Spravato (esketamine) is a nasal spray used for depression and was approved by the FDA in 2019. It is approved for use with other antidepressant medicines that are taken by mouth. It is specifically for treatment-resistant depression, meaning depression symptoms that have not gotten better after trying other antidepressant medicines. It is also for major depressive disorder with acute suicidal ideation or behavior, meaning depression with an immediate or very short-term risk of acting on suicidal thoughts or plans.
How Does Spravato Work for Major Depressive Disorder?
Spravato is a specific form of a medicine called esketamine. You may have heard of ketamine being used as an IV in the hospital for treating pain or being used as an anesthetic, or being used similarly in veterinary clinics. You may have also heard of ketamine because of its misuse related to its potential to cause euphoria (intense happiness or excitement) and hallucinations (seeing or hearing things that others do not see or hear).
Spravato, when used with other antidepressants, helps to lessen the symptoms of depression by acting on the N-methyl D-aspartate (NMDA) receptors, therefore changing mood-related chemicals in the brain.
How Was Spravato Studied for Major Depressive Disorder?
Four clinical studies were conducted to test if Spravato was safe and effective for adults with treatment resistant depression and major depressive disorder with acute suicidal ideation or behavior. The scoring system used to measure the severity and improvement in depression symptoms was the Montgomery-Asberg Depression Rating Scale (MADRS). This is a 10-item questionnaire that assesses depression symptoms through questions about mood, guilt, sleep quality, and suicidal thoughts. The total score ranges from zero to 60, with higher scores meaning more severe depression symptoms. A larger decrease in MADRS score shows a bigger improvement in depression symptoms. The effectiveness of Spravato was measured with MADRS scores at the beginning and end of the study. The studies included adults aged 18 to 64. The studies included people who were White, Black, Asian, and other races.
What Benefits Were Seen With Spravato?
Results from the clinical studies are provided below, so you can have an idea of what result you may have with Spravato. Your results may be different from what was seen in clinical studies.
Spravato for treatment-resistant depression
Two studies compared Spravato to placebo for people with treatment-resistant depression who were experiencing a major depressive episode and did not respond to treatment with two prior antidepressant medicines. People with a history of certain mental health conditions, recent suicidal intent, substance or alcohol use disorder within the last 6 months, any history of ketamine use disorder, and certain other conditions were excluded from the study.
People in these studies started taking another antidepressant by mouth at the same time as Spravato. The first study showed that after 4 weeks, people taking Spravato had a larger decrease in MADRS scores compared to placebo. Therefore, Spravato was shown to be more effective than placebo at decreasing depression symptoms.
Spravato 56 mg or 84 mg Twice Weekly | Placebo | |
By how much did the MADRS score go down after 4 weeks? | 20 points | 16 points |
Some people from the first study went on to participate in a second study that showed that after 16 weeks, people who continued taking Spravato went longer before having their depression symptoms worsen or return.
Spravato for depressive symptoms in major depressive disorder with acute suicidal ideation or behavior
Two other identical studies compared Spravato to placebo for people with major depressive disorder with acute suicidal ideation or behavior. All people in the study had at least one suicide attempt in the past. People with a history of certain mental health conditions, substance or alcohol use disorder within the last 6 to 12 months, and certain other conditions were excluded from the study.
People in these studies started taking another antidepressant by mouth at the same time as Spravato. Both of these studies had nearly the same results and showed that after 24 hours, people taking Spravato had a larger decrease in MADRS scores compared to placebo. Therefore, Spravato was shown to be more effective than placebo at decreasing depression symptoms. These studies also showed that Spravato significantly helped reduce depressive symptoms within the first 24 hours of taking it, which is much quicker than most traditional antidepressants.
Spravato 56 mg or 84 mg Twice Weekly | Placebo | |
By how much did the MADRS score go down after 24 hours? | 16 points | 12 points |
What Types of Medicine Interactions Can Happen?
Spravato can cause your blood pressure to increase. Taking Spravato with certain other medicines may further increase your risk of getting high blood pressure from Spravato. These other medicines include another type of antidepressant called a monoamine oxidase inhibitor (MAOI) and stimulants (including amphetamines, armodafinil, methylphenidate, and modafinil). Closely monitor your blood pressure if you are taking Spravato with MAOIs or stimulants.
Spravato may cause dizziness and sleepiness, and using it with any other medicines that cause similar side effects can make it worse. This includes medicines called central nervous system depressants such as benzodiazepines (including alprazolam, clonazepam, diazepam, or lorazepam), opioids (including codeine, fentanyl, oxycodone, or morphine) and alcohol.
It is OK if you are not sure if you are taking any of the medicines mentioned above. Let your health care provider know what medicines you are taking and they will let you know if it is safe to take Spravato with your other medicines. Talk to your health care provider before starting any new medicines, vitamins, or supplements.
How Can I Get Spravato?
Let your health care provider know if you are interested in Spravato. You can discuss this with your primary care provider or mental health provider such as a psychiatrist. If you and your health care provider think that Spravato is a good addition to your medicines, your health care provider will reach out to a treatment center that can provide Spravato. After the treatment center receives all of the needed information from your health care provider, you will have a consultation with the treatment center to further discuss Spravato. If after the consultation you and the health care provider at the treatment center decide that Spravato is a good fit, you will be able to start Spravato on your second visit to the treatment center.
How Do I Take Spravato?
Because of the possible side effects of Spravato, it can only be given at treatment centers that are certified to do so and are enrolled in the Spravato Risk Evaluation and Mitigation Strategy (REMS) program. The treatment center where you get Spravato may require you to enroll in the REMS program as well. Your health care provider will help you through this process.
Spravato is a nasal spray that is taken once or twice weekly under the supervision of a health care provider at your Spravato treatment center. Your health care providers will decide your Spravato dosage and will show you how to use the Spravato nasal spray. Your health care provider will keep an eye on your blood pressure during your visit because Spravato can cause an increase in blood pressure. Since Spravato can cause nausea and vomiting, avoid eating 2 hours before and avoid drinking liquids 30 minutes before your treatment. If you use a steroid or other decongestant nasal spray and you plan to use this the same day as your Spravato dose, take the steroid or decongestant nasal spray at least an hour before your Spravato dose.
After you take Spravato, there will be an observation period of at least 2 hours during which your health care provider will monitor you for side effects. Because Spravato can affect your ability to drive, you will need to plan for a ride home from the treatment center. Spravato stays in the body about 1 to 2 days after your dosage.
How Can I Tell if Spravato Is Working?
You can tell if Spravato is working because your depression symptoms or suicidal thoughts or behaviors will lessen. Your health care provider may measure this through the use of a questionnaire or scoring system such as a MADRS, AOQ, or PHQ-9.
How Can I Prevent Side Effects or Tell if a Side Effect Is Happening?
Spravato can cause sedation (drowsiness or sleepiness), fainting, dizziness, and feeling mentally disconnected (dissociation). Spravato can cause changes to your memory, judgment, or thinking. Spravato can also affect your alertness or coordination. Do not drive or do other activities that require alertness or coordination until the day after your Spravato dose, after you have had a good night’s sleep.
Spravato may cause slow or shallow breathing, especially if you have breathing problems from another condition or take other medicines that can slow your breathing. Your health care provider will monitor you for this for at least 2 hours after your dose. Tell your health care provider right away if you feel like you cannot stay awake or if you feel like you are going to faint.
Auvelity or other antidepressants may increase the risk of suicidal thoughts or actions. If you or your child is about to harm themselves, call 911 or call or text 988, the Suicide & Crisis Lifeline. Call your health care provider right away if you have new or increased thoughts of suicide or death, anxiety, depression, changes in your mood or behavior, or a suicide attempt.
There is a risk of your body becoming dependent on Spravato. Misusing Spravato or other forms of ketamine can lead to serious side effects like coma or death. Your health care provider will help you take Spravato safely and correctly. Tell your health care provider if you have ever misused or been dependent on alcohol, prescription medicines, or illicit chemical substances (also known as street drugs). Tell your health care provider if you feel that Spravato is not working. Call your health care provider right away or go to the nearest emergency room if you have trouble breathing, sudden confusion or feel disoriented, paranoia, suicidal thoughts or actions, or seizures.
Spravato can cause a short-term increase in blood pressure, which can last up to 4 hours after your dose. Your health care provider will check your blood pressure before and after your dose. Let your health care provider know right away if you have chest pain, shortness of breath, a severe headache, vision changes, or seizures after your dose.
Some urinary symptoms were seen with Spravato. Let your health care provider know if you have any changes in your urination or any new symptoms when urinating.
Spravato should not be used while pregnant or breastfeeding due to possible risk to your baby. Let your health care provider know right away if you plan to become pregnant, become pregnant, or if you are breastfeeding.
Reports of side effects by persons are very important and are used to add information to the prescribing information. You don’t need to be certain that something you experienced was caused by Spravato. If you experience anything that you think may be caused by Spravato, you can report it by calling the FDA at 800-FDA-1088.
Spravato cost support from the manufacturer may help with the cost of treatment. Whether you are eligible depends on the type of insurance plan you have, and if your insurance covers Spravato. You can find out more at www.spravato.com/insurance-coverage.
