Bruce H. Robinson, MD, FACS, MSOM (Hon)
Let's face it: Most people who seek your care are likely taking medication. These medications have distinct effects on their physical condition, as well as their mental and emotional condition, which may affect the treatment you select for them and also their response to your treatment. An important aspect of your careful evaluation is to sort through what medications your patients are taking.
I believe drugs are widely overprescribed in America today. We are an overdrugged nation. In particular, many people are on antidepressants and tranquilizers who should not be. In many cases, these people are addicted to their medications, and it is very hard to get them off their drugs when the acute episode that prompted use of the drug is over. By then, they have become dependent on their pharmacological support.
It is also true that some drugs are among the greatest developments of all time. General anesthesia, for example was one of the major discoveries of the 19th century. Then we have penicillin, morphine and insulin. I have always been a reluctant prescriber of drugs, but I've been very grateful for them when they were needed. Yet who really wants to spend the rest of their life on a drug that numbs or tranquilizes them? We should always avoid the use of drugs where there are other valid alternatives we can choose to get them better. Yes, I know, I'm preaching to the choir!
A Brief Primer on Drugs
All drugs have four descriptors: 1) the class of drug. Examples include corticosteroids, H2 inhibitors, NSAIDs, beta-blockers, ACE inhibitors, and SSRIs (selective serotonin reuptake inhibitors); 2) the chemical name of the drug; 3) the generic drug name; and 4) the brand name.
For example, consider Valium:
- Class: a benzodiazepine drug (a class of tranquilizers).
- Chemical name: 7-chloro-1,3-dihydro-1-methyl-5-phenyl-1,4-benzodiazepin-2(3H)-1
- Generic drug name: diazepam
- Brand names: Valium (U.S. and Canada); Antenex (Australia)
Rule to remember: The generic name of a drug is lowercase; the brand name of the drug is capitalized. Examples: The drug diazepam is better known by its brand name, Valium. The drug acetylsalicylic acid is better known by its major brand name, Aspirin.
Government Regulation
The FDA classifies and controls the availability of drugs according to their "abuse potential." This is often based on social convention as much as on research:
- Schedule I: high abuse potential, with no accepted medical use: heroin, LSD, marijuana (still on this list, at least for now, although this is highly controversial, as you know). These drugs cannot be prescribed and their use is illegal.
- Schedule II: drugs with high abuse potential, but medical uses as well: opiates, barbiturates, amphetamines, cocaine. These drugs can only be obtained with a narcotic prescription written by a physician.
- Schedule III: low to moderate abuse potential, with many medical uses: some tranquilizers and sedatives. These drugs require a regular prescription, written by a physician.
- Schedule IV: low abuse potential, many medical uses: codeine, Valium, some other widely-used tranquilizers, as well as a vast number of other drugs. These also require a regular prescription by a physician or nurse practitioner.
- Schedule V: drugs with minimal abuse potential. These are over-the-counter drugs: NSAIDS, antacids, laxatives, etc.
Clinical Trials in Drug Testing
To bring a new drug from its discovery to becoming a drug that can be prescribed takes up to 10 years (sometimes more), and costs many millions of dollars. Drug companies then charge consumers later on for this cost of bringing the drug to market. As a result, Viagra may now cost only a few cents per tablet to manufacture, but it can be marketed for over $20 a tablet. Knowing that drug companies need to recover their development costs does not seem to offset the sense of outrage we often feel when we pay an arm and a leg for such a drug. These drugs now reap enormous profits for the companies that market them. The newest drugs that are based on monoclonal antibodies, very popular in treating arthritis, various forms of cancer, and neurological conditions, are also very expensive.
There are four phases of testing and clinical trials required to get a drug approved for market distribution:
- Phase 0: animal testing of a promising drug.
- Phase 1: the drug is tried out on a small number of healthy volunteers, usually 20 to 100, to determine clinical safety of the drug in general terms, and the proper dosage for various people, based on age, gender, and weight of the patient.
- Phase 2: further testing (usually about 300 volunteers) to determine how well the drug works compared to a placebo. These must be randomized, double-blind clinical trials.
- Phase 3: controlled multicenter trials on hundreds to thousands of patients, the actual number depending on the disease being studied (rarer diseases = fewer patients).
Drugs for Mood Disorders
Antidepressants: Minor episodes of depression are a part of daily life, and they are best treated without drugs. Unfortunately, this wise rule is not regularly adhered to by physicians, who often place their patients on tranquilizers to bring them out of a down period in their life when what they really need is support, understanding, friendship and love.
Major depression is associated with chemical imbalances in the brain, and is characterized by anhedonia: the loss of the ability to enjoy life or find any pleasure or comfort in it. There are feelings of intense sadness, a strong sense of worthlessness, loss of sex drive, weight loss or weight gain associated with the depression, either insomnia or hypersomnia, and there are often thoughts of death or suicide (or actual plans to commit suicide). Major depression and suicide often go together, and constitute serious problems and much heartbreak in our society, as we all know.
Drugs are very helpful in treating major depression. Again, they are vastly overprescribed for minor depression. There are three classes of effective medications for major depression: tricyclic antidepressants, monoamine oxidase inhibitors (MAO inhibitors), and selective serotonin reuptake inhibitors (SSRIs). All three classes increase the levels of "feel good" neurotransmitters in the synapses of the brain: dopamine, epinephrine (adrenalin), norepinephrine (noradrenalin), and serotonin (5-hydroxytryptamine). These are all monoamine neurotransmitters (one amine group on the end of the molecule: NH2)
Tricyclic antidepressants: The best known are Elavil, Tofranil and Sinequan. They block the reuptake of monoamine neurotransmitters from the synapses of the brain, thus prolonging their availability at these brain receptor sites. These neurotransmitters enhance alertness, facilitate coping skills and generally improve mood. Elavil is particularly popular, and although it is a stimulant, its use before bedtime can curiously help with sleep, as it makes the person feel less nervous and anxious about their problems.
Monoamine oxidase inhibitors (MAO inhibitors): Nardil and Marplan are the most common, but there are many others as well. These drugs block the chemical breakdown of monoamine neurotransmitters, increasing their concentration in the brain. Very popular a few years ago, they are less prescribed today because of their side effects, which are frequent with both tricyclic antidepressants and MOA inhibitors.
The tricyclic antidepressants have anticholinergic effects on the body, which decrease parasympathetic function and result in a dry mouth and throat, pupil dilation with possible blurred vision, tachycardia, trouble voiding, and constipation. Side effects of MAO inhibitors include weight gain, impotence, postural hypotension, agitation, uncontrollable bursts of temper, and sometimes, hallucinations or seizures.
Selective serotonin reuptake inhibitors (SSRIs): These drugs inhibit the reuptake of serotonin and, with some of them, norepinephrine as well. This increases the concentration of these "feel good" neurotransmitters in the synapses of the brain, which elevates mood and enhances coping skills. Examples of these drugs are Prozac, Zoloft, Paxil, Effexor and Wellbutrin.
SSRIs generally have milder side effects than the tricyclic antidepressants or the monoamine oxidase inhibitors. As a result, they have become very popular and have largely replaced the other two classes of antidepressants. (Elavil, as I noted, is still used by many patients.) They do cause headaches, nausea, diarrhea, nervousness, skin rashes, or insomnia, and problems in some people with controlling their temper. Sometimes these side effects tend to diminish over time.
Drugs for Attention Deficit Hyperactivity Disorder (ADHD)
ADHD, the diagnosis of which now includes ADD (with less of a hyperactivity component) is characterized by restlessness, easy distractibility, short attention span and compulsivity. Amphetamines or similar-acting drugs are mild CNS stimulants that reduce or even eliminate symptoms in almost 90 percent of children who take them reliably and appropriately. It is curious that these stimulants do indeed help people, especially children, with this group of related disorders. The increased serotonin and dopamine in the brain helps the child to focus better and filter out distractions.
Dextroamphetamine (Dexadrine), methyphenidate (Ritalin) and the newer, longer-acting drug pemoline (Cylert) are the most widely used drugs. Strattera is also becoming popular. These drugs are combined with family counseling and psychotherapy for best results.
ADD and ADHD are highly overdiagnosed in the U.S., in my opinion. ADHD is often confused with gifted kids, mentally challenged kids, and kids with family or social problems, dyslexia, hearing disabilities, or other medical disorders that also cause children to not pay attention in school. These children are often wrongly put on these drugs. They do not improve or may actually get worse. If the ADD diagnosis is correct, most children benefit from these medications (it can be dramatic).
The most common side effect is CNS overstimulation, with insomnia, dizziness, agitation and/or loss of appetite. These symptoms tend to diminish with continued use of the drug. Hypertension can sometimes occur, or even cardiac arrhythmias, but both of these serious side effects are uncommon. Patients need to be carefully monitored and changed to another drug or have the drug withdrawn without replacement if these occur.
If the child with ADHD can be effectively managed by family and school counselors without drugs, that is best. Rule to follow: It is best to avoid drugs in treating medical conditions whenever another treatment is likely to be successful. If drugs are resorted to, always weigh the benefits of using the drug versus the risks of not using it. Do the benefits clearly outweigh the risks?
Drugs for Excessive Anxiety and Sedation
The two major classes of drugs used for these clinical situations are barbiturates and benzodiazepines. They are among the most widely used drugs in the U.S., as well as in many other countries (modern life is very stressful). The most sedative neurotransmitter in the brain is GABA (gamma amino butyric acid). It resides in the reticular activating system and makes us relax and go to sleep when the time is right to do so. The challenge for drug inventors has been to design a drug that will make us relax (tranquilizer effects) without getting too sleepy (sedative effects). All of these drugs enhance the levels of GABA in the brain.
Barbiturates (such as phenobarbitol): Phenobarbitol was first marketed by Bayer in 1912. It facilitates the retention of GABA and chloride, causing sedation, a sense of euphoria and hypnosis. Barbiturates are more directly sedating than the newer benzodiazepines, and so they are no longer used as tranquilizers. They are still used as sleeping medications, as a supplement to general anesthetics, and for control of seizures.
Barbitol and phenobarbitol are long-acting barbiturates (effects last for 8-10 hours). They work well as sleeping pills, but you wake up with a hangover! Well-known short-acting barbiturates include secobarbital (Seconal, a popular sleeping pill in the 1960s and 1970s), amobarbital (Sodium Amytal) and pentobarbital (Sodium Pentothal, the so-called truth serum featured in many classic movies).
Many depressed individuals have attempted or succeeded in committing suicide taking a bottleful of these drugs. Ultra-short acting thiopental is used as an anesthetic agent (administered via IV).
Benzodiazepines (such as Valium): These drugs enhance GABA secretion in the brain, thus causing sedative effects and skeletal muscle relaxation. They are used to treat anxiety states, nervous tension, agitation, delirium tremens during alcohol withdrawal, and as anticonvulsants. They work well as relaxants, without major sedative effects. These attributes have made them enormously popular all over the world. The most widely known and utilized is diazepam (Valium), one of the most popular drugs of the past 50 years in America and other countries. Valium was first marketed in 1963.
Dalmane, Librium, Tranxene and Klonopin are also widely used long-acting drugs of this class. Valium is the most rapidly absorbed of all these drugs and has a prolonged length of active time in the body. This is why it has been so popular. Shorter-acting benzodiazepines include Versed, Xanax, Ativan, Serax and Restoril.
Xanax works quickly and is very popular with those who need a quick calming-down in the midst of their stress-filled lives. It has a short half-life in the body, which is also desirable for such situations. Klonopin helps the most with those who have muscle spasms or a sense of jerking movements with their attacks of anxiety, as it quiets these down. Versed, administered via IV, is widely used as a short-acting anesthetic (for colonoscopy, biopsies).
Side effects of both classes of drugs are similar: drowsiness, dysarthria (trouble speaking clearly), ataxia, dermatitis, and a curious paradoxical overstimulation with strange behavior due to the loss of inhibition that we normally have (somewhat similar to the effects of alcohol in this regard, but causing more bizarre behavior).
Dr. Robinson's next article on this topic discusses pain medications, drugs for respiratory problems and drugs for diseases of the gastrointestinal tract. This article and those the follow appeared originally in DC's sister publication, Acupuncture Today.
