We are ab today to identify new targets for antidepressants with nonmonoamincrgic mechanisms. As a result,

there arc od number of such compounds in development, whic in the treatment, of mood disorders, gives hope for novel, more effective, and safer antidepressants. Selected abbreviations and acronyms AMPA alpha-amino-3-hydroxy-5-methyl-4-isoxazolepro-pionic acid BDNF brain-derived neurotrophic factor CREB cAMP-response element binding protein LTP long-term potentiation MAOI monoamine oxidase inhibitor NMDA N-methyl-D-aspartic acid SNRI serotonin and noradrenaline reuptake inhibitor SSRI selective serotonin reuptake inhibitor TCA tricyclic antidepressant
Depression Inhibitors,research,lifescience,medical is one of the most pressing public health issues because of its high lifetime prevalence of about 15%, and because it is associated with substantial disability.1 Depression was the fourth leading cause of disease burden in 2000 and accounted for 4.4% of total disabilityadjusted life Inhibitors,research,lifescience,medical years (DALY).1

Depression is projected to be the second leading cause of disease burden worldwide, and the leading cause in high-income countries for DALY in 2030.2 Depression is Inhibitors,research,lifescience,medical also responsible for the greatest proportion of disease burden attributable to nonfatal health outcomes, accounting for almost 12% of total years lived with Imatinib mw disability worldwide.2 Often, depression assumes a chronic course, and over time is associated with increasing disability.3,4 Inhibitors,research,lifescience,medical .Furthermore, depression has been shown to be an independent predictor of the development of cardiovascular disease,5 the leading cause of death worldwide. For all of these reasons, it is important to treat depression aggressively. Remission, the virtual

absence of symptoms, is the aim of depression treatment, because remission is associated with better function and a better prognosis than is response without, remission. However, in clinical trials only about one third of patients achieve remission.6,7 ‘there are several predictors Inhibitors,research,lifescience,medical of nonremission, among which somatic and psychiatric comorbidity have a prominent role. This article will shed some light on the role of somatic and psychiatric comorbidity in incomplete remission in depression. Psychiatric comorbidity In depressed patients, Terminal deoxynucleotidyl transferase psychiatric comorbidity is the rule rather than the exception. In the National Comorbidity Survey replication (NCS-R), nearly three fourths (72%) of participants with lifetime major depressive disorder also met. criteria for at least one of the other DSM-IV disorders assessed in the NCS-R, including about 60% with anxiety disorders and 24% with substance-use disorder.8 Another large epidemiological study (The National Epidemiologic Survey on Alcoholism and Related Condition, NES ARC) found that 40% of depressed patients had a comorbid anxiety disorder and 40% had comorbid alcohol abuse or dependence.