Feeling Good: The New Mood Therapy
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640
gabapentin (Neurontin)
651
lamotrigine (Lamictal)
652
lithium (Eskalith)
617
valproic acid (Depakene) and divalproex sodium (Depakote)
634
aMany of the antidepressants are now available as generic brands (see Table 20–1). Only the trade names of the original brands are listed in this table.
Costs of Antidepressant Medications
We often think that more expensive means better, but this is not always the case with antidepressants. As it turns out, there are some very dramatic differences in the costs of the different antidepressants that do not reflect differences in effectiveness. In other words, sometimes a drug that is much cheaper will be just as effective, or even more effective, than another drug that costs more than forty times more. Therefore, if the cost of the medication is a concern for you, then a little education may save you a great deal of money.
The costs and doses of the most commonly prescribed antidepressants and mood stabilizing agents are listed in Table 20–1 on pages 518–523. Note that I am quoting the cheapest wholesale price for each antidepressant drug in Table 20–1. The retail price you pay for the same medication at the drug store will probably be higher. If you choose a different brand of the same medication, it may be higher yet. Please keep this in mind in all of the following discussions of drug costs.
If you compare the costs of the different types of drugs and the different doses, it will provide you with some interesting information. You will see, for example, that many of the older tricyclic and tetracyclic drugs are now available generically. When a drug is first manufactured, the drug company gets a seventeen-year patent so it can market the drug exclusively. The relatively high cost of the newer drugs that are still protected by patents helps to cover the costs of the research, development, and testing. After the patent expires, other companies can compete and manufacture the drug, and so the price goes down drastically.
You will see in Table 20–1 that these so-called “generic” medications are much less costly than the newer drugs that are still under patent. Let’s assume that your doctor prescribes a dose of 150 mg per day of imipramine for your depression. The cost of the three 50-mg pills you will take will be less than 10 cents per day, or roughly $3 per month. This is because imipramine is now available generically. In contrast, if your doctor prescribes two 20-mg Prozac pills per day, your cost will be nearly $4.50 per day or $135 per month—over forty times more than the imipramine. And if she or he prescribes four Prozac pills—the maximum dose—your cost will be $270 per month. This is a steep price for many people. Don’t forget these are wholesale prices—you may pay even more.
Is Prozac forty to a hundred times more effective than imipramine? Definitely not. As you will learn below, most of the antidepressants tend to be comparably effective. Research studies have not confirmed that Prozac is any more effective than imipramine—in fact it may be slightly less effective for severe depressions. However, the big advantage of Prozac is that it has fewer side effects (such as dry mouth or sleepiness) than imipramine. This may be quite important to some people and may make the price difference worthwhile. On the other hand, you will learn that Prozac has some side effects of its own, such as problems with sexual functioning (difficulty achieving orgasm) in as many as 30 percent to 40 percent of patients, and possibly more. People who don’t like this particular side effect might actually prefer the cheaper medication.
You will also see in Table 20–1 that pills which contain a larger quantity of a particular drug are not necessarily more expensive than pills which contain a smaller quantity. This is especially true if you are taking one of the newer drugs that is still under patent, so you may be able to save money by buying pills containing a larger dose. For example, you will see in Table 20–1 that the cost of a hundred nefazodone (Serzone) tablets is $83.14 for the 100-mg size. The price for a hundred tablets of the larger sizes (150 mg to 250 mg) is exactly the same. So if you are taking a large dose, say 500 mg per day, you could either take five of the 100-mg pills (cost of $4.16 per day) or two of the 250-mg pills (cost of $1.66 per day).
In addition, you can often save money by buying a larger size of a medication and breaking a pill in half. So to continue with the same example, if you are taking 250-mg pills, it will cost you approximately half as much if you purchase 500-mg pills and break them in half.
For the generic drugs, things are different. On the average, the costs are low overall and depend on the dose, and the savings at higher doses are not so drastic. In addition, because so many different companies manufacture these drugs, the prices for the different doses are not always entirely consistent—sometimes a smaller dose will actually cost more than a larger dose. For example, look at the pricing structure for the tricyclic antidepressant, desipramine (trade name Norpramin) on page 518. You will see that a hundred of the 10-mg pills cost $15.75, while a hundred of the 25-mg pills costs only $7.14. So the larger pill is actually cheaper. This is because different companies manufacture the two sizes.
To make things even more confusing, there are ether cases where a larger dose costs substantially more and you can save money by taking a smaller size. For example, take another look at the costs of desipramine on page 518. You will see that a hundred 75-mg desipramine pills cost $12.42, and that a hundred 150-mg desipramine pills cost $109.95 (again, because of different manufacturers). So you can save lots of money by taking two 75-mg pills instead of one 150-mg pill. Again, this is because different companies manufacture the 75-mg and 150-mg sizes. This may strike you as odd, but the pricing structure in some instances is completely out of whack.
Table 20–1. Names, Doses, and Costs of Antidepressant Medications
aIf your doctor prescribes the chemical or “generic” name on the prescription, your pharmacist can often substitute an inexpensive brand that can be much less costly than the trade-name drugs.
bOnly the brand name of the original drug is listed. Generic versions of these drugs have their own brand names.
cCost source: Mosby’s GenRx. 1998 (8th Edition): The Complete Reference Guide for Generic and Brand Drugs. St. Louis: Mosby. The average wholesale price for 100 pills of the least expensive brand currently available is listed. This is the price your local retail pharmacist would have to pay for the product without any special discounts. Your cost will be more and will depend on the markup by your pharmacist.
dThe doses would be used for the treatment of an episode of depression. Some patients may benefit from doses higher or lower than the normal range. If prolonged treatment is necessary following recovery, a smaller dose may be sufficient. Always consult with your doctor before changing the dose.
eThese are drugs with generic brands available in 1998. More of the current antidepressant drugs will become available as generic brands when their original drug patents expire.
fMaprotiline should not exceed 175 mg per day if a patient is kept on the drug for an extended period. The manufacturer suggests that the dose should not exceed a maximum of 225 mg for periods of up to six weeks.
gThe doses of several mood stabilizers must be monitored by blood tests and will therefore be highly individualized for each patient, depending on your age, gender, weight, diagnosis, and individual metabolism, as well as other medications you may be taking.
hHigher doses may be required during acute mania because the body appears to metabolize lithium more rapidly during manic episodes.
iThis is also available as Depakote Sprinkle (125 mg), which can be sprinkled onto food.
jThe price of the 25 mg Lamictal was not listed in Mosby’s GenRx (1998 edition).
kThis is the recommended dose range for epilepsy when given in conjunction with valproic acid. When given alone, the recommended dose range for epilepsy is 300 mg to 500 mg per day.
If you or a family member is taking an antidepressant, make sure you study Table 20–1 and discuss these cost issues wit
h your druggist. A little quick and easy research on your part may result in large savings.
Another important point, not illustrated in the table, is that the cost of the same generic drug and dose can vary greatly because the generics often have so many different manufacturers. In Table 20–1, I have always listed the least costly generic brand of each pill; other more costly versions of the same pill are not listed. For example a hundred 50-mg imipramine pills manufactured by the drug company HCFA FFP will cost only $3.08. Because this was the lowest-priced generic brand, I listed it in Table 20–1. In contrast, a hundred of the same size imipramine manufactured by Novartis, another drug company, will cost $74.12—more than twenty times more. Keep in mind that if your doctor prescribes the antidepressant by its chemical name (as listed in Table 20–1), your druggist will have the freedom to provide you with the least costly generic brand if one is available.
My goal is not to promote any one drug or class of drug. All antidepressants have merit, and they all have some drawbacks. The key point is this: more expensive does not always mean better. If you review the costs of these drugs, you can work with your doctor and pharmacist to choose the medication and brand that will make the most sense for you.
Specific Kinds of Antidepressants
Tricyclic and Tetracyclic Antidepressants
The first drugs listed in the Table of Antidepressants on page 514 are called “tricyclic” and “tetracyclic” antidepressants. The tricyclic and tetracyclic antidepressants differ slightly in their chemical structures. “Tri” means three and “tetra” means four. “Cyclic” refers to a circle or ring. The tricyclic compounds consist of three linked molecular rings, while the tetracyclics consist of four.
You will see that eight tricyclic and two tetracyclic antidepressants are listed in the Table of Antidepressants. The eight tricyclic drugs include amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Aventyl), protriptyline (Vivactil), and trimipramine (Surmontil). These eight tricyclic drugs used to be the most widely prescribed antidepressants. They are still among the most effective of all the antidepressants. Many of them are also the least expensive because generic brands have become available. However, tricyclics tend to have more side effects than the newer drugs, and so they are less popular than they used to be. By the same token, they have been prescribed for several decades and have a long track record of reasonably good effectiveness and safety.
The two tetracyclic antidepressant medications listed on the table are called amoxapine (Asendin) and maprotiline (Lu-diomil). These two tetracyclics were synthesized and released after the tricyclics had been in use for some time. It was hoped that they would represent significant improvements in treatment, either because of increased effectiveness for certain types of depression, or because of fewer side effects.
Unfortunately, these expected improvements did not really materialize. For the most part, the effectiveness, mechanism of action, and side effects of the eight tricyclic and the two tetracyclic antidepressants are quite similar.
Doses for the Tricyclic and Tetracyclic Antidepressants. Table 20–1 on pages 518–523 lists the costs and dose ranges of the eight tricyclic and the two tetracyclic antidepressant medications. As noted above, many of them are inexpensive because they are no longer on patent, and so generic brands are readily available. Don’t be fooled into thinking the cheaper antidepressants are less effective, however. A number of studies suggest they may be slightly more effective than many of the newer antidepressants such as Prozac.
The most common error your doctor is likely to make is to prescribe a dose of a tricyclic antidepressant that is too low. This statement may run against your grain if you feel you should take the lowest dose possible. In the case of tricyclics, if the prescribed dose is too low, the medication will not be effective. If you insist on taking a dose that is too low, you may be wasting your time. It simply will not help you. On the other hand, dosages above those recommended in Table 20–1 can be dangerous and may lead to a worsening of your depression.
Having said that, let me also say that there are cases in which people do respond to doses that are smaller than those listed (especially the elderly), and there are also times when people may need larger doses. One reason for this is that there can be considerable differences in how rapidly people metabolize antidepressant drugs. These differences are partially genetic, and are due to levels of certain enzymes in your liver, as described previously. If you are a “fast meta-bolizer” you will need a larger dose to maintain an effective blood level, and if you are a “slow metabolizer” you will need a smaller dose. In addition, you will learn below about other drugs that can make tricyclic blood levels fall and lose their effectiveness or increase and become more toxic.
If you suspect you may be taking an inappropriately large or small dose, review the dose ranges in Table 20–1 and discuss your concerns with your physician. Blood-level testing for most of the tricyclic antidepressants is readily available, so your doctor may order a blood test to make sure that the dose you are taking is neither too high nor too low for you.
The best way to begin taking a tricyclic medicine is to start out with a small dose and to increase the amount each day until a dose within the normal therapeutic range is achieved. This buildup can usually be completed within one or two weeks. For example, a typical daily dose schedule for imipramine, one of the most commonly prescribed tricyclic antidepressant drugs listed in Table 20–1, might be the following:
Day one—50 mg at bedtime;
Day two—75 mg at bedtime;
Day three—100 mg at bedtime;
Day four—125 mg at bedtime;
Day five—150 mg at bedtime.
You and your doctor may prefer to build up the dose a bit more gradually. Doses of up to 150 mg per day can be conveniently taken once a day at night. The antidepressant effect will last all day long, and the most bothersome side effects will occur at night, when they will be least noticed. If doses larger than 150 mg per day are required, the additional medicine should be given in divided doses during the daytime.
For the more sedating tricyclic antidepressants, up to half the maximum indicated dose may be taken on a once-per-day basis before bedtime. This dosage promotes sleep. Several of the tricyclic antidepressants, including desipramine, nortriptyline, and protriptyline, can be stimulating. They can be taken in divided doses in the morning and at noon. If taken too late in the day, they may interfere with sleep.
If you reduce the dose of a tricyclic antidepressant or if you decide to stop taking the medicine, it is best to reduce the dose gradually and never abruptly. Sudden discontinuation of any antidepressant may result in side effects. These include upset stomach, sweating, headache, anxiety, or insomnia. Usually, you can go off a tricyclic antidepressant safely and comfortably by tapering the dose gradually over a one- or two-week period.
Side Effects of the Tricyclic Antidepressants. The most frequent side effects of the tricyclic antidepressants are listed in Table 20–2 on pages 530–532. You will see in this table that all the tricyclic antidepressants have quite a number of side effects, and this is their greatest drawback. The most common side effects include sleepiness, dry mouth, a mild hand tremor, temporary light-headedness when you suddenly stand up, weight gain, and constipation. They can also cause excessive sweating, difficulties with sex, twitches or jerking when you fall asleep at night, and a number of other effects listed in Table 20–2. Most of these side effects are not dangerous, but they can be annoying.
You learned earlier that the side effects of antidepressant drugs can be predicted if you know how strongly they block histamine receptors, alpha-adrenergic receptors, and muscarinic receptors (also called cholinergic receptors) in the brain. You can see from Table 20–2 that each antidepressant has a different profile of side effects depending on its action on these three receptor systems in the brain.
Blockade of the brain’s histamine
receptors makes you hungry and sleepy. Table 20–2 indicates that four of the tricyclic antidepressants (amitriptyline, clomipramine, doxepin, and trimipramine) have rather strong effects on the histamine receptors. Consequently, these four antidepressants are more likely to make you feel sleepy and hungry. If you are having trouble sleeping, this side effect could be a benefit, but if you are already feeling sluggish and unmotivated, these drugs may make things worse for you. If you have been losing weight due to depression, the appetite boost could be beneficial. However, if you are overweight, you might have to pay more attention to your diet and exercise more in order to avoid weight gain, which can be demoralizing. Since there are now many available antidepressants that do not cause weight gain, it might be better to switch to one of them. You can see in Table 20–2 that three of the tricyclics (desipramine, nortriptyline, and protriptyline) have only weak effects on the histamine receptors. These antidepressants will be less likely to cause sleepiness and weight gain. There are many antidepressants in other categories as well that do not cause sleepiness and weight gain.
You may also recall that blockade of the brain’s alphaadrenergic receptors causes a drop in blood pressure. This can result in temporary light-headedness or dizziness when you suddenly stand up because your leg veins become more relaxed, and blood temporarily pools in your legs. As a result, your heart temporarily does not have enough blood to pump up to your brain, and so your vision may get black and you may feel dizzy or woozy for a few seconds. Antidepressants with relatively strong effects on the brain’s alpha-adrenergic receptors will be more likely to cause dizziness when you suddenly stand up. You will see in Table 20–2 that many tricyclics have strong effects on alpha-adrenergic receptors, but that two of them (desipramine and nortriptyline) have only weak effects on them. Consequently, these two drugs are less likely to cause dizziness or a drop in blood pressure.