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How the Various Types of Drugs Help With Mental Problems and Most Common Side Effects General: What Psychoactive Drugs Do in the Brain. Mental problems may occur because of imbalances in the brain. The brain is an extremely complex organ whose "working parts" are nerve cells, called neurons. There are tens of billions of these neurons, and each neuron communicates with other neurons, in almost all cases with many others. Chemicals are released by one neuron and received by another in order to bring about the communication; this, on a microscopic scale, is like smelling a rose; the rose gives off chemicals, and receptors in your nasal cavity are excited by the chemicals, producing an odor. In the brain there are about 100 known chemicals that produce this communication between neurons, and there may be at least that many more that we have not yet identified. If these chemicals get out of balance, the communication between neurons may be distorted and a mental problem may result. The chemicals are called "neurotransmitters" because what they do is transmit excitation from one neuron to another. This name is a little misleading because some "neurotransmitters" decrease, rather than increase, transmission. Thus some neurotransmitters are called excitatory, and some are called "inhibitory" because the latter tend to stop excitation. If the excitatory and inhibitory neurotransmitters get out of balance, mental problems may follow. For example, people who are depressed may have too little excitatory, or too much inhibitory, neurotransmitter present. Another possibility is that the receptors for the neurotransmitters are too sensitive, or not sensitive enough. People with some types of schizophrenia, or with panic disorder, may have the opposite problem with their neurotransmitters: too much excitatory, or too little inhibitory. Most psychoactive drugs are designed to correct excitatory-inhibitory imbalances. They can do this in several ways. First, they can increase the amount of a neurotransmitter in the brain by inserting it directly, by increasing its production, or by preventing the breakdown or "reuptake" of a neurotransmitter that otherwise occurs after the "message" has been sent to the next neuron. Second, they can increase the effectiveness of the neurotransmitter by stimulating the same receptors as the neurotransmitter. Third, they can decrease the effectiveness of a neurotransmitter by blocking its reception; this class of psychoactive drugs plugs up the receptor that otherwise would be activated by the neurotransmitter. This is like spraying a deodorant to cover up bad smells. Fourth, psychoactive drugs can decrease the effectiveness of a neurotransmitter by breaking it down more rapidly than it would otherwise break down, thus limiting its action. Still other drugs are psychoactive, but nobody knows why. We probably do not understand completely how any psychoactive drug works, partly because we don't understand completely what is wrong in the first place when a person is anxious, depressed, schizophrenic, or has some other psychological problem. If the mode of action of a drug is thought to be known, however, the theory is usually that its action fits into one of the four categories mentioned in the preceding paragraph. One class of psychoactive drugs is called tricyclic antidepressants, or TCAs. They fall into the first class above, and are "tricyclic" because they have a 3-ring chemical structure; their primary action is to block the reabsorption of two neurotransmitters, called norepinephrine and serotonin. The tricyclics also affect other neurotransmitters, and different members of the tricyclic class have different "secondary" effects. Another antidepressant, maprotiline, has a 4-ring structure, and is thus called "tetracyclic." Its action is primarily on norepinephrine, with no appreciable effect on serotonin, and it seems to be especially effective when anxiety and depression are combined. When more norepinephrine and serotonin are available to excite neurons, the mood of most depressed patients improves. TCAs do not, however, improve the mood of nondepressed people. Another class of antidepressants is called "monoamine oxidase inhibitors," MAOIs for short. These drugs counteract the effect of monoamine oxidase, which otherwise breaks down norepinephrine and serotonin. Although the way MAOIs act is not the same as the way TCAs act, the MAOIs also fall into the first class of psychoactive drug because they increase the available amounts of these two neurotransmitters. A third class of antidepressant is the serotonin-specific reuptake inhibitors, or SSRIs. These do just what their name implies: they prevent the reuptake of serotonin, thus making more of this excitatory neurotransmitter available for stimulating neurons. Because they act on only one neurotransmitter, their side effects are fewer, making them safer for use with patients who have medical problems. Some researchers now believe that both serotonin and another treatment for depression, electroconvulsive shock, increase the creation of new cells in the brain, thus relieving the depression. If they are correct, the emphasis on drug development could shift from drugs that affect neurotransmission to drugs that stimulate the creation of neurons in the brain. Side effects of antidepressant medications. The antidepressant drugs available at this time are crude tools for use on something as complex and delicate as the brain. They are a little like operating on a Rolex watch with a tack hammer; they may get the watch running again, but some incidental damage is possible. If an antidepressant improves the balance of from one to three or four neurotransmitters, out of perhaps a hundred, and if it acts on those neurotransmitters throughout the brain, it is not surprising that there may be some bad effects along with the good effects. We are very fortunate that the good effects usually outweigh the bad effects by so great a margin. It is difficult to limit the effects in the brain to exactly and only what we want to achieve; it is also very difficult to confine the effects to the brain. Drugs first go into the stomach, into muscle, or directly into the blood (if injected) and then into the brain. Some drugs cannot get into the brain from the blood; we all have what is called a "blood-brain barrier" that helps to keep microorganisms and poisons out of the brain. For many psychoactive drugs, the blood level must be higher than we would like before enough drug enters the brain to be effective. This means that the drugs have an opportunity to act on many organs besides the brain, and side effects thus occur both in the brain and in other susceptible parts of the body. Different antidepressants may have different side effects, and patients should always consult their physicians or pharmacists to find out exactly what to expect. However, some of the more common side effects of antidepressants include dry mouth, constipation, anxiety, heart and circulatory symptoms, and gastric upset. In a few cases, seizures have occurred. This is only a partial list; a complete list might make one hesitate to take antidepressants, but refusing to take a prescription recommended and monitored by a mental health professional would be a serious error. Most of the side effects are infrequent, and those that do occur can usually be managed via other medication or by adjusting dosages. The intended effects, on the other hand, may be dramatic and life-enhancing, as is the case for other kinds of psychoactive drugs. The side effects are a serious, but usually manageable, concern. Medication is prescribed only if the effects of the mental illness are much more serious and less manageable without medication. Check our table for a comparison of the various antidepressants available. Because anxiety is so prevalent in our society, drugs to alleviate anxiety are used more often than any other kind. Unfortunately, many of these "medications" are not prescribed by physicians. Anxious people may drink alcohol or use street drugs to alleviate their anxiety, and such "self-prescribed" drug use can be very dangerous. The most popular prescription drugs for anxiety are the benzodiazepines (BZDs), with well-known brand names like Valium, Librium, and Xanax. These drugs belong in the second class of drugs above, those that enhance the action of a neurotransmitter without changing its amount. The BZDs are thought to increase the activity of a neurotransmitter usually called GABA (the long name, gamma-Aminobutyric acid, is hard to deal with). GABA is an inhibitory neurotransmitter, so increasing its effectiveness decreases overactivity in the brain, and hence tends to decrease anxiety. The older anti-anxiety drugs were barbiturates. Their known mechanism of action also involves increasing the effectiveness of GABA, but the barbiturates probably have more widespread effects that are not well understood. Barbiturates are much more addictive than benzodiazepines, are more dangerous in large doses, and have more side effects. Thus prescribing them for the control of anxiety is seldom, if ever, justified. Side effects of anti-anxiety medications. Benzodiazepines can be addictive, but the addiction is usually mild, and the withdrawal effects are usually moderate and short-lived. The side effects of benzodiazepines are usually so mild that anxious patients can take therapeutic doses for years with no noticeable negative effects. However, gradual reduction of the dosage is recommended every few months if anxiety is no longer present to see whether medication is still required. Patients are probably more likely to continue benzodiazepines for too short a time rather than too long a time because of misguided fears of side effects or a feeling that taking medication is a weakness, rather than a strength. Barbiturates are much more addictive than benzodiazepines, and overdoses are far more dangerous. Withdrawal effects, like the addictive possibilities, are more severe. With any drug, withdrawal effects are more severe after a drug has been taken for a longer time and at higher doses. There are also large differences between people in their reactions to drugs and to the drugs' withdrawal. Overdoses of barbiturates suppress respiration and can be fatal. Even with relatively safe benzodiazepines, as with all psychoactive drugs, great care should be taken to comply with medical advice about taking the medication, to report any side effects, and to take any recommended tests to check the physical effects of the medication. Check our table for a comparison of the various anti-anxiety medications available. Medications for bipolar disorder. A bipolar patient who is depressed may initially receive treatment similar to that prescribed for a depressed patient who is not bipolar. If the patient is manic, the most common prescription is for Depakote (divalproex sodium), a relatively new drug that is not yet available as a generic drug. It works more quickly than the traditional drug, lithium. Its mode of action is unclear, but probably involves an effect on the neurotransmitter, GABA (see antianxiety drugs, above). Side effects of medications for bipolar disorder. When antidepressant medications are administered, their effects are the same for bipolar patients as for depressed patients (see above). Lithium is more dangerous than Depakote and requires blood tests as prescribed to adjust its blood levels and guard against kidney damage and other side effects. Depakote (also "Valproate" in a slightly different form) has caused liver damage, but apparently only in infants who were also taking other medication. The usual cautions apply, however: always follow medical advice about taking any medication. Even the safest medications may interact with other medications to cause serious problems. Check our table for a comparison of the various medications available for bipolar disorder. These drugs are most simply and appropriately called "antipsychotic drugs," but they are sometimes called "major tranquilizers," or "neuroleptics," two names that misrepresent their function. They are not primarily tranquilizers, and should not be used as antianxiety drugs except in very rare circumstances. They do not just reduce psychic or neural tension, so they are not just neuroleptics. They are dramatically effective in reducing psychotic symptoms like hallucinations and delusions, and they do usually calm agitated psychotic patients. Antipsychotics are most frequently and appropriately used to reduce the symptoms of schizophrenia. Unfortunately, antipsychotics, like the other psychotropic medications, do not "cure" the underlying conditions that lead to the mental problem. Hence patients must usually continue the medication for long periods of time. In some cases antipsychotic medication is prescribed for temporary relief of extreme mania, for depressed patients who also have psychotic symptoms like hallucinations and delusions, and in low doses for disturbed demented patients. Different antipsychotic drugs have somewhat different effects that are best described in connection with the individual drug, but all of the antipsychotic drugs now available share several possible side effects. Side effects of antipsychotic medications If antipsychotic drugs are properly prescribed, their benefits are greater than their risks. The latter, however, can be substantial. A side effect most often seen in younger males is muscular spasms ("dystonia"), usually in the head and neck. Antidotes correct the problem in seconds, and antidotes are now often prescribed right along with the antipsychotic medication. A second, probably related, side effect is Parkinsonian Syndrome, involving tremor, rigidity, and other symptoms. This side effect is treated by the same antidotes as the dystonia, which supports the belief that the same, or a similar, mechanism underlies both effects. A third side effect could also be related to the first two: an inability to sit still, a restlessness almost irresistible, called akathisia. This effect is so disturbing that it tempts many patients to discontinue their medication. Although it is more difficult to treat than the preceding symptoms, it may respond to benzodiazepines like diazepam (Valium is probably the best-known brand). Yet a fourth side effect may be related to the first three: patients sometimes become lethargic, move very little, and seem apathetic about the situation. The same drugs that counteract the first three side effects also counteract this one. Long-term use of an antipsychotic medication can lead to the side effect that is of most concern because it is common, unpredictable, and hard to counteract: tardive diskinesia (TD), which involves involuntary and purposeless movements, most often of the mouth, tongue, neck, trunk, hands, or feet. TD is sometimes self-correcting after the antipsychotic drug is stopped, but it can also occur when the antipsychotic drug is stopped. The step that is most often successful in correcting TD is increasing the dosage slightly, and other medications are helpful in some cases (levodopa, for example). Finally, in rare cases a sixth, life-threatening, side effect may occur. It is called neuroleptic malignant syndrome. The patient becomes rigid, has a rapid heartbeat, fever, and other symptoms; the first three are more than sufficient indications that the patient should be taken immediately to an emergency room for treatment, which is usually effective--but the antipsychotic medication is stopped immediately. Because of all these side effects, the amount of antipsychotic medication prescribed should obviously be set at the minimum level needed to achieve the therapeutic effect. One study at the University of Toronto indicated that desirable effects could be maintained even though brain levels of the antipsychotic medication dropped to very low levels between doses. A later study reported in the April, 2000, issue of the American Journal of Psychiatry indicates that this level can sometimes be as much as 10 times lower than it was earlier thought to be, with the same amount of positive effect. Although these studies should be repeated with larger samples to insure that their conclusions are correct, consumers should make sure that their mental health professional is aware of the latest findings in this area of research. It may be possible to reduce both the expense of medication and the side effects of medication if these results are verified. Check our table for a comparison of the various antipsychotic medications available. Last updated 12/19/03 |
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