Selective serotonin reuptake inhibitors (SSRIs) are considered the gold standard in treating depression and anxiety disorders. This class of medications includes well-known medications such as Prozac (fluoxetine), Zoloft (sertraline), and Lexapro (escitalopram).
As a PMHNP who works in outpatient psychiatry, it is rare for me to see a patient who has not trialed at least one of these medications. SSRIs are often started in primary care and are first-line for chronic management of both depressive and anxiety symptoms. They are known for being well tolerated, having minimal side effects, and for being effective. As I alluded to in a prior post, there are key differences with SSRIs and it is beneficial to understand the differences and indications for each medication.
One key point to emphasize with patients is SSRIs are not necessarily adding an external substance to the brain, but rather changing how the brain manages serotonin. Serotonin (5-HT) is an inhibitory neurotransmitter that plays a vital role in the limbic system, which is the part of the brain involved in emotion, motivation, memory, and behavior. The whole goal in targeting serotonin in the treatment of depression and anxiety is to increase the amount of serotonin available to relieve common mental health symptoms.
A starting point at understanding the mechanism of action of SSRIs is to understand SERT. SERT stands for serotonin transporter, a protein located on presynaptic neurons (the “sending” neurons before the synapse), that transports serotonin from the synaptic cleft (the space between neurons) back to the presynaptic protein in a process known as reuptake. When an SSRI is given, SERT is blocked, resulting in more serotonin being available in the synaptic cleft.
Consider this image:
Blocking SERT increases serotonin levels relatively quickly, but I warn patients it takes 4-8 weeks to see the therapeutic effects of the medication. This is because the process is much more complex than simply increasing the amount of serotonin. Over time, the serotonin receptors become less sensitive to increased serotonin and we see receptor adaptation. This, along with neuroplasticity and the effect on other neurotransmitters (downstream effects), results in the resolution of symptoms.
It is important to review treatment expectations with patients. If I had a magic wand I could wave over a patient, I would wave it immediately. Unfortunately, when it comes to treating mental health symptoms, such a modality does not exist (although there are interventional modalities such as TMS and Spravato which I will discus in the future).
Now that you know the mechanism of action, some general points to consider with SSRIs:
SSRIs can influence the gut microbiome. I tell patients when we alter amounts of serotonin, we run the risk of causing nausea. This is usually mild and transient in nature, but as a general rule of thumb, it is a good idea to take the medication with food. It does not have to be Thanksgiving dinner, but just something to help combat a known side effect. Diarrhea can also be problematic in the induction stage but again, taking the medication with food and staying hydrated will help.
There is a bleeding risk with SSRIs and caution should be taken when starting one on a patient on an anticoagulant, especially warfarin. There are serotonin receptors on platelets and sometimes, surgeons will request SSRIs be stopped before surgery.
In addition to gastrointestinal effects, SSRIs can cause sexual side effects such as erectile dysfunction and anorgasmia. These side effects can be one of the biggest reasons a patient stops the medication. Some SSRIs are worse than others, but it is something to review with patients. Sometimes, a prescription of a phosphodiesterase-5 inhibitor (such as sildenafil), is all a patient needs to continue treatment. I implore patients to be forthcoming about sexual side effects, explaining I cannot address what I do not know.
Hyponatremia is a known risk, with SSRIs having the potential to induce Syndrome of Inappropriate Antidiuretic Hormone. This is because serotonin can stimulate the release of antidiuretic hormone. Populations at risk are those over the age of 65, with reduced renal function, or postmenopausal women. I will order a CMP in at-risk populations, especially if the patient reports a history of hyponatremia. The risk for developing hyponatremia is more common to occur in the induction phase or with dosage changes. Again the risk is rare, but as my patients know, I am pretty militant about following CMPs in all patients (I call it being paranoid, others have said I’m just cautious).
There is no perfect medication and all medications have side effects. The discussion that must be had is how problematic are the side effects and do they negate the therapeutic benefit of the drug?
SSRIs carry a black box warning from the FDA that they can increase suicidal thoughts and behaviors in some individuals under the age of 25. There continues to be a lot of research in attempt to answer this question. It is important to note it is an increase in thoughts and behaviors, not an increase in suicide completions. The way it was first taught to me (shout out to Shelia) was patients started on SSRIs lacked the energy and motivation for such behaviors and the activation caused by the SSRI plays a part. In practice, I tend to have more concern over my younger patients because they are more impulsive. Remember, the prefrontal motor cortex is not fully matured until the mid 20s. Explaining this risk is also a good time to go over the safety plan, which needs to be done with every single patient.
Often times when treating depression, symptoms such as fatigue, diminished appetite, and insomnia lift first, with the depressed mood hanging on to the bitter end. This could most certainly play a role in the black box warning and it is definitely something to discuss when reviewing treatment expectations.
SSRIs are not indicated as monotherapy in individuals with bipolar disorder. I touched on this in a previous post, but I tend to avoid SSRIs completely in bipolar patients, but if starting one, it should be done in conjunction with a mood stabilizer or second-generation antipsychotic. Symbyax (olanzapine/fluoxetine) is FDA approved for bipolar depression and for treatment-resistant depression.
I had intended to address specific medications in this post, but I will save them for future entries in attempt to keep the length more manageable. I will start with Prozac (fluoxetine) in my next post and go from there.
This post was written by Richard Gray, PMHNP-BC. The above information is for educational/entertainment purposes and is not intended to be treated as medical advice. If you have questions about a medication you are taking, discuss these questions with your medical provider.