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Reviews

Two Techniques to Lessen the Risk of Drug Side Effects

Timothy B. McCall, M.D.

Using the Smallest Effective Dose

It is sometimes possible to increase the safety of a drug by taking it at a lower dose. When deciding on the dose of a drug, consider the following:

• For most drugs, there is a trade-off between effectiveness and side effects. If you take too small a dose, they won’t work. Higher doses are more effective but the risk of side effects rises. The effectiveness of some drugs plateaus with increasing doses while side effects continue to increase. For non-life-threatening situations, it often makes sense to start with a small dose of a drug and see how you do. If you are tolerating its side effects and the drug is effective, fine. If you're tolerating it and it's not as effective as you'd like, the dose can be increased. If you're not tolerating it, you can get off it and be thankful that you weren't taking a higher dose from the start.
• Doses of drugs once recommended are now considered too high. The sleeping pill Halcion, for example, was once commonly prescribed at the dose of half a milligram (mg). They no longer even manufacture pills that big. The largest currently available is half that dose and most experts feel that even that’s dose is too much for many people. Not long ago, many doctors prescribed a 50 mg dose of the blood pressure medicine hydrochlorothiazide (HCTZ), once or even twice per day. Today many patients are successfully treated with 12.5 mg per day, some with only 6.25 mg. One study found that a lower dose was equally effective in reducing blood pressure but didn’t cause a drop in the blood potassium level, a common and potentially dangerous side effect.
• Resist increasing the dose of a drug until you've given it enough time to work. It often takes a week or two for a drug to reach its full effectiveness. This is especially true for pain-relieving non-steroidals and for drugs for high blood pressure. In the thiazide diuretic study mentioned above, the drugs were increasingly lowering the blood pressure eight weeks after they were started. The dictum, particularly true for the elderly, is “start low and go slow.”
• By using non-drug therapy along with drugs, it is sometimes possible to reduce the dose even further. Arthritis, for example, can be helped by exercise, weight loss, hot packs before activity, ice packs afterwards and the use of canes and walkers. High blood pressure may respond to exercise, weight loss, less salt in the diet and stress reduction. Some people can get off drugs entirely when they make changes in their lifestyle.

Using Drugs for the Shortest Effective Duration

The longer you're on a drug, the more likely it is to cause side effects. Consider the example of choosing the optimal length to treat women for bladder infections. As recently as a few years ago, women with uncomplicated bladder infections were usually treated for 10 to 14 days with antibiotics.

This treatment was quite effective but a significant number of women developed diarrhea, yeast infections or other side effects from the antibiotic. About 10 years ago, in an effort to reduce the rate of side effects, single dose therapy became popular but there have been concerns that a single dose of antibiotic is not as effective a cure.

A doctor from the University of Lund in Sweden examined dozens of studies that compared antibiotics given for different lengths of time. He compared single dose treatment, with three days of treatment, with five days or greater of treatment. For sulfa drugs, for example, he found the following results:

	cure rate	side effect rate
single dose	89.0%	7.4%
three days	94.6%	6.7%
five days or more	95.5%	24.9%

From these results, he concluded that for sulfa drugs, three days of treatment was optimal, balancing effectiveness with side effects. The best length of treatment, of course, may vary from drug to drug.

Be particularly careful when the doctor wants to put you on medicine for what may be the rest of your life, as is common for high blood pressure or for elevated cholesterol. In these instances, you want to be sure you need the drug and have pursued non-drug options fully.

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