More threads by David Baxter PhD

David Baxter PhD

Late Founder
Selective Serotonin Reuptake Inhibitors (SSRIs)
July 1, 2005

Selective serotonin reuptake inhibitors are the most popular antidepressants because they are easy to take and, for most people, the side effects are better tolerated than those of older antidepressants.

SSRIs have a specific effect on the chemical messenger (neurotransmitter) called serotonin. By increasing this chemical’s availability, these drugs modify nerve pathways involved in regulating mood.

Types And Doses
In general, no one SSRI is more effective than any other SSRI. There may, however, be variations in which drug is right for you. If the first one you try doesn’t help or if you cannot tolerate the side effects, try another SSRIs.

SSRIs are usually taken once per day in the morning. If your SSRI makes you feel sedated, take it in the evening, when the effects may help you get a good night's sleep. If you experience stomach discomfort with their SSRI, take it in the evening, so you can sleep instead of experiencing the discomfort. Another way to reduce stomach distress is to take the medicine with food.

In most cases, it is best to start with a low dose and increase slowly. This helps limit side effects, especially the uncomfortable stimulation or edginess that can occur at the beginning of treatment. After a few days or a week, your doctor will increase the dose gradually until you notice improvement or begin to have uncomfortable side effects.

Sometimes you need the highest dose to get a therapeutic effect. This doesn't mean that your depression is more severe. It simply means your body absorbs and uses the drug differently than others. This probably has more to do with your digestive tract, kidneys and liver than with your brain.

Typical dose ranges
[pre]Citalopram (Celexa) 20-60 milligrams per day
Escitalopram (Lexapro, Cipralex) 10-20 milligrams per day
Fluoxetine (Prozac) 20-80 milligrams per day
Fluvoxamine (Luvox) 50-300 milligrams per day
Paroxetine (Paxil) 20-50 milligrams per day
Sertraline (Zoloft) 25-200 milligrams per day [/pre]
*These ranges are averages for otherwise healthy adults.

If you are prescribed a higher dose, however, it does not mean that your depression is more severe. It is simply a reflection of your metabolism. It may have more to do with your digestive tract, your kidneys and your liver than with your brain.

Side Effects
Although many people tolerate SSRIs without a problem, side effects do occur, including (depending on the specific medication)2:

  • Stomach upset
  • Nausea
  • Diarrhea
  • Constipation
  • Sleep disturbance
  • Insomnia
  • Drowsiness
  • Problems with sexual functioning
  • Decreased sexual desire
  • Delayed or absent orgasm
  • Erectile difficulties
  • Decreased vaginal lubrication
  • Headaches
  • Skin rashes
  • Weight gain or weight loss
Some people experience a stimulating effect in the first few days of using an SSRI. This can be a positive experience or cause a nervous or restless feeling that some people find distressing. This experience may explain why a few people taking SSRIs seem to get worse instead of getting better.

Any mental-health drug has the potential to make you feel uncomfortable. Report any changes in your feelings to your doctor immediately, no matter which drug you are taking.

Suicide Risk. All antidepressants (not just SSRIs) carry warnings about suicide. In October 2004, the Food and Drug Administration began requiring that manufacturers include a warning on package inserts for all antidepressants. The warning mentions the risk of suicidal thoughts, hostility and agitation in both children and adults.1

After you start taking any antidepressant, there is a risk that at first you may feel worse rather than better. The danger is greatest in the first few weeks of treatment, so make sure you follow-up with your doctor. There is also a small risk for an increase in suicidal thinking and behavior.1 Fortunately, research shows that the overall suicide rate lowers in people taking antidepressants. However, a small number of people using antidepressants encounter a lower mood, and feel more anxious, irritable, self-destructive or impulsive.

Drug Interactions. Drugs tend to interact with one another. SSRIs can increase the blood level or lengthen the effects of other drugs, including other antidepressants.3

Never mix SSRIs with monoamine oxidase inhibitors (MAOIs). The combination can cause dangerous changes in vital signs, mental state and muscle control.

Discontinuation of SSRIs. SSRIs can cause symptoms if you stop taking them suddenly. This is particularly true of paroxetine (Paxil) and fluvoxamine (Luvox), which leave the body more quickly than other SSRIs. Suddenly stopping these drugs can cause dizziness and trouble with coordination. Other symptoms are headache, nausea, lethargy, tingling, electric-shock-like sensations, vivid dreams, flu-like symptoms, irritability, anxiety and lowered mood. When a change in mood occurs, it is difficult to differentiate symptoms caused by discontinuation from those that indicate a recurrence of depression.

In general, symptoms you experience when you stop taking an SSRI will peak within the first week and then fade away, though sometimes symptoms last for weeks. Fluoxetine (Prozac) is the least likely of all SSRIs to cause symptoms when it is stopped because it is eliminated from the body slowly. If you are having trouble stopping another SSRI, your doctor may recommend that you switch to fluoxetine and taper your dose.

Comments (added by David Baxter):
1 Recent evidence questions the suggestion that SSRIs may cause increased suicidal thinking. See SSRIs and Suicide Risk.

2 Note that many people, possibly the majority, experience NO side-effects at all with SSRIs, other than perhaps some transitory adaptation effects in the first few days. For those who experience continuing side-effects, I gennerally advise speaking to your doctor if there are no indications that the side-effects are diminishing within 5-7 days. In the majority of cases, switching to a different SSRI can fix the problem.

3 Make sure to tell your doctor about ALL other medications you are taking, including over the counter medications and herbal or "natural" remedies!


Drug Interactions. Drugs tend to interact with one another. SSRIs can increase the blood level or lengthen the effects of other drugs, including other antidepressants.3

3 Make sure to tell your doctor about ALL other medications you are taking, including over the counter medications and herbal or "natural" remedies!

I would submit that the issue of drug interactions with SSRI's is considerably more complex than this article alludes to.

The footnote to report to the doctor and pharmacist every medication, over the counter remedy as well as supplements and herbal preparations cannot be overstated.

SSRI's are subject to a variety of potential methods of causing drug/drug and drug/food interactions. Common over the counter remedies that are subject to drug interactions with some SSRI's are cough and cold preparations and antacids, notably cimetidine.

The issue of drug interactions with SSRI's is complex and requires an understanding of the way each of these compounds is metabolized.

A rather technical article describing the methods of drug interactions with SSRI's can be seen HERE

The article describes the [DEF]pharmacokinetics[/DEF], the manner in which SSRI's are metabolized, distributed and eliminated and the methods in which various other medications can interact.

Although the article was presented with elderly patients in mind, the same metabolic pathways and cautions would apply to the general population.

The concern with elderly patients is reduced capacity to clear medications from the system, and so dosages are generally reduced in people in their late 60's and older.

There are a number of credible sites online where drug/drug interactions can be determined. One that's simple to use and is accurate is Discovery Health Drug Interaction Checker

The attached table is taken from the Cadieux article.


  • Cadieux Table2.jpg
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