Pre‑Infusion Medication Checklist: What Helps or Hinders Ketamine’s Effect?

Ketamine therapy has rapidly emerged as a groundbreaking option for treating depression, PTSD, chronic pain, and a host of treatment-resistant conditions.

However, what many patients and even some providers overlook is the subtle, yet powerful, role that medications can play in shaping the effectiveness of each infusion.

Certain prescriptions, supplements, and even over-the-counter drugs can either amplify ketamine’s therapeutic benefits or diminish them significantly.

If you're preparing for a ketamine infusion, knowing what helps or hinders the process can mean the difference between a transformative experience and a missed opportunity.

This article walks you through a pre-infusion medication checklist to help you get the most out of your treatment.

Why Your Medication Regimen Matters

Ketamine works differently from traditional antidepressants. Instead of modulating serotonin or norepinephrine, it primarily targets the NMDA receptor and enhances glutamate signaling.

This means that its interactions with other drugs aren’t always predictable. Some medications can blunt ketamine’s effect by blocking its mechanism, while others may increase side effects like dissociation, nausea, or blood pressure spikes.

In other words, what you take before your infusion, whether it’s a prescribed antidepressant, a beta-blocker, or a natural supplement, can either help your brain open up or keep the doors tightly shut.

Medications That May Hinder Ketamine’s Effect

Let’s begin with the most critical aspect: what could potentially interfere with your infusion?

1. Benzodiazepines (e.g., Xanax, Ativan, Klonopin)

These are among the most commonly prescribed drugs for anxiety and sleep. Unfortunately, they are also known to dampen the dissociative and antidepressant effects of ketamine.

Benzodiazepines enhance GABA activity, which slows brain activity, essentially working against ketamine’s goal of neuroplastic stimulation.

Recommendation: Tapering use (under medical supervision) prior to your infusion may be advised.

2. Lamotrigine (Lamictal)

Used to treat bipolar disorder and seizures, lamotrigine may reduce ketamine’s antidepressant response. Its mechanism works by stabilizing mood through glutamate inhibition, which may cancel out ketamine’s excitatory push.

Recommendation: Some clinicians recommend holding the dose 24 hours before an infusion if safe to do so.

3. Opioids

These drugs alter perception and pain but may interfere with ketamine’s own analgesic and antidepressant pathways.

While there isn’t a universal consensus, certain opioids may dull the transformative experience, especially in mood-related treatments.

Recommendation: Discuss your opioid use with your ketamine provider; alternatives may be explored temporarily.

4. High-Dose SSRIs or SNRIs

Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors may compete for metabolism or receptor activity. Although not always problematic, high doses, especially of drugs like Effexor (venlafaxine), could reduce ketamine’s emotional processing window.

Recommendation: Doses don’t always need to be changed, but your provider should evaluate whether an adjustment is warranted.

5. Beta-Blockers (e.g., Propranolol)

Often used to control blood pressure or anxiety, beta-blockers may reduce the cardiovascular and emotional response to ketamine.

This might sound like a good thing for people nervous about infusions, but too much blunting can dampen the subjective and therapeutic effects.

Recommendation: Continue only if medically necessary and under physician guidance.

Medications and Supplements That May Help

On the other side of the coin, there are substances that may enhance ketamine’s impact, either by improving neuroplasticity, reducing inflammation, or easing side effects.

1. Magnesium

Some research suggests magnesium may enhance the antidepressant effects of ketamine by supporting NMDA receptor balance. Low magnesium has been linked to increased depression and anxiety.

Recommendation: A moderate supplement in the days leading up to the infusion may help, but avoid overuse.

2. Omega-3 Fatty Acids (EPA/DHA)

Known for supporting brain health, omega-3s may play a synergistic role in mood regulation and neuroplasticity, possibly extending ketamine’s benefits.

Recommendation: Daily supplementation is typically safe and may be beneficial long-term.

3. L-Theanine

This amino acid may help smooth the transition into the dissociative state by promoting relaxation without sedation. It may also reduce post-infusion anxiety for some patients.

Recommendation: Consider a low dose under your provider’s advice.

4. Hydration and Electrolytes

It sounds simple, but proper hydration enhances metabolic processing and minimizes nausea and dizziness, two common side effects during ketamine therapy.

Recommendation: Stay well hydrated 24 hours before your infusion. Electrolyte-rich fluids are ideal.

Non-Medication Factors That Interact With Ketamine’s Effectiveness

Not everything that helps or hurts ketamine’s action comes in pill form.

• Sleep quality: Poor sleep before an infusion can increase anxiety and impair the therapeutic experience.
• Caffeine: High levels may increase pre-infusion jitters and raise blood pressure.
• Alcohol and cannabis: Both substances can dull the experience or interact with ketamine’s dissociative state.
• Diet: Fasting is typically required for a few hours before infusion, but nutrient-rich meals earlier in the day can support mental clarity.

Key Questions to Ask Before Your Infusion

When preparing for ketamine treatment, communication with your provider is essential. Here are a few questions worth asking:

• Should I pause or adjust any current medications before my infusion?
• What supplements are safe or even beneficial to continue using?
• How will my medication history affect dosing or outcomes?
• What should I avoid on the day of the treatment?

Each person’s chemistry is different. What hinders one patient may not hinder another. That’s why individualized planning matters so much.

The Body is the Terrain, Ketamine is the Tool

A ketamine infusion doesn’t happen in a vacuum. Your body and mind are the environment in which the medicine does its work. If the terrain is compromised by unbalanced medications, poor sleep, or inadequate hydration, the outcome will reflect that.

Think of the pre-infusion period not as passive waiting, but as active preparation. What you choose to take, or not take, can significantly influence how ketamine opens your neural pathways, disrupts depressive loops, and sets the stage for healing.

When in doubt, always consult a medical professional who specializes in ketamine-assisted therapy. An informed patient is an empowered one, and with ketamine, that empowerment can begin even before the first drip.