SSRIs Can Have Dangerous Interactions With Other Drugs

Selective serotonin reuptake inhibitors (SSRIs) are used by millions of Americans every year to treat depression, obsessive compulsive disorder and other psychiatric diseases.

In 2006 alone, 70 million prescriptions were filled in the U.S. for SSRIs. Two of these drugs were among the 10 most-prescribed drugs in that year: LEXAPRO (5th) and ZOLOFT (10th).

There are six SSRIs sold in the U.S.: citalopram (CELEXA), escitalopram (LEXAPRO), fluoxetine (PROZAC), fluvoxamine (LUVOX), paroxetine (PAXIL) and sertraline (ZOLOFT). Because they are often taken with other medications, it is important to recognize potentially dangerous drug interactions.

Do all SSRIs interact similarly with other medications?
No; the various SSRIs have different kinetic interactions, which occur when one drug causes the blood level of another drug to be abnormally high or low.

The SSRI most likely to cause a kinetic drug interaction is fluvoxamine because it inhibits several of the most important drug-metabolizing enzymes, including CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Most medications are broken down by one or more of these enzymes, so it is virtually impossible for a person taking fluvoxamine to avoid drug interactions when also taking other medications, resulting in abnormally high blood levels of these other drugs.

The one drug-metabolizing enzyme that fluvoxamine seems to have little effect on is CYP2D6, but the functions of that enzyme are markedly inhibited by other SSRIs such as fluoxetine and paroxetine.

The three other SSRIs have only mild effects or no effect on drug-metabolizing enzymes and are less likely to cause kinetic interactions.

Table 1 shows the enzymes affected by each of the SSRIs and the differing degrees of kinetic interactions of these drugs. Citalopram, escitalopram and sertraline have the lowest potential for kinetic interactions among SSRIs because they have a weak affect on only one drug-metabolizing enzyme. However, these drugs are not necessarily preferred to other SSRIs – especially if the patient is either not taking any other drug or the specific SSRIs do not interact with other drugs a patient is taking.

Does the effect of SSRIs on serotonin cause other kinds of drug interactions?
Yes. The desired effect of SSRIs is to increase the level of serotonin in the brain. Unfortunately, this action can result in excess serotonin elsewhere in the body, especially if SSRIs are used along with other drugs that also increase serotonin levels. (These interactions fall into the category of “Pharmacologic Drug Interactions” described in the November 2007 issue of Worst Pills, Best Pills News.)

All SSRIs have similar effects on serotonin levels, but their serotonin-related interactions vary. Some of the serotonin-related drug interactions of SSRIs are life-threatening, while others are less dangerous (See Table 2, which lists both kinetic and the serotonin-related interactions).

The primary danger of increased serotonin levels is a side effect called “serotonin syndrome” – a rare but serious condition that occurs when drugs interact to create too much serotonin in the body. In mild forms, the condition may be simply a nuisance. In severe cases, seizures, coma and death can occur. Symptoms of severe serotonin syndrome include jerking of muscles, rigid muscles, tremor, overactive reflexes, fever, sweating, shivering, confusion and agitation.

Are there any antidepressants available that produce fewer drug interactions than SSRIs?
Yes. By and large, the older tricyclic antidepressants such as amoxapine (ASENDIN), desipramine (NORPRAMIN), doxepin (SINEQUAN), imipramine (TOFRANIL), nortriptyline (AVENTYL), protriptyline (VIVACTIL) and trimipramine (SURMONTIL) have fewer drug interactions than the SSRIs. Unlike SSRIs, tricyclic antidepressants generally do not inhibit drug metabolizing enzymes.

However, some tricyclic antidepressants have more side effects than SSRIs. An example of this is amitriptyline (ELAVIL), a long-time Do Not Use drug in Worst Pills, Best Pills, which produces more harmful side effects than any other drug in its family.

What You Can Do
Patients requiring SSRI antidepressants in addition to other drugs should provide their prescriber and/or pharmacist with a full list of drugs he or she is on to avoid potentially harmful drug interactions.

Patients taking SSRIs should tell their physician if they develop any symptoms of serotonin syndrome. This is especially important if patients develop several symptoms of serotonin syndrome.