Fetzima (Levomilnacipran) is a serotonin-norepinephrine reuptake inhibitor that was approved by the FDA in 2013 to treat major depression. It is similar to the older drug milnacipran, but contains the “levo”-stereoisomer – making it slightly different. This antidepressant is regarded as being significantly different from other SNRIs in that it inhibits norepinephrine reuptake to a greater extent than serotonin.

In fact, the ratio of norepinephrine reuptake to serotonin reuptake is approximately 2:1 – even greater than its predecessor milnacipran. Most would consider this drug to be one of the newer (2013) antidepressants on the market, despite the fact that it is merely an adjusted formula of the older drug milnacipran. Since depression and other mental health disorders are among the biggest issues facing modern society, you can bet many will turn to trying this drug for relief.

The upside is that this is a drug that is different than most SNRIs on the market – it demonstrates how targeting low norepinephrine for depression can be beneficial. The downside is that like many antidepressants, many people won’t find them effective and/or be able to put up with their side effects. If you are considering trying Fetzima or are already taking it, below are some side effects and factors that can influence their severity.

Factors that influence Fetzima side effects

When taking any antidepressant, there are going to be factors that influence the side effects that you experience. These factors tend to include: individual physiology, the dosage, how long you’ve been taking the drug, as well as whether you are using any other medications.

1. Individual Variation

Perhaps the biggest influence of side effects is your individual genetics and physiology. Your nervous system may adapt quickly to the drug and learn to function fine under its influence. Another person may experience an adverse reaction and/or experience many unwanted side effects that never seem to go away. This why one person may experience headaches as a side effect and another person may experience something completely different like loss of appetite.

Two people of the same age and with the same diagnosis may take Fetzima and one person may get relief from depression with a few side effects, while the other may get no relief from depression and have many side effects. Individual variation is why it is impossible to predict how you will respond to a certain medication and why a drug that you find void of side effects may be problematic for someone else.

2. Dosage (20 mg, 40 mg, 80 mg, 120 mg)

The dosage of Fetzima can play a big role in determining the number of side effects and their severity. As you increase the dosage, you are essentially under the influence of a greater quantity of the drug. The more milligrams of the drug you take, the more your physiology has to change to accommodate the drug’s influence. At lower doses, you may not notice many side effects, but as the dose increases, they may become intolerable.

For Fetzima, most doctors prescribe a starting dose of 20 mg and have a person titrate the dosage upwards to 40 mg. The typical dose range is between 40 mg and 120 mg. Typically the greater the dose you are on, the more side effects you can expect. This is why it is always recommended to stay on the lowest possible dose that produces an antidepressant effect – to help you avoid side effects.

3. Time Span

Most people notice a bulk of their side effects within a week or two of starting a new medication. When you start Fetzima, you may notice wicked side effects for the first few weeks. However, if you continue to stay on the drug and put up with the initial “short-term” side effects, you may find that they eventually subside. There can be an initial adaptation period that is needed for your nervous system to adjust to the drug.

Once you have made it through this period, many side effects go away. It is important to also understand that there are sometimes more long-term side effects that can develop among people who have taken the drug for an extended term. Long-term side effects typically develop when the body has become tolerant to the effects of the drug and a dosage increase is required to yield the same antidepressant effect.

4. Other drugs

If you are taking any other drugs in addition to Fetzima, it is important to understand that they could have an interaction. Be sure to read about any contraindications that this drug may have with other drugs that you’ve been prescribed. Most doctors will be able to tell you whether Fetzima can be safely taken with other pharmaceutical drugs. Just know that taking other psychiatric and/or illicit substances with this medication may lead to interaction-based side effects.

Fetzima Side Effects: List of Possibilities

Below is a list of possible side effects that you may experience while taking Fetzima. Understand that everyone’s experience will be different and that you may not experience everything on this list. Based on clinical trials, the most common side effects included: nausea, vomiting, sweating, increased heart rate, and palpitations.

  • Agitation: The stimulation from this drug may make certain people increasingly agitated. This usually has to do with the norepinephrine aspect of the reuptake inhibition. If you notice that you have become filled with anxiety and or unnecessary excitement, this can sometimes lead to agitation.
  • Anger: Some individuals have noted that this drug made them angry and mean. If you are becoming angered by everything, chances are it could be a side effect of the neurotransmitter changes that Fetzima is making. Usually if anger is your experience, it’s probably not helping your depression.
  • Anxiety: Another very common symptom from a drug that affects norepinephrine is feeling anxious. Since it inhibits norepinephrine to a greater extent than serotonin, it may be too stimulating for certain people – leading to worsened anxiety.
  • Appetite loss: People have reported losing their appetite while on this drug. Usually appetite loss is more common within the first few weeks of trying it due to nausea and other side effects. If your appetite loss is tough to deal with and you are losing a lot of weight, you may want to switch medications.
  • Constipation: If you notice that you have started to feel constipated since you started taking this drug, you are not alone. Constipation was reported as being one of the most common side effects in clinical trials. This may improve over time and/or you can consult your doctor if you need help dealing with it.
  • Depression: This is an antidepressant and its primary purpose is to alleviate depression. However, not everyone has a positive reaction to antidepressants. Certain drugs actually make them feel more deeply depressed and hopeless. If you have given this medication a chance for a few weeks and are feeling worse, it’s probably not a good fit.
  • Dizziness: Another very common side effect is that of feeling dizzy. You may feel very dizzy and/or sensations of vertigo within a few weeks of taking the drug. Usually the dizziness will go away after a month or so of treatment.
  • Fatigue: Do you feel tired all the time since starting Fetzima? Although this is more of a stimulating drug, not everyone reacts by feeling on edge and with increased energy. Some people may experience the opposite effect and become tired, sleepy, or lethargic.
  • Feeling “wired”: A significant number of people taking this drug will notice that it makes them feel “wired.” In other words, they feel stimulated and as if their level of arousal significantly increased. This can be beneficial for those who were previously lacking energy, but feeling too wired can interfere with focus and lead to excessive anxiety.
  • Flu-like symptoms: A combination of initial nausea, dizziness, vomiting, and frequent nausea will make anyone feel as though they’ve contracted the flu. This side effect is certainly unpleasant, but one you may have to put up with until your body adjusts to the drug.
  • Headache: The increased stimulation that your nervous system receives from this drug may lead to frequent headaches. In fact, some people have gone as far as to describe severe headaches, tension, and migraines from their Fetzima. Although headaches may be part of an adjustment phase to the drug, for some they do not improve.
  • High blood pressure: If your blood pressure increases (which is common on drugs affecting norepinephrine), you may need to monitor it closely. If your blood pressure were to get too high, it could cause other health concerns. Be sure to tell your doctor if you notice any significant increase because it could be dangerous.
  • Increased heart rate: Another effect from this drug is increased resting heart rate or tachycardia. Fast or irregular heart rate is common while taking Fetzima. This is another result of targeting norepinephrine to a greater extent than serotonin.
  • Insomnia: For some people, taking this drug will cause significant insomnia. In other words, you may be so stimulated from its effects that you cannot fall asleep at night. If you already have a problem with insomnia, this is probably not a good solution.
  • Irritability: Not only could you become a little irritable on this medication, but many people are reporting that they became super irritable. This is an unfortunate side effect of many drugs that increase norepinephrine, leading to a “wired” feeling and also increases in anger.
  • Jaw clenching: You may notice that you are clenching your jaw more and/or there is more tension throughout your jaw area. This is usually more common to experience while asleep, but can occur throughout the day as well.
  • Mania / hypomania: Among patients with bipolar I and bipolar II disorders, experiencing a manic switch can occur with any antidepressant. Since this medication tends to be more stimulating, some believe it increases the likelihood of triggering mania or hypomania.
  • Mood swings: Any antidepressant can lead to mood swings as a side effect. You may feel slightly happier, then all of a sudden irritable, then sad, etc. This is usually your brain adjusting to the medication. If you experience more frequent mood swings, you may want to consider other treatments.
  • Nausea: This is among the most common side effects of Fetzima. Some hypothesize that the norepinephrine reuptake inhibition can make certain individuals prone to feeling nauseated. Since Fetzima does this to a significant extent, it is common to feel nauseous.
  • Palpitations: These are often perceived as loud heart beats, flutters, or sensations that your heart is beating abnormally. Typically these are influenced by increased levels of arousal and can be exacerbated by anxiety. Although these are uncomfortable, you may have to accept them as part of the treatment.
  • Poor concentration: Your concentration may suffer as a result of taking this drug. Although for some people norepinephrine can benefit concentration (e.g. Strattera), others will find that the extra arousal actually makes it more difficult to concentrate. If your ability to focus decreases, you’ll know why.
  • Sexual dysfunction: Specifically erectile dysfunction seemed to be a problem in approximately 6% of men who took Fetzima in clinical trials. Additionally delayed ejaculation in males was another extremely common side effect that was noted. For certain individuals, this drug may significantly interfere with your sex life.
  • Sleep changes: In addition to experiencing insomnia, you may notice that you expeirence other sleep changes. These can include crazy dreams, changes in sleep patterns, and/or feeling as though you’re getting less restful sleep. If you feel as though your sleep quality is suffering as a result of this drug, you may want to talk to your doctor.
  • Suicidal thoughts: There is evidence that antidepressants can cause increased depression and suicidality in certain cases. If you notice yourself feeling even more depressed and feeling suicidal, the medication probably isn’t a good fit. Seek immediate medical attention if you notice you are feeling suicidal while taking Fetzima.
  • Sweating: Many people notice that they start sweating more after they start this drug. The increased sweats may occur throughout the day or at night. This is a physiological reaction and may be caused by increased stimulation from the norepinephrine reuptake inhibition.
  • Urinary retention: One of the most uncomfortable side effects from Fetzima is that of urinary retention or hesitation. This is where you know you have to pee, but when you attempt to “go” the urine won’t seem to come out. This can be a very frustrating side effect and is likely linked to the norepinephrine reuptake inhibition.
  • Vomiting: Another very common reaction that people have to this drug is vomiting. It can be difficult to put up with feeling nauseous and puking just to feel less depressed, but this is a reality for some people. Fortunately as the body adapts to the drug this symptom usually gets better.
  • Weight changes: In both an 8-week and a full year study, Fetzima was not associated with any more weight gain than a placebo. However, this does not mean that people won’t experience weight changes as a side effect. Most people report losing weight if taking the drug decreases their appetite and vice versa. (Read: “Fetzima & Weight Loss vs. Gain“).

Note: There may be other side effects that were not reported in the list above.  Consider reading antidepressant side effects as a more general reference for various medications.

Fetzima: Serious Side Effects (Adverse Reactions)

In addition to having a standard list of common side effects, there are always some serious side effects that you should know. These more serious side effects are usually rare and are referred to as “adverse reactions.” If you experience any of these, it is recommended to seek immediate medical attention.

  • Abnormal bleeding: In a few cases, Fetzima can increase risk of bleeding and bruising. This is more common among those who take blood thinner medications, NSAIDs, or aspirin. If you notice any problems with bleeding or bruising, talk to your doctor.
  • Glaucoma: This medication is not to be used by individuals with glaucoma, as it may worsen the condition. People taking Fetzima have noted increased eye pressure, which could theoretically damage the optic nerve. If you notice any increase in eye pressure, this probably isn’t a good medication to take.
  • Hyponatremia: A lesser known side effect is that this drug can cause low sodium (salt) levels in the blood. The low sodium levels can lead to other effects including: weakness, confusion, memory difficulties, and balance issues. If not treated, this can actually lead to death, so be sure to note any symptoms related to hyponatremia.
  • Rash: Although this is a rarer side effect, some people notice that they develop a rash. In most cases this will be considered an adverse or allergic reaction and the medication will be discontinued.
  • Seizures: There is evidence suggesting that Fetzima can lead to seizures (or convulsions). Obviously if you are prone to seizures, this may be a medication to avoid. Additionally if you notice any potential warning signs of a seizure, be sure to seek medical attention.

Fetzima: Weighing the Cons (Side Effects) vs. Pros (Benefits)

When taking Fetzima, it is important to weigh the cons (your side effects) with the pros (the benefits from the drug). If the drug isn’t producing any benefit in your depressive symptoms, then it should be a no-brainer to switch to another medication. Things can get tricky if the drug is producing some sort of benefit in your depression, but the side effects are very difficult to cope with.

In most cases, it is a good idea to wait at least 4 to 6 weeks to determine whether the side effects subside. If the side effects do not improve at all after a month has passed, then you should be able to make an educated decision as to whether it is worth staying on the drug or transitioning to something else. Some side effects like constipation and insomnia may be easier to deal with than others like nausea, vomiting, and irritability.

It is ultimately up to you to make the final call on whether you are willing to put up with Fetzima’s side effects for an antidepressant benefit. If this is the first medication you’ve tried for your depression, but you have many side effects – then you may want to ask a medical doctor about Fetzima withdrawal and alternative treatment options.  However, if you’ve tried many medications and this is the only one making you feel less depressed, you may be able to justify putting up with a few unwanted side effects.

Have you tried Fetzima and noticed some side effects? If so, feel free to share your personal experience in the comments section below. Realize with most drugs there are often many side effects that go unreported in clinical trials and preliminary studies.