Can one experience withdrawal from ketamine (Ketamine hydrochloride)?

From the Guidelines

Yes, you can withdraw from ketamine, but it is crucial to do so under medical supervision to manage potential withdrawal symptoms and reduce the risk of complications. Discontinuing ketamine, especially after regular or heavy use, can lead to withdrawal symptoms including cravings, anxiety, insomnia, tremors, sweating, and mood disturbances. Withdrawal typically begins within 24-48 hours after the last dose and may last for several days to weeks, depending on usage patterns 1. The effects of ketamine, such as amnesia, delirium, vivid hallucinations, tachycardia and arrhythmias, mild respiratory depression, confusion, irrationality, violent or aggressive behavior, vertigo, ataxia, slurred speech, delayed reaction time, euphoria, altered body image, analgesia, and coma, occur within 20 minutes and last for less than 3 hours 1.

Key Considerations for Withdrawal

• Withdrawal symptoms can be managed supportively with medications like benzodiazepines for anxiety (such as diazepam 5-10mg as needed), sleep aids for insomnia, and sometimes antidepressants for mood symptoms.
• Gradual tapering rather than abrupt cessation may help reduce withdrawal severity, as seen in the management of physical dependence on opioids, where tapering can avert withdrawal symptoms 1.
• Medical supervision is strongly recommended during ketamine withdrawal, particularly for heavy users, as psychological symptoms can be intense.
• The withdrawal process occurs because regular ketamine use causes adaptations in brain chemistry, particularly affecting glutamate and NMDA receptor systems, and the brain needs time to readjust to functioning without the drug.

Important Notes

• Ketamine is detectable in urine from 24 to 72 hours after ingestion, and toxicology screening should be performed as soon as possible if there is suspicion of its use 1.
• Common prescription benzodiazepines and over-the-counter antihistamines are also being used to facilitate sexual assault, so testing should be performed for these medications as well 1.

From the FDA Drug Label

Ketamine dependence and tolerance are possible following prolonged administration. A withdrawal syndrome with psychotic features has been described following discontinuation of long-term ketamine use.

• Yes, withdrawal from ketamine is possible.
• The withdrawal syndrome may include psychotic features.
• Ketamine should be prescribed and administered with caution due to its potential for abuse and dependence 2.

From the Research

Ketamine Withdrawal

• Ketamine withdrawal can lead to depressive symptoms, as evidenced by a study published in 2020, which found that patients with ketamine dependence undergoing withdrawal treatment reported moderate-to-severe depression and anxiety symptoms 3.
• The study also found that patients with greater cravings for ketamine reported more severe depressive symptoms, suggesting a link between craving and negative affect 3.
• Another study published in 2016 reported a case of spontaneous remission of ketamine withdrawal-related depression, where a patient's mood symptoms remitted without medication after 1 month 4.

Withdrawal Symptoms

• Common withdrawal symptoms associated with ketamine include depression, anxiety, and craving 3, 4.
• A review of ketamine and depression published in 2019 found that ketamine can provide a rapid antidepressant effect, but its effect lasts for only 1-2 weeks after infusion, and there is a lack of data concerning its long-term effects 5.
• A study published in 2021 found that the most common treatment-emergent adverse events associated with ketamine are dissociation, anxiety, nausea, increased blood pressure, and headache, which are usually mild, transient, and dose-dependent 6.

Management of Withdrawal Symptoms

• Screening and management of depression are recommended for patients with ketamine dependence undergoing withdrawal treatment 3.
• Patient education and supportive interventions can play a central role in the prevention and management of select adverse events, including withdrawal symptoms 6.
• Adjunctive medications may be necessary to manage severe and/or clinically significant adverse effects, including withdrawal symptoms 6.