allopurinol and Depressive-Disorder

Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.

Topics: Antioxidants; Depressive Disorder; DNA Damage; Humans; Mitochondria; Oxidative Stress; Vitamins; Xanthine Oxidase

The authors critically review several drug combinations that may be of promise in the management of depressions that do not respond to treatment with a single drug. These include the use of tricyclic antidepressants with monoamine oxidase inhibitors (MAOI's), L-triiodothyronine (T3), methylphenidate, lithium carbonate, L-tryptophan, reserpine, and neuroleptics; MAOI's with lithium and L-tryptophan; and L-tryptophan with allopurinol. The authors stress the need for further double-blind, controlled studies to evaluate the safety and efficacy of these combinations.

Topics: Allopurinol; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Humans; Lithium; Methylphenidate; Monoamine Oxidase Inhibitors; Reserpine; Triiodothyronine; Tryptophan

To investigate whether continued use of non-aspirin NSAID, low-dose aspirin, high-dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using Danish nationwide population-based registers.. All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in-patient or out-patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants.. A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low-dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose aspirin were associated with an increased rate of incident depression.. The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population-based registers to systematically identify drugs with repurposing potential.

Topics: Adult; Aged; Allopurinol; Angiotensins; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Aspirin; Denmark; Depression; Depressive Disorder; Drug Repositioning; Female; Gout Suppressants; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Inflammation; Male; Middle Aged; Outcome Assessment, Health Care; Registries; Stress, Physiological

We used the 5% random Medicare claims from Americans 65 years or older from 2006-2012 to examine the association of gout with the risk of developing incident (new) depression using multivariable-adjusted Cox proportional hazards model, adjusting for demographics (age, race, sex), common cardiovascular medications, allopurinol, and febuxostat and medical comorbidity. Of the 1.69 million people, 142,596 developed depression. In multivariable-adjusted analyses, gout was independently associated with 42% higher hazard of depression in older adults, confirmed in sensitivity analyses. This finding suggests the gout patients should be screened for depression and may trigger research to assess the role of inflammation and oxidative stress pathways in older people with depression.

Topics: Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Comorbidity; Depressive Disorder; Febuxostat; Female; Follow-Up Studies; Gout; Humans; Incidence; Male; Mass Screening; Medicare; Proportional Hazards Models; Retrospective Studies; Risk; United States

The role of hepatic tryptophan 2,3 dioxygenase (TDO) was assessed in the provocation of stress-induced depression-related behaviour in the rat. TDO drives tryptophan metabolism via the kynurenine pathway (KP) and leads to the production of neuroactive metabolites including kynurenine. A single 2 h period of restraint stress in adult male Sprague-Dawley rats provoked an increase in circulating concentrations of the glucocorticoid corticosterone and induction of hepatic TDO expression and activity. Repeated exposure to stress (10 d of 2 h restraint each day) provoked an increase in immobility in the forced swimming test (FST) indicative of depression-related behaviour. Immobility was accompanied by an increase in the circulating corticosterone concentrations, expression and activity of hepatic TDO and increase in the expression of TDO in the cerebral cortex. Increased TDO activity was associated with raised circulating kynurenine concentrations and a reduction in circulating tryptophan concentrations indicative of KP activation. Co-treatment with the TDO inhibitor allopurinol (20 mg/kg, i.p.), attenuated the chronic stress-related increase in immobility in the FST and the accompanying increase in circulating kynurenine concentrations. These findings indicate that stress-induced corticosterone and consequent activation of hepatic TDO, tryptophan metabolism and production of kynurenine provoke a depression-related behavioural phenotype. Inhibition of stress-related hepatic TDO activity promotes antidepressant activity. TDO may therefore represent a promising target for the treatment of depression associated with stress-related disorders in which there is evidence for KP activation.

Topics: Allopurinol; Animals; Antidepressive Agents; Cerebral Cortex; Chronic Disease; Corticosterone; Depressive Disorder; Disease Models, Animal; Enzyme Inhibitors; Kynurenine; Liver; Male; Neuropsychological Tests; Rats, Sprague-Dawley; Restraint, Physical; RNA, Messenger; Stress, Psychological; Tryptophan; Tryptophan Oxygenase; Weight Gain

A growing body of literature suggests persistent and selective structural changes in the cortico-limbic-thalamic-striatal system in patients with recurrent depressive disorder (DD). Oxidative stress is thought to play a key role in these processes. So far, the main scientific focus has been on antioxidant enzymes in this context. For the first time, this proof of concept study examines the activity of the free radicals producing the enzyme, xanthine oxidase (XO), directly in the cortico-limbic-thalamic-striatal system of patients with recurrent depression. The activity of XO was ascertained in the cortico-limbic-thalamic-striatal regions in post-mortem brain tissue of patients with recurrent depressive episodes and individuals without any neurological or psychiatric history (7/7). We measured the XO activity in following brain areas: hippocampus, regio entorhinalis, thalamus, putamen and caudate nucleus. In this study, we report a significant increase of XO activity in the thalamus and the putamen of patients with depression. Our findings contribute to the growing body of evidence suggesting that oxidative stress plays a pivotal role in certain brain areas in recurrent depressive disorder.

Topics: Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Brain; Depressive Disorder; Female; Hippocampus; Humans; Male; Middle Aged; Oxidative Stress; Putamen; Regression Analysis; Sex Factors; Statistics, Nonparametric; Thalamus; Xanthine Oxidase

A patient showed excessive concentrations of desmethylclomipramine after receiving normal daily doses of clomipramine (Anafranil) and the elimination kinetics of the desmethylated metabolite was zero-order/saturable. Investigation showed that she was a poor metabolizer of debrisoquine and that, in addition, she had been treated with allopurinol, an inhibitor of hepatic drug metabolism.

Topics: Allopurinol; Clomipramine; Debrisoquin; Depressive Disorder; Female; Humans; Hydroxylation; Kinetics; Middle Aged