Introduction

Antidepressants are medications used to treat depression or prevent its recurrence. Several types of antidepressants are utilised, based on the individual needs of the patient. While some antidepressants work by preventing the breakdown of serotonin, others increase the availability of mood-enhancing neurotransmitters like dopamine and serotonin. More recent guidelines advise selective serotonin reuptake inhibitors (SSRIs) as a first-line treatment for patients with severe depression.¹

Due to their relatively low side effect profile compared to other antidepressants, SSRIs are often prescribed for the treatment of severe or persistent depression. They are frequently used in conjunction with behavioural therapy. SSRIs assist in reducing depressive symptoms such as irritability, restlessness, low mood, and insomnia.¹

What are selective serotonin reuptake inhibitors?

SSRIs are a class of antidepressants that work by inhibiting the reabsorption (or reuptake) of the neurotransmitter serotonin in the brain. This action leads to an increased level of serotonin in the synaptic cleft. SSRIs specifically target serotonin and do not affect dopamine or any other neurotransmitters. Hence the term “selective”.²

Medications belonging to the selective serotonin reuptake inhibitor class are often prescribed for PTSD, depression, anxiety, and other behaviour-related disorders. This is because serotonin plays a crucial role in regulating mood and emotional stability, making its availability important for treatment.²

When SSRIs are not utilised according to medical directions, the risk of both short- and long-term adverse effects is significant. Specific precautions should be taken before prescribing these drugs to a child or adolescent.

How do selective serotonin reuptake inhibitors work?

By preventing serotonin’s reuptake, SSRIs work within the brain to raise the amount of serotonin (5-HT) in the synaptic gap. Being selective means that SSRIs only impact the reuptake transporters that regulate serotonin. Their effects peak within 3–8 hours and are effectively absorbed when taken orally. The absorption of sertraline, in particular, is enhanced by meals. The CYP-450 enzyme metabolises all SSRIs in the liver. Although they have a broad therapeutic index, meaning they are generally safe within a wide dosage range,  SSRIs can still interact with other medications and may inhibit or slow down their metabolism.³

SSRIs primarily inhibit serotonin reuptake, with minimal impact on nor-epinephrine and dopamine receptors. Therefore, a high dosage may heighten the risk of side effects without significantly increasing the efficacy of antidepressants.³

While patients may see improvement even after a few doses, the treatment takes weeks to become clinically meaningful. The mechanism of SSRIs extends beyond simply increasing serotonin levels. The ultimate goal of treatment is to gradually adjust the dosage, and if appropriate, reduce or discontinue medication as the patient achieves long-term stability and can live a normal, healthy life without it.

Types of selective serotonin reuptake inhibitors

The first drug in the SSRI class was Prozac (Fluoxetine), which was FDA-approved on December 29, 1987.⁴ It was hailed as a breakthrough in the treatment of depression and paved the way for other SSRIs in later years. The most common types of SSRIs (and their brand names) used are:

• Citalopram (Cipramil)
• Dapoxetine (Priligy)
• Escatilopram (Cipralex)
• Fluoxetine (Prozac or Oxatin)
• Fluvoxamine (Faverin)
• Paroxetine (Seroxat)
• Sertraline (Lustral)
• Vortioxetine  (Brintellix)

Where are selective serotonin reuptake inhibitors being used?

Because they have fewer negative effects on the heart and are less toxic than other antidepressants, SSRIs have dominated the market today and are recommended as the first line of treatment for depression by medical professionals and mental health experts. SSRIs are primarily prescribed to address conditions such as:

• Major depressive disorder
• Generalised anxiety disorder
• Panic disorder
• Obsessive-compulsive disorder(OCD)
• Post-traumatic stress disorder (PTSD)
• Bulimia
• Severe phobias (agoraphobia and social phobia)

Other off-label uses – SSRIs are also used to treat co-occurring conditions in patients with medical conditions such as:¹

• Bipolar Depression 
• Psychosomatic Condition
• Irritable Bowel Syndrome
• Menopausal Symptoms
• Premature Ejaculation
• Migraine Headache Prophylaxis
• Chronic Headache
• Musco-skeletal pain
• Fibromyalgia

The table below provides an overview of each SSRI, including its primary indications, contraindications, as well as special considerations and precautions.⁵

Table 1 SSRIs characteristics.

Side effects of selective serotonin reuptake inhibitors?

SSRIs can have different side effects depending on factors such as a person’s sex, age, body weight, co-morbidities, pregnancy, and history of substance abuse. Some of the common side effects are:¹

• Nausea (especially with sertraline)
• Headache (especially with fluoxetine)
• Sexual dysfunction (especially with paroxetine and sertraline)
• Vomiting
• Dry mouth (especially with paroxetine)
• Abdominal pain
• Weight gain (paroxetine) or weight loss (fluoxetine)

Adverse effects of SSRIs include:

• Increased risk of bleeding⁷
• Discontinuation syndrome (especially with paroxetine and fluvoxamine)
• Paraesthesia
• Tremor
• Extrapyramidal disorders
• Cardiovascular side effects such as QT Prolongation, torsade-de-pointes, and palpitation⁸
• Serotonin syndrome⁹
• Seizure (especially with fluoxetine at doses more than 100mg/day)¹⁰

Things to consider before taking SSRIs?

There are several important factors to consider before starting SSRIs. Some of them are listed below:⁵

• Age: The use of SSRIs is not recommended for children and adolescents under 18. In cases of severe depression in children, the use of anti-depressants should be supervised by a child psychiatrist¹¹
• Driving and operating machinery: Some SSRIs can cause dizziness and blurred vision. These activities should be avoided after taking the medicine
• Bipolar disorder: SSRIs can be beneficial during depressive phases of bipolar disorder but may trigger manic episodes during manic phases (a period where you're extremely excitable).
• Bleeding disorders
• Type 1 diabetes or Type 2 diabetes
• Epilepsy: SSRIs should only be taken if your epilepsy is well managed. If seizures worsen, the medication should be discontinued
• Kidney disease
• Other Antidepressants: Combining TCAs or MAOIs with SSRIs should only be done under a doctor’s supervision because it can lead to life-threatening side effects
• Alcohol and other Substance abuse: SSRIs should not be taken with alcohol or by individuals addicted to illegal drugs such as cocaine, meth, heroin, and cannabis
• Pregnancy and Breastfeeding: SSRIs are generally not advised during pregnancy or breastfeeding as they can affect a baby's serotonin levels
• Interaction with other drugs: SSRIs are known to interact with other drugs, especially with NSAIDs
• Interaction with food: Some fruits, such as grapefruit, can interfere with the metabolism of SSRIs and can increase the risk of toxicity.

Summary

SSRIs are essential treatments for depression as they increase serotonin availability in the brain. By blocking serotonin reuptake, these medications ensure serotonin remains in the synaptic cleft, which is crucial for mood regulation. SSRIs, including fluoxetine, sertraline, paroxetine, and escitalopram, are widely regarded as some of the most effective and commonly prescribed treatments for depression and other mental health disorders. They play a critical role in psychiatric care due to their high efficacy in reducing symptoms and improving overall functioning.

Although SSRIs are highly effective in treating depression, they can cause side effects such as nausea, changes in body weight, and sexual dysfunction. However, these side effects should not overshadow the importance of SSRIs, as they offer a lifeline for those struggling with mental health issues, helping individuals regain stability and lead fulfilling lives.