Selective Serotonin Reuptake Inhibitors (SSRIs)

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Selective Serotonin Reuptake Inhibitors (SSRIs)

General information about the SSRIs, their relative merits, and their side effects.

Prime Candidates

The SSRIs are particularly helpful in heading off depression in the early stages, before it becomes deeply rooted. Some studies suggest that SSRIs are ideal for those people with minor depressive illness -- much better than tricyclics, such as imipramine, or the complication-prone MAOIs. The SSRIs are effective for major depression, too.

"Before taking Zoloft, I had a bad case of the blahs. Everything just seemed colorless. But now, sometimes I'll just lie in bed and rub the blanket between my fingers," says Sharon, 38. "It's not sexual, but my sensitivity is heightened. The feel-goodness goes right down into my bones."

Research seems to suggest that you can head off serious full-blown illness by taking an SSRI during the early stages of depression.

This doesn't mean that SSRIs are the only worthwhile antidepressant, of course. There is still a place for the older drugs. Research has shown that the older tablets (Tricyclics) are just as effective as the newer ones (SSRIs) but, on the whole, the newer ones seem to have fewer side-effects. A major advantage of the SSRIs is that they are not so dangerous if someone takes an overdose.

Researchers also note that the SSRIs don't work for 20 percent to 40 percent of depressed or anxious people who try them -- the same failure rate as for the older antidepressants.

Which SSRI Is Best?

Most experts agree that no single SSRI is better than the rest, despite Prozac's image as a miracle drug that not only cures depression but can make many healthy people "better than well". Each drug has a certain profile of its own particular side effects; some have markedly similar side effects, while others vary widely.

For example, Zoloft and Paxil don't last as long in the body as Prozac; the half-life of Zoloft is about 26 hours, and the half-life of Paxil is about 21 hours. ("Half-life" is the time it takes for a drug in the blood to decrease by half of its original dose.)

It's important to understand that all the SSRIs may cause nausea, headache, anxiety, dry mouth, insomnia, and a variety of sexual dysfunctions. But as mentioned, what makes Prozac less desirable is that it lingers in the body much longer than other SSRIs; up to six weeks after you stop taking the drug, traces of Prozac and its metabolites can still be found in your body. If you have a bad reaction to Zoloft or Paxil, symptoms last for a week or two. But side effects while taking Prozac can last for up to six weeks before all traces of the drug leave your body.

Of course, none of the SSRIs are any sort of wonder drug. They all have some side effects, although they are less severe than those of other antidepressants.

One of the biggest problems with these drugs is their cost. All of them are much more expensive than the generic versions of older drugs like MAOIs or tricyclics. Generic versions of the older drugs are available because their patents have expired.

No matter how wonderful a drug may be, if you can't afford it, it's not going to do you much good. The high cost of the SSRIs can be a real hardship for someone with no insurance, or whose insurance doesn't cover drugs. At about $2 to $3 per pill, the pharmacy bill can be overwhelming.

It's a problem for Mary, 28, whose health insurance covers all drugs except medications for mental health problems. "My psychiatrist is very aware of this problem," Mary explains. "He doesn't give me Zoloft alone because it would be too expensive. So he prescribes a smaller amount of Zoloft with desipramine (a less-expensive tricyclic)." The desipramine boosts the effects of Zoloft, and the combination costs less than a full dose of Zoloft alone.

SSRI Antidepressants, Suicidal Feelings and Young People

There is evidence of increased suicidal thoughts and behaviors and other side effects in young people taking antidepressants. So SSRI antidepressants, with the exception of Prozac, are not approved by the FDA for use in people under 18.

In fact, in 2004, the FDA ordered the strongest safety warning possible:

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need.

The complete black box warning and additional details on antidepressant use in children and adolescents can be found here.

There is no clear evidence of an increased risk of self-harm and suicidal thoughts in adults - age 18 years or over. But, individuals mature at different rates. Young adults are more likely to commit suicide than older adults, so a young adult should be particularly closely monitored if he or she takes an SSRI antidepressant.

Medical Cautions

Severe kidney or liver disease could result in higher-than-normal blood levels of the SSRIs. In addition, the SSRIs may not be the best choice in the treatment of patients with mania, or in those with a history of seizures.

Side Effects

The side effects of SSRIs are usually mild and manageable, although once in a while a sensitive person gets a severe reaction. Like most antidepressants, SSRIs may cause nausea, dizziness, or dry mouth, not to mention a range of sexual-function side effects, including decreased sexual interest (in men), increased sexual interest (in women), ejaculation problems, impotence, or menstrual changes.

During the first couple of weeks of taking them, you may feel sick and more anxious. Some of these tablets can produce nasty indigestion, but you can usually stop this by taking them with food. More seriously, as noted above, they may interfere with your sexual function. There have been reports of episodes of aggression, although these are rare.

The list of side effects looks worrying - there is even more information about these on the leaflets that come with the medication. However, most people get a small number of mild side-effects (if any). The side effects usually wear off over a couple of weeks as your body gets used to the medication. It is important to have this whole list, though, so you can recognize side effects if they happen. You can then talk them over with your doctor. The more serious ones - problems with urinating, difficulty in remembering, falls, confusion - are uncommon in healthy, younger or middle-aged people.

The most common side effects with Zoloft, launched in 1991, and Paxil, introduced in 1993, are insomnia, diarrhea, tremor, and drowsiness. If you get side effects while taking either of these, your doctor may switch you to Wellbutrin, as long as you don't have any of the conditions that might make you vulnerable to seizures with this drug (such as previous severe head injury or epilepsy). And like Prozac, Zoloft, Paxil, Celexa, Lexapro and other SSRIs, it can produce mild mania in some people with a genetic tendency in that direction.

Sexual dysfunction may occur in SSRI users from one to five percent according to the drug companies (although actual incidence of the problem may be much higher, critics charge -- as high as 40 percent).

It is common, if you are depressed, to think of harming or killing yourself. Tell your doctor - suicidal thoughts should pass once the depression starts to lift.

Drug Interactions

Given together, tryptophan and any of the SSRIs may cause headache, nausea, sweating, and dizziness. Taking an SSRI within two weeks of an MAOI (such as Marplan or Parnate) may cause serious side effects; you should wait at least two weeks between stopping MAOIs and starting an SSRI, or at least five weeks after stopping an SSRI and starting an MAOI.

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Combining Paxil and warfarin may cause excess bleeding. If you're taking cimetidine, which can cause an increase in the blood levels of Paxil, your dosage of Paxil should be adjusted.

Research suggests that Zoloft, unlike MAOIs or tricyclics, doesn't necessarily appear to cause problems when mixed with alcohol. However, Zoloft's manufacturers don't recommend the combination.

There are no known dangerous reactions between nonprescription drugs and Zoloft, but because it's theoretically possible, be sure to talk to your doctor about any other drugs you take. Combining Zoloft with either digitoxin (Crystodigin) or warfarin (Coumadin) may cause unwanted side effects.

Pregnancy and Breast-Feeding

It is always best to take as little as possible in the way of medication during pregnancy, especially during the first 3 months. However, some mothers do have to take antidepressants during pregnancy. The evidence so far is that their babies don't show any harmful effects from this.

Most SSRIs, however, haven't been studied in nursing mothers or pregnant women. Animal studies have suggested that Zoloft may cause developmental problems or decrease survival of offspring. Animal studies with Paxil haven't revealed any birth defects.

Postpartum Depression

After giving birth, it is not uncommon for a woman to experience some level of depression - this is called post-natal depression or postpartum depression. It usually gets better with counseling and practical support.

However, if you are unlucky enough to get it badly, it can exhaust you, stop you from breast-feeding, upset your relationship with your baby and even hold back your baby's development. In this case, antidepressants can be helpful.

What about the baby? He or she will get only a small amount of antidepressant from mother's milk. Babies older than a few weeks have very effective kidneys and livers. They are able to break down and get rid of medicines just as adults do, so the risk to the baby is very small. Some antidepressants are better than others in this regard and it is worth discussing this with your doctor or pharmacist. On balance, bearing in mind all the advantages of breast-feeding, it seems best to carry on with it while taking antidepressants.

Other Disorders

The SSRIs may be an effective treatment for other disorders besides depression. Some have been approved for treating various anxiety disorders including panic attacks, obessive-compulsive disorder, ptsd and social anxiety disorder. Some are used to treat eating disorders and chronic pain.

Antidepressant Withdrawal

Antidepressant drugs don't cause the addictions that you get with tranquilizers, alcohol or nicotine, in the sense that:

You don't need to keep increasing the dose to get the same effect
You won't find yourself craving them if you stop taking them

However, there is a debate about this. In spite of not having the symptoms of addiction described above, up to a third of people who stop SSRIs and SNRIs have withdrawal symptoms. These include:

Stomach upsets
Flu like symptoms
Anxiety
Dizziness
Vivid dreams at night
Sensations in the body that feel like electric shocks

In most people these withdrawal effects are mild, but for a small number of people they can be quite severe. They seem to be most likely to happen with Paxil and Effexor. It is generally best to taper off the dose of an antidepressant rather than stop it suddenly.

Some people have reported that, after taking an SSRI for several months, they have had difficulty managing once the drug has been stopped and so feel they are addicted to it. Most doctors would say that it is more likely that the original condition has returned.

The Committee of Safety of Medicines in the UK reviewed the evidence in 2004 and concluded "There is no clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome according to internationally accepted criteria."

Last updated: Jan. 2005

Sources:

"From Making the Prozac Decision: A Guide to Antidepressants," by arrangement with RGA Publishing, Inc."
Antidepressant discontinuation reactions.
British Medical Journal 1998; 316:1105-1106 (11 April)
Depression in primary care, Vol 2. "Treatment of Major Depression," US Department of Health and Human Services, 1993 (Clinical practice guidelines No. 5).
"Antidepressants," Royal College of Psychiatrists, Dec. 2004

Selective Serotonin Reuptake Inhibitors (SSRIs)

General information about the SSRIs, their relative merits, and their side effects.

Prime Candidates

Which SSRI Is Best?

SSRI Antidepressants, Suicidal Feelings and Young People

Medical Cautions

Side Effects

Drug Interactions

Pregnancy and Breast-Feeding

Other Disorders

Antidepressant Withdrawal

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