Can 20mg of Prozac cause serotonin syndrome? (3+ factors)

In this article, we will answer the question “Does 20mg of Prozac cause serotonin syndrome?”. We will discuss how Prozac causes serotonin syndrome and what research findings have to say in this regard. We will also discuss what factors influence the occurrence of serotonin syndrome while on Prozac and what to do if Prozac causes such a side effect.

Can 20mg of Prozac cause serotonin syndrome?

Yes, 20mg of Prozac can cause serotonin syndrome. In fact, Prozac in any dosage can produce this effect. Higher doses do have a bit more risk than the lower ones.

The response of individuals to Prozac may vary from person to person. Hence, some individuals may tolerate even higher doses while others may experience the serotonin syndrome even at the lowest dose.

Prozac (also known as Fluoxetine), is an antidepressant belonging to the class of selective serotonin reuptake inhibitors (SSRIs) approved by the FDA for the treatment and management of depressive illnesses like major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa, and panic disorder (PD) with or without agoraphobia. It can also help to stabilize mood. (1).

Serotonin syndrome is a drug-induced syndrome caused by the increased levels of the neurotransmitter, serotonin in the brain. This can be a potentially life-threatening condition if it is not treated.

Prozac and other SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs) tend to produce serotonin syndrome in individuals taking the medication. The risk increases when these are used in combination with other serotonergic medications tricyclic antidepressants (TCAs), triptans, amphetamines, buspirone etc.) (1).

How does Prozac cause serotonin syndrome?

Serotonin is a neurotransmitter shown to have a role in depression and mood regulation. It drops to a lower level in individuals suffering from depressive illnesses. Prozac works by inhibiting the reuptake of serotonin and hence increasing the levels of serotonin in the brain (2).

Prozac may sometimes increase the levels of serotonin to such an extent that the serotonin syndrome or serotonin toxicity occurs. This may be seen with SSRIs (including Prozac), SNRIs, MAOIs and any other serotonergic drugs.

The serotonin syndrome is more possible if any individual has been prescribed a combination of these medications or any other medications that can alter the metabolism of serotonin. Some symptoms of this condition are as follows:

  • Agitation
  • Nausea
  • Vomiting
  • Anxiety
  • Dizziness
  • Diarrhoea
  • Tachycardia
  • Changes in blood pressure
  • Tremors
  • Seizures
  • Muscle rigidity
  • Disorientation
  • Restlessness
  • Hallucinations
  • Mania
  • Hypomania
  • Delirium
  • Coma

Some of these symptoms may also occur at the initiation of treatment with Prozac and subside after your body adjusts to the medication. However, if the side effects do not subside, or get worse, you should consult your healthcare provider about your condition.

What does research suggest?

Case studies regarding the occurrence of serotonin syndrome with Prozac at a dose of 20mg have been published.

One case study of a 38-year-old woman reported the occurrence of serotonin syndrome within 48 hours after the administration of an MAOI, tranylcypromine. She was using 20mg/day of Fluoxetine up to 7 days before the use of an MAOI. Even in low doses, the medications when used in combination caused the emergence of serotonin syndrome (3).

Another case of a 57-year-old male, taking 20mg of Fluoxetine for the management of depression and posttraumatic stress disorder (PTSD), reported experiencing dizziness, confusion and diarrhoea. These symptoms were attributed to the occurrence of serotonin syndrome (4).

One case of a 40-year-old male, who was prescribed 20mg Fluoxetine returned after eight weeks and reported the occurrence of side effects like nausea, diarrhoea, insomnia, tachycardia, mania and muscle twitching for almost six weeks. These effects were found to be due to the increased serotonin levels causing serotonin syndrome (4).

A study was published of a 37-year-old man who developed serotonin syndrome with the addition of buspirone to his treatment regimen. He was taking 20mg/day of Fluoxetine for the treatment of generalised anxiety disorder (GAD). He developed confusion, diarrhoea, myoclonus, and incoordination when buspirone was added (5).

Another case of a 31-year-old woman was reported, in which she had been using Fluoxetine 20mg/day for almost three years. She was prescribed tramadol and developed the symptoms of agitation, restlessness, anxiety and tremors. These were proposed to be due to the occurrence of serotonin syndrome. Both medications were discontinued to stabilize the patient (6).

What factors contribute to serotonin syndrome while taking Prozac?

Several different factors can contribute towards the development of serotonin syndrome while taking Prozac (7):

Dosage of Prozac

If the dose of Prozac changes, you may experience the symptoms of serotonin syndrome. This is especially common for individuals who are prescribed a higher dose of Prozac, after being on a lower dose for quite some time.

Combining serotonergic drugs

If your regimen consists of more than one serotonergic medication, the risk for the emergence of serotonin syndrome may increase manyfold. A combination of other SSRIs, SNRIs, MAOIs and TCAs with Prozac can cause this effect.

Drug abuse

Sometimes drugs of abuse like hallucinogens may increase the levels of serotonin and the risk of serotonin syndrome in individuals.

Herbal supplements

Herbal supplements like St. John’s wort can increase serotonin levels and cause serotonin syndrome. 

Pre-existing medical conditions

If the individual has any pre-existing medical conditions which interfere with the metabolism of serotonin or the pharmacokinetics of serotonergic medications, the risk of serotonin syndrome increases in such patients.

Interactions with other medications

Sometimes two medications when combined may interact with each other and elevate the risk of serotonin syndrome.

Individual susceptibility to serotonin syndrome

Some individuals may be more susceptible to the occurrence of serotonin syndrome. They may have a genetic predisposition that makes them vulnerable to such side effects.

Keep in mind that your healthcare provider should know about all the medications and herbal supplements that you take, so a potential drug interaction can be avoided

What to do if you experience Prozac-induced serotonin syndrome?

If you experience Prozac-induced serotonin syndrome, here are some things you can do to help manage your symptoms:

Consult your healthcare provider

The first and foremost thing that you should do if you feel that Prozac is causing unwanted symptoms is to inform your healthcare provider. You should consult your doctor for guidance on how to manage your symptoms.

Seek medical help

Make sure to seek medical help regarding your condition. Do not wait for your symptoms to pass or subside on their own.

Call emergency services if needed

If your symptoms become severe or life-threatening, go to the nearest emergency department. If you cannot go on your own and do not have anyone to help you get there, call emergency services immediately.

Inform healthcare providers

Inform your healthcare provider or the doctor attending you in the emergency department, about all the medications and herbal supplements that you are taking. This will help doctors get to the underlying cause of your symptoms much faster.

It is most likely that your doctor will recommend the discontinuation of Prozac and any other medication if used, that may be causing serotonin syndrome. Keep in mind that you should not abruptly stop taking your medication before consulting a healthcare provider.

How to prevent, manage and treat Prozac-induced serotonin syndrome?

Different recommendations can be followed to prevent, manage and treat Prozac-induced serotonin syndrome (8). 

Preventing serotonin syndrome

The following things can be done to prevent the occurrence of serotonin syndrome while taking Prozac:

Avoid triggering combinations

When using Prozac, if another medication is to be added to the regimen, make sure that it does not interact with Prozac to cause serotonin syndrome. If the other agent is required, then Prozac can be alternated with another medication.

Constant monitoring

If any individual is on Prozac treatment, he should be constantly monitored for the emergence of serotonin syndrome. If any individual is taking a combination of medications that may cause this effect, then the healthcare provider must inform the individual of the side effect, and conduct rigorous monitoring to check for even the slightest of symptoms.

Managing serotonin syndrome

The following things can be done to manage or treat Prozac-induced serotonin syndrome:

Discontinue causative agent

If any individual is found to be experiencing the symptoms of serotonin syndrome, it may be in the best interest to find the causative agent and discontinue it. Usually, the symptoms do resolve within 24 hours of removing the cause.

Serotonin antagonists

Sometimes, if the symptoms are severe the individual may require external care in the form of serotonin antagonists like cyproheptadine, chlorprothixene and propranolol.

Sedatives and anticonvulsants

The benzodiazepines like lorazepam or diazepam, or antipsychotic medications like chlorpromazine can be used as sedatives and hypothermic medications.

Cooling blankets

If the hyperthermia is severe, cooling blankets can help lower the temperature to a bit safer range. However, in such a condition aggressive treatment is required to reverse the effects of serotonin syndrome.

Keep in mind that all individuals are different and the response of each individual to Prozac may vary. So the side effects and the occurrence of serotonin syndrome cannot be predicted, and the prevention strategies may not work in some cases.

In my opinion, a 20mg dose of Prozac can cause serotonin syndrome. It may occur in rare cases or mostly in combination with another medication. However, such low doses still may be potentially fatal for some individuals.

The combination of any medication that may directly or indirectly affect serotonin levels should not be used with Prozac. If there is some clinical benefit of such a combination, then the individuals should be informed and constantly monitored for the emergence of serotonin syndrome, in which case, the medications should be discontinued.

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References

1.-

The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. PROZAC® (fluoxetine capsules) for oral use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018936s108lbl.pdf 

2.-

Sohel AJ, Shutter MC, Molla M. Fluoxetine. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459223/

3.-

Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome. Journal of clinical psychopharmacology. 1997 Jun 1;17(3):208-21. https://journals.lww.com/psychopharmacology/abstract/1997/06000/selective_serotonin_reuptake_inhibitor_induced.12.aspx

4.-

DeSilva KE, Le Flore DB, Marston BJ, Rimland D. Serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine. Aids. 2001 Jul 6;15(10):1281-5. https://journals.lww.com/aidsonline/Fulltext/2001/07060/Serotonin_syndrome_in_HIV_infected_individuals.10.aspx

5.-

Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Annals of Pharmacotherapy. 2000 Jul;34(7-8):871-4. https://journals.sagepub.com/doi/abs/10.1345/aph.19341

6.-

Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. Journal of the Royal Society of Medicine. 1999 Sep;92(9):474. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297365/

7.-

Garel N, Greenway KT, Tabbane K, Joober R. Serotonin syndrome: SSRIs are not the only culprit. Journal of Psychiatry and Neuroscience. 2021 May 1;46(3):E369-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327977/

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