SSRIs, short for serotonin selective reuptake inhibitors, are one of the most widely prescribed depression medications that are well tolerated and have the least side effects.

Most people do not experience any adverse outcomes but some do. The majority of these side effects are acute, not permanent, and tend to disappear within a few days or weeks.

Compared with Tricyclic antidepressants (TCAs), SSRIs were originally considered free of side effects.

They could be used safely in the elderly and children, both of whom are particularly sensitive to the adverse effects of other antidepressants such as TCAs. SSRIs could also be prescribed to patients with multiple comorbidities.

The information leaflet that comes with the medication explains the possible side effects and the contraindications for taking the medicine.

Side effects of SSRIs

Antidepressants are not without side effects. All types of antidepressants exhibit them. In this post, we discuss those that are particularly caused by SSRIs.

According to the National Institute of Health, 38% of the patients surveyed reported experiencing one or more side effects as a result of taking an SSRI antidepressant. Of these, only 26% indicated that these side effects were “very bothersome”

The possible adverse effects of SSRIs include:

  • Diminished libido, impotence, delayed ejaculation, or difficulty to reach an orgasm
  • Headache and nausea
  • Fatigue and dizziness
  • Dryness of the mouth
  • Nervousness and restlessness
  • Drowsiness
  • Insomnia (difficulty in falling asleep)
  • Indigestion and diarrhea
  • Change in weight. This could manifest as weight gain or weight loss. Weight gain, however, is more common with SSRIs.
  • Heart problems with SSRIs are extremely rare. An overdose of Fluoxetine is known to cause cardiac arrhythmias and myocardial infarction. Cardiovascular patients on SSRIs should be carefully monitored with ECG monitoring.
  • Hyponatremia (low sodium levels) induced by intake of SSRIs, fluoxetine, or paroxetine, is found to occur in 1 out of 200 elderly patients. However, it is less common with other SSRIs such as venlafaxine.
  • Another side effect, which causes concern, is that some people develop suicidal thoughts. This can be serious because young people have committed suicide when put on antidepressants. A detailed note on this is given below.

However, some of these side effects do go away with time.

SSRIs and sexual side effects

Sexual problems associated with SSRIs, which are also caused by other antidepressants occur in about 50% of the patients who take SSRIs.

However, the effects of SSRIs on sexual functioning are dose-related and may therefore vary. They are the most common long-term side effects caused by SSRIs.

Paroxetine appears to be responsible for the highest rate of sexual dysfunction. Citalopram has been associated with loss of libido and is associated with a higher level of sexual dysfunction when compared with sertraline.

Fluvoxamine and fluoxetine are less likely to produce sexual side effects as compared to paroxetine and sertraline.

Paroxetine produces more orgasm delay than fluvoxamine, fluoxetine, and sertraline

Here are the statistics percentage-wise for the sexual dysfunction caused by various SSRIs:

  • Citalopram —  72.7%
  • Paroxetine —  70.7%
  • Sertraline —  62.9%
  • Fluvoxamine —  62.3%
  • Fluoxetine —  57.7%

Research data make it clear that SSRIs and SNRIs are potential destroyers of sexual function, and the harmful sexual complications can at times continue for years or even indefinitely after discontinuation of the drug. Sometimes, these adverse effects are seen or worsen only when you stop taking the drug.

Why do SSRIs cause nausea?

Nausea and vomiting are caused due to the stimulation of serotonin 3 receptors located in the hypothalamus and the brainstem.

This stimulation can lead to the increased motility of the gastrointestinal tract causing GI cramps. If severe, it can lead to diarrhea.

Taking the medication with food will reduce the risk of nausea. Another convenient measure would be to take it at bedtime if it does not cause insomnia.

Paroxetine and sertraline are SSRIs that have been associated with slightly more cases of nausea.

Why do SSRIs cause CNS side effects?

Central nervous system side effects are caused by the stimulation of the 5HT2A receptor stimulation by SSRIs.

CNS side effects include Akathisia (a movement disorder), psychomotor retardation, Parkinsonism, and Distonic movements (repetitive muscle contractions).

Experiencing a side effect does not mean you should stop taking the medicine. The repercussions of stopping the drug can be worse. You should talk to your doctor. He will exercise other options.

Which SSRIs cause weight gain?

According to experts, 25% of the people who are on SSRI drugs can gain weight 10 pounds or more. According to WebMD, the most common SSRIs with this side effect are Lexapro, Paxil, Prozac, and Zoloft.

Of the SSRIs, paroxetine is responsible for the highest risk of causing weight gain.

Which SSRIs cause weight loss? 

According to Livestrong, some SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) can cause weight loss in some people. This weight loss is temporary and can last up to 3 months.

Fluoxetine suppresses appetite and may cause modest but insignificant weight loss.

It is seen above that Lexapro, Paxil, Prozac, and Zoloft cause weight gain in some people while some people lose weight with these drugs. The reason for this paradox is not yet known.

SSRIs and anticoagulants

If you are on any SSRI, do not take aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), or any anticoagulants because such a combination will increase the risk of bleeding.

Serotonin syndrome

Rarely, SSRIs can cause serotonin syndrome, which occurs due to high levels of serotonin. This can occur usually when two drugs, which increase serotonin in the brain, are given in combination for depression.

These could be antidepressants or some other drug given for some other illness. Even giving an herbal supplement like St John’s wart with an SSRI can cause such a complication.

Serotonin syndrome can cause side effects such as confusion, fever, dilated pupils, and increased and irregular heartbeat. It can even cause unconsciousness.

The appearance of such symptoms requires immediate medical attention.

SSRIs and suicide risk

All antidepressants carry the risk of a suicide attempt especially in young children, teens, and young adults and it is mandatory that such a warning be displayed on the label of the medication.

The first few weeks of treatment with antidepressants should be watched carefully for signs of worsening depression and should be reported immediately to the treating doctor if anything untoward is noticed.

Side effects after stopping SSRIs

Though SSRIs are not addictive and don’t give you a “high”, abruptly stopping them can give you withdrawal symptoms. This is called discontinuation syndrome.

They include a headache, nausea, dizziness, lethargy, fever, and body ache. To avoid the symptoms of discontinuation syndrome, they are discontinued by gradually tapering off the dose.

Common, less common, and rare SSRIs side effects: Comparison chart

Common                     Less common                                Rare

Insomnia                       Agitation                                 Suicidal thoughts

Drowsiness                   Restlessness                            Serotonin syndrome

Changes in appetite      Impulsive behavior                 Bleeding disorders

Nausea                          Irritability                                Hyponatremia

Dryness of mouth         Aggressive behavior               Mania

Headache                      Constipation

Sexual side effects        Dizziness/Tremors/Diarrhea

SSRIs in pregnancy and breastfeeding

All SSRIs (except paroxetine) are classified as Pregnancy Category C, which means that they may not be safe for use during pregnancy and breastfeeding.

Antidepressants can cause harm to the unborn or nursing child. Using antidepressants in late pregnancy can lead to withdrawal symptoms in the newborn. These withdrawal symptoms are of short duration. Such symptoms include mild respiratory problems, a weak cry, restlessness, and tremors.

If you are pregnant, planning to become pregnant, or are breastfeeding your child, you should talk to your doctor about your mental state. He will weigh the risks and benefits and take an appropriate decision.

Paxil, in particular, which is an SSRI and pregnancy category D medication can cause congenital defects including defects in the lungs and heart of the developing fetus.

Drug interactions with SSRIs

Drug interactions with SSRIs are known and no drug should be included for use without talking to your treating doctor when on SSRI.

Some drugs, which interact with SSRIs are blood thinners (warfarin), NSAIDs (ibuprofen), drugs given for cardiac arrhythmias (propafenone), and tricyclic antidepressants (imipramine).

The interaction between MAOIs and SSRIs is the most significant drug interaction that limits the use of SSRIs.

SSRIs sertraline, citalopram, and escitalopram have the lowest potential for drug interactions and are preferred in patients who are on other drugs for coexisting medical conditions

How to overcome SSRI side effects?

As a patient with depression or anxiety, there is only one way to deal with SSRI adverse effects and that is to consult your doctor.

He will exercise an option that will be one of the following:

  • Change the medication
  • Add another drug to your present prescription to counter the side effects
  • Change the dose of the current SSRI you are taking

On your own, you could follow some tips to manage the side effects. They will go away on their own in due course of time.

Why are SSRIs preferred over other antidepressants?

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. The reason they are most used is that they reduce the symptoms of moderate to severe depression and anxiety and are relatively safer than other types of antidepressants.

Although the efficacy of the SSRIs matches that of the TCAs, the SSRIs have considerably fewer side effects. Another advantage is that fewer patients discontinue therapy.

Secondly, SSRIs require less laboratory monitoring and fewer office follow-up visits for dosage adjustments,

Unlike TCAs, SSRIs rarely cause cardiac conduction abnormalities (cardiac arrhythmias) in overdose and have a lower tendency to cause seizures.