salicylates and Depressive-Disorder--Major

The roles of the kynurenine pathway (KP) of tryptophan (Trp) degradation in serotonin deficiency in major depressive disorder (MDD) and the associated inflammatory state are considered in the present study. Using molecular docking in silico, we demonstrate binding of antidepressants to the crystal structure of tryptophan 2,3-dioxygenase (TDO) but not to indoleamine 2,3-dioxygenase (IDO). TDO is inhibited by a wide range of antidepressant drugs. The rapidly acting antidepressant ketamine does not dock to either enzyme but may act by inhibiting kynurenine monooxygenase thereby antagonising glutamatergic activation to normalise serotonin function. Antidepressants with anti-inflammatory properties are unlikely to act by direct inhibition of IDO but may inhibit IDO induction by lowering levels of proinflammatory cytokines in immune-activated patients. Of six anti-inflammatory drugs tested, only salicylate docks strongly to TDO and apart from celecoxib, the other five dock to IDO. TDO inhibition remains the major common property of antidepressants and TDO induction the most likely mechanism of defective serotonin synthesis in MDD. TDO inhibition and increased free Trp availability by salicylate may underpin the antidepressant effect of aspirin and distinguish it from other nonsteroidal anti-inflammatory drugs. The controversial findings with IDO in MDD patients with an inflammatory state can be explained by IDO induction being overridden by changes in subsequent KP enzymes influencing glutamatergic function. The pathophysiology of MDD may be underpinned by the interaction of serotonergic and glutamatergic activities.

Topics: Anti-Inflammatory Agents; Antidepressive Agents; Depressive Disorder, Major; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Inflammation; Kynurenine; Molecular Docking Simulation; Salicylates; Serotonin; Tryptophan

Headache after administration of electroconvulsive therapy (ECT) is common, affecting approximately half of patients treated. Post-ECT headache is typically treated with acetaminophen or nonsteroidal anti-inflammatory drugs but occasionally requires agents such as sumatriptan, opioids, or β-blockers. We report on a patient whose severe post-ECT headaches responded completely to methyl salicylate ointment, applied to the area of his temporalis and masseter muscles. Topical methyl salicylate is generally well tolerated and may be a viable option for some patients with post-ECT headache.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Depressive Disorder, Major; Electroconvulsive Therapy; Headache; Humans; Ketorolac; Male; Ointments; Salicylates; Stress Disorders, Post-Traumatic

Topics: Adjustment Disorders; Adolescent; Adult; Aged; Anxiety Disorders; Barbiturates; Bipolar Disorder; Child; Dementia; Depressive Disorder, Major; England; Female; Humans; Male; Middle Aged; Paranoid Disorders; Personality Disorders; Salicylates; Schizophrenia; Suicide; Suicide Prevention