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Treatment: Medication
CBS CARES: How many of the adults experiencing depression take medication?
DR. WEISSMAN: I would say only about a third, or even less, have received some medication. The rates of treatment for depression are relatively low.
CBS CARES: If the experience of depression is so variable to each individual, how can standard treatments maximize results?
DR. KAHN: Standard treatment in any medical disorder improves the odds of a good outcome, but does not guarantee it. We have many different drugs to treat hypertension, diabetes, arthritis, and depression, to name several common disorders. Some people respond well to the first treatment, while others must try several before achieving results. Why is this so? People vary in how they metabolize medication, what kind of side effects they experience, and also in the underlying chemistry that leads to a common final picture of illness. Consequently, recommending a first medication in most medical disorders, including depression, is often an educated guess, which must be fine-tuned by ongoing attention. In addition, lifestyle changes are often helpful, though these are much easier to recommend than to carry out, and that accounts for some of the variation in treatment response.
CBS CARES: How far are we from genetic testing to match the best drugs to the person's genetic profile?
DR. ROOSE: With respect to genetic testing, while it is possible to evaluate how a patient will metabolize a particular medication, that is different from determining whether that medication will be most effective. Most of the research in genetics is focused on understanding the genetic contribution to the vulnerability to the illness. It has already been established that genes contribute significantly to the development of depression but it is unlikely that a single is responsible. Establishing the genetic contribution to depression will be only one part of understanding why some people develop this illness.
CBS CARES: Are some antidepressants safer than others?
DR. ROOSE: With respect to the safety of antidepressants, all of the medications are relatively safe when taken as prescribed. In overdose, the older medications (tricyclic antidepressants) are particularly dangerous, whereas the newer medications (SSRIs) are relatively safer in overdose. Safety is also determined by the underlying medical condition of the patient. For example, the tricyclic antidepressants are not safe in patients with some types of heart disease.
CBS CARES: How does treatment of depression in pregnancy affect the fetus or baby?
DR. MUSKIN: All of the research on the effects of antidepressant treatment on the fetus/baby/child has been in the form of naturalistic studies. Women who have taken antidepressants are followed, or are contacted, so that their children can be studied. The available evidence to date has not shown significant harm to the fetus, or to the child.
We do not do "experiments" on pregnant women to see what would happen if they were placed on antidepressants. However, there is scientific evidence that untreated depression causes an increase in problems at birth and has a negative impact on the developing fetus. Depressed women may be unable to adequately obtain medical care for themselves, or eat properly. They may feel so miserable that they take illicit drugs, use alcohol, smoke cigarettes, or attempt to harm themselves. These activities all have an adverse impact on the baby. Depressed mothers may be unable to provide adequate nurturing for their babies. For all of these reasons, treatment for depression during pregnancy and in the post-partum period is extremely important. But not all treatment for depression during pregnancy and in the post-partum period has to be done with medication. Psychological treatment, in particular cognitive-behavioral therapy and interpersonal psychotherapy, have been demonstrated to be effective for mild to moderate depression.
CBS CARES: Why do antidepressants increase depression and suicide rates among kids and teens?
DR. SHAFFER: It is not true that antidepressants have increased suicide rates in children and adolescents. There has been a very large increase in the number of children and adolescents who have received antidepressant treatment for their depression. But, in nearly all countries where the newer, less toxic antidepressants, such as the SSRIs, have become available, the increase in use has coincided with a fall in the suicide rate. Furthermore, careful studies of the body fluids of young people who have committed suicide show that only a very small proportion were taking antidepressants at the time of their death. What has been noticed in many studies is that after a young person (and possibly adults as well) starts taking an antidepressant, they will often start to talk more openly about suicidal ideas and might express a wish or actually engage in a suicide attempt. It is not clear whether the medications simply relax the patient, so that they are more forthcoming about revealing what they might have been thinking about possibly committing suicide, or whether they have induced a state of discomfort that has induced the suicidal ideas. Regardless, at the present time, there is no evidence that the increased talk about suicide, or even the increase in the number of suicide attempts, becomes translated into actual deaths.
CBS CARES: If antidepressants do not increase suicidal tendencies of teens, why has the European drug regulator (The European Medicine Agency) just instructed physicians not to prescribe SSRI antidepressants to children under 18… asserting an increased risk of suicidal and aggressive behavior?
DR. SHAFFER: The EMA is not banning their use, but is "recommending the inclusion of strong warnings across the whole of the EU." Doctors and parents are being advised that SSRIs should not be used in children and adolescents, except for anxiety and depression. The EMA allows a doctor to make a decision based on the individual's clinical needs and recommends, just as the FDA does, that teenagers being treated with antidepressants be watched carefully for the appearance of suicidal behavior, self-harm, or hostility, especially at the beginning of treatment.
CBS CARES: The defense of Chris Pittman, who murdered his grandparents, was essentially that "Zoloft" made him do it. What are your comments on this defense?
DR. SHAFFER: The first question we have to ask is why Chris Pittman was put on to Zoloft in the first instance. It is my understanding that he was put on to Zoloft because of aggressive, impulsive behavior following a previous assault on his grandparents.
CBS CARES: Is there a difference between the treatment of regular depression and delusional depression?
DR. SHAFFER: Most depressions involve a delusional element. This is usually quite mild and is commonly referred to as a "cognitive distortion," i.e., when people are depressed, they see the glass half empty, are pessimistic about the future, and convince themselves that other people do not like them or respect them. Taken to extremes, distortions of this kind can be seen as delusions. The treatment of delusional and non-delusional depression is not necessarily different. When these distortions of thought are present, it can be very difficult to undertake psychotherapy, which will usually have to wait for some medication-induced improvement. Some people with very severe forms of delusional depression who fail to respond to the usual antidepressants can obtain dramatic relief with ECT, i.e., electric-shock treatment. The mechanisms by which this works are not known. But the reader should be aware that electric-shock treatment is not a form of punishment. The electric current induces a convulsion, and the patient will normally be anesthetized and have been given a muscle relaxant, which will prevent the convulsion from causing injury. The ways in which experiencing a convulsion can improve a depression are not well understood. (CBS CARES: for more information on ECT see interviews with Drs. Fink and Glass below).
CBS CARES: Is it difficult to treat someone who is both anxious and depressed?
DR. GLASSMAN: Some people feel that individuals who show both symptoms are more difficult to treat, but the evidence supporting this is not very strong and if there is a difference is not big.
CBS CARES: For example, by treating the anxiety, can't you increase the depression?
DR. GLASSMAN: Although depressed and anxious states frequently coexist, the drugs that relieve anxiety do not really improve depressive states. isIf a person is both anxious and depressed, it is often unnecessary to use both anti-anxiety and antidepressant medication. Many of the antidepressant drugs are also useful to treat anxiety. This is true of the old TCAs (Tricyclic antidepressants) and of the newer SSRIs. However, not all antidepressants are good for anxiety, and there is a general impression that bupropion (Wellbutrin) is a reasonable antidepressant, but may actually increase anxiety. It certainly does have stimulant effects and can interfere with sleep. However, unlike many other antidepressants, it does not interfere with sexual function and has little if any propensity towards weight gain.
CBS CARES: Why do antidepressants sometimes cause sexual dysfunction?
DR. ROOSE: The SSRI medications are associated with sexual dysfunction, but probably too much sexual dysfunction has been ascribed to the medication and not enough recognized as an independent condition. Sexual dysfunction occurs in a significant number of people who are not depressed. According to an extensive study published in JAMA, the rate of decreased sexual desire in women in their 20's and 30's is about 25% and a significant number of men begin to have erectile difficulties beginning by age 40. Therefore, when a patient is experiencing sexual dysfunction while taking an antidepressant medication, it is important to determine if the problem is a pre-existing sexual dysfunction unrelated to the medication, or if it may in fact be an unresolved symptom of the depression itself.
SSRIs definitely interfere with orgasmic function in about 5%-15% of patients. In these cases, orgasm may be delayed or entirely absent. However, other complaints of sexual dysfunction, such as "loss of desire," should be investigated further and not simply assumed to be a side effect of the medication.
CBS CARES: Aside from sexual dysfunction, what other major side effects are associated with either short or long term use of antidepressant medications?
DR. ROOSE: Another major side effect of many antidepressant is that a small number of people, estimates are from 4-12%, can experience significant weight gain over 6 to 12 months of treatment. In terms of long term effects there are no commonly occurring long-term negative effects that have been manifest. Interestingly one long-term effect that may be positive is that antidepressant treatment has been associated with an increase in neurochemical substances such as brain derived neurotropic factor (BDNF), which have protective and perhaps regenerative effects on brain tissue.
CBS CARES: What promising antidepressant drugs are in development now?
DR. ROOSE: Research is underway on two new approaches to the treatment of depression involving medications that affect gluco-corticord receptors and an important hormone, corticotropin releasing factor. These medications are probably a number of years away from clinical use if, in fact, they prove to be both safe and effective. There are also exciting new developments in treatment for depression involving brain stimulation techniques. Most people are familiar with electroconvulsive therapy as a way of directly affecting the brain and treating severe depression. There are also new methods, including transcranial magnetic stimulation and vagal nerve stimulation. These new approaches to treating patients with depression do not have some of the side effects of electroconvulsive therapy. They are clinically available now.
CBS CARES: How do you know whether and when to begin weaning a patient off antidepressants?
DR. KAHN: Antidepressants that helped resolve a first episode of depression can be weaned after 6 to 12 months of well being. About 50% of people with a single episode will have recurrences in the future, however, and after 2 or 3 recurrences, the rate is over 90% in terms of having future episodes. So after 2 or 3 episodes, it is often advisable to remain on antidepressants indefinitely, much as one would treat hypertension, diabetes, or other long-term medical conditions.
CBS CARES: Primary care doctors often prescribe antidepressants-are you comfortable with this in that there's not the supervision of a qualified psychiatrist or psychologist?
DR. MUSKIN: The prescription of antidepressants in the primary care setting is an important part of health care for many patients. Some patients are reluctant to see a mental health professional and have a good relationship with their primary care physician. In addition, managed care plans often create barriers to obtaining specialty mental health care. Thus patients may find it difficult to find a psychiatrist who is part of their managed care plan. The important thing is that primary care physicians who treat depression should obtain adequate training to understand the diagnosis and therapeutic options. This includes how to use several different antidepressants, the dosing strategies for antidepressants, and how to handle the side effects in order to enhance patient adherence with treatment.
Not all psychiatric disorders should be treated with medication. Research indicates that the combination of psychotherapy and psychopharmacology is the most effective treatment for most psychiatric disorders for which medication is indicated. And, iIf therapy may be needed in addition to antidepressant drugs, it is important for the primary care physician to connect or encourage the patient to connect with a psychiatrist or psychologist.
CBS CARES: Are there other issues associated with patients being able to receive the right kind of care?
DR. MUSKIN: Yes, a significant issue is the financing of health care. Currently, most patients who have psychiatric disorders will be seen in the primary care setting. As managed care has an increasing impact on health care, there is a financial disincentive to physicians spending the amount of time needed to sit and talk with patients. This issue cannot be ignored because physicians, like everybody else, have to earn a living. A standard needs to be set, perhaps at the Federal level, requiring that the time it takes to take care of patients is paid for by insurance. Another reason people are seen in the primary care setting is the shortage of psychiatrists. There were predictions that there would be too many psychiatrists, thus the funding for training was reduced. If the funding for patients with psychiatric disorders achieved parity with that for medical disorders, and there were adequate numbers of psychiatrists, we could then begin to provide real collaborative treatment in the primary care setting.
CBS CARES: What advice would you have for someone who is depressed and lacks health insurance coverage? What about someone whose coverage will not pay for specialty mental health services, or covers those services at a minimal level?
DR. KAHN: As in any other illness where a person lacks insurance, it is best to seek out a local hospital that has a clinic where care is provided for reduced fees, or a university medical center where there may be a research study available. Insurance discriminates against mental illness, so advocacy for fair coverage is essential.
CBS CARES: What are the consequences of untreated depression?
DR. ROOSE: This is an important issue to consider when balancing the benefits and risks of antidepressant treatment. The World Health Organization has projected that, by the year 2020, depression will be the second cause of disability worldwide, with the first cause being infectious disease. In this country, suicide is the eighth leading cause of death, and that is probably a significant underestimate, since probably half of suicides are not reported as such. Without question, untreated depression is the leading risk factor for suicide. Furthermore, there is now overwhelming evidence that depression early in life is a risk factor for the development of cardiovascular and cerebrovascular disease. Patients who have depression are at much greater risk to have heart attacks and strokes. In addition, patients with untreated depression have significantly less happy lives in terms of marital difficulties, career dissatisfaction, and low self-esteem. If untreated, depression is an illness that causes a significant increase in morbidity and mortality and results in a very poor quality of life.
CBS CARES: What is the relationship between suicide and depression in teens?
DR. SHAFFER: The majority of depressed teenagers will not attempt or commit suicide. However, about two thirds of them will give suicide some thought. In any one year, depression will affect 3,000 teenagers in every 100,000. By contrast, we can expect that, in one year, 6 out of 100,000 teenagers will commit suicide. Depression is, therefore, about 500 times more common than suicide in teenagers.
By contrast, a majority of the very small number of teenagers who commit suicide are depressed at the time.
The types of depression experienced by suicide victims are different in boys and girls. For girls, the depression is usually longer lasting and might have no obvious cause. Unrecognized or untreated, it can last a long time. The teen usually commits suicide as they are starting to feel better and are more active.
Compared to girls, most of the depression in the boys who commit suicide seems to start after a stressful event, such as getting into trouble at school or with the law or after relationship difficulties. In these teenagers, suicide is most likely to take place just before an event that the teenager fears is scheduled, e.g., a court appearance or a confrontation with a feared or estranged adult, or just after an episode, such as being arrested or suspended from school or being bullied or getting into a fight, where humiliation is involved.
CBS CARES: Why do some teens who are not depressed commit suicide?
DR. SHAFFER: Fear and dread and feeling agitated and very upset seem to be the most common states of mind when a person decides to commit suicide. In teenagers who are not depressed, there are several situations that figure commonly at the time a decision is made to commit suicide.
The young person has just learned that they are in trouble, caught playing hookey or caught stealing. They don't yet know what the consequences are going to be, and so cannot check their fears against reality. They fear the worst and might be so preoccupied with their fears that they cannot weigh up their true situation.
A. A teenager is approaching a feared event or circumstance. For example, they are about to start at a new school or change neighborhoods, take a particularly important test, etc. In a typical case, they will be young people who have worked excessively hard, perhaps driven by a conviction or a fear that they will fail. Sometimes, the feeling of dread before an event is so great that they just want to close their eyes and get away from the problem.
B. Many attempts follow a dispute between a teen and their parent over limit setting. The parent and the child experience difficulty knowing what is appropriate and what is reasonable or unreasonable. The youngster might exaggerate the importance of a restriction-most commonly, not being allowed to see a boyfriend or girlfriend-and decide that their parent's interference is going to spoil their chances for future happiness. Their decision to commit suicide might also be mixed with a wish to exert revenge, knowing that their surviving family will feel overwhelmingly distressed by the event.
C. Finally, a very small number of suicides occur in psychotic patients, e.g., those suffering from a disease like schizophrenia. A decision to commit suicide might be based on a delusion or hallucination, and the victim might feel that they are responding to the expectations of a higher being.
The situations outlined above are relatively common. And readers might recognize some that they themselves have experienced. However, the usual response to these problems is to turn these thoughts into a problem-solving approach, hold firm and wait to see what tomorrow will bring, or force oneself to see and accept the other person's point of view-reactions that most of us will have. They might be interfered with by the suicide victim's characteristic impulsivity, aggressiveness, and intolerance for indecision. We believe that the impulsivity found in people who have committed suicide has a biological origin and is related to impaired functioning in the part of the cortex (forebrain) that normally invokes consideration and conciliation.
CBS CARES: Why do some depressed adolescents have suicidal thoughts whereas others only feel hopeless?
DR. SHAFFER: About 60 percent of depressed adolescents entertain suicidal thoughts. Suicidal thoughts are very much more common than attempts and very, very much more common than suicide completions, as indicated above. In adolescents, the factors that differentiate between the depressed suicidal and the depressed non-suicidal teenager seem to lie very largely in the area of aggression, which is strongly related to committing or attempting suicide.
CBS CARES: A 26-year-old man was arrested recently for persuading 30 people, through the Internet, to commit mass suicide on Valentine's Day. How can a stranger on the Internet manipulate and persuade so many people to end their lives?
DR. SHAFFER: Cases of Internet suicide in Japan and elsewhere have received a lot of publicity. Only rarely does the Internet commitment to engage in a suicide pact lead to an actual death. What is clear is that some youth acquire knowledge from the Internet about the type of method that should be used to commit suicide and the availability of substances that can be used for this purpose.
Suggestibility is common during youth, and, when accompanied by example and true peer pressure, it can lead to mass self-destructive behavior, as in Jonestown or in other youth suicide epidemics, or acts of equally dangerous heroism in a wartime situation. Suggestibility of this kind does not appear to be strongly related to depression.
CBS CARES: Why is a child of someone who committed suicide more likely to commit suicide themselves?
DR. SHAFFER: To a very limited extent, suicide runs in families. Having a first-degree relative (i.e., mother, father, or sibling) who has committed suicide increases the likelihood that one will commit suicide about two fold. This might not be because the parent has set an example that is then followed by other family member, although this might happen. Other ways in which the transmission of suicide might occur within families include the inheritance of conditions, such as bipolar disorder or schizophrenia, both of which increase the risk of suicide.
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