Marketing Scoops: Results From Largest Review of Its Kind On Antidepressant Withdrawal Symptoms

The largest review of ‘gold standard’ antidepressant withdrawal studies to date has identified the type and incidence of symptoms experienced by people discontinuing antidepressants, finding most people do not experience severe withdrawal. In a systematic review and meta-analysis of previous randomised controlled trials relating to antidepressant withdrawal, a team of researchers led by Imperial College London and King’s College London concluded that, while participants who stopped antidepressants……Continue reading…..

By: Dr. Sameer Jauhar

Source: King’s College London

Critics:

Ketamine is a rapid-acting antidepressant, but its effect is transient. Intravenous ketamine infusion in treatment-resistant depression may result in improved mood within 4 hours reaching the peak at 24 hours. A single dose of intravenous ketamine has been shown to result in a response rate greater than 60% as early as 4.5 hours after the dose (with a sustained effect after 24 hours) and greater than 40% after 7 days.

Although only a few pilot studies have sought to determine the optimal dose, increasing evidence suggests that 0.5 mg/kg dose injected over 40 minutes gives an optimal outcome. The antidepressant effect of ketamine is diminished at 7 days, and most people relapse within 10 days. However, for a significant minority, the improvement may last 30 days or more. One of the main challenges with ketamine treatment can be the length of time that the antidepressant effects last after finishing a course of treatment.

A possible option may be maintenance therapy with ketamine, which usually runs twice a week to once in two weeks. Ketamine may decrease suicidal thoughts for up to three days after the injection. An enantiomer of ketamine – esketamine – was approved as an antidepressant by the European Medicines Agency in 2019. Esketamine was approved as a nasal spray for treatment-resistant depression in the United States and elsewhere in 2019. The Canadian Network for Mood and Anxiety Treatments (CANMAT) recommends esketamine as a third-line treatment for depression.

A Cochrane review of randomized controlled trials in adults with major depressive disorder found that when compared with placebo, people treated with either ketamine or esketamine experienced reduction or remission of symptoms lasting 1 to 7 days. There were 18.7% (4.1 to 40.4%) more people reporting some benefit and 9.6% (0.2 to 39.4%) more who achieved remission within 24 hours of ketamine treatment. Among people receiving esketamine, 12.1% (2.5 to 24.4%) encountered some relief at 24 hours, and 10.3% (4.5 to 18.2%) had few or no symptoms.

These effects did not persist beyond one week, although a higher dropout rate in some studies means that the benefit duration remains unclear. Ketamine may partially improve depressive symptoms among people with bipolar depression at 24 hours after treatment, but not three or more days. Potentially, ten more people with bipolar depression per 1000 may experience brief improvement, but not the cessation of symptoms, one day following treatment. These estimates are based on limited available research.

In February 2022, the US Food and Drug Administration (FDA) issued an alert to healthcare professionals concerning compounded nasal spray products containing ketamine intended to treat depression. Ketamine is used to treat status epilepticusn that has not responded to standard treatments, but only case studies and no randomized controlled trials support its use. Ketamine has been suggested as a possible therapy for children with severe acute asthma who do not respond to standard treatment.

This is due to its bronchodilator effects. A 2012 Cochrane review found there were minimal adverse effects reported, but the limited studies showed no significant benefit. Some major contraindications for ketamine are:

Severe cardiovascular disease such as unstable angina or poorly controlled hypertension
Increased intracranial or intraocular pressure (however these remain controversial, with recent studies suggesting otherwise)^[50]
Poorly controlled psychosis
Severe liver disease such as cirrhosis
Pregnancy
Active substance use disorder (for serial ketamine injections)
Age less than 3 months

Turner died prematurely due to drowning during presumed unsupervised ketamine use. In 2006, the Russian edition of Adam Parfrey’s Apocalypse Culture was banned and destroyed by authorities owing to its inclusion of an essay by Woodard about the entheogenic use of, and psychonautic experiences with, ketamine. Recreational ketamine use has been implicated in deaths globally, with more than 90 deaths in England and Wales in the years of 2005–2013.

They include accidental poisonings, drownings, traffic accidents, and suicides.The majority of deaths were among young people. Several months after being found dead in his hot tub, actor Matthew Perry’s October 2023 apparent drowning death was revealed to have been caused by a ketamine overdose, and, while other factors were present, the acute effects of ketamine were ruled to be the primary cause of death.Due to its ability to cause confusion and amnesia, ketamine has been used for date rape.

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