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Adult Depression http://www.healthline.com/galecontent/antidepressant-drugs Definition Antidepressant drugs are medicines that relieve symptoms of depressive disorders. Purpose Depressive disorders may be either unipolar (depression alone) or bipolar (depression alternating with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least two weeks. These symptoms include, but are not limited to mood changes, insomnia or hypersomnia, and diminished interest in daily activities. The symptoms are not caused by any medical condition, drug side effect, or adverse life event. The condition is severe enough to cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Secondary depression, depression caused by unfavorable life events, is normally self limiting, and may be best treated with cognitive/behavioral therapy rather than drugs. Antidepressant agents act by increasing the levels of excitatory neurostransmitters. The main types of antidepressant drugs in use today are: tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor): Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs selective serotonin reuptake inhibitors (SSRIs or serotonin boosters), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) monoamine oxidase inhibitors (MAO inhibitors), such as phenelzine (Nardil), and tranylcypromine (Parnate): Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted in therapy because of their high risk of severe adverse effects, most notably severe hypertension tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson's disease) and the herb, St. John's wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors. All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued. Antidepressant Drugs Brand Name (Generic Name) Possible Common Side Effects Include: Desyrel (trazodone hydrochloride) Allergic skin reactions, blurred vision, decreased appetite, fluid retention, headache Effexor (venlafaxine hydrochloride) Diarrhea, dizziness, gas, headache, insommia, rash, vomiting Antidepressant Drugs Brand Name (Generic Name) Possible Common Side Effects Include: Elavil (amitriptyline hydrochloride) Constipation, idzziness, high blood pressure, fever, nausea, rash, weight gain or loss Nardil (phenelzine sulfate) Dry mouth, fatigue, headache, muscle spasms, tremors Norpramin (desipramine hydrochloride) Blurred vision, cramps, hallucinations, hair loss, vomiting Pamelor (nortriptyline hydrochloride) Diarrhea, fatigue, headache, decreased coordination Paxil (paroxetine hydrochloride) Cold symptoms, drowsiness, nervousness, stomach pain Prozac (fluoxetine hydrochloride) Bronchitis, drowsiness, fatigue, nausea, tremors Sinequan (doxepin hydrochloride) Bruising, constipation, fluid retention, itching, increased heartbeat Surmontil (trimipramine maleate) Disorientation, flushing, headache, nausea, vomiting Tofranil (imipramine hydrochloride) Bleeding sores, fever, hives, decreased coordination Travil Asthma, diarrhea, dizziness, fatigue, seizures Wellbutrin (bupropion hydrochloride) Agitation, dry mouth, headache, nausea, rash Zoloft (sertraline) Diarrhea, fainting, gas, headache, nervousness http://www.healthline.com/sw/wl-about-selective-serotonin-reuptake-inhibitors-ssris Each year millions of Americans are prescribed antidepressants known as selective serotonin reuptake inhibitors (SSRIs) to treat depression, panic disorder and compulsive behavior. Examples of these drugs include Prozac, Lexapro, Zoloft, Celexa and Paxil. These medications work by affecting substances in the brain called neurotransmitters. If you take an antidepressant, it's important to continue to do so for at least four to nine months after you begin to feel better, to prevent a recurrence of the depression. When the doctor feels the medication can be discontinued, you may have no trouble with withdrawal symptoms if you follow your provider's instructions. But some people experience withdrawal side effects when discontinuing medication; these side effects can include balance problems, flulike symptoms, blurred vision, irritability, tingling sensations, vivid dreams, nervousness and nausea. If you do, these should be reported to your doctor promptly. SSRIs. The most common side effect of SSRIs is excitation and insomnia. Excitation has been reported in over 20% of patients, and insomnia in 33%. Significant weight loss has been frequently reported, but most commonly in patients who are already underweight. SSRIs may cause some sedation, and patients should be cautioned not to perform tasks requiring alertness until they have evaluated the effects of these drugs. SSRIs are pregnancy category C drugs. Most SSRIs are excreted in breast milk, and there have been anecdotal reports of somnolence in infants whose mothers were taking SSRIs while breastfeeding. Tricyclic antidepressants. Amoxepine (not marketed by brand, generic available), although a tricyclic antidepressant rather than a neuroleptic (major tranquilizer), displays some of the more serious effects of the neuroleptics, including tardive dyskinesias (drug induced involuntary movements) and neuroleptic malignant syndrome, a potentially fatal syndrome whose symptoms include high fever, altered mental status, irregular pulse or blood pressure, and changes in heart rate. These adverse effects have not been reported with other tricyclic antidepressants. The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic effects, such as dry mouth, dry eyes, and difficult urination. Alterations in heartbeat are also common, and may progress to congestive heart failure, stroke, and sudden death. Tricyclic antidepressants are in pregnancy categories C or D, although there have been no formal studies of the drugs on fetal development. There are no studies of effects on newborns, but some anecdotal reports of malformations have resulted from animal studies. The drugs are excreted in breast milk. SSRIs should not be administered with MAOIs. Allow a wash-out period of about four weeks before switching from one class of drugs to the other. Allow five weeks if switching from fluoxetine (Prozac) to an MAOI. MAOIs have many interactions; however the best known are those with foods containing the amino acid tyramine. These include aged cheese, chianti wine, and many others. Patients and providers should review the MAOI diet restrictions before using or prescribing these drugs. Because of the severity of MAOI interactions, all additions to the patient's drug regimen should be reviewed with care. SSRIs interact with a number of other drugs which act on the central nervous system. Use care in combining these drugs with major or minor tranquilizers, or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol). http://www.healthyplace.com/depression/antidepressants/antidepressant-medications-for-depression/menu-id-68/ Most people do best with a combination of medications for depression and therapy. http://www.healthyplace.com/depression/psychotherapy/nimh-psychotherapy-and-antidepressant-medications-work-best/menu-id68/ Most do best with combined treatment: antidepressant medication to gain relatively quick symptom relief and psychotherapy to learn more effective ways to deal with life's problems, including depression. Depending on the patient's diagnosis and severity of depression symptoms, the therapist may prescribe antidepressant medication and/or one of the several forms of psychotherapy that have proven effective for depression. http://www.healthyplace.com/depression/antidepressants/antidepressant-medications-for-depression/menu-id-68/ Most antidepressants are believed to work by slowing the removal of certain chemicals from the brain. These chemicals are called neurotransmitters (such as serotonin and norepinephrine). Neurotransmitters are needed for normal brain function and are involved in the control of mood and in other responses and functions, such as eating, sleep, pain, and thinking. Antidepressants help people with depression by making these natural chemicals more available to the brain. By restoring the brain's chemical balance, antidepressants help relieve the symptoms of depression. Specifically, antidepressant drugs help reduce the extreme sadness, hopelessness, and lack of interest in life that are typical in people with depression. These drugs also may be used to treat other conditions, such as obsessive compulsive disorder, premenstrual syndrome, chronic pain, and eating disorders. Selective serotonin reuptake inhibitors act only on the neurotransmitter serotonin, while tricyclic antidepressants and MAO inhibitors act on both serotonin and another neurotransmitter, norepinephrine, and may also interact with other chemicals throughout the body. Tricyclic Antidepressants The tricyclics have been used to treat depression for a long time. They act on both serotonin and another neurotransmitter, norepinephrine, and may also interact with other chemicals throughout the body. They include amitriptyline (brand name: Elavil), desipramine (brand name: Norpramin), imipramine (brand name: Tofranil) and nortriptyline (brand names: Aventyl, Pamelor). Common side effects caused by these medicines include dry mouth, blurred vision, constipation, difficulty urinating, worsening of glaucoma, impaired thinking and tiredness. These antidepressants can also affect a person's blood pressure and heart rate. Other Antidepressants Other antidepressants exist that have different ways of working than the SSRIs and tricylics. Commonly used ones are venlafaxine, nefazadone, bupropion, mirtazapine and trazodone. Less commonly used are the monoamine oxidase inhibitors (MAOIs). Effective Depression Recovery We believe that long-term recovery from depression ultimately requires addressing the underlying relationship causes of depression, not simply symptoms such as chemical imbalance and depressive thoughts. This is why healing both the relationship environment and the whole person is vital in preventing relapse. (The Uplift Program has a 94% success rate, according to follow-up questionnaires up to 2 years later.) Good relationships: studies show that relationships with partners, carers, teachers, co-workers and a supportive social network results in physical and emotional healing, happiness and life satisfaction, and prevents isolation and loneliness, major factors in depressive illness. [25] [Caring Relationships Crucial to Healing | If Richer Isn't Happier, What Is? | Happiness Is...] Understanding the real causes of depression so that people don't feel inadequate for not having been cured. [26] Learning how to create relationships that meet needs not met in childhood. [27] Identifying emotional, cognitive, relationship and neuromuscular patterns and learning concrete tools to change these, including many CBT techniques. A safe, supportive and non-judgemental group environment. A good relationship with a therapist or physician. [Therapy Can Change Brain Neurobiology | Couples Therapy Beats Antidepressants] Techniques to boost self-esteem and a sense of competence. Feldenkrais or Repatterning Movements (RPMs) that promote immediate improvements in wellbeing and effective movement while stimulating the brain to learn to form new connections on the basis of function instead of habit. [28] Moderate and even gentle exercise such as a brief walk. [29] Feldenkrais-type movements also help ease chronic pain often associated with depression and enable people to learn more functional, efficient and pleasurable ways of walking. [Better Mood a Short Walk Away | Why Exercise Cheers You Up] Meditation, prayer and relaxation exercises such as yoga or our own Meditations in Movement. [30] [Buddhists are Happier | Saying the Rosary is Good for Health] Fostering spiritual beliefs and a sense of purpose and sharing them with others. [31] [Faith, Social Ties "Protective" | Spiritual Belief Helps Grieving Process | Spiritual Beliefs Ward Off Depression] Spending time in nature and with pets. Even a potted plant or view from your office will help. [32] [Natural Scenes Calm Drivers | Dr Rex to the Rescue] Experiencing an ongoing environment that is free from trauma and very supportive so that the body and the brain can heal and develop. Note that it is important to consult a healthcare practitioner or physican and never come off antidepressants without their advice. http://www.upliftprogram.com/contact.html This uplift program would be a great connection for your nutritional health solutions. 1] NIMH. “The Numbers Count: Mental Illness in America,” Science on Our Minds Fact Sheet Series. [2] Australian Institute of Health and Welfare, 1998. “National Health Priority Areas Mental Health: A Report Focusing on Depression.” Depression statistics in Australia are comparable to those of the US and UK. [3] Study published in Psychiatric Services, April 2004. Reported in our health news archive: Pill-Popping Pre-Schoolers, Even Toddlers Get the Blues [4] Harvard University study reported in Harvard Mental Health Newsletter, February 2002. [5] World Health Organization (WHO) report quoted in BBC-Online January 9, 2001. [6] National Institute of Mental Health (NIMH). “The Numbers Count: Mental Illness in America,” Science on Our Minds Fact Sheet Series. [7] National Mental Health Association (NMHA) study reported in MSNBC Health Today, March 10, 2004. [8] NMHA Survey, 1996. NMHA factsheet on women and depression. [9] “National Healthcare Quality Report”, 2003. [10] D F Bailey, and J L Moore, III. “Emotional Isolation, Depression, and Suicide Among African American Men: Reasons for Concern.” In C Rubin (Ed), Linking Lives Across Borders: Gender-Sensitive Practice in International Perspective, (Pacific Grove, CA Books/Cole). [11] Agency for Healthcare Research and Quality, 2003. “National Healthcare Quality Report.” This is a widely quoted statistic, though some experts such as Dr Christopher L Summerville, Executive Director of the Manitoba Schizophrenia Society, member of the Board of Directors of Mood Disorders of Canada, have cited higher figures. [12] WHO report on mental illness released October 4, 2001. Health news stories: Depression Link to Heart Disease, Hostility, Depression May Boost Heart Disease [13] According to a 2004 Rand Corporation report. [14] Newer figures are lower but this figure was reported in the NY Times article Antidepressants Lift Clouds, But Lose 'Miracle Drug' Label, June 30, 2002. Also C Bruce Baker, MD, “Quantitative Analysis of Sponsorship Bias in Economic Studies of Antidepressants,” The British Journal of Psychiatry 2003, 183: 498-506. [15] S. Vedantam. “FDA Links Antidepressants, Youth Suicide Risk.” Washington Post, 23 February, 2004, page A01. W. Meijer, et al. “Association of Risk of Abnormal Bleeding with Degree of Serotonin Reuptake Inhibition by Antidepressants,” Archives of Internal Medicine 2004, 164:2367-2370. Health news story: Antidepressants May Increase Risk of Abnormal Bleeding. [16] J. Jureidini, et al. “Efficacy and Safety of Antidepressants for Children and Adolescents,” British Medical Journal 2004, 328:879-883. Health news story: The Antidepressant Storm Rages On: Ely Lily Knew of Prozac Risk. [17] B Timothy Walsh, et al., “Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing,” JAMA, Apr 2002, 287:1840-1847. Irving Kirsch, Ph.D., and David Antonuccio, Ph.D. “Antidepressants Versus Placebos: Meaningful Advantages Are Lacking,” Psychiatric Times 2004, 19:9. Also see Burns et al., “Rumble in Reno: The Psychosocial Perspective on Depression,”. Health news stories: Antidepressants Versus Placebos: Meaningful Advantages Are Lacking, Placebos as Good as Antidepressants. [18] Jackie Gollan, University of Washington, report presented to the Association For the Advancement of Behavior Therapy, December 1999. [19] Virtually every recent study has linked depression to childhood trauma and abuse including Deborah Lott, “Childhood Trauma, CRF Hypersecretion and Depression,” Psychiatric Times, October 1999, 16:(10); Danya Glaser, “Child Abuse and Neglect and the Brain,” J Child Psychol. & Psychiat. 2000, 41:1:97-116; L Rowell Huesmann, et al., University of Michigan, “Longitudinal Relations Between Children's Exposure to TV Violence and Their Aggressive and Violent Behavior in Young Adulthood: 1977 - 1992,” Developmental Psychology, 39:2. An up-to-date definition of what constitutes childhood abuse can be found in the American Academy of Pediatrics report, “The Psychological Maltreatment of Children,” April 2, 2002. Health news stories: Stress and Trauma Increase Risk of Depressive and Anxiety Disorders, Maternal Deprivation Triggers Manic Depression. [20] Studies include Meena Vythilingam, “Childhood Trauma Associated With Smaller Hippocampal Volume in Women With Major Depression,” American Journal of Psychiatry, 2002, 159:2072-2080, see Smaller Hippocampal Volume Predicts Vulnerability to Psychological Trauma. J D Connolly et al., “Human fMRI Evidence for the Neural Correlates of Preparatory Set,” Nature Neuroscience, 2002, 5:1345-1352. Also Daniel Amen, MD, “Why Don't Psychiatrists Look at the Brain,” Neuropsychiatry Review, February 2001, 2:1. [21] David Burns et al., “Rumble in Reno: The Psychosocial Perspective on Depression,” Psychiatric Times, 2000, 17(8). Health news story: Myths of Depression Challenged. [22] Widely known, but see Prof Steven Dubovsky, Mind Body Deceptions (New York, Norton & Co, 1997). [23] J I Escobar et al, “Somatization in the Community,” Archives of General Psychiatry (1987) 44:713-718; and Z J Lipowski, “Somatization: Medicine's Unsolved Problem,” Psychosomatics, 1987, 28:294-297. More recent studies have come to the same broad conclusions. See A J Barsky, “Somatization and Medicalization in the Era of Managed Care,” Journal of the American Medical Association (JAMA), 1995, 274:1931-1934. Health news stories: Depression Lowers Immunity, Depression and Illness [24] For diabetes: “Depression in Adults With Diabetes” by Patrick J Lustman, PhD, and Ryan Anderson, Psychiatric Times, January 2002, 19:1, see Depression May Cause Diabetes; for vision loss: see article in Ophthalmology by Stuart I Brown MD, chairman of UCSD's Department of Ophthalmology; for heart disease: many, including “Treating the Patient as a Whole Person” by Elizabeth Fried Ellen, LICSW, Psychiatric Times, June 2001, 17:6; Julia Hippisley Cox et al, “Depression as a Risk Factor for Ischaemic Heart Disease in Men,” British Medical Journal (BMJ), 1998, 316:1714-1719, also Prof Michael Frenneaux, University of Wales College of Medicine study for the British Heart Foundation, see Depression Link to Heart Disease and Hostility, Depression May Boost Heart Disease; for breast & prostate cancer: study by Joseph Gallo, Johns Hopkins School of Public Health, “Major Depression and Cancer,” Cancer Causes and Control, September 2000, 11:8, see Breast Cancer, Depression and PTSD. [25] Numerous studies support our assertion that good relationships are the most important healing mechanism in mood disorders. See Roy F Baumeister, and Mark R Leary, “The Need to Belong: Desire for Interpersonal Attachments as a Fundamental Human Motivation,” Psychological Bulletin, 1995, 117(3)497-529. Press release: Caring Relationships Crucial to Healing. For relationships as factors in happiness and life satisfaction see our health news stories If Richer Isn't Happier, What Is?, Happiness Is.... [26] See T Stompe et al., “Guilt and Depression: A Cross-Cultural Comparative Study,” Psychopathology, 2001, 34(6):289-98. [27] For a thorough overview of our theory of “needs-based” relationships see our book Creating Optimism: A Proven, 7Step Program for Overcoming Depression, (New York, McGraw-Hill, 2004). See Abraham Maslow for other theories of need. [28] Alicia Fortinberry has applied the work of Moshe Feldenkrais to develop Repatterning Movements (RPMs), which address emotional patterns and help heal depression. [29] For example J Blumenthal et al., "Effects of Exercise Training on Older Patients With Major Depression," Archives of Internal Medicine 1999, 159:2349-2356. In a follow-up study carried out 6 months later the team found that walkers relapsed far less than those only on antidepressants. Health news stories: Better Mood a Short Walk Away, Why Exercise Cheers You Up. [30] For example Owen Flanagan, “The Colour of Happiness,” New Scientist May 2003, 178(2396):44. See Buddhists are Happier, Saying the Rosary is Good for Health. [31] For example Bridget Murray, “Getting to the Essential 'We' in Wellness,” Monitor on Psychology, November 2002, 33(10). More specifically H G Koenig, et al., “Modeling the Cross-Sectional Relationships Between Religion, Physical Health, Social Support, and Depressive Symptoms,” American Journal of Geriatric Psychiatry, (1997) 5:131-143. Health news stories: Faith, Social Ties "Protective", Spiritual Belief Helps Grieving Process, Spiritual Beliefs Ward Off Depression. [32] For example Rebecca Clay, “Green is Good for You,” Monitor on Psychology, 2001, 32(4). And Sandra B Barker, “Therapeutic Aspects of the Human-Companion Animal Interaction,” Psychiatric Times, 1999, 16(2). Health news stories: Natural Scenes Calm Drivers, Dr Rex to the Rescue. Top of page About the Authors Dr Bob Murray is a widely published psychologist and expert on emotional health and optimal relationships. Alicia Fortinberry is a psychotherapist, health writer and executive coach. Together they are the founders of the highly successful Uplift Program, and authors of Raising an Optimistic Child (McGraw-Hill, 2006) and Creating Optimism (McGraw-Hill, 2004). New York Times article about failed success of anti depresents: http://www.nytimes.com/2002/06/30/us/antidepressants-lift-clouds-but-lose-miracle-druglabel.html?sec=health Antidepressants Lift Clouds, But Lose 'Miracle Drug' Label The following article was reported by Erica Goode, Melody Petersen and Andrew Pollack and was written by Ms. Goode. Published: June 30, 2002 Sign in to Recommend Twitter Print Sign In to E-Mail Single-Page Correction Appended Fourteen years after Eli Lilly introduced a small green and white capsule called Prozac, antidepressants have mushroomed from a modest market into a $12 billion industry. And Americans, little by little, are coming to think of depression as an illness like any other, a topic discussed on dates and at dinner parties. But the euphoria that greeted the arrival of the generation of drugs that Prozac heralded has faded. Millions are helped by antidepressants, with some studies indicating that 35 to 45 percent of those who take them experience complete relief from their symptoms. But millions more, 55 to 65 percent, are not helped nearly enough. Some people experience no side effects, but for others, sexual dysfunction, emotional numbing, insomnia, weight gain, restlessness and memory lapses make the drugs unusable -- or simply not worth the trouble. Many patients end up on a merry-go-round of medication trials, switching repeatedly from one drug to another or combining drugs to maximize their effects. ''There is no question that the drugs work,'' said Dr. Steven Hyman, the director of the National Institute of Mental Health before becoming the provost at Harvard, ''but they leave a lot to be desired.'' At the same time, the approaching expiration of the the exclusive patents on many bestselling drugs of the 1990's has given pharmaceutical companies other worries. Eli Lilly's patent on Prozac ran out last August, opening the field to a crowd of generic equivalents and resulting in a drop of more than 80 percent in sales of the brand-name drug. The market for antidepressants, which in 1998 grew by 24 percent, is expected to expand by only 5 percent this year, said Richard T. Evans, an analyst at Sanford C. Bernstein & Company. Scrambling to regain their competitive edge, the drug manufacturers are searching for new molecules that are more effective and have fewer side effects. They are tweaking the chemical structures of existing drugs and reharnessing old standbys for new uses, marketing them for everything from social phobia to generalized anxiety and severe premenstrual distress. Psychiatrists argue that such conditions are real illnesses that cause real suffering. But others say the impression often conveyed by commercials for the drugs is clear: almost anyone could benefit from them. ''The symptomatology is so broad and vague that almost any one of us could say, yeah, that is me,'' said Arthur A. Levin, director of the Center for Medical Consumers. Yet even the most aggressive advertising is unlikely to be enough to solve the industry's problems, analysts say. What is really needed is a new class of drugs, one that will have as much impact -- clinically and financially -- as Prozac did 14 years ago. ''The field is waiting for the next breakthrough in terms of new treatments, through new mechanisms,'' said Dr. Alan Schatzberg, the chairman of psychiatry at Stanford University School of Medicine. ''That's what people are hungering for.'' Several new antidepressants will reach the market soon. Lexapro, from Forest Laboratories, maker of Celexa, is expected to reach drugstores as early as next month, and Eli Lilly's drug Cymbalta should arrive late this year or early next. But no breakthrough product is in sight. The very complexity of depression as an illness, experts say, makes it unlikely that the next Prozac will arrive soon. The Promise in a Pill The earliest antidepressants were discovered by accident. Iproniazid, a drug first used for depression in the 1950's, was a treatment for tuberculosis before doctors noticed its moodelevating effects. Prozac, in its way, was also a product of serendipity. It arrived at a time when scientists were first exploring in earnest the biological underpinnings of depression, and when organizations like the National Alliance for the Mentally Ill and the National Depressive and Manic-Depressive Association were working to convince Americans that depression and other serious mental disorders were illnesses like diabetes or heart disease, not weaknesses or failures of character. 1 2 3 4 5 NEXT PAGE > Correction: July 7, 2002, Sunday A front-page article last Sunday about changing attitudes toward Prozac and other antidepressants misstated the chemical relationship between Allegra and Seldane, two anti-allergy medicines cited in the article as examples of drug companies' efforts to develop new drugs from older ones. Allegra was developed from a chemical formed when Seldane was metabolized in the body; it is not an enantiomer, or mirror-image isomer, of Seldane. Sign In to E-Mail Print Single-Page http://www.academon.com/Cause-and-Effect-Essay-Anti-Depressants-and-Teenagers/117807 the actual increase of suicidal thoughts, an increased chemical dependence on the drugs itself and the long-term damage to brain and neural development as a result of the use of anti-depressants at a young age. The paper praises the trend of doctors recommending extensive therapy to teenagers with emotional problems and severe depression rather than prescribing anti-depressant medications. http://bipolar.about.com/cs/bpbasics/a/what_causes_bp.htm A 2000 study in the American Journal of Psychiatry reported "in those with bipolar disorder, two major areas of the brain contain 30 percent more cells that send signals to other brain cells." This report theorizes that "the extra signal-sending cells may lead to a kind of overstimulation, which makes sense considering the symptoms of bipolar disorder(1)." Neurotransmitters However, exactly what is inherited? The neurotransmitter system has received a great deal of attention as a possible cause of bipolar disorder. Researchers have known for decades that a link exists between neurotransmitters and mood disorders, because drugs which alter these transmitters also relieve mood disorders(4). A neurotransmitter is a chemical substance that transmits nerve impulses across a synapse - the space between nerve cells or neurons. In bipolar disorder, the important neurotransmitters are serotonin, dopamine, norepinephrine and GABA. (http://bipolar.about.com/od/glossary/g/gl_neurotrans.htm) Some studies suggest that a low or high level of a specific neurotransmitter such as serotonin, norepinephrine or dopamine is the cause. Other studies indicate that an imbalance of these substances is the problem, i.e., that a specific level of a neurotransmitter is not as important as its amount in relation to the other neurotransmitters(2). Still other studies have found evidence that a change in the sensitivity of the receptors on nerve cells may be the issue(4). Stress Triggers For mental, emotional and environmental issues, stressful life events are thought to be the main element in the development of bipolar disorder. These can range from a death in the family to the loss of a job, from the birth of a child to a move. It can be pretty much anything, but it cannot be precisely defined, since one person's stress may be another person's piece of cake. With that in mind, research has found that stressful life events can lead to the onset of symptoms in bipolar disorder. However, once the disorder is triggered and progresses, "it seems to develop a life of its own." Once the cycle begins, psychological and/or biological processes take over and keep the illness active(2). • • Genetic Factors When talking about biological causes, the first issue is whether bipolar disorder can be inherited. This question has been researched through multiple family, adoption and twin studies. In families of persons with bipolar disorder, first-degree relatives (parents, children, siblings) are more likely to have a mood disorder than the relatives of those who do not have bipolar disorder(3). Studies of twins indicate that if one twin has a mood disorder, an identical twin is about three times more likely than a fraternal twin to have a mood disorder as well(2). http://bipolar.about.com/od/causes/Causes_of_Bipolar_Disorder.htm Bipolar disorder - also known as manic depression or manic-depressive illness - is a serious illness for which researchers are trying to discover a cause. This article presents the theories now considered to be the most likely cause of bipolar disorder. http://psychcentral.com/lib/2007/the-causes-of-bipolar-disorder-manic-depression/ The cause of bipolar disorder is not entirely known. Genetic, neurochemical and environmental factors probably interact at many levels to play a role in the onset and progression of bipolar disorder. The current thinking is that this is a predominantly biological disorder that occurs in a specific part of the brain and is due to a malfunction of the neurotransmitters (chemical messengers in the brain). As a biological disorder, it may lie dormant and be activated spontaneously or it may be triggered by stressors in life. http://www.antidepressantsfacts.com/casualties.htm - Amazing fact regarding the shootings and killings due to antidepressants http://www.antidepressantsfacts.com/antidepressants-placebo2.htm Antidepressants Proven to Work Only Slightly Better Than Placebo By Dr. Irving Kirsch E-mail: [email protected] Although antidepressant medication is widely regarded as effective, a recent metaanalysis of published clinical trials indicates that 75 percent of the response to antidepressants is duplicated by placebo. The report analyses the data submitted to the U.S. Food and Drug Administration (FDA) for approval of recent antidepressant medications. We analyzed the efficacy data submitted to the FDA for the six most widely prescribed antidepressants approved between 1987 and 1999: Prozac Paxi Zoloft Effexor Serzone and Celexa. Results are reported from all well controlled efficacy trials of the use of these medications for the treatment of depression. FDA medical and statistical reviewers had access to the raw data and evaluated the trials independently. The findings of the primary medical and statistical reviewers were verified by at least one other reviewer, and the analysis was also assessed by an independent advisory panel. More important, the FDA data constitute the basis on which these medications were approved. Approval of these medications implies that these particular data are strong enough and reliable enough to warrant approval. To the extent that these data are flawed, the medications should not have been approved. In order to generalize the findings of the clinical trial to a larger patient population, FDA reviewers sought a completion rate of 70% or better for these typically 6week trials. Only 4 of 45 trials, however, reached this objective. In clinical trials, the effect of the active drug is assumed to be the difference between the drug response and the placebo response. This report showed that the FDA clinical trials data indicate that 18% of the drug response is due to the pharmacological effects of the medication. Overall, the drug/placebo difference was less than 2 points on the HAM-D, a highly reliable physician-rated scale that has been reported to be more sensitive than patient-rated scales to drug/placebo differences. Although mean differences were small, most of them favored the active drug, and overall, the difference was statistically significant. There were only 4 trials in which mean improvement scores in the placebo condition were equal to or higher than those in the drug condition, and in no case was placebo significantly more effective than active drug. This may indicate a small but significant drug effect. However, it is also possible that this difference between drug and placebo is an enhanced placebo effect due to the breaking of blind. These data raise questions about the criteria used by the FDA in approving antidepressant medications. The FDA required positive findings from at least two controlled clinical trials, but the total number of trials can vary. Positive findings consist of statistically significant drug/placebo differences. The clinical significance of these differences is not considered. To summarize, the data submitted to the FDA reveal a small but significant difference between antidepressant drug and inert placebo. This difference may be a true pharmacological effect, or it may be an artifact associated with the breaking of blind by clinical trial patients and the psychiatrists who are rating the severity of their conditions. In any case, the difference is relatively small (about 2 points on the HAM-D), and its clinical significance is dubious. Research is therefore needed to assess the additivity of antidepressant drug and placebo effects. If there is a powerful antidepressant effect, then it is being masked by a nonadditive placebo effect, in which case current clinical trial methodology may be inappropriate for evaluating these medications, and alternate methodology need to be developed. Conversely, if the drug effect is as small as it appears when drug/placebo differences are estimated, then there may be little justification for the clinical use of these medications. The problem, then, would be to find an alternative, as the clinical response to both drug and placebo is substantial. Placebo treatment has the advantage of eliciting fewer side effects. However, the deception that is inherent in clinical administration of placebos inhibits their use. Thus, the development of nondeceptive methods of eliciting the placebo effect would be of great importance. Prevention & Treatment, Volume 5, Article 23, July 15, 2002 First Posted in Red Flags Weekly July 17, 2002 Kids Depression http://www.healthline.com/healthday/kids-suicide-risk-same-for-all-antidepressants Kids' Suicide Risk Same for All Antidepressants Findings support FDA's 'black box' warning on all SSRIs, researchers say MONDAY, April 12 (HealthDay News) -- There appears to be no difference among antidepressants in raising a kid's risk of suicidal thoughts, a new long-term study shows. The research supports the U.S. Food and Drug Administration's decision in 2004 to mandate a "black box" warning on all antidepressants for an increased suicidality risk in children and adolescents who go on the medications. And it answers an oft-raised question about which medications carry the most risk. "Across the most frequently prescribed antidepressant agents, there was no difference in risk of suicide attempts and completed suicides," said lead researcher Dr. Sebastian Schneeweiss, an associate professor of epidemiology at the Harvard School of Public Health. The FDA showed a doubling in the risk of suicidal ideation among children taking antidepressants, compared with placebo, Schneeweiss noted. But, Schneeweiss added, the FDA analysis did not specify which medications were used. so there was no way to tell whether there were differences in risk. "Physicians need to know if there is an agent where the risk is reduced or particularly elevated," he said. "That is important for clinical practice." The report is published in the April 12 online edition of Pediatrics. For the study, Schneeweiss's team collected data on 20,906 children aged 10 to 18 who had been diagnosed with depression in British Columbia. They were followed for nine years. The children and adolescents in the study were on a variety of commonly prescribed antidepressants called selective serotonin reuptake inhibitors (SSRIs), including citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). In the first year after starting treatment with antidepressants, there were 266 suicide attempts and three completed suicides. However, no significant difference in suicide attempts or completed suicides was noted based on which antidepressant the adolescent was taking, the researchers found. Given these findings, doctors can focus their attention on which of the several SSRIs is most effective for an individual patient and not be concerned about increasing the potential risk of suicide, Schneeweiss said. Different SSRIs act differently in individual patients, so now the doctor can find the most effective one and, because the risk is the same with all, "take safety out of the equation," he added. "Nevertheless, you will still have to monitor the patient very carefully, because the elevated risk is still there," Schneeweiss said. Much debate followed the FDA's decision to place a black box warning on antidepressants. One of the continuing arguments is that by imposing such a warning, clinicians will shy away from prescribing antidepressants to children and adolescents who really need them. This could in turn make their depression worse, which could lead to suicide. Dr. David Fassler, a clinical professor of psychiatry at the University of Vermont College of Medicine, said that "the results of this study are consistent with previous reports and with general clinical experience." The article represents a contribution to the growing literature on this complex issue, Fassler said. "However, it does not shed much light on the larger question of whether or not the decision to impose a black box warning on these medications was correct and justified in the first place. Nor does the current analysis contribute to our understanding of the public health consequences of the FDA's action. Hopefully, subsequent large-scale, longitudinal studies will be designed, which will help us more fully address these critical, and as-yet unanswered, questions," he said. Another expert, Dr. David A. Brent, a professor of psychiatry at the University of Pittsburgh, said that he was "not sure how they draw the conclusion that these findings support the black box warning." The fact that those who use the drugs have similar rates of suicide does not justify the black box warning; it just indicates that whatever the warning should be, it should be similar across drugs, Brent said. "The authors themselves say that the fivefold increased rate of suicide is probably a function of comorbidity and depression rather than drug. In fact, most psychological autopsy studies estimate the risk for suicide with depression to be 10 to 30 times higher, and most of those kids were untreated," he said. "So there may actually be a protective effect, but certainly the rate is not any higher than in depressed folks without exposure to antidepressants." "The conclusions from the paper supporting the black box warning don't logically follow from the data that they provide," Brent added. "At a minimum, you would have to show that the incidence of suicidal acts and completions is higher in those who were treated vs. those not treated, and that was not done." More information