Ketamine Shows Promise in Treating Benzodiazepine Withdrawal

Ketamine does something super cool and important, yet again.

Sub-anesthetic ketamine infusions, which are already used for treatment-resistant depression (TRD), may also help people through benzodiazepine withdrawal, new research published in Neuropsychopharmacology reports. 

Benzodiazepines (often abbreviated as “BZDs” or better known as “benzos”) are a class of psychoactive drugs that treat anxiety, insomnia, seizures, and muscle spasms. They include Xanax, Klonopin, and Ativan. And, as anyone who has taken any of those knows, benzos also feel really, really, good. 

Benzos work on the neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which has inhibitory effects on the central nervous system. As a result, pills like Xanax lull you into calm and sedation and melt away worries like magic. For people with anxiety and panic disorders, there’s no shame in taking them, ideally on an as-needed basis and under a doctor’s supervision.

Benzos are delicious and dangerously so. They’re also super physically addictive, and benzo withdrawal is hell. Like, in addition to making your body hurt, giving you panic, anxiety, and insomnia (basically everything you started to take them for), you can also have heart palpitations and even seizures if not done correctly. The experience makes you feel like you’re not put together right and is so brutal that plenty of people end up right back on them. There’s also some evidence that long-term use could lead to cognitive decline. But, as it turns out, ketamine could not only offer patients with PTSD, anxiety, and depression an alternative to benzos but also help them safely and comfortably wean off them. 

In the recent study, 22 patients who have been taking benzos long-term (> six months in this case, which some reading this may say is nothing; plenty of people use benzos for years), with severe unipolar or bipolar treatment-resistant depression received a course of six subanesthetic ketamine infusions over four weeks. The researchers investigated the rates of successful BZDRs (benzos) deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of one year. 

They also looked at significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase. 

Of the 22 participants, 91% (20 out of 22) successfully discontinued all benzos by the end of the four weeks, which the researchers medically confirmed with a urine analysis. Less than 25% of the patients experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment, which is quite miraculous.

Furthermore, during the follow-up, with a mean duration of 12 [three – 24] months), 64% (14 out of 22) of patients remained abstinent from any benzos. Such findings suggest that ketamine infusions for TRD may also help people get off benzos, even if patients are still experiencing depression and anxiety, insomnia, and all the other comorbidities that come with it. 

It’s worth noting that one of the first things a ketamine provider will tell you, if you’re already on benzos, is to try to take as little as possible around the time you get an infusion, as benzos could make the depression-busting effects less effective. 

While ketamine therapy has shown to be revolutionary, whether treating depression or weaning one off benzos, it’s not without its own side effects. If you abuse ketamine, you can risk hurting your bladder or kidneys with ketamine bladder syndrome. Another, perhaps more immediate, concern regarding ketamine infusions is its accessibility. Ketamine infusions can cost a few hundred to thousands of dollars per session. The regimen for treatment-resistant depression is typically six sessions over two weeks; this study had its participants do the six sessions over four weeks) so there’s also a major time commitment; many people can’t get away from work that often. Because if you’re wondering if a nice ketamine infusion in the middle of the day can make it tricky to want to go back to the office, the answer is yes, yes, it can. 

Ketamine nasal spray is also available, famous for being the first psychedelic (it’s technically a dissociative anesthetic with hallucinogenic properties). The FDA-approved version is actually “esketamine,” the S enantiomer of ketamine, rather than regular ole’ ketamine, simply because that’s how Johnson & Johnson could patent and sell it under the brand name Spravato. Some doctors prescribe an off-label ketamine nasal spray that one can pick up at a compound pharmacy and use in the comfort of their home rather than trekking to a clinic. Although, of course, do this with someone around in case you take too much and need support or supervision. 

Ketamine is already valuable because it treats depression rapidly (SSRIs can take up to six weeks, while ketamine gets to work in a matter of hours). The news that it can also help people comfortably kick a Klonopin dependency is a much-needed and welcome breakthrough in treating mental health conditions. 

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