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Selective Serotonin Reuptake Inhibitors (SSRIs)1 are the most frequently prescribed medication for major depression. They work very well for about two out of three people and they produce fewer side effects than other comparable antidepressants. SSRIs are most commonly prescribed as the medication pillar of a more comprehensive treatment plan for depression that includes psychotherapy and lifestyle changes.

Doctors generally prescribe SSRIs first and only prescribe other varieties of anti depressants should the SSRI fail to work.

SSRIs allow for more efficient use of the brain's natural levels of the neurotransmitter serotonin. Low serotonin levels are thought to play a role in depression and SSRIs increase the functional amount of serotonin in the brain.

Here are some commonly asked questions about these common and effective medications.

What Are Some Common Types of SSRIs?

American doctors have prescribed SSRIs since 1987; the year Fluoxetine (Prozac) first became available.

Other types of SSRIs include:

  • Setraline (Zoloft)
  • Escitalopram (Lexapro) 
  • Paroxetine (Paxil)
  • Citalopram (Celexa)

How Well Do SSRIs Work?

SSRIs work about as well as other types of anti depressants (MAOIs and tricyclic antidepressants) which is a little better than two thirds of the time. Doctors generally prescribe SSRIs before trying other types of antidepressant medications due to the reduced side effects and greater safety associated with the SSRIs.

How Do SSRIs Work?

Serotonin is sent from one cell, through an extracellular medium, to another cell which has a serotonin receptor ready to catch the neurotransmitter. Once the serotonin has been 'passed and caught' a serotonin reaction can occur, and the more serotonin that floats in the extracellular space between 'passing' neurons and the 'catching' serotonin receptors, the greater the effects of the serotonin.

After a neuron 'passes' a quantity of the neurotransmitter to a 'catching' neuron, the 'passing' neuron will suck back in any extra neurotransmitter floating in the extracellular space. SSRIs work by limiting the amount of serotonin that gets sucked back into the 'passing' neuron cell and thereby increase the amount available over time to stimulate the 'catching' neuron's receptors. The net effect of SSRIs is to increase the efficiency and effect of existing neural levels of serotonin.

SSRIs are preferred over other anti depressants, as they are much more selective. They do not influence the activity of other neurotransmitters as much as older and less selective medications. This limits the dangers and side effects of the medication.

Why Does It Take Several Weeks for SSRIs to Start Working?

SSRIs take a while to start fully working, between 2 and 8 weeks, most typically, depending on the medication used and genetic variations.

As soon as a person starts taking an SSRI, neural levels of serotonin between brain cells (in the synaptic gap) increase dramatically. The brain adjusts to this sudden increase in serotonin by decreasing the sensitivity of serotonin receptors in the brain, over a period of several weeks. SSRIs do not become fully effective until the serotonin receptors are modified to handle the suddenly increased quantity of serotonin available to them.

How Long Does Antidepressant Treatment Take?

SSRI treatment takes a while. It takes a number of weeks for the medication to become fully active, and even once depressive symptoms subside, most doctors recommend that patients continue to take the medication for several months longer, to reduce the likelihood of a relapse back to depression.

SSRI Side Effects?

SSRIs are a very well tolerated type of medication, and most people that use them report no or only very minor side effects. A small minority of people will experience intolerable side effects and will need to try a different anti depressant medication or a different dose of SSRI.

Some side effects sometimes associated with SSRIs include:

  • Sexual dysfunction
  • Shakiness
  • Heavy sweating
  • Headaches
  • Dry mouth
  • Anxiety
  • Nausea
  • Diarrhea
  • Changes in appetite
  • Light headedness

Some people will feel increased anxiety during the first weeks of treatment, but this will usually go away as your body gets accustomed to the medication.

People tend to tolerate these medications very well.

Although all SSRIs work similarly, slight differences between the various types can cause varying side effect responses. If you experience severe side effects to one SSRI, you might find that switching to a different SSRI offers the same symptoms relief with fewer side effects.

Although taking large quantities of any medication can be dangerous, SSRIs are safer than other anti depressant medications.

Can You Get Addicted to Antidepressants?

SSRIs are not addictive and if you stop taking the medications suddenly, you won’t feel drug cravings for the medication.

Stopping the use of SSRIs very suddenly can lead to a "discontinuation syndrome" similar to a syndrome of withdrawal symptoms. This can be avoided by tapering down your dosage over time, instead of stopping all at once.

Discontinuation symptoms can include:

  • Nausea
  • Light headedness
  • Lethargy
  • Symptoms similar to the flu
  • Headache

SSRIs and Suicide?

SSRIs may be associated with an increased risk of suicidal thoughts and suicide2, particularly when taken by people under the age of 24; particularly during the first months of treatment.

What is Serotonin Syndrome?

Combining SSRIs with certain other medications can cause very high levels of serotonin in the brain, a condition called serotonin syndrome.

Combining anti depressant medications of the MAOI class with any SSRI can be very dangerous and can lead to this syndrome. People are advised to wait at least 2 weeks after the last use of an SSRI before taking an MAOI.

Taking other medications, such as tramadol (Ultracet, Ultram), sumatriptan (Imitrex), rixatriptan (Maxalt) and St John's Wort with any SSRI can lead to serotonin syndrome.

Serotonin syndrome can be fatal. Symptoms of the condition include:

  • Diarrhea
  • Rapid heart beat
  • Confusion, agitation or restlessness
  • Hallucinations
  • Nausea
  • Un-coordination
  • Vomiting
  • Changes in body temperature
  • Coma
  • Seizures
  • Fever

Anyone suspecting serotonin syndrome needs immediate emergency medical attention.

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Page last updated Jun 24, 2012

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