et al. Inhibition of the dopamine transporter as an animal model of bipolar disorder mania: Locomotor response, neuroimmunological profile and pharmacological modulation. Journal of Psychiatric Research, v. 102, p. 142–149, jul. 2018.
BERMAN, R. M. et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. The
Journal of clinical psychiatry, v. 68, n. 6, p. 843–53, jun. 2007.
BERMAN, R. M. et al. Aripiprazole augmentation in major depressive disorder: a double- blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS
spectrums, v. 14, n. 4, p. 197–206, abr. 2009.
BERTON, O.; NESTLER, E. J. New approaches to antidepressant drug discovery: beyond monoamines. Nature reviews. Neuroscience, v. 7, n. 2, p. 137–51, fev. 2006.
alterations by antidepressant treatments. Journal of affective disorders, v. 64, n. 1, p. 43–51, abr. 2001.
BOYER, P. et al. Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and
100 mg/day for major depressive disorder in a placebo-controlled trial. International Clinical
Psychopharmacology, v. 23, n. 5, p. 243–253, set. 2008.
BROMET, E. et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC
Medicine, v. 9, n. 1, p. 90, 26 dez. 2011.
BURDA-MALARZ, K. et al. Evaluation of antidepressant and memory-improving efficacy of aripiprazole and fluoxetine in alcohol-preferring rats. Acta Neuropsychiatrica, v. 26, n. 02, p. 112–119, 6 abr. 2014.
CASTANEDA, A. E. et al. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. Journal of Affective Disorders, v. 106, n. 1–2, p. 1– 27, 1 fev. 2008.
CELADA, P. et al. The therapeutic role of 5-HT1A and 5-HT2A receptors in depression.
Journal of psychiatry & neuroscience : JPN, v. 29, n. 4, p. 252–65, jul. 2004.
CHESNEY, E.; GOODWIN, G. M.; FAZEL, S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World psychiatry : official journal of the World
Psychiatric Association (WPA), v. 13, n. 2, p. 153–60, jun. 2014.
CIPRIANI, A. et al. Comparative efficacy and acceptability of 12 new-generation
antidepressants: a multiple-treatments meta-analysis. The Lancet, v. 373, n. 9665, p. 746– 758, 28 fev. 2009.
CORRELL, C. U.; LEUCHT, S.; KANE, J. M. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. The American
journal of psychiatry, v. 161, n. 3, p. 414–25, mar. 2004.
DARCET, F. et al. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease. Pharmaceuticals, v. 9, n. 1, p. 9, 17 fev. 2016. DAVIES, K. J. Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB life, v. 50, n. 4–5, p. 279–89, 1 out. 2001.
DE SOUSA, C. N. S. Efeitos Comportamentais E Neuroquímicos De Ácido Alfa - Lipóico E Desvenlafaxina Em Modelo Animal De Depressão Induzido Por Corticosterona. p. 95, 2015. DE SOUSA, C. N. S. et al. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression. Psychiatry research, v. 230, n. 2, p. 211–9, 15 dez. 2015.
DE SOUSA, C. N. S. et al. Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression. Naunyn-Schmiedeberg’s
DEBATTISTA, C.; HAWKINS, J. Utility of Atypical Antipsychotics in the Treatment of Resistant Unipolar Depression. CNS Drugs, v. 23, n. 5, p. 369–377, maio 2009.
DEMARTINIS, N. A. et al. A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. The Journal
of clinical psychiatry, v. 68, n. 5, p. 677–88, maio 2007.
DIAS, R.; ROBBINS, T. W.; ROBERTS, A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature, v. 380, n. 6569, p. 69–72, 7 mar. 1996.
DÍAZ-MATAIX, L. et al. Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. The Journal of
neuroscience : the official journal of the Society for Neuroscience, v. 25, n. 47, p. 10831–
43, 23 nov. 2005.
DIETRICH-MUSZALSKA, A.; KOLIŃSKA-ŁUKASZUK, J. Comparative effects of
aripiprazole and selected antipsychotic drugs on lipid peroxidation in plasma. Psychiatry and
Clinical Neurosciences, v. 72, n. 5, p. 329–336, maio 2018.
DOWLATI, Y. et al. A Meta-Analysis of Cytokines in Major Depression. Biological
Psychiatry, v. 67, n. 5, p. 446–457, 1 mar. 2010.
DUMAN, R. S.; MONTEGGIA, L. M. A Neurotrophic Model for Stress-Related Mood Disorders. Biological Psychiatry, v. 59, n. 12, p. 1116–1127, 15 jun. 2006.
EREN, I.; NAZIROĞLU, M.; DEMIRDAŞ, A. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochemical
research, v. 32, n. 7, p. 1188–95, 23 jul. 2007.
EVANS, V. C. et al. The Relationship Between Neurocognitive and Psychosocial Functioning in Major Depressive Disorder. The Journal of Clinical Psychiatry, v. 75, n. 12, p. 1359– 1370, 24 dez. 2014.
FARDET, L.; PETERSEN, I.; NAZARETH, I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. The American journal of
psychiatry, v. 169, n. 5, p. 491–7, maio 2012.
FAVA, M. et al. A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (ADAPT-A Study). Psychotherapy and Psychosomatics, v. 81, n. 2, p. 87–97, 2012.
FERREIRA MELLO, B. S. et al. Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. Journal of Psychiatric Research, v. 47, n. 10, p. 1521–1529, out. 2013.
FILOMENI, G.; CIRIOLO, M. R. Redox Control of Apoptosis: An Update. Antioxidants &
Redox Signaling, v. 8, n. 11–12, p. 2187–2192, nov. 2006.
Nature, v. 408, n. 6809, p. 239–247, 9 nov. 2000.
FLEISCHHACKER, W. W. et al. Effects of aripiprazole once-monthly on domains of personal and social performance: Results from 2 multicenter, randomized, double-blind studies. Schizophrenia Research, v. 159, n. 2–3, p. 415–420, nov. 2014.
FORLENZA, M. J.; MILLER, G. E. Increased Serum Levels of 8-Hydroxy-2′-
Deoxyguanosine in Clinical Depression. Psychosomatic Medicine, v. 68, n. 1, p. 1–7, jan. 2006.
GODLEWSKA, B. R.; NEAR, J.; COWEN, P. J. Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology, v. 232, n. 3, p. 501– 507, fev. 2015.
GORENSTEIN, C.; SCAVONE, C. Avanços em psicofarmacologia -mecanismos de ação de psicofármacos hoje Advances in psychopharmacology: mechanism of action of psychoactive drugs today. Rev Bras Psiquiatr, v. 21, n. 211, 1999.
GRACE, A. A. Dysregulation of the dopamine system in the pathophysiology of
schizophrenia and depression. Nature Reviews Neuroscience, v. 17, n. 8, p. 524–532, 3 jun. 2016.
GREENAWAY, M.; ELBE, D. Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Journal of the Canadian Academy of Child and Adolescent
Psychiatry = Journal de l’Academie canadienne de psychiatrie de l’enfant et de l’adolescent, v. 18, n. 3, p. 250–60, ago. 2009.
GRÜNDER, G. et al. Brain and Plasma Pharmacokinetics of Aripiprazole in Patients With Schizophrenia: an [18F]fallypride PET Study. American Journal of Psychiatry, v. 165, n. 8, p. 988–995, ago. 2008.
HAAPAKOSKI, R. et al. Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain, behavior,
and immunity, v. 49, p. 206–15, out. 2015.
HARA, Y. et al. Risperidone and aripiprazole alleviate prenatal valproic acid-induced
abnormalities in behaviors and dendritic spine density in mice. Psychopharmacology, v. 234, n. 21, p. 3217–3228, 10 nov. 2017.
HERKEN, H. et al. Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Archives of
medical research, v. 38, n. 2, p. 247–52, fev. 2007.
HERMAN, J. P. et al. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Frontiers in
neuroendocrinology, v. 24, n. 3, p. 151–80, jul. 2003.
HINKELMANN, K. et al. Cognitive impairment in major depression: association with salivary cortisol. Biological psychiatry, v. 66, n. 9, p. 879–85, 1 nov. 2009.
HOLSBOER, F. The Corticosteroid Receptor Hypothesis of Depression.
Neuropsychopharmacology, v. 23, n. 5, p. 477–501, nov. 2000.
IIJIMA, M. et al. Pharmacological characterization of repeated corticosterone injection- induced depression model in rats. Brain Research, v. 1359, p. 75–80, nov. 2010. JACOBS, B. L.; AZMITIA, E. C. Structure and function of the brain serotonin system.
Physiological Reviews, v. 72, n. 1, p. 165–229, jan. 1992.
KAREGE, F. et al. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Molecular Brain Research, v. 136, n. 1–2, p. 29–37, 20 maio 2005.
KATZUNG; MASTERS; TREVOR. Farmacologia básica e clínica. 13a ed. Porto Alegre: 2017.
KHANZODE, S. D. et al. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox report : communications in free
radical research, v. 8, n. 6, p. 365–70, 19 dez. 2003.
KIRSCHBAUM, K. M. et al. Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects. The World Journal of Biological Psychiatry, v. 9, n. 3, p. 212– 218, 12 jan. 2008.
KNORR, U. et al. Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis. Psychoneuroendocrinology, v. 35, n. 9, p. 1275–86, out. 2010. KOMOSSA, K. et al. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database of Systematic Reviews, 8 dez. 2010.
KOSHIMIZU, H.; LEITER, L. M.; MIYAKAWA, T. M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition. Molecular brain, v. 5, n. 1, p. 10, 2 abr. 2012.
KRISHNAN, V.; NESTLER, E. J. The molecular neurobiology of depression. Nature, v. 455, n. 7215, p. 894–902, 16 out. 2008.
LEE, M. et al. Relationship between dopamine deficit and the expression of depressive
behavior resulted from alteration of serotonin system. Synapse (New York, N.Y.), v. 69, n. 9, p. 453–60, set. 2015.
LEE, R. et al. Regulation of cell survival by secreted proneurotrophins. Science (New York,
N.Y.), v. 294, n. 5548, p. 1945–8, 30 nov. 2001.
LEUCHT, S. et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in
schizophrenia: a multiple-treatments meta-analysis. The Lancet, v. 382, n. 9896, p. 951–962, 14 set. 2013.
LIEBOWITZ, M. R. et al. Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder. Current Medical Research and
Opinion, v. 24, n. 7, p. 1877–1890, 22 jul. 2008.
LUCKI, I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behavioural pharmacology, v. 8, n. 6–7, p. 523–32, nov. 1997.
MAES, M. et al. Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness. Journal of affective disorders, v. 58, n. 3, p. 241–6, jun. 2000.
MALETIC, V. et al. The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review. Frontiers in Psychiatry, v. 8, p. 42, 17 mar. 2017.
MARCUS, R. N. et al. The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder. Journal of Clinical Psychopharmacology, v. 28, n. 2, p. 156– 165, abr. 2008.
MARIA, S. et al. Steroidal antiinfl ammatory drugs: glucocorticoids. v. 6, n. 1, p. 159–65, 2008.
MATTSON, M. P.; MAUDSLEY, S.; MARTIN, B. BDNF and 5-HT: a dynamic duo in age- related neuronal plasticity and neurodegenerative disorders. Trends in neurosciences, v. 27, n. 10, p. 589–94, out. 2004.
MCEWEN, B. S. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiological reviews, v. 87, n. 3, p. 873–904, 1 jul. 2007.
MELTZER, M.D., C. et al. Serotonin in Aging, Late-Life Depression, and Alzheimer’s Disease: The Emerging Role of Functional Imaging. Neuropsychopharmacology, v. 18, n. 6, p. 407–430, 1 jun. 1998.
MELTZER, H.; MASSEY, B. The role of serotonin receptors in the action of atypical antipsychotic drugs. Current Opinion in Pharmacology, v. 11, n. 1, p. 59–67, fev. 2011. MEYER, J. H. et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. The
American journal of psychiatry, v. 161, n. 5, p. 826–35, maio 2004.
MONTEGGIA, L. M. et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proceedings of the National Academy of Sciences, v. 101, n. 29, p. 10827–10832, 20 jul. 2004.
MORIGUCHI, S. et al. Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2. The
international journal of neuropsychopharmacology, v. 20, n. 12, p. 957–962, 1 dez. 2017.
NELSON, J. C.; PAPAKOSTAS, G. I. Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials. American
NEMEROFF, C. B. The neurobiology of depression. Scientific American, v. 278, n. 6, p. 42–9, jun. 1998.
NEMEROFF, C. B.; OWENS, M. J. Treatment of mood disorders. 2002.
NESTLER, E. J. et al. Neurobiology of depression. Neuron, v. 34, n. 1, p. 13–25, 28 mar. 2002.
NG, F. et al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. The International Journal of Neuropsychopharmacology, v. 11, n. 06, p. 851–76, 21 set. 2008.
NILGÜN. Altered levels of malondialdehyde and vitamin E in major depressive disorder and generalized anxiety disorder. Düşünen Adam: The Journal of Psychiatry and Neurological
Sciences, v. 25, n. 3, p. 206–211, 2012.
NOWAKOWSKA, E. et al. The influence of aripiprazole, olanzapine and enriched
environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats. Pharmacological Reports, v. 66, n. 3, p. 404–411, jun. 2014.
OHKAWA, H.; OHISHI, N.; YAGI, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, v. 95, n. 2, p. 351–358, jun. 1979. OLIVEIRA, T. DE Q. et al. Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone.
Journal of Affective Disorders, v. 219, p. 49–57, set. 2017.
ORMEL, J. et al. Psychosocial Disability Before, During, and After a Major
DepressiveEpisode. Archives of General Psychiatry, v. 61, n. 4, p. 387, 1 abr. 2004. OTSUKA AMERICA PHARMACEUTICAL. Abilify highlights of prescribing
informationTokyo, 2014. Disponível em:
<https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,02172 9s022,021866s023lbl.pdf>. Acesso em: 27 dez. 2017
OTTE, C. et al. Major depressive disorder. Nature Reviews Disease Primers, v. 2, p. 16065, 15 set. 2016.
OWEN, A. J. et al. Low plasma vitamin E levels in major depression: diet or disease?
European journal of clinical nutrition, v. 59, n. 2, p. 304–6, 27 fev. 2005.
PAL, S. N.; DANDIYA, P. C. Glutathione as a cerebral substrate in depressive behavior.
Pharmacology, biochemistry, and behavior, v. 48, n. 4, p. 845–51, ago. 1994.
PAPAKOSTAS, G. I. et al. Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder. The Journal of clinical
psychiatry, v. 66, n. 10, p. 1326–30, out. 2005.
Nature Reviews Neuroscience, v. 14, n. 1, p. 7–23, 20 jan. 2013.
PENNINX, B. W. J. H. et al. Understanding the somatic consequences of depression:
biological mechanisms and the role of depression symptom profile. BMC medicine, v. 11, n. 1, p. 129, 15 maio 2013.
PERRY, R.; CASSAGNOL, M. Desvenlafaxine: A new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder. Clinical Therapeutics, v. 31, p. 1374–1404, jan. 2009.
PITTENGER, C.; DUMAN, R. S. Stress, Depression and Neuroplasticity: A Convergence of Mechanisms. Neuropsychopharmacology, v. 33, n. 1, p. 88–109, 12 jan. 2008.
PORSOLT, R. D.; BERTIN, A.; JALFRE, M. Behavioral despair in mice: a primary screening test for antidepressants. Archives internationales de pharmacodynamie et de
thérapie, v. 229, n. 2, p. 327–36, 1 out. 1977.
RANG, H.P; RITTER, J.M.; FLOWER, R.J.; HENDERSON, G. Rang & Dale
Farmacologia. 8a ed. Rio de Janeiro: [s.n.].
RATAJCZAK, P. et al. Influence of aripiprazole and olanzapine on behavioral dysfunctions of adolescent rats exposed to stress in perinatal period. Pharmacological reports : PR, v. 65, n. 1, p. 30–43, 2013.
RATAJCZAK, P. et al. The influence of aripiprazole and venlafaxine on the antidepressant- like effect observed in prenatally stressed rats (animal model of depression). Human &
Experimental Toxicology, v. 37, n. 9, p. 972–982, 14 set. 2018.
REAGAN-SHAW, S.; NIHAL, M.; AHMAD, N. Dose translation from animal to human studies revisited. The FASEB Journal, v. 22, n. 3, p. 659–661, 17 out. 2007.
REYNOLDS, G. P.; KIRK, S. L. Metabolic side effects of antipsychotic drug treatment-- pharmacological mechanisms. Pharmacology & therapeutics, v. 125, n. 1, p. 169–79, jan. 2010.
RODRIGUES, F. T. S. et al. Major depression model induced by repeated and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and
neuroprogressive alterations. Journal of Psychiatric Research, v. 107, p. 57–67, dez. 2018. ROSLAND, J. H.; HUNSKAAR, S.; HOLE, K. Diazepam Attenuates Morphine
Antinociception Test-Dependently in Mice. Pharmacology & Toxicology, v. 66, n. 5, p. 382–386, maio 1990.
ROY, A. et al. CSF corticotropin-releasing hormone in depressed patients and normal control subjects. American Journal of Psychiatry, v. 144, n. 5, p. 641–645, maio 1987.
RUSH, A. J. et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. American Journal of Psychiatry, v. 163, n. 11, p. 1905–1917, nov. 2006.
RUSSO, E. et al. Ameliorating effects of aripiprazole on cognitive functions and depressive- like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity.
Neuropharmacology, v. 64, p. 371–379, jan. 2013.
SAHAY, A.; HEN, R. Adult hippocampal neurogenesis in depression. Nature Neuroscience, v. 10, n. 9, p. 1110–1115, 28 set. 2007.
SARANDOL, A. et al. Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder. Progress in neuro-
psychopharmacology & biological psychiatry, v. 30, n. 6, p. 1103–8, 30 ago. 2006.
SARIN, L. M. et al. Antipsicóticos atípicos na depressão refratária Atypical
antipsychotics in treatment refractory depression ConferênCia ClíniCa Definição e Critérios DiagnóstiCos. [s.l: s.n.]. Disponível em:
<http://www.scielo.br/pdf/jbpsiq/v58n2/v58n2a01.pdf>. Acesso em: 15 jun. 2019. SARTER, M.; BODEWITZ, G.; STEPHENS, D. N. Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology, v. 94, n. 4, p. 491–5, 1988.
SAWAGUCHI, T.; GOLDMAN-RAKIC, P. S. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science (New York, N.Y.), v. 251, n. 4996, p. 947–50, 22 fev. 1991.
SELFANI, K. et al. Movement Disorders Induced by the “Atypical” Antipsychotic Aripiprazole. The Neurologist, v. 22, n. 1, p. 24–28, jan. 2017.
SEO, H.-J. et al. Desvenlafaxine succinate: a newer antidepressant for the treatment of depression and somatic symptoms. Postgraduate medicine, v. 122, n. 1, p. 125–38, 13 jan. 2010.
SHIRAYAMA, Y. et al. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. The Journal of neuroscience : the official journal of the
Society for Neuroscience, v. 22, n. 8, p. 3251–61, 15 abr. 2002.
SIES, H. Oxidative stress: oxidants and antioxidants. Experimental physiology, v. 82, n. 2, p. 291–5, mar. 1997.
SILVA, M. C. C. et al. Augmentation therapy with alpha-lipoic acid and desvenlafaxine: a future target for treatment of depression? Naunyn-Schmiedeberg’s archives of
pharmacology, v. 386, n. 8, p. 685–95, 16 ago. 2013.
SILVA, M. C. C. et al. Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. Progress in neuro-psychopharmacology &
biological psychiatry, v. 64, p. 142–8, 4 jan. 2016.
SPIELMANS, G. I. et al. Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. PLoS
Medicine, v. 10, n. 3, p. e1001403, 12 mar. 2013.
de Janeiro: 2014.
STERNER, E. Y.; KALYNCHUK, L. E. Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Progress in neuro-
psychopharmacology & biological psychiatry, v. 34, n. 5, p. 777–90, 30 jun. 2010.
STERU, L. The tail suspension test : A new method for screening antidepressants in mice.
Psychopharmacology, v. 85, p. 367–370, 1985.
STOCKMEIER, C. A. et al. Cellular changes in the postmortem hippocampus in major depression. Biological Psychiatry, v. 56, n. 9, p. 640–650, 1 nov. 2004.
STORY, T. J. et al. Neurocognitive correlates of response to treatment in late-life depression.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, v. 16, n. 9, p. 752–9, set. 2008.
SURGET, A. et al. Drug-Dependent Requirement of Hippocampal Neurogenesis in a Model of Depression and of Antidepressant Reversal. Biological Psychiatry, v. 64, n. 4, p. 293–301, ago. 2008.
TAKAHASHI, K. et al. Antidepressant-like effect of aripiprazole via 5-HT1A, D1, and D2 receptors in the prefrontal cortex of olfactory bulbectomized mice. Journal of
Pharmacological Sciences, v. 137, n. 3, p. 241–247, jul. 2018.
TAYLOR TAVARES, J. V. et al. Distinct Profiles of Neurocognitive Function in
Unmedicated Unipolar Depression and Bipolar II Depression. Biological Psychiatry, v. 62, n. 8, p. 917–924, 15 out. 2007.
TOPOLOV, M. K.; GETOVA, D. P. Cognitive Impairment in Schizophrenia,
Neurotransmitters and the New Atypical Antipsychotic Aripiprazole. Folia Medica I, v. 58, n. 2, 2016.
TRIVEDI, M. H. et al. Medication Augmentation after the Failure of SSRIs for Depression.
New England Journal of Medicine, v. 354, n. 12, p. 1243–1252, 23 mar. 2006.
TRIVEDI, M. H. et al. Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. The Journal of clinical
psychiatry, v. 69, n. 12, p. 1928–36, dez. 2008.
TSIGOS, C.; CHROUSOS, G. P. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. Journal of psychosomatic research, v. 53, n. 4, p. 865–71, out. 2002.
VALKO, M. et al. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology, v. 39, n. 1, p. 44–84, jan. 2007.
VETULANI, J. Early maternal separation: a rodent model of depression and a prevailing human condition. Pharmacological reports : PR, v. 65, n. 6, p. 1451–61, 2013.
Alterations Induced by Acute Ethanol Administration in Mice. Basic & Clinical
Pharmacology & Toxicology, v. 112, n. 5, p. 319–324, maio 2013.
VOS, T. et al. The burden of major depression avoidable by longer-term treatment strategies.
Archives of general psychiatry, v. 61, n. 11, p. 1097–103, 1 nov. 2004.
WALLACE, D. L. et al. CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nature neuroscience, v. 12, n. 2, p. 200–9, 18 fev. 2009.
WANG, L.-J. et al. Neurocognitive effects of aripiprazole in adolescents and young adults with bipolar disorder. Nordic Journal of Psychiatry, v. 66, n. 4, p. 276–282, 23 set. 2012. WILLNER, P. Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-