Spravato Side Effects and What Patients Should Know

In studies of adults with treatment-resistant depression, the adverse reactions reported most commonly were dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, and headache. [FDA label]

In studies of adults with major depressive disorder and acute suicidal ideation or behavior, the most commonly reported reactions were dissociation, dizziness, sedation, increased blood pressure, hypoesthesia, vomiting, euphoric mood, and vertigo.

“Most commonly reported” describes what occurred in trial populations. It is not a prediction for any individual, and it does not mean most people experience every listed effect.

Dissociation is among the most frequently reported effects and typically occurs during the period immediately after dosing, which is spent under observation. Patients are monitored until effects resolve and clinical stability is assessed before discharge.

People describe the experience differently, and it can vary between sessions for the same person. Telling the monitoring clinician what you are experiencing is useful — both for your comfort and for the clinical record.

The boxed warning states that patients are at risk for sedation after administration, and that respiratory depression has been observed in postmarketing experience. [FDA label] Respiratory status, including pulse oximetry, is monitored for at least two hours after dosing.

Sedation risk is one reason the labeling addresses combination with other substances: concomitant use with central nervous system depressants, including alcohol and benzodiazepines, may increase sedation. Give the treating clinician a complete medication and substance history, including anything taken occasionally.

The prescribing information states that Spravato causes increases in systolic and/or diastolic blood pressure at all recommended doses, that the increase peaks approximately 40 minutes after administration, and that it lasts approximately four hours. [FDA label]

During the first four weeks of treatment, approximately 3 to 19 percent of treated patients had an increase of at least 40 mmHg systolic or at least 25 mmHg diastolic within the first 1.5 hours after dosing.

This is why blood pressure is measured before the dose and again around 40 minutes afterward, and monitored until it declines and the patient is stable. Pre-existing hypertension or cardiovascular disease does not automatically exclude treatment, but it changes the risk calculation and is part of the screening described in safety, warnings, and contraindications.

Dizziness, vertigo, nausea, and vomiting are among the reactions reported most commonly in both indications. [FDA label] They contribute to the practical reason for the food and liquid timing before a dose — avoiding food for at least 2 hours and liquids for at least 30 minutes before administration.

Because dizziness and vertigo can affect balance, movement during and immediately after the monitoring period is supervised in the treatment setting.

The labeling addresses cognitive impairment and impaired ability to drive and operate machinery as distinct concerns. Short-term declines in measured cognitive performance occurred around 40 minutes after dosing and had returned toward baseline by two hours in the studies described; in longer open-label studies, cognitive performance over time remained generally stable. [FDA label]

The practical instruction is unambiguous: do not engage in activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, until the next day following a restful sleep. This applies after every session.

The prescribing information reports a higher rate of lower urinary tract symptoms in esketamine-treated patients than in placebo-treated patients — urinary frequency, painful urination, urinary urgency, nighttime urination, and cystitis. No cases of esketamine-related interstitial cystitis were observed in studies of up to one year, and the labeling directs monitoring for urinary tract and bladder symptoms during treatment. [FDA label]

Report urinary symptoms to your clinician rather than waiting for a scheduled visit, so they can be assessed while treatment continues.

Esketamine hydrochloride is a Schedule III controlled substance, and the boxed warning states that Spravato has the potential to be abused and misused. [FDA label] The labeling directs that the risk of abuse or misuse be assessed before prescribing and that patients be monitored for signs and symptoms during treatment.

The restriction on take-home dispensing under the REMS program is part of how this risk is managed — the medication remains in the certified healthcare setting. [SPRAVATO REMS] A history of substance use disorder is not automatically disqualifying, but it is directly relevant information for the evaluating clinician.

Some symptoms should not wait for the next appointment. Independent of Spravato, the following are medical emergencies — call 911 or go to the nearest emergency department:

• chest pain or pressure;
• severe or sudden headache;
• shortness of breath or difficulty breathing;
• sudden change in vision;
• sudden confusion, weakness, or difficulty speaking;
• loss of consciousness.

Contact your clinician promptly, though not necessarily by emergency, for:

• dissociation, sedation, or dizziness that persists well beyond the treatment day;
• new or worsening urinary symptoms;
• blood pressure readings substantially above your usual range at home;
• new or worsening anxiety, agitation, or depression.

If you are having thoughts of harming yourself, treat that as urgent. Call 911 if you may be in immediate danger, or call or text 988 for the Suicide & Crisis Lifeline. [988 Lifeline]

The two-hour minimum is not administrative. It maps onto the timing of the effects themselves: blood pressure peaks around 40 minutes and declines over the following hours; dissociation and sedation are most pronounced early and are observed until they resolve; respiratory status is watched because respiratory depression has been reported after administration. [FDA label]

Because those risks require a clinical setting, the medication is only dispensed and administered in certified healthcare settings under the REMS program — see what is the Spravato REMS program.

Most Spravato side effects occur close to the time of dosing and are the reason the monitoring period exists: dissociation, sedation, dizziness, nausea, and a blood pressure increase that peaks around 40 minutes and lasts about four hours. The boxed warning covers sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.

Effects that persist past the monitoring period, symptoms suggesting a cardiovascular or neurological emergency, urinary symptoms, and any thoughts of self-harm are all reasons to contact a clinician — urgently, in the case of the second and fourth.