Substances To Avoid With Ketamine

Resources: Ketamine and AnxietyResources: Ketamine Who and WhatService: Ketamine TherapyService: Medication Management
Written By Dr. David Danish

When considering ketamine or esketamine (Spravato) for treatment-resistant depression (TRD), several medications and substances are either relatively contraindicated or absolutely contraindicated due to potential interactions or diminished efficacy. Here's a breakdown of some of these medications and substances:

Relatively Contraindicated Medications

  1. Stimulants (e.g., Adderall):

    • Reason: Stimulants can increase blood pressure and heart rate, which may exacerbate the hypertensive effects of ketamine, increasing the risk of cardiovascular complications[1][2].

  2. Benzodiazepines (e.g., Ativan):

    • Reason: Benzodiazepines may lower the response rates to ketamine by inhibiting neuroplasticity, which is key to ketamine's antidepressant effects[1][2]. If benzodiazepines cannot be avoided:

      • Use shorter-acting benzodiazepines.

      • Avoid taking them on the morning of the infusion or for a few hours afterward.

  3. Naltrexone:

    • Reason: Although ketamine is not an opioid, naltrexone may reduce both the antidepressant and anti-suicidal effects of ketamine[5]. This interaction remains controversial and requires further research.

Possibly OK, but Caution Recommended

  1. MAO Inhibitors (MAOIs):

    • Reason: Preliminary evidence suggests that ketamine can be co-administered with MAOIs in some cases, but there is a theoretical risk of hypertensive crisis due to increased blood pressure[6]. Vital signs should be closely monitored when using this combination.

  2. Lamotrigine:

    • Reason: Some studies suggest that lamotrigine may antagonize ketamine's effects, potentially reducing its antidepressant efficacy[3]. However, other research has not confirmed this, and it may even reduce adverse effects like cravings in patients receiving IV ketamine treatments[4].

Absolutely Contraindicated Medications/Substances

  1. Cannabis Use and Ketamine Treatment:

    • Cannabis use is contraindicated on the day of ketamine treatment due to its potential to impair synaptic plasticity, which is crucial for ketamine's antidepressant effects. Cannabis activates CB1 receptors, which can diminish the long-term potentiation processes necessary for ketamine to exert its full therapeutic benefit8. Therefore, patients are advised to avoid cannabis use before and during ketamine therapy to maximize treatment efficacy.

  2. Alcohol:

    • Reason: Alcohol increases the risk of sedation and agitation, which can lead to falls or other accidents during ketamine treatment[7].

  3. Illicit Drugs:

    • Reason: Various illicit drugs, when combined with ketamine, can cause a myriad of complications including but not limited to agitation, stroke, heart attack, over-sedation, severe hypotension, or other unpredictable side effects[7].

In summary, while certain medications like stimulants, benzodiazepines, and lamotrigine are relatively contraindicated with ketamine due to their potential to reduce efficacy or increase risks, others like MAOIs require caution. Absolute contraindications include conditions that increase blood pressure risks, alcohol use, and illicit drug use.

Dr. David Danish
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