Orexin antagonists
Orexin receptor antagonists are a more recently introduced class of sleep medications and include suvorexant, lemborexant, and daridorexant, all of which are FDA-approved for treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Antipsychotics
Certain atypical antipsychotics, particularly quetiapine, olanzapine, and risperidone, are used in the treatment of insomnia. However, while common, use of antipsychotics for this indication is not recommended as the evidence does not demonstrate a benefit, and the risk of adverse effects are significant. A major 2022 systematic review and network meta-analysis of medications for insomnia in adults found that quetiapine did not demonstrate any short-term benefits for insomnia. Some of the more serious adverse effects may also occur at the low doses used, such as dyslipidemia and neutropenia. Concerns regarding side effects are greater in the elderly. Other sedatives
Gabapentinoids like gabapentin and pregabalin have sleep-promoting effects but are not commonly used for treatment of insomnia.Barbiturates, while once used, are no longer recommended for insomnia due to the risk of addiction and other side effects. Comparative effectiveness
A major systematic review and network meta-analysis of medications for the treatment of insomnia was published in 2022. It found a wide range of effect sizes (standardized mean difference (SMD)) in terms of efficacy for insomnia. The assessed medications included benzodiazepines (SMDs 0.58 to 0.83), Z-drugs (SMDs 0.03 to 0.63), sedative antidepressants and antihistamines (SMDs 0.30 to 0.55), quetiapine (SMD 0.07), orexin receptor antagonists (SMDs 0.23 to 0.44), and melatonin receptor agonists (SMDs 0.00 to 0.13).
Over many generations, the human body became well-adapted to a high level of iron content in the diet. Neolithic
In the Neolithic era, significant changes are thought to have occurred in both the environment and diet. Some communities of foragers migrated north, leading to changes in lifestyle and environment, with a decrease in temperatures and a change in the landscape which the foragers then needed to adapt to. As people began to develop and advance their tools, they learned new ways of producing food, and farming also slowly developed. These changes would have led to serious stress on the body and a decrease in the consumption of iron-rich foods. This transition is a key factor in the mutation of genes, especially those that regulated dietary iron absorption. Iron, which makes up 70% of red blood cell composition, is a critical micronutrient for effective thermoregulation in the body. Iron deficiency will lead to a drop in the core temperature. In the chilly and damp environments of Northern Europe, supplementary iron from food was necessary to keep temperatures regulated, however, without sufficient iron intake the human body would have started to store iron at higher rates than normal. In theory, the pressures caused by migrating north would have selected for a gene mutation that promoted greater absorption and storage of iron. Viking hypothesis
Studies and surveys conducted to determine the frequencies of haemochromatosis help explain how the mutation migrated around the globe. In theory, the disease initially evolved from travelers migrating from the north.