When alcohol consumption is stopped too abruptly, the persons nervous system experiences uncontrolled synapse firing. This can result in symptoms that include anxiety, life-threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure. Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common. Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal.A kindling effect also occurs in people with alcohol use disorders whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression. Kindling also results in the intensification of psychological symptoms of alcohol withdrawal. There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal.
Both diflunisal and inotersen may also mitigate declines in quality-of-life, though the evidence for this effect is unclear. For people with cardiac ATTR the effect of inotersen use is inconclusive and requires further investigation. In 2018, inotersen was approved by the European Medicines Agency to treat polyneuropathy in adults with hereditary transthyretin amyloidosis. It has since been approved for use in Canada, the European Union and in the USA.Patisiran functions similarly to inotersen. Moderate-certainty evidence suggests that patisiran mitigates worsening of peripheral neuropathy and disability from disease progression. Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate of adverse events versus placebo. There is no evidence of an effect on mortality rate. A review of early data from use of patisiran in people with variant cardiac ATTR suggests that it may reduce mortality and hospitalization, however this is still being investigated and requires further investigation. In 2018, patisiran was not recommended by NICE in the UK for hereditary transthyretin-related amyloidosis. As of July 2019 further review however is occurring.