Selective Serotonin Reuptake Inhibitors (SSRIs)

About the AuthorDr. Steven P. Levine is a board-certified psychiatrist internationally recognized for his contributions to advancements in mental health care. Though he is a psychiatrist who places great emphasis on the importance of psychotherapy, medication is often a necessary component of treatment, and he was dissatisfied with the relatively ineffective available options with burdensome side effects. Dr. Levine pioneered a protocol for the clinical use of ketamine infusions, has directly supervised many thousands of infusions and has helped establish similar programs across the country and around the world.

SSRIs: The Bedrock of Depression Treatment & How Ketamine Infusions Can Help When SSRI Treatment Isn’t Working

Unfortunately, for the past 20 years, the number of people taking one or more antidepressants has continued to rise. It is believed that 1 in 10 Americans is currently on an antidepressant and amongst women in their 40s and 50s the rate is as high as 25%.¹ In 2016, over 16 million American adults suffered at least one major depressive episode!¹ When treating patients with depression, psychiatrists and other mental health providers often rightly reach for medications and the most commonly used medication class for treating depression is SSRI (Selective Serotonin Reuptake Inhibitors).

At Actify, patients who receive Ketamine infusion therapy to treat their depression, anxiety, and other mood disorders have often failed two or more medication trials and often these failed medications include selective serotonin reuptake inhibitors (SSRI). In fact, those patients who have failed two or more medications are considered to have “treatment resistant” depression and are perfect candidates for ketamine infusion therapy. Ketamine infusions have proven effective in significantly improving symptoms of depression in over 70% of “treatment-resistant” patients³ and we are thrilled to have helped over 1000 patients to date!  

What are SSRI Medications and how do they work?

Selective Serotonin Reuptake Inhibitors, also known as SSRIs, are the most commonly prescribed antidepressant medication. They are considered relatively safe with fewer side effects than most other oral antidepressant medications and thus are often prescribed as a first-line treatment for major depressive disorder.

There are several different kinds of SSRIs, but they all work in the same basic way. Nerve cells in the brain “talk” to each other via chemical neurotransmitters. Serotonin is one such neurotransmitter. One of the many theories of depression is that there is a deficiency in serotonin among other neurotransmitter chemicals in the brain. SSRIs work by blocking serotonin receptors in the brain, preventing the reuptake of serotonin back into the brain cells (neurons), thus allowing more serotonin to be present to help transmit signals between the brain cells.

There are several SSRI drugs in this class: Prozac (Fluoxetine), Luvox (Fluvoxamine), Paxil (Paroxetine), Zoloft (Sertraline), Celexa (Citalopram) and Lexapro (Escitalopram).

What conditions do SSRI Medications treat?

In general, the SSRIs, as a class of medications, can all be used to treat major depressive disorder (depression). In addition, they are often used in conjunction with mood stabilizers in those individuals with bipolar depression. As a general rule, most SSRIs are also commonly used to treat generalized anxiety disorder, panic disorder, PTSD (Post Traumatic Stress Disorder) and OCD (obsessive compulsive disorder), although only a few are actually FDA approved for these disorders.

For example, Paxil (Paroxetine), Prozac (Fluoxetine) and Zoloft (Sertraline) are FDA approved for the treatment of panic disorder. For PTSD, both Zoloft (Sertraline) and Paxil (Paroxetine) are FDA approved. For generalized anxiety disorder, only Lexapro (Escitalopram) and Paxil (Paroxetine) are FDA approved. In OCD, Paxil (Paroxetine) is approved along with Zoloft (Sertraline), Prozac (Fluoxetine) and Luvox (Fluvoxamine). Of note, Prozac (Fluoxetine) is the only SSRI approved for children over 8 years old for depression. Of course, just because a medication is not FDA approved for a given condition, does not mean it is unsafe or should not be prescribed to treat that condition. Off-label prescribing of SSRIs (and many other medications) is common and accepted by psychiatrists and mental health providers and is in fact necessary as there are not great alternatives otherwise.

What are the side effects of taking an SSRI?

SSRIs typically can cause side effects such as: insomnia, headache, rash, blurred vision, drowsiness, dry mouth, nervousness, dizziness, joint pain, upset stomach, diarrhea, nausea, weight gain and sexual dysfunction, including erectile dysfunction. Some people, especially children, may be more likely to develop suicidal thoughts when taking SSRIs. In addition, SSRIs must be taken daily, and once started, they should not be abruptly stopped nor should you miss several doses in a row. If this happens, some people will experience withdrawal or “flu-like” symptoms. Another rare but serious problem that can occur from taking SSRIs is a condition called serotonin syndrome that results from too high levels of serotonin in your body.

How long does it take for SSRIs to work and how effective are they at treating depression?

Treatment with SSRIs does not yield instant results. If SSRIs are going to work, patients will usually feel some positive benefit by 4-6 weeks after starting treatment, but it can take up to several months before a patient feels the full effect.

Efficacy rates are variable depending on the study, but results from the famous STAR*D trial demonstrated that approximately ⅓ of patients achieved remission on a first antidepressant such as an SSRI.² Since roughly ⅔ of patients do not improve after just one antidepressant, often multiple trials of different medications are therefore necessary before the patient will see any benefit. Many patients will end up trying several different medications and some of the medications will have no benefit or intolerable side effects.

What can I do if SSRIs and other medications are not working to treat my depression?

In the past, after multiple failed medication trials, patients were forced to then undergo ECT and/or TMS, but now a safer, faster alternative is available: ketamine. Ketamine infusions have been proven, in numerous controlled studies, to have a 70% response rate in reducing the symptoms of depression.³ In addition, ketamine infusions work quickly. Patients will know after 1-2 infusions whether or not these treatments are working, which is much faster than typical oral antidepressants such as SSRIs.

Ketamine infusions have truly revolutionized depression treatment and our doctors, nurses, and staff at Actify feel lucky to be able to provide this service to thousands of patients across the country. If you or your loved one is suffering from treatment-resistant depression despite trying medications such as SSRIs, give us a call at 888-566-8774 or email us at to learn more about how ketamine can help!


  1. NIMH.Prevalence of Major Depressive Episode Among Adults. November 2017.
  2. Rush AJ, Trivedi MH, Wisniewski, SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905.
  3. Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013;74(4):250-256. doi:10.1016/j.biopsych.2012.06.022.