Ketamine pleiotropics: signaling reloaded, neurochemistry revolution, mood resurrection

Monoaminergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) take weeks to months to take effect and do not work for more than one in three patients. For patients diagnosed with treatment-resistant depression, or in immediate crisis, access to safe, effective, rapid-acting antidepressants can improve lives and decrease suicide. WHO report estimated around 800,000 people die from suicide annually. Though it cannot be said how many reach this choice for depression or unresponsive depression, this number is unacceptable for clinicians as well as for our society. Besides, for the 280 million people worldwide suffering from depression relief cannot wait. One current possibility being investigated is ketamine, which can improve depression, even in treatment-resistant patients. Ketamine is an anesthetic used for over 50 years, but it has serious side-effects, including dependence, hallucinations and delusions. This is due to its interaction with a surface receptor called NMDAR, one of the receptor subtypes used by glutamate in nervous system. Therefore, while preclinical studies have shown that a single dose of ketamine can have beneficial long-term effects on mental health and is only used to treat depression as a last resort. There are good reasons to be cautious; in addition to the side-effects, the way ketamine alters brain chemistry is not fully understood. If the biological mechanisms in the brain that ketamine influences are discovered, new drugs could be developed to target the beneficial antidepressant effect specifically. The study demonstrated ketamine treatment led to an increase in insulin-like growth factor 1 (IGF-1). This is a peptide growth factor essential for brain developent since the embryonal stages; in the adult, it partially mediates insulin bodily effects and is also a known antidepressant brain molecule. medicomunicare.it/2022/06/02/ketamine-pleiotropics-signaling-reloaded-neurochemistry-revolution-mood-resurrection/