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At the end of the presentation, you should have a global overview of some of the factors that drive the prescribing of medication along with an idea of what factors are important in selecting psychotropic medication. It is hoped that this information will be of value to you in communicating with primary care doctors or psychiatrists and in understanding decision making around psychotropic medication. These are the answers to the questions that you will have to correctly complete in order to obtain continuing education credit for the presentation. 1) The trend is one of increasing utilization of psychotropic medications; 2) When selecting anti-depressants, the SSRI type are generally utilized first and the traditiona TCA's or Tri Cyclic Antidepressants are generally utilized last; 3) Whereas there had really only been one mood stabilizer for a considerable number of years, we now have more choices; 4) The trend in prescribing of anti-psychotics is to move toward Atypical Antipsychotics; and 5) When having to prescribe anxiolytics, the trend is toward non-addicting types when ever it is appropriate. The overal trend is toward an increase in the prescribing of psychotropic medication. The reasons for the increase are the availability of more medications which are effective, safer medications which decrease the risk of mobidity or fatality from overdose, the increasing comfort level of primary care doctors in the prescribing of psychotropic medication, the decreased stigma in taking psychotropic medication along with an enhanced awareness of the benefits that can accrue from these medications, and finally new imaging techniques are confirming the foundation of psychiatric illness is in biology and that this disorders represent abnormal biological functioning of the brain -- not a weakness of character. Accordingly, the use of medication seems more appropriate and acceptable. The first antidepressant was discovered by accident in the 1940's. The antidepressants on this slide are some of the more common ones that belong to the first category of antidepressants. This category of traditional antidepressants are generally referred to as "Trycyclic Antidepressants, or TCA's". Though these first group of antidepressants remain among the most effective of antidepressants, they do have serious shortcomings. Foremost is the risk of fatality when these medications are taken in overdose. The Trycyclic antidepressants are known to cause ventricular arrythmias and status epilipticus which can both be fatal. Other common but often bothersome side effects associated with these type antidepressants are dizziness upon standing up, constipation, weight gain, blurred vision, and problems with memory. The next class of antidepressant medication to be discovered and utilized were the Mono Amine Oxidase Inihibitors -- or MAOI's for short. These antidepressants were found to be especially helpful for what we call "atypical depression" wherein people tend to eat more, not less, and sleep more, not less, and where they are able to appreciate some enjoyment in life when something pleasing occurs. They seemed especially helpful as well for people who experienced rejection sensitivity and for those suffering from panic attacks. Unfortunately, these antidepressants carried with them the risk of developing malignant hypertension and cerebral vascular strokes. These events were likely to occur if the individual taking these antidepressants consumed foods that contained the amino acid tyramine (the precursor to norepinephrine). The dangerous elevation in blood pressure could also occur of the individual were administered certain types of medications. Naturally, these MAOI antidepressant medications could only be given to knowledgeable people who were conscientious, and not so depressed that they would intentionally disregard the dietary restrictions. Other bothersome side effects associated with the MAOI's were weight gain and dizziness when standing up from a sitting or lying position -- called orthostatic hypotension. The New Generation of antidepressants began with Prozac. It belonged to a brand new category of antidepressants called "Selective Serotonin Reuptake Inhibitors". The other SSRI antidepressants that were developed after Prozac are listed on this slide -- paroxetine or Paxil, Sertraline or Zoloft, and fluvoxamine or Luvox. Within 2 years of its introduction, Prozac became the number one selling antidepressant in the world and in the U.S.A. The SSRI's are so called because of their mechanism of action which is to block the serotonin reuptake pump which scavenges the released serotonin through the cell wall back into the intracellular space. The reason why Prozac stormed the market has to do with it being much more safe than the antidepressants which predated it. Not only was it more safe, but people found they had less bothesome side effects. Further, in most cases, Prozac was found to be as effective as the older generation antidepressants. Because of Prozac's success, other pharmaceutical companies wanted to have a similar type anti-depressant and that led to the arrival of the other SSRI's mentioned on the previous slide. The SSRI's, however, do have some shortcomings. They are not always as effective for severe depression as are the Tricyclic Antidepressants. Further, there is usually some impairment of sexual function. This adverse side effect can affect as much as 80-90% of those who are prescribed SSRI's. Because of the desire to maintain the safety aspects of the SSRI's but to have enhanced effectiveness, and to combat the problem with sexual functioning, additional antidepressants have been developed. These new antidepressants are also considered "New Generation" but they are actually a little closer to the Tricyclics in their mechanism of action. These new antidepressants target more than the SSRI system, or they target neurotransmitter systems that are different from Serotonin. These new antidepressants are listed on this slide.The advantages of the 2nd tier of new generation antidepressants include enhanced clinical effectiveness relative to the SSRI's. Additionally, they remain about as safe as the SSRI's and are still relatively well tolerated. Though these newer model antidepressants of the newer generation offer some additional features, they still do not work in all patients. Further, the ratio of reuptake inhibition of the various neurotransmitters may not be ideal. This would lead to intolerable side effects and limited usefulness. Therefore, there is developing a trend to combine neurotransmitter specific antidepressants according to the apparent clincial response of individual patients. The goal is to enhance effectiveness of treatment and diminish problematic side effects. The combinations shown on this slide are some examples of what might be tried in some person who has not responded well to a single antidepressant. This slide demonstrates how the patient profile might infuence the initial selection of an antidepressant. The medications listed for the various patient profiles have been found, over past years, to be of more usefulness than the other antidepressants for that particular type of problem. If the outcome is not so desireable, then an antidepressant that works via a different neurotransmitter system or mechanism might be given a trial. This slide depicts what appears to be the current trend in prescribing of antidepressants. The first effort is generally made with an SSRI because of safety and improved tolerance. Then, should the response not be optimal, another antidepressant that targets a different neurotransmitter system or mechanism of action is often selected. When this, too, seems not to work, then consideration would be given to the older generation antidepressants such as the TCA's and MAOI's. For the longest time, when individuals needed a mood stabilizer, as is often the case with individuals suffering from bipolar disorder, Lithium was the only answer. However, we now have a good many choices. The medications are listed here in the order in which it was recognized that these medications had some therapeutic effect upon mood stabilization. Lithium was the first recognized treatment for mania and John Cade is the individual given credit for this discovery in 1949. Beginning in the 1960's, lithium became widely used in the U.S. for treatment of bipolar disorder. In the 1970's, carbamazepine, known by its brand name of Tegretol, was first used for bipolar disorder. Valproate, known by the brand name of Depakote, was only just recently approved by the FDA for use in bipolar disorder. Gabpentin, or Neurontin, and Lomotrigine, or Lomictal, are newer anticonvulsants which are currently being used as mood stabilizers, though they have not yet been approved for such by the FDA. To summarize the trend as regards mood stabilizers, whereas for the longest time there has been just one or two mood stabilizers, we now have an increasing number of mood stabilizers available. Lithium, however, remains the mood stabilizer of "first choice". Shifting now to antipsychotics, which are sometimes referred to as Neuroleptic medications, we will start by mentioning Chlorpromazine. Chlorpromazine, known by the brand name of Thorazine was the first antipsychotic and it came into use in the 1950's. It was a great tool and gave a degree of control of psychotic disturbances that was up to that point, not available. Many other neuroleptic medications were also developed. None were any more effective but they differed in terms of dosing and side effects. In the 1960's, haloperidol, known by the brand name of Haldol, was developed. Since that time, Haldol has come to probably represent the drug of first choice when it comes to control of psychotic disorders. Listed here are the common adverse side effects of the "typical" neuroleptic medications. The "typicals" are the neuroleptics that we have already been talking about. These side effects include: tremor, stiffness, cogwheeling, acute muscle dystonias, and tardive dyskinesia. One important point about the typical neuroleptics is that they are not effective at treating what we call the "negative" symptoms of schizophrenia. The negative symptoms include affective blunting, alogia, anergia, anhedonia, and avolition. This slide lists the new medications which have collectively come to be called the "Atypical" neuroleptics. The atypicals derive their name because they do not specifically block the D2 (dopamine 2) receptors as do the typical neuroleptics. The first of these atypical neuroleptics to be developed was Clozaril. However, it has not found great favor due to its propensity to cause agranulocytosis (failure to develop blood cells and platelets), and because of its propensity to cause seizures. The atypicals are listed here in the order of their development from the first to the most recent. They are clozapine, risperdone, olanzapine, and quietepine. The advantages of the atypical neuroleptics are listed on this slide. They include reduced tremulousness, muscle stiffness, cogwheeling, muscle dystonias, and reduced risk of tardive dyskinesia. These listed side effects are quite common with the typical neuroleptics. Tardive dyskinesia is especially undesireable and devastating. This side effect is often irreversible and leads to involuntary persistent rhythmic movements of various muscles. One additional advantage to the atypical neuroleptics is that, unlike the typicals, they do help to reverse the negative symptoms of schizophrenia. What would be the disadvantages, then of the atypical neuroleptics? They are listed on this slide. One big disadvantage is the cost. Whereas a month's supply of haloperidol might be about $15, a similar month's supply of olanzapine or risperdone might be $200. Clozaril, because of the federally mandated requirement for blood work and the price of the medication itself, might cost around $10,000 per year. The other disadvantage is that these medicines have been used for so little a period of time, that we do not know if there will develop an untoward outcome if individuals take these medications over prolonged periods of years. This slide summarizes the trend that is occurring in antipsychotic medication prescription practices. The trend is to move away from typical antipsychotics and toward atypical antipsychotics. Shifting now to anxiolytics, or medications which reduce anxiety, we find that the first preparations were barbiturates and non-barbiturate medications such as glutethamide and meprobamate. Prior to the benzodiazepines, these were the prime medications used to reduce anxiety. The disadvantages of these medications were identical. They had a low therapeutic index. This is to say that the amount of medication needed to have a clinical benefit was uncomfortably close to the amount of medication that would have a lethal outcome. In addition, these medications quickly led to tolerance and escalating doses and they were highly abused. With the arrival of the benzodiazepines, we had a new age dawn -- the era of the benzodiazepines. Listed here are some members of the benzodiazepine class of medications. The advantages of the benzodiazepine class of medications was safety safety safety. Whereas it was quite common for people to die from the pre-benzodiazepine era anxiolytics, it was quite uncommon that someone could die from these type anxiolytics. Further, there later developed an antidote that would reverse the sedative effects of benzodiazepine medications in an individual who had taken an overdose. An additional welcome feature of the benzodiazepines is that tolerance did not develop. This meant that if a certain dose was effective to calm a certain level of anxiety in a particular person, it would continue to have the same degree of effectiveness despite the person taking the medication even for years. Despite the dramatic improvement in safety and despite the fact that tolerance does not develop, some people did abuse the benzodiazepines. These people tended to be ones who by their personality make up were invested in abusing other substances. The short duration quick acting benzodiazpines were the ones that tended to be abused. And, there did exist some risk of fatality with the benzodiazpeines. This would be especially so if these medications were taken in overdose with other medications, or with alcohol. For the reasons sited on the past slide, attempts were made to develop a tranquilizer or anxiolytic that was not addictive or abused. One such anxiolytic has been developed. It is called buspirone, or Buspar by its trade name. Additionally, other medications not specifically developed for tranquilization, but which had sedative type side effects were also considered for use in selected cases. These medications included antihistamines, beta blockers, and serotonin (5HT) reuptake inhibitors, or anti-depressants. Therefore the trend in prescribing anxiolytics has been toward increasingly safe, increasingly non addictive, and increasingly non abused medications. 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