What are the prospects for improvement in the pharmacotherapy of depression
What are the prospects for improvements in the pharmacology of depression? Depression, depressive illness, or affective disorder refers to disorders of the affect or mood. ... Treatment for depression involves psychotherapy and drug therapy, but here I will only mention drug therapies. To answer the question regarding prospects for improvements of treatments, I will review the abnormalities thought to be manifest in depression, including early hypotheses through to more recent cellular developments, and how current treatments are thought to intervene and thus have clinical efficacy for improvement of symptoms. ... Taking that in mind, finding a mechanism in the pathophysiology of depression has been studied at the neurochemical single cell level, to perhaps give a mechanism that could elucidate the more macroscopic processes in the disease. The monoamine hypothesis, that depressive symptoms are associated with reductions in monoamine neurotransmission, particularly serotonin and noradrenaline, is supported by both neurochemical findings (at the synaptic level) and the successful treatment of major depression (MD) with compounds that enhance monoaminergic neurotransmission. ... TCAs were discovered to have antidepressant properties following phenothiazine use for its anti-histamine effects, and anti-tuberculosis treatment isoniazid was the first MAOI used in depression. ... low trypophan diet) and NA (by enzyme inhibitor) does not cause depression. ... using tryptophan hydroxylase inhibitors), depression is induced in patients (Shopsin et al 1975). ... There is no robust evidence for selective NA augmentation leading to improvement; however amphetamine and cocaine do not reduce core symptoms, although some selective NA reuptake inhibitors are antidepressant (Blier and Montigny 1994), which clouds the opinion on NA facilitation being a useful area of future research. ... But is depression solely due to reduced synaptic levels of monoamines, as the hypothesis predicts? ... Therefore new receptor subtypes open up an area for pharmacotherapy in the future. ... The learned helplessness test in rats, an animal model for antidepressants, VN2222 reduced significantly the number of escape failures, and has very good prospects regarding future treatments. ... SSRIs are no more effective at treating symptoms than old TCA agents, it seems that the only real improvement is greatly reduced side effects. ... At present most antidepressant drugs alleviate depression in about 70% of patients. ... Druss and Hoff, 2000, report that there are disturbingly low rates of drug treatment for major depression in the United States. Depression is associated with marked suffering, morbidity, and high risk of recurrence and/or chronicity. ... This includes early/readily reached remission (which can be defined as attainment of a total score *7 on the Hamilton Rating Scale for Depression), significantly improved long-term outcome, including a reduced risk of relapse and improved functioning. ... An example of this is depression in schizophrenia, and the general opinion in the early ‘90s at least was that some sort of frontal lobe dysfunction, probably resembling that in schizophrenia, could be the underlying abnormality for major depression (MD). ... The authors go on to postulate the possibility of this subgenual PFC dysfunction in disturbed stress-related autonomic, neuroendocrine and dopamine reward responses, hence provide an anatomical substrate, or neural model for manifestations of depression. ... However, the findings of reduced PFC volume is varied according to subtype of depression, also in studies related to caudate nucleus volume, and third ventricular enlargement, making it difficult to find a common anatomical substrate. ... How much is the pathophysiology of moderate depression related to this model? ... If the same mechanisms but less severe are leading to moderate depression as opposed to MD and bipolar disorders, then this could have good prospects. ... What are the differences in the abnormalities seen in bipolar and MD models of depression? ... Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) are established in depression (Rothschild et al 1993). ... Central administration of CRF produces many of the physiological and behavioural effects of stress and of anxiety and depression. ... Recent studies employing pharmacologic or genetic inactivation of neurokinin-1 (NK1) receptors demonstrate the important role of the SP-NK1 receptor system in the regulation of affective behaviour and suggest that inhibition of this pathway may be a useful approach to treatment of depression and associated anxiety. Kramer and Cutler et al 1998, however argue that there is little evidence for Sub P overactivitity in pathophysiology of depression and anxiety.