Depression and anxiety were once thought to be completely different in nature and treated separately, or often not at all. Then during the pharmacological explosion that took place from the 1950′s onward psychiatrists and other mental health professionals, as well as patients, began noticing that medicine known to treat one condition would often have beneficial effects for other conditions.  So if you were taking medicine for depression, you might also notice that your anxiety was significantly decreased.

There are two distinctly interesting possible explanations with such a scenario, either 1. depression and anxiety share a similar source or 2. depression is a contributing causation to anxiety.  There are of course other explanations, but these two have the most beneficial implications and deserve more in depth consideration.

Regardless of which of the above thesis may be accurate (there is evidence for both) the implications for patient care and outcomes is the same. Anxiety treatment in conjunction with treatment for depression can help a patient recover from both more quickly than treating one in isolation. It is most likely that both conditions share neurotransmitter pathologies and are psychologically reinforcing.

There are innumerable books and websites that discuss ways of dealing with anxiety. One site that has proven to help reduce anxiety and help people change the way they engage with the world is AnxietySelfTreatment.com. This service utilizes a protocol similar to EMDR which has been shown to be effective for a wide range of anxiety disorders.

If anxiety and depression share a similar source within the structure of the brain or the constructs of the psychology (which are likely reflections of one another), then treating one successfully should also have positive impacts on the other.

Similarly, if one is found to cause the other or perhaps there is circular causation, in other words, anxiety causes depressions with causes anxiety and so on, then again successfully treating one should provide a reduction in symptoms of the other.

Following this same line of logic, treating both simultaneously should provide the patient with the best possible chances of recovering from both while providing the most rapid recovery possible.

“ACNE DRUG LINKED TO SUICIDE RISK.” That was the headline over a Reuters story earlier this year that began: “The US Food and Drug Administration (FDA) issued a statement…advising physicians and consumers about reports of “depression, psychosis, and rarely suicidal thoughts and actions” related to use of the acne drug isotretinoin (Accutane).”

Isotretinoin (Accutane) is now commonly used to combat the cutaneous curse of adolescence, acne. Why?

The skin inflammation acne is in part due to increased secretion from the sebaceous glands in the skin with secondary irritation and subsequent scarring (keratinization).

Accutane decreases the secretions and size of the sebaceous glands, minimizing scarring from acne.

The FDA became particularly concerned about the psychological side-effects of Accutane after it received some two dozen reports of patients whose psychological symptoms improved after they stopped the drug, but worsened upon re-starting it. “To us that’s an important clue that something might be occurring,” said Jonathan Wilkin, director of the FDA’s division of dermatologic drugs.

However, Accutane is not merely an anti-acne drug that “may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide.” It has effects that can go well beyond the skin and psyche.

Do not forget that Accutane is a potent teratogen: an agent capable of causing human congenital malformations.

To quote the March of Dimes Birth Defects Foundation: “There is an extremely high risk of fetal malformations if pregnancy occurs while taking Accutane in any amount, even for short periods. Potentially all exposed fetuses can be affected. Birth defects include hydrocephaly (enlargement of the fluid- filled spaces in the brain); microcephaly (very small head); mental retardation; small and malformed ears and other facial abnormalities; and heart defects.”

Accutane can cause these major malformations in the early weeks of pregnancy soon after conception, a time when many women may not yet know they are pregnant. Therefore, doctors recommend that:

* Accutane must not be used by women who are pregnant, plan on being pregnant, or have a chance of becoming pregnant.
* Abstinence or effective birth control methods should be used and pregnancy tests should be performed prior to starting treatment and repeated monthly during treatment.
* Pregnancy should be avoided until at least one month after stopping Accutane. Nursing mothers should not use Accutane.
* Any woman of child bearing age should seriously discuss potential side effects with her doctor before using Accutane.

Whenever two or more drugs are taken concurrently, there is a chance that there will be an interaction among the drugs. The interaction may increase or decrease the effectiveness and/or the side effects of the drugs. It also may result in a new side effect, that is, a side effect not seen with the use of any one drug alone. The likelihood of drug interactions increases as the number of drugs being taken by a patient increases. Therefore, people who take several medications are at the greatest risk for interactions. Drug interactions contribute to the cost of healthcare because of the medical care costs that are required to treat them. Interactions can also lead to pain and suffering that could be avoided. This month’s topic discusses the issue of drug interactions and several ways to avoid them.

What are drug interactions?

A drug interaction can be defined as an interaction between a drug and another substance that prevents the drug from performing as expected. This definition applies to interactions of drugs with other drugs (drug-drug interactions), as well as drugs with food (drug-food interactions) and other substances.

How do drug interactions occur?

There are several mechanisms by which drugs interact with other drugs, food, and other substances. An interaction can result when there is an increase or decrease in: (1) the absorption of a drug into the body; (2) distribution of the drug in the body; (3) changes made to the drug by the body (metabolism); and (4) elimination of the drug from the body. Most of the important drug interactions result from a change in the absorption, metabolism, or elimination of a drug. Drug interactions also may occur when two drugs that have similar (additive) effects or opposite (canceling) effects on the body are administered together. Another source of drug interactions occurs when one drug alters the concentration of a substance that is normally present in the body. The alteration of this substance reduces or enhances the effect of another drug that is being taken. The drug interaction between warfarin (Coumadin) and vitamin K-containing products is a good example of this type of interaction. Warfarin acts by reducing the concentration of the active form of vitamin K in the body. Therefore, when vitamin K is taken, it reduces the effect of warfarin.

Change in absorption

Most drugs are absorbed into the blood and then travel to their site of action. Most drug interactions that are due to altered absorption occur in the intestine. There are various potential mechanisms through which the absorption of drugs can be reduced. These mechanisms include an alteration in blood flow to the intestine, metabolism (alteration of the drug) by the intestine, increased or decreased intestinal motility (movement) within the intestine, alterations in acidity in the stomach, and a change in the bacteria of the intestine. Drug absorption also can be affected if the drug’s ability to dissolve (solubility) is changed by another drug, or if a substance (e.g., food) binds to the drug and prevents its absorption.

Change in drug metabolism and elimination

Most drugs are eliminated through the kidney in either an unchanged form or as a by-product that results from the metabolism (alteration) of the drug by the liver. Therefore, the kidney and the liver are very important sites of potential drug interactions. Some drugs are able to reduce or increase the metabolism of other drugs by the liver or their elimination by the kidney.

Metabolism of drugs is the process through which the body converts (alters or modifies) drugs into forms that are easier for the body to eliminate through the kidneys. (This process also converts drugs that are given in inactive forms into active forms that actually produce the desired effect.) Most drug metabolism takes place in the liver, but other organs also may play a role (e.g., the kidneys). The cytochrome P450 enzymes are a group of enzymes in the liver that are responsible for the metabolism of most drugs. They are, therefore, often involved in drug interactions. Drugs and certain types of food may increase or decrease the activity of these enzymes and therefore affect the concentration of drugs that are metabolized by these enzymes. An increase in the activity of these enzymes leads to a decrease in the concentration and effect of an administered drug. Conversely, a decrease in enzyme activity leads to an increase in drug concentration and effect.

What are the consequences of drug interactions?

Drug interactions may lead to an increase or decrease in the beneficial or the adverse effects of the given drugs. When a drug interaction increases the benefit of the administered drugs without increasing side effects, both drugs may be combined to increase the control of the condition that is being treated. For example, drugs that reduce blood pressure by different mechanisms may be combined because the blood pressure lowering effect achieved by both drugs may be better than with either drug alone. The absorption of some drugs is increased by food. Therefore, these drugs are taken with food in order to increase their concentration in the body and, ultimately, their effect. Conversely, when a drug’s absorption is reduced by food, the drug is taken on an empty stomach.

Drug interactions that are of greatest concern are those that reduce the desired effects or increase the adverse effects of the drugs. Drugs that reduce the absorption or increase the metabolism or elimination of other drugs tend to reduce the effects of the other drugs. This may lead to failure of therapy or warrant an increase in the dose of the affected drug. Conversely, drugs that increase absorption or reduce the elimination or metabolism of other drugs increase the concentration of the other drugs in the body and lead to more side effects. Sometimes, drugs interact because they produce similar side effects. Thus, when two drugs that produce similar side effects are combined, the frequency and severity of the side effect are increased.

How often do drug interactions occur?

Drug interactions are complex and chiefly unpredictable. A known interaction may not occur in every individual. This can be explained because there are several factors that affect the likelihood that a known interaction will occur. These factors include differences among individuals in physiology, age, lifestyle (diet, exercise), underlying diseases, drug doses, the duration of combined therapy, and the relative time of administration of the two substances. (Sometimes, interactions can be avoided if two drugs are taken at different times.) Nevertheless, significant drug interactions occur frequently and they add millions of dollars to the cost of healthcare. Moreover, many drugs have been withdrawn from the market because of their potential to interact with other drugs and cause serious healthcare problems.

How can drug interactions be avoided?

1. Give healthcare providers a complete list of all of the drugs that you are using or have used within the last few weeks. This should include over-the-counter medications, vitamins, food supplements, and herbal remedies.
2. Inform healthcare providers when medications are added or discontinued.
3. Inform healthcare providers about changes in lifestyle.
4. Ask your healthcare provider about the most serious or frequent drug interactions with the medications that you are taking.
5. Since the frequency of drug interactions increases with the number of medications, work with your healthcare providers to eliminate unnecessary medications.
6. This brief overview of drug interactions does not cover every possible scenario. Viewers should not be afraid to use their drugs because of the potential for drug interactions. Rather, they should use the information that is available to them to minimize the risk of such interactions and to improve the success of their therapy.

GENERIC NAME: amitriptyline

BRAND NAME: Elavil, Endep

DRUG CLASS AND MECHANISM: Amitriptyline is an antidepressant medication.Depression is an all-pervasive sense of sadness and gloom. In some patients with depression, abnormal levels of brain chemicals called neurotransmitters may relate to their depression. Amitriptyline elevates mood by raising the level of neurotransmitters in brain tissue.

PRESCRIPTION: yes

GENERIC AVAILABLE: yes

PREPARATIONS: Tablets: 10mg, 25mg, 50mg, 75mg, 100mg, 150mg.

STORAGE: Amitriptyline should be stored at room temperature in a tight, light resistant container.

PRESCRIBED FOR: Amitriptyline is used to elevate the mood of patients with depression. Amitriptyline is also a sedative, and is useful in depressed patients with insomnia, restlessness, and nervousness. It has also been found to be helpful for treating fibromyalgia and symptoms related to chronic pain.

DOSING: Amitriptyline may be taken with or without food. Amitriptyline is metabolized by the liver and should be used with caution in patients with liver dysfunction.

DRUG INTERACTIONS: Amitriptyline should not be used with monoamine oxidase inhibiting drugs. High fever, convulsions and even death can occur when these two drugs are used together. Epinephrine should not be used with amitriptyline, since together they can cause severe high blood pressure. Amitriptyline is used with caution in patients with seizures, since it can increase the risk of seizures. Amitriptyline is used with caution in patients with prostate enlargement because of risk of urine retention. Amitriptyline can cause elevated pressure in the eyes of certain patients with glaucoma. Alcohol blocks the antidepressant action of amitriptyline but increases its sedative effect. Amitriptyline can aggravate paranoid symptoms in patients with schizophrenia, and increase symptoms of mania in patients with manic-depressive disease. Cimetidine (Tagamet) can increase blood levels of amitriptyline and its side effects. Overdose with amitriptyline can cause life threatening abnormal heart rhythms. The sedative effect of the medication can possibly impair the mental and physical abilities required for driving or operating machinery.

PREGNANCY: Safety in pregnancy and children is not established.

NURSING MOTHERS: Amitriptyline is secreted in human milk, and potentially can adversely affect the nursing infant.

SIDE EFFECTS: Sometimes troublesome side effects include fast heart rate, blurred vision, urinary retention, dry mouth, constipation, weight gain or loss, and low blood pressure on standing. Rash, hives, seizures, and hepatitis are rare side effects.

“If antidepressants are discontinued abruptly, symptoms may occur such as dizziness, headache, nausea, changes in mood, or changes in the sense of smell, taste, etc. (Such symptoms even may occur when even a few doses of antidepressant are missed.) Therefore, it is recommended that the dose of antidepressant be reduced gradually when therapy is discontinued.”

MUNICH & SAN ANTONIO–Depression is a common disorder worldwide. While many medications exist that can dramatically reduce symptoms of depression, the potential side effects frequently limit their use. Extracts from plants have been used for a wide variety of maladies for centuries. Many of the drugs currently manufactured by the pharmaceutical industries are derivatives of chemicals from plants.

In a recent study published in the British Medical Journal (1996:313:253-8), Klaus Linde and associates reported findings of a review of 23 published reported trials, including 1757 patients, which indicate that extracts of the flowering plant, St. John’s Wort (Hypericum perforatum), are indeed more effective than placebo for the treatment of mild to moderately severe depression.

The authors emphasize that many issues regarding the use of the St. John’s Wort extracts remain unclarified. It is not known whether the extracts are more effective in certain types of depression than other types. It is also not yet known whether the extracts are as effective as traditional medications for depression, or even if they have fewer side effects.

The authors conclude by recommending further studies to clarify the issues above and compare the St. John’s Wort extracts with traditional medications for depression as well as determine the potential long-term side effects.

It should also be noted that animal studies using high doses of St. John’s Wort have noted skin inflammation after sun exposure (phototoxicity). Also fatigue, stomach upset, and allergic reactions have been reported in humans. If the published results above are verified by longer term comparison studies, the way could be paved for a new, less toxic approach to managing depression.

Depression is a substantial and potentially very serious cause of poor functioning and disability. Warning flags for the presence of depression can allow doctors to guide patients ideally toward recovery and health.

Recent research has highlighted specific symptoms that will hopefully help alert doctors to the possibility of depression in their patients.

Cheryl Carmin, PhD of the University of Illinois at Chicago and John Klocek, PhD of the University of Montana reported results of their evaluation of depression in a study of 357 consecutive patients. Their results were published in a recent issue of the periodical, The International Journal of Psychiatry in Medicine.

Drs. Carmin and Klocek designed and administered a 21-item questionnaire to evaluate patients for depression in an outpatient university family practice clinic. Of all patients, 15.7 percent reported significant symptoms of depression.

Five symptoms occurred in at least 90 percent of the clinic patients with depression. These symptoms were:

* Disappointment with self,
* Less enjoyment from usual activities,
* Hopelessness,
* Irritability, and
* Difficulty sleeping.

The study detected differences in symptoms between depressed women and depressed men. Women most often felt self-disappointment, while men most often reported less enjoyment from usual activities and difficulty sleeping.

The study concludes that physicians should actively question patients for these symptoms of depression as an easy method of screening for the illness. Persons with these symptoms may well warrant further evaluation for depression.

NEW YORK-Miscarriage can represent a physical stress to the body of a woman as well as lead to emotional trauma affecting women and their families.

According to the National Center for Health Statistics, the pregnancies of approximately half a million women annually in the United States end in miscarriage. The impact of miscarriages is further underscored by current estimates that nearly 20 percent of recognized pregnancies end in miscarriage.

In a recent study published in the Journal of the American Medical Association (1997;277:383-388) Dr. Richard Neugebauer and colleagues compared the risk for an episode of major depressive disorder among miscarrying women in the first 6 months after their loss of pregnancy with community women who had not been pregnant.

Dr. Neugebauer’s study found that there was a significant risk of depression in women after miscarriage. Furthermore, 72 percent of the episodes of major depression occurred during the first month after the loss of the pregnancy.

The study also found that the risk for depression was substantially higher for those miscarrying women who had no children. Further, the data demonstrated that over half of the women with prior histories of major depression experienced recurrences after they had miscarriages.

The authors conclude that women should be monitored for signs of depression during the weeks after miscarriage.

Doctors recommend that pregnant women alert their doctors to any past history of depression. Women who develop depression after a miscarriage might benefit by supportive counseling and even medical treatments.

HealthDay ReporterTUESDAY, Oct. 3 (HealthDay News) — New insights into how genes affect an individual’s response to particular drugs could someday speed the effective treatment of depression, researchers say.

Reporting in the Oct. 4 issue of the Journal of the American Medical Association, scientists say variations in a serotonin transport gene accurately predicted which patients would respond to selective serotonin reuptake inhibitor (SSRI) drugs such as Prozac.

They also identified key variations in the norepinephrine transporter (NET) gene. Those variants predicted response to nortriptyline, an antidepressant in a class of drugs called norepinephrine reuptake inhibitors (NRIs).

“I don’t think this is going to change the way we treat depression, but it’s another piece of the puzzle that will help us individualize treatment,” said Dr. Julio Licinio, chairman of psychiatry at the University of Miami Miller School of Medicine. He was not involved in the research.

The study, conducted by researchers in the United States and Korea, shows “that it’s important to look at gene variants in terms of treatment response,” Licinio said.

Some 30 percent to 40 percent of patients fail their first drug treatment for major depression. Experts say that, right now, it’s not possible to predict with any degree of accuracy which drug will work best for each patient.

Clinicians are pinning future hopes on “pharmacogenetics,” or genetic factors that influence an individual’s response to drugs.

There’s reason for some optimism. Previous studies have shown that polymorphisms (individual differences in the DNA sequence) in the serotonin transporter gene might predict response to SSRIs, which include drugs such as Celexa, Prozac, Paxil and Zoloft.

Ethnic variations may also play a role. Prior studies have shown that gene variants linked to poor response to SSRIs among white patients were actually associated with a good response in Japanese and Korean patients.

“This raises some basic genetic questions about what exactly is the signal coming from the polymorphisms as to function and as to interaction with the drugs,” Bernard Carroll, co-author of the research and scientific director of the Pacific Behavioral Research Foundation in Carmel, Calif., said in a prepared statement. “And it serves as a caution that results found in one ethnic group can’t necessarily be transposed straight across to another ethnic group.”

The new research was conducted at Samsung Medical Center in Seoul and was supported by the South Korean Ministry of Health and Welfare.

The study authors tracked the outcomes of a group of 241 Koreans diagnosed with major depression that had begun, on average, in the individuals’ early-to-mid 50s.

The researchers were interested in two different types of antidepressants and associated pathways in the body: SSRIs and the serotonin transporter gene, as well as NRIs and the associated norepinephrine transporter (NET) gene.

Participants were treated for six weeks with an SSRI (either Prozac or Zoloft) or the NRI nortriptyline (brand names Aventyl or Pamelor).

Individuals who carried the “GG” polymorphism of NET had a better rate of response to NRI treatment than to SSRI treatment (83.3 percent and 58.7 percent, respectively).

“That’s a 25 percent difference in response rate, so that is going to have a major impact, we would predict, on clinical practice,” Carroll said.

The research also confirmed that response to SSRIs was associated with a genetic variation in the serotonin transporter gene.

Although the findings are preliminary and need to be replicated, particularly in a white population, “we’re certainly optimistic that it’s going to stand up,” Carroll said.

More than half (56 percent) of Koreans and about 45 percent of whites have the GG polymorphism, the researchers noted.

“This is likely to still be a major finding in [whites] if the replications studies hold up,” Carroll said. “If our findings are confirmed and if this genotyping is taken up in clinical services, then the market for SSRI drugs as first-line treatment will fall by around 50 percent. Another implication is that new drug development will shift to dual-action agents.”

“The word is now out that depression is a very serious disorder with major public health and economic consequences,” he continued. “There is a great deal of motivation on the professional side to do a better job of treating depression and this genetic prediction is an obvious place to start.”

SOURCES: Bernard Carroll, MBBS, Ph.D., scientific director, Pacific Behavioral Research Foundation, Carmel, Calif.; Julio Licinio, M.D., chairman of psychiatry, University of Miami Miller School of Medicine; Oct. 4, 2006, Journal of the American Medical Association

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