Introduction Description A depressive disorder is a whole-body illness, involving your body, mood, and thoughts. It affects the way you eat and sleep, the way you feel about yourself, and the way you think about things. A depressive disorder is not the same as a passing blue mood. It is not a sign of personal weakness or a condition that can be willed or wished away. People with a depressive illness cannot merely “pull themselves together” and get better. Without treatment, symptoms can last for weeks, months, or years. The appropriate treatment, however, can help most people who suffer from depression. Types Of Depression Depressive disorders come in different forms. The three most prevalent types of depression are major depression, bipolar disorder, and dysthymia. Within these types there are variations in the number of symptoms, their severity, and persistence. Major depression is manifested by a combination of symptoms that interfere with the ability to work, sleep, eat, and enjoy once pleasurable activities. These disabling episodes of depression can occur once, twice, or several times in a lifetime. Bipolar disorder, formerly called manic-depressive illness, involves cycles of depression and elation or mania. Sometimes the mood switches are dramatic and rapid, but most often they are gradual. When in the depressed cycle, a patient can have any or all of the symptoms of a depressive disorder. When in the manic cycle, any or all symptoms listed under mania may be experienced. Mania often affects thinking, judgment, and social behavior in ways that cause serious problems and embarrassment. Bipolar disorder is often a chronic recurring condition. A less severe type of depression, dysthymia, involves long- term, chronic symptoms that do not disable, but keep you from functioning at “full steam” or from feeling good. Sometimes people with dysthymia also experience major depressive episodes. Symptoms Of Major Depression And Bipolar Disorder Not everyone who is depressed or manic experiences every symptom. Some people experience a few symptoms, some many. Also, severity of symptoms varies with individuals. Here are some of the possible symptoms of major depression and bipolar disorder. Major Depression: Persistent sad, anxious, or “empty” mood Feelings of hopelessness, pessimism Feelings of guilt, worthlessness, helplessness Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex Insomnia, early morning awakening, or oversleeping Appetite and/or weight loss or overeating and weight gain Decreased energy, fatigue, being “slowed down” Thoughts of death or suicide; suicide attempts Restlessness, irritability Difficulty concentrating, remembering, making decisions Persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain Bipolar Disorder: Inappropriate elation Inappropriate irritability Severe insomnia Grandiose notions Increased talking Disconnected and racing thoughts Increased sexual desire Markedly increased energy Poor judgment Inappropriate social behavior Causes Of Depression The causes of depression have not yet been established and explanations for the occurrence of the disorder vary to the theoretical method that is applied to it. Biological, family, and social factors have all been found to play a role in the disorder. Depression may be most clearly seen as occurring due to both biological and environmental factors. The biological theory of depression postulates that the disorder is caused by a deficiency in one or more neurotransmitters, most likely serotonin and norepinenphrine, and possibly dopamine. Support for this theory comes from the fact that drugs that potentate the effects of these neurotransmitters tends to result in a decrease in depressive symptoms in most patients. Psychological theories of depression vary greatly in their explanation of the disorder and include causes such as unconscious conflict, distorted thinking, and lack of positive reinforcement. There is evidence suggesting that depression may have a genetic basis. In studies of adoptive children whose biological parents had depression, these children tended to show a higher incidence of the disorder than the general population. Treatment Treatment choice will depend on the outcome of the evaluation. There are a variety of antidepressant medications and psychotherapies that can be used to treat depressive disorders. Some people do well with psychotherapy, some with antidepressants. Some do best with combined treatment: medication to gain relatively quick symptom relief and psychotherapy to learn more effective ways to deal with life’s problems. Depending on the diagnosis and severity of symptoms, the patient may be prescribed medication and/or treated with one of the several forms of psychotherapy that have proven effective for depression. The medictions are classified as follows: Tricylics and Tetracylics Monoamine Oxidase Inhibitors Serotonin-Specific Reuptake Inhibitors Miscellaneous (the chemical structures of some do not fit in with any of the above categories) At times, electroconvulsive therapy (ECT) is useful, particularly for individuals whose depression is severe or life threatening or who cannot take antidepressant medication. ECT often is effective in cases where antidepressant medications do not provide sufficient relief of symptoms. In recent years, ECT has been much improved. The treatment is given in the hospital under sedation so that people receiving ECT do not feel pain. ——————————————————————————– Articles 1. The Mood Molecule, by Micheal D. Lemonick, Time, September 29, 1997 New research is now being conducted on a wide variety of drugs that involve the neurotransmitter serotonin. Serotonin is associated with altering mood states. The lack of serotonin has been implicated in depression, appetite disorders and eating disorders, obsessive compulsive disorder, autism, social phobias, anxiety disorders, migraines, excessive violent behavior, and even schizophrenia. Sertonin is manufactured in the raphe nuclei, and then transported to nerve endings. Scientists have identified at least fifteen different serotonin receptors. The serotonin neurotransmitter is already being used as a form of anti-depressant, the selective serotonin reuptake inhibitors which are now being combined with noradrenaline and norepinenphrine reuptake inhibitors. The serotonin acting antidepressants work by making serotonin and in some cases norepinenphrine available in the brain for longer than usual, which enhances mood states. The new natural antidepressant drug commonly known as St. John?s Wort contains substances that enhance serotonin, dopamine and norepinenphrine. There is now being extensive research done on serotonin and the other neurotransmitters for there effects on disorders like depressive disorders, and though it is unlikely that one drug will be targeted as the antidepressant, a wider variety of medical treatments can treat a wider variety of patients. 2. Nature’s Prozac?, by Madeline Nash, Time, September 22, 1997 Prozac does have its side effects on some of its users, like hypertension, and anyone who has experienced hypertension knows that it is a debilitating side effect that usually causes the user to discontinue use. Prozac is typically used to treat mild depression, and so is the new drug to hit North America called Hypericum, or St. John?s Wort. It is being sold as the ?natural? or ?organic? antidepressant, and it has been known to cause less side effects that any of the other anti-depressants. The British Medical Journal published a review of 23 clinical trials that measured, or attempted to measure the therapeutic potential of Hypericum. Most of the studies showed that Hypericum did improve the moods of some patients in contrast to the placebo, however the studies were small, so more research is needed. In fact, unless Hypericum has generated some mass delusion, which is very unlikely, Hypericum must have a positive effect on mood, or else the sale of the drug would not be soaring. Hypericum also effects serotonin levels. It prolongs the activity of serotonin in the brain. Hypericum seems to prevent the reabsorbtion of norepinenphrine and dopamine by nerve fibers. The biggest problem with Hypericum is the fact that most individuals with mild depression respond better to psychotherapy than medication. This means that affected individuals can just go to the store and begin his or her own pharmacotherapy with Hypericum for just 30c per day, and not deal with the cause of the depression! Also, individuals who are not clinically depressed are beginning to take Hypericum because he or she feels ?blue?, instead of dealing with the environmental factors. This behavior is extremely self-destructive. 3. ECT (Electroconvulsive Therapy) Update, by Dr. Max Fink, the Psychiatric Times, April 1997 The treatment called electroconvulsive therapy has changed very much over the past decade, for the better. It is now safer and has fewer side effects than in the past. Some individuals who suffer from serve depression often do not respond to conventional treatments. Most are extremely suicidal and/or in a manic or catatonic state, and who need constant protection from him or herself. These individuals usually reside in an inpatient facility, where ECT can be performed. Presently, the initial course of treatment is ECT two or more times per week. Later, as the symptoms are reduced, the treatment is reduced to once per week. Then, as the patient’s symptoms are alleviated, and may return home, treatment may drop to once every ten to twenty-one days. After the ECT treatment is complete, drug therapy will begin. It is important to note however, that anticonvulsants are not to be used. Also, Lithium Carbonate is destructive to the course of therapy. An interesting new finding with ECT is that caffine and Theophylline have been found to encourage an earlier clinical response to the treatment, because they enhance the seizure duration. ——————————————————————————– Technologies 1. Reboxetine A new noradrenaline reuptake inhibitor. It is a new discovery that is based on the same biochemical idea as the serotonin reuptake inhibitors. Generic name is Edronax. Developed by Pharma & Upjohn Inc.. It is being promoted as more a more efficient drug than Prozac, and with fewer side effects. Edronax was launched in Britain in July, an is awaiting approval in the rest of Europe. It has not been submitted for approval by the U.S. FDA as of yet. Prozac acts on Serotonin levels, where as Reboxetine acts on the noradrenaline levels. Some experts believe that drive and motivation are related to noradrenaline, and mood states are associated with serotonin. Like the SSRI?s (specific serotonin reuptake inhibitors), the noradrenaline reuptake inhibitor Reboxetine does not have the major adverse side effects as the trycilic antidepressants, such as sexual dysfunction. Reboxetrine has been shown to take effect much faster than any other antidepressant, like Prozac. Has also been seen to be particularly effective in the severe depression group. (I think that this could be due to the quicker results, and that its usage in the severely affected patients should be closely monitored.) 2. Hypericum Perforatum A new drug on the market as an organic substitute Prozac, which is usually prescribed to treat mild depression. Its name Hyperieum is derived from the Greek and means ?over an apparition?. (A reference to its resinous smell.) Commonly know as St. John?s Wort, it is a stalky plant with yellow leaves that has anti-depressant qualities. It is a herbaceous perennial with four-hundred species that grows extremely well and wild except in extreme conditions. The yellow flowers are used. Although it is new to the North American market, it is licensed for treatment of depression, anxiety and sleeplessness in Germany. A study in the British Medical Journal showed that the extract is as effective as conventional anti-depressants, but is cheaper and has fewer side effects. No long term study has been done on the effects of long term usage. Since no research has been done on the long-term effects of usage, this medical trend poses the same potential disaster as was found in the usage of fenfluramine and phentermine (damage to cardio-valves). 3. Lithium Carbonate A medication usually prescribed for the treatment of an acute manic episode (bipolar depression). It acts as an antidepressant by altering the excitability of the central nervous system. How it works as an antidepressant: The mechanism whereby lithium controls manic episodes is not yet known. Lithium is a monovalent cation which belongs to the group of alkali metals together with sodium, potassium and other elements with which it shares some of its properties. There is evidence that lithium alters sodium transport and may interfere with ion exchange mechanisms and nerve conduction. Fluid and electrolyte metabolism are believed to be altered in affective disorders and this may be related to the therapeutic action of lithium. Lithium can replace sodium in extracellular fluid and during the process of depolarization it has an extremely rapid intracellular influx. However, it is not effectively removed by the sodium pump, thereby preventing the cellular reentry of potassium. As a result, it interferes with electrolyte distribution across the neuronal membrane, leading to a fall in membrane potential and changes in conduction and neuronal excitability. Then, it is important to note that the sodium intake of the patient being treated has his sodium intake monitored, so that it is normal, and stable. (The intake level of sodium should not increase or decrease.) Usage: Some common brand names of Lithium Carbonate are: Carbolith, Cibalith-S, Duralith, Eskalith, Lithane, Lithizine, Lithobid, Lithonate, Lithotabs The therapeutic dose for the treatment of acute mania should be based primarily on the patient’s clinical condition. It must be individualized for each patient according to blood concentrations and clinical response. After the acute manic episode subsides, (usually within a week), the dosage is rapidly reduced because there is then a decreased tolerance to the drug in the patient. Lithium may be used concomitantly with neuroleptic drugs, but additional studies are required to determine the relative advantage of single, combined or sequential treatment of manic episodes. Periodic review and monitoring of kidney and cardiovascular function is essential for safe therapy with lithium carbonate. The formation of nontoxic goiters has been reported during lithium therapy. Hypercalcemia, (associated with lithium induced hyper- parathyroidism), has also been reported. Recent research indicates that: lithium may produce a transitory diuresis with increase in sodium and potassium excretion. therapeutic doses of lithium decrease the 24-hour exchangeable sodium. a possible intracellular retention of lithium may be occurring. lithium may affect the metabolism of potassium, magnesium and calcium. lithium may increase the incidence of cardiac and other anomalies, especially Ebstein’s anomaly. new research (reported to the Clinical Psychology Seminar 1996-1997) points to Lithium?s adverse effects on pregnancy. (In particular, Lithium passes into the mother?s milk, and breast feeding is optional and can be avoided.) Adverse Affects: The most frequent adverse effects are the initial postabsorptive symptoms, believed to be associated with a rapid rise in serum lithium concentrations. They include: gastrointestinal discomfort nausea vertigo muscle weakness a dazed feeling The more common and persistent adverse reactions are: fine tremor of the hands fatigue thirst polyuria nephrogenic diabetes insipidus ——————————————————————————– Career Profiles 1. Neurologist A neurologist may focus on researching the causes, prevention and treatments of depressive disorders. Duties and Working Conditions: Research laboratories of hospitals, universities, or most likely commercial pharmaceutical corporations. Research of the disorder?s basis, causes, prevention and possible treatments. Educational Qualifications: A bachelors degree, or two to four years of pre-medical school. Four years of medical school. A internship of 12-16 months. 2. Psychiatrist The Psychiatrist is needed to diagnose, assess and prescribe medical treatments to individuals affected by a depressive disorder. Psychiatrists may also conduct psychotherapy with an affected patient. Duties and Working Conditions: Psychiatric ward or hospital to diagnose and assess the disorder in individuals. Private practice to treat affected patients and family members. Research of the disorder?s basis, causes, prevention and possible treatments. Educational Qualifications: A bachelors degree, or two to four years of pre-medical school. Four years of medical school. A internship of 12-16 months. A license to practice psychiatric medicine. 3. Psychologist The field of psychology is broad and growing. In the treatment of both Major and Bipolar Depressive Disorder, a clinical psychologist will analyze, diagnose, and assess the disorder in an affected patient. Also, a psychologist may conduct psychotherapy with an affected patient. Duties and Working Conditions: Psychiatric ward or hospital to diagnose and assess the disorder in individuals. Private practice to treat affected patients and family members. Research of the disorder?s basis, causes, prevention and possible treatments. Educational Qualifications: Four years of undergraduate study in clinical psychology at university. Four years of graduate study in clinical psychology at university. A internship of 12-16 months. A license to practice psychological analysis and therapy. ——————————————————————————– Conclusion Up to 15% of patients with severe Major Depressive Disorder die by suicide. Over age 55, there is a quadruple increase in death rate. 10-25% of patients with Major Depressive Disorder have preexisting Dysthymic Disorder. These “double depressions” (i.e., Dysthymia + Major Depressive Disorder) have a poorer prognosis. There are no laboratory findings that are diagnostic for this disorder. Males and females are equally affected by Major Depressive Disorder prior to puberty. After puberty, this disorder is twice as common in females as in males. The highest rates for this disorder are in the 25- to 44-year-old age group. The lifetime risk for Major Depressive Disorder is 10% to 25% for women and from 5% to 12% for men. At any point in time, 5% to 9% of women and 2% to 3% of men suffer from this disorder. Prevalence is unrelated to ethnicity, education, income, or marital status. Onset And Course: Average age at onset is 25, but this disorder may begin at any age. Stress appears to play a prominent role in triggering the first 1-2 episodes of this disorder, but not in subsequent episodes. (An average episode lasts about 9 months.) Recurrence: The risk of recurrence is about 70% at 5 year follow up and at least 80% at 8 year follow-up. After the first episode of Major Depressive Disorder, there is a 50%-60% chance of having a second episode, and a 5-10% chance of having a Manic Episode (i.e., developing Bipolar I Disorder). After the second episode, there is a 70% chance of having a third. After the third episode, there a 90% chance of having a fourth. The greater number of previous episodes is an important risk factor for recurrence. Recovery: For patients with severe Major Depressive Disorder, 76% on antidepressant therapy recover, whereas only 18% on placebo recover. For these severely depressed patients, significantly more recover on antidepressant therapy than on interpersonal psychotherapy. For these same patients, cognitive therapy has been shown to be no more effective than placebo. Familial Pattern And Genetics: Individuals who have parents or siblings with Major Depressive Disorder have a 1.5-3 times higher risk of developing this disorder. The concordance for major depression in monozygotic twins is substantially higher than it is in dizygotic twins. However, the concordance in monozygotic twins is in the order of about 50%, suggesting that factors other than genetic factors are also involved. Children adopted away at birth from biological parents who have a depressive illness carry the same high risk as a child not adopted away, even if they are raised in a family where no depressive illness exists. Interestingly, families having Major Depressive Disorder have an increased risk of developing Alcoholism and Attention-Deficit Hyperactivity Disorder.
British Medical Journal (abstract on the effectiveness of Hypericum Perforatum) No.7052 Volume 313, August 1996. Judith Michelsen, notes by Abbey Strauss, M.D., A Layperson?s Short Classification Of Psychotherapeutic Drugs, Online Psychological Services. Stuart Yudofsky, Psychiatric Drugs, American Psychicatric Press, 1991. D.F. Klien and P.F. Wender, Understanding Depression: A Complete Guide To It?s Diagnosis And Treatment, 1993.