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A BRIEF DIGEST ON EVERYTHING YOU EVER WANTED TO KNOW ABOUT THE CHEMISTRY OF EMOTIONS THIRTEEN MEDICATION TYPES THAT CAN CHANGE BRAIN CHEMICALS AND EMOTIONS FRANK B. MINIRTH, M.D. - DIPLOMATE AMERICAN BOARD OF PSYCHIATRY & NEUROLOGY " . . . the mind and the body are one and should not be treated separately . . . ." Plato INTRODUCTION An Untapped Resource. "You're my last hope, Doc. I pray you can help," the middle aged man said. "Well, I hope I'm not anyone's last hope; but perhaps I can help. I will certainly try," I responded. He went on to share how he had struggled with certain emotions for years. Although he believed in counseling, counseling alone had not brought the relief he so wanted. I started the appropriate medication and in two weeks he felt "normal" for the first time in many years. He cried out, "Why didn't someone do this years ago?" Perhaps this is an all too common scenario. There are medications today that may help in almost any emotionally connected issue: obsessive worry, panic anxiety, generalized anxiety, restless legs, too much weight, too little weight, inattention, decreased memory, drug addiction, manic highs, depressive lows, premature ejaculation, impotence, decreased sex drive, too much sex drive, PMS, anger insomnia, pain, psychosis, and many more. The tools are powerful. They must be used in an appropriate, sensitive manner, by a skilled medical doctor. They can decrease symptoms and increase functioning for Christ. I. THE BRAIN - THE LAST FRONTIER. The study of the brain may be the last and most exciting biological frontier. More than fifty percent of the human genome is dedicated to the central nervous system. "No computer has yet to come close" to the human brain (Merck Manual, 1997). The 1990s have been declared the decade of the brain. Research is intense, and the findings are highly encouraging to the understanding of depression, anxiety, panic, obsessive worries, weight issues, inattention problems, pain, memory, anger, energy, sleeplessness, logic, motivation, association, drug abuse, and sexual issues, to name just a few. From research we know that chemicals in the brain (neurotransmitters) play a large part in the symptoms listed above. Psychiatric medications today can often help significantly in abating issues such as those listed above. Often the results are extremely helpful if not dramatic, as the neurotransmitters of the brain are shifted in the appropriate direction through use of the medications. II. NEUROTRANSMITTERS AND EMOTIONS. The neurotransmitters float between the nerve cells (from the synaptosomes of one cell to the dendrite of the next cell, in the space called the synapse). When one considers that there are perhaps upward of one hundred billion nerve cells in the brain, with each having upward of one hundred thousand synapses, then the total number of synapses in one brain becomes unimaginable. There would perhaps be more synapses in one brain than all the stars in the known galaxies. Thus, the power of these synapses and the neurotransmitters in them is awesome. We now know from research that these neurotransmitters are altered in mental disorders. To be overly simplistic: If dopamine is altered, then one may be out of touch with reality; if GABA is altered, one may be anxious; if Acetylcholine is altered, then one may have memory problems; if norepinephrine is altered, one may be manic high; and if serotonin is altered, one may be depressed, worried, more irritable, and have insomnia. Indeed, in depression for example, serotonin is often low (as may be norepinephrine and/or dopamine). Antidepressant medications often block the reuptake (and, therefore, the metabolism) of serotonin at the presynaptic nerve terminal. If serotonin (or norepinephrine and/or dopamine) is not taken up and metabolized, then it increases in the synapse, the mood lifts, and anger and worry may go down. Today we not only know which neurotransmitters produce certain emotions, we even know about neurotransmitter subsystems. For example, there are at least eighteen subtypes of serotonin receptors alone. We even know what the subneurotransmitters do, and we have medications that will not only affect specific neurotransmitters but also subsystems. The biochemistry of emotions has become a science in and of itself. III. THE PARTS OF THE BRAIN AND EMOTIONS. Several parts of the brain are extremely important in emotions. For example, the midbrain (with the Raphe Nucleus [serotonin production], Locus Ceruleus [norepinephrine production], and the Substantia Nigra [dopamine production]) is very important. The limbic system (with the Hippocampus [important in memory], the Amygdala [important in anger], the Nucleus Accumbens [important in addictions and motivation/reward], and the Hypothalamus [important in eating and endocrine regulation issues]) also plays significant roles. The frontal lobes of the brain are the centers for higher thoughts, planning, impulse control, motivation, actions, and volition. Finally, the autonomic nervous system can affect almost any organ system in the body. There are many known neurotransmitters and often there are many different functions of one neurotransmitter. Here are some over simplifications but nonetheless helpful points. Serotonin may play a role in depression, anxiety, sleep, sexual issues, eating issues, pain perception, obsessive worry, panic disorders, aggression, and PMS. Norepinephine may play a role in bipolar disorders, depressions, and attention problems. Dopamine may play a role in a loss of touch with reality, attention deficit issues, drug addictions, and in mood, as well. GABA may play a strong role in anxiety and some addiction issues. Acetylcholine plays a role in memory. Histamine may play a role in sleep and weight gain. Thus, psychiatric medications that can alter the above neurotransmitters have unbelievable potential benefits. Consider this quote from Journal Watch for Psychiatry, "Where Are Emotions in the Brain?" (October 1997): Functional imaging techniques have started to yield refined correlations between localized brain activity and subtle emotional states. These researchers used positron emission tomography to examine correlates of human emotions and identify brain activity associated with happiness, sadness, and disgust. Twelve healthy women were shown both emotionally charged film clips to represent external stimuli and neutral film clips. They also read autobiographical scripts of recent emotional experiences to represent internal stimuli. Subjects were told to feel the emotions during emotional stimuli and to feel emotionally neutral during neutral stimuli. Both externally and internally generated emotions were associated with increased bilateral activity in the medial prefrontal cortex (Broadmann's area 9) and thalamus. The film clips, but not the narratives, were associated with increased activity in the bilateral occipitotemporoparietal cortex, later cerebellum, hypothalamus, and other temporal area brain regions. Sadness was associated with increased activity in the anterior insular cortex and happiness was distinguished from sadness by activation in the ventral frontal cortex. Comment: These findings show complex specificity in neuroanatomical and neurophysiological activities underlying emotional experiences. As technology allows increasingly better localization of thoughts and emotions in the living brain, we may achieve additional insights into psychiatric disorders of mood and cognition as well as the essence of our humanness. In fact, some day soon we may be able to watch ourselves change our mind (J. Yager. Reiman EM et al.) Neuroanatomical correlated of externally and internally generated human emotions (Am J Psychiatry 1997 Jul; 154: 918-25. Lane RD et al.) Neuroanatomical correlated of happiness, sadness, and disgust (Am J Psychiatry 1997 Jul; 154: 926-33). We also know from PET scans of the brain that there are often anatomical changes in specific parts of the brain in many mental issues: OCD - "Positron emission tomography (PET) studies have shown elevated metabolic rates in the cingulate region and the heads of the caudate nuclei and orbital gyri" (Psychiatry Diagnosis & Therapy, A Lange Clinical Manual, Prentice Hall, 1993); Schizophrenia - "Important PET scan findings include reduced prefrontal metabolism and an increased density of D2 receptors in schizophrenia . . ." (ibid, 33); Bipolar - "The main findings in bipolar patients shown with MRI is that they tend to have what are called subcortical hyperintensities . . ." (Psychiatric Times, February 1998, Vol. XV, No 2). In Alzheimer's Dementia, "Cummings has found, with single photon emission computer tomography (SPECT) perfusion studies, that the presence of apathy is also associated with frontal cortex changes. 'Our strongest correlations with apathy are with reduced perfusion in [the] anterior cingulate region, and then to a lesser extent in orbital-frontal and anterior temporal regions,' he said. As with the presence of delusions, there was little association of apathy with changes in the parietal area, which, Cummings noted, is the site most greatly burdened with the plaque and tangle deposition characteristic of Alzheimer's disease . . . The cholinergic deficits from neuronal destruction that are implicated in the cognitive impairment of Alzheimer's disease may also contribute to behavioral disturbances. Cummings explained that atrophy of the small nucleus at the base of the brain, the nucleus basalis, occurs early in the disease process. Cholilne acetyltransferase is synthesized at this site, and its decreased production as the site atrophies leads to decreased production of acetylcholine . . . Cummings and colleague Daniel Kaufer, M.D., University of Pittsburgh, noted the unique anatomy of the nucleus basalis as poised between limbic and paralimbic afferents and cortical efferents. This site is positioned, then, to influence environment (Cummings and Kaufer, 1996). 'Diseases such as Alzheimer's disease affecting nucleus basalis disrupt the integration of limbic-neocortical interactions that mediate cognitive and emotional functions,' they wrote" (Advances in Psychiatric Medicine, Supplement to Psychiatric Times, August 1998, pages 1-2). IV. FACTORS THAT ALTER NEUROTRANSMITTERS AND EMOTIONS. A. Five Negative Factors That Can Alter Brain Chemicals Of Emotions. There are several factors that can alter neurotransmitters for the worse and have potentially profound influences on the emotions. They are: 1. Stress. Stress certainly can alter the neurotransmitters of the brain with profound influence on the emotions and body. Stress can be defined as emotional tension. It can come from present issues such as relationship conflicts, financial worries, and job stress, or from past issues such as abuse, abandonment, and self-image issues. It is determined by one's perception (what is stress to one is not to another). Also, one's general physical health may be a factor in stress. With stress the body is posed for either "fight or flight." With the "fight or flight" reaction, chemical changes take place that may have far reaching implications. With stress corresponding behavioral changes may take place such as angry verbal responses, being ready to run, exercising, drinking, smoking, binge eating, etc. With stress, the autonomic nervous system balance is altered and the blood pressure increases (which, in some individuals, may trigger a heart attack), along with many other physiological parameters. The blood pressure may not go back down totally, and may result in hypertension and acceleration of atherosclerosis. Also with stress the hypothalamus is affected which, in turn, affects the pituitary gland which, in turn, affects the adrenal medulla (with the resulting release of adrenaline) and the adrenal cortex (with the resulting release of cortisol) which eventually results in accelerated aging, decreased bone mineral density, alterations in immune system response, and possible permanent alterations in the functioning of the brain through their effects on the hippocampus, the amino acids of the brain, and the neurotransmitters themselves. Because stress may alter the hippocampus (which controls memory), continued stress may result in an inability to access the information needed to decide that a situation is no longer a threat. Thus, stress begets stress. In fact, according to an article in The New England Journal of Medicine we find: "Magnetic resonance imaging has shown that stress-related disorders such as recurrent depressive illness, post-traumatic stress disorder, and Cushing's disease are associated with atrophy of the hippocampus. Whether this atrophy is reversible or permanent is not clear" (Vol. 338, Jan 1998, 176). Furthermore, ongoing stress may result in a dysregulation of the hypothalamus - pituitary - adrenal axis resulting in cognitive impairment. Finally, stress alters the neurotransmitters of the brain that control mood, logic, disposition, sleep, attention, weight, and pain perception. 2. Genetic Factors. Not only can stress affect the neurotransmitters of the brain, genetic factors can as well. For example, ninety percent of individuals with bipolar disorder also have a first-degree relative with bipolar disorder; fifty percent of individuals with a major depression have a first-degree relative with the same disorder; forty percent of individuals with obsessive compulsive disorders have a first-degree relative with the same or related disorder; thirty-five percent of individuals with attention deficit disorders have a first-degree relative with the same disorder. Furthermore, if one identical twin has schizophrenia, there is a high (eighty to ninety percent) probability the other twin will have it as well; if one identical twin has bipolar disorder, there is a sixty percent chance the other twin has the disorder; and the probability drops significantly in non-identical twins or other siblings as compared to identical twins. The research is perhaps the most interesting in the area of identical twins. Even the personality traits to some degree are inherited. Identical twins reared apart from birth show behavioral similarities; many laugh alike, and show similar nervous mannerisms. "Bridget" and "Dorothy," for instance, met for the first time on the plane bringing them from England to Minneapolis. Both wore seven rings, and each had several bracelets on each wrist; one had named her children Richard Andrew and Katherine Louise, and the other had named hers Andrew Richard and Karen Louise. A pair of male twins both turned out to love carpentry, to have workshops in their homes, and to have built very similar circular benches around trees in their yards - both, for some reason, found round benches very appealing. One of the most interesting pairs had strikingly different backgrounds. "Oscar" had been raised as a German Catholic and had once joined the Hitler Youth. Oscar's twin, "Jack," had been reared as a Jew in Trinidad. Now in their fifties, the two showed up for Bouchard's interview in blue shirts with epaulets and nearly identical aviator glasses. Both kept rubber bands on their wrists, both had a habit of flushing the toilet before and after use, and both enjoyed startling people in elevators by sneezing. (Introduction to Psychology, Seventh Edition, page 605; Clifford T. Morgan, Richard A. King, John R. Weisz, John Schopler) A " . . . set of identical twins from Bouchard's University of Minnesota study of the roles of genetics vs. environment provides some striking support for the prominence of the genetic influence. Jim Springer and Jim Lewis were separated four weeks after their birth in 1940. They grew up forty-five miles apart in Ohio. After they were reunited in 1979, they discovered they had some eerie similarities: both chain-smoked Salems, both drove the same model blue Chevrolet, both chewed their fingernails, and both had dogs named Toy. Further, they had both vacationed in the same neighborhood in Florida. And when tested for such personality traits as sociability and self-control, they responded almost identically." (Abnormal Psychology and Modern Life, Eighth Edition, page 57; Robert C. Carson, James N. Butcher, James C. Coleman) Finally, a recent study " . . . supports the view that constitutionally shaped temperaments powerfully influence the way individuals perceive and interact with the world" (Journal Watch for Psychiatry, Volume 3, Number 12, December 1997). We even know which chromosome, the genetic factor, is carried in some disorders (chromosome X, 11, and 18). 3. Illegal and Addictive Drugs. Illegal and addictive drugs can be so dangerous because not only can they hurt or kill many organs, but they may also permanently alter the brain chemistry, functioning, and emotions. Marijuana is of special concern because it actually becomes part of the brain structure. Its changes are so insidious as it produces "amotivational syndrome." 4. Medical Disease. Medical diseases can produce many emotions. For example, in depression possible causes are pernicious anemia, mononucleosis, hypothyroidism, Cushing's syndrome, Addison's disease, cancer of the pancreas, multiple sclerosis, various drugs and, perhaps to some degree, even an upper respiratory infection. In anxiety, possible causes include mitral value prolapse, hyperthyroidism, hypoglycemia, pheochromocytoma, and drugs such as caffeine and nicotine. In a loss of touch with reality, possible causes include porphyria, prescription drugs, brain tumors, and endocrine abnormalities, Wilson's disease, alcohol, bromide-containing compounds, LSD, PCP, marijuana, and cocaine. Personality changes may be caused by Alzheimer's disease, dementia, various illegal drugs such as marijuana ("amotivational syndrome"), vascular disorders, viral infections of the central nervous system, Parkinson's Disease, disease of the central nervous system, lupus, multiple sclerosis, temporal lobe epilepsy, etc. To some degree even violence may be related to such disorders as temporal lobe epilepsy, various illegal drugs, alcohol, etc. Medical causes of insomnia include sleep apnea, myoclonic jerks, caffeine, etc. Obsessive compulsive disorder is possibly in some cases precipitated by an untreated strep throat. Panic-like feelings can come from mitral value prolapse and hyperthyroidism. B. Seven Positive Factors That Can Alter Brain Chemistry and Emotions. There are also positive factors that can alter neurotransmitters for the better and have potentially profound influence on the emotions. They are: 1. Behavioral - Cognitive Techniques. From PET scans of the brain we know that simple, repeated, behavioral, cognitive techniques can actually alter the metabolism of the brain for the better. 2. Volition. We have powerful chemicals in our brains that, to some degree I believe, are released through our own volition. For example, even placebos work to some degree perhaps thirty percent of the time. 3. Laughter. Laughter probably releases endorphins and enkephalins which help to lift mood and decrease pain. 4. Herbs and Vitamins. This is an area of much debate and should be at least briefly mentioned. Herbs and vitamins probably as most issues have a pro and a con. I will try to present both. The pro side is that in some circumstances they probably work. The con side is that many times they do not work; just because they are "natural" does not mean they are safe (strychnine and cyanide are also "natural"); there is no FDA control over safety or dosage; and in some cases, they could have dangerous interactions with medicines. The claims are interesting to ponder and worthy of great caution (St. John's Wort for depression?, Ginkgo for dementia?, Ginseng for low sex drive?, Melatonin for sleep?, Omega-3 fatty acids for bipolar issues? DHEA for energy? Inositol for OCD and Depression?). 5. Sex. Powerful chemicals are released during sex. These chemicals have a relaxing effect and also a calming effect. They are so strong that when used inappropriately they seem to have the potential to become addicting. A new medication that has gained great media attention is Viagra (sildenafil citrate). It is used in erection dysfunctions in men. For example, sexual emotions throughout history have often overruled sound logic. However, used appropriately in marriage they are a gift blessed by God Himself. 6. Exercise. Exercise releases adrenaline (epinephrine) and endorphins which are natural stimulants and mood enhancers. 7. Medication. a. Psychiatric Medications Today. What psychiatric mediations can do today is almost frightening. Moods can be lifted, and stability can be returned. Attention can be focused. Pain can be released. Worries can be abated. Energy can be increased. Anxiety can be mitigated. Sex drive can be increased (or decreased). Anger can be lessened. Hallucinations can be eliminated, and the ability to relate can be enhanced. b. Psychiatric Medications in History. Most of the unbelievable advances in psychiatric medication have occurred in the last fifty years. In 1949 lithium for bipolar disorder was introduced. In 1952 the first antipsychotic was introduced, sending seventy percent of individuals in the mental hospitals home. In 1954, the first antidepressant was introduced, helping to prevent untold numbers of suicides. In the 1960s, the first benzodiazepine antianxiety medication was introduced and antiseizure medications were starting to be used for bipolar disorders. About ten years ago, the proliferation of new, dramatic, psychiatric drugs were accelerated with the introduction of Prozac. Since then, a whole science with many new and very specific drugs with less side effects, in general, continue to multiply. The upcoming new drugs will be so specific and dramatic that it is almost alarming. In skilled hands the tools will be a miracle to behold. TESTING FOR THE CHEMISTRY OF EMOTIONS In the near future, in all probability a single blood test will document whether one has significant chemical depression, anxiety, OCD, ADHD, schizophrenia, etc. Even now, dramatic advances are being made with PET scans and other research tools. To some degree even now we can track the chemistry of emotions. In the recent past in depression, blood tests were used (DST/dexamethosone suppression test; TRH/thyroid releasing hormone test) along with sleep studies - REM/rapid eye movement and reflected disturbances in the onset of REM sleep. However, these tests needed more specificity and reliability. Other tests are also being used and providing exciting results (EEG/electroencephalography; PET/positron emission tomography; MRI/magnetic resonance spectroscopy; CT/computerized axial tomography; MRS/magnetic resonance spectroscopy; Functional MRI; SPECT/single photon emission computed tomography; and EEG/EP topographical mapping). V. TWELVE MEDICATION TYPES THAT CAN CHANGE BRAIN CHEMICALS AND EMOTIONS. Psychiatric medications alter emotions by altering the neurotransmitters. They can work at several different sites (presynaptic receptor, postsynaptic receptor, mitochondria, secondary messengers, reuptake sites, by releasing neurotransmitters, by being an agonist, by being an antagonist, etc.). Below is a discussion of the various psychiatric medications and how they work on the neurotransmitters and emotions. I often tell my clients that the newer agents are often wonderful and may, as a class, offer less side effects than the old medications. Nevertheless, almost any medication can have almost any side effects, possibly hurt almost any organ with possible drug interactions and thus, they should be respected and prescribed by a medical doctor, and possibly by a psychiatrist. A. Antidepressant Medications. Studies have indicated that there is a seventy percent effective rate of depression being lessened with the use of medication. The old Tricyclics were TCAs, such as Elavil (Amitriptyline), Pamelor (Nortriptyline), Sinequan (Doxepin HC1), Vivactil (Protriptyline), and Tofranil (Imipramine) were effective in blocking many neurotransmitters, but there were many possible side effects. Then along came the Monamine Oxidase Inhibitors (MAOI, such as Nardil [Phenelzine], and Parnate [Tranylcypromine]) that have also been effective, but may also have many possible side effects. About twelve years ago, a new broad spectrum antidepressant series came along known as Selective Serotonin Reuptake Inhibitors (SSRI). Among the best of these new SSRIs are Celexa, Paxil (Paroxetine), Luvox (Fluvoxamine), and Prozac (Fluoxetine), Zoloft (Sertraline) which target one very specific neurotransmitter with possible decreased side effects, but drug interactions may still be a significant concern at times. Zoloft is also approved for use in children and adolescents. The SSRIs have been used in a broad array of depressions with specific symptoms such as panic attacks, pain, PMS, eating disorders, anger and OCD. More recent antidepressants have come along that in general may have less side effects and less drug interaction (such as Wellbutrin, Serzone, Effexor and Remeron). Wellbutrin (Bupropion) is a dopamine and norepinephrine reuptake blocker that may be at times helpful in low sex drive. There is usually no increase in weight and may lead to increased energy, a decrease in smoking addiction, and an increase in attention of depressives with ADHD issues. Effexor (Venlafaxine) is a serotonin/norepinephrine reuptake inhibitor that is used not only in "regular depression," but also in "resistant depression." It may also be helpful for anxiety. Remeron (Mirtazapine) has proven effective for depression with anxiety and insomnia. It may provide a fast onset leading to an increase in norepinephrine and 5-HT presynaptic terminal. It also works by antagonism of the 5-HT2, postsynaptic terminal. Desyrel (Trazodone) and Serzone (Nefazodone) are two similar compounds that may be beneficial to depressives who also have insomnia and anxiety. Serzone, a 5-HT2 antagonist, blocks the reuptake of norepinephrine and Serotonin. Vestra/Reboxetine, a norepinephrine reuptake inhibitor, is to be introduced soon. Xanax (Alprazolam), a minor tranquilizer, may help in depression. Augmentations with BuSpar (a 5-HT1A agonist), Beta Blockers (such as Visken), Lithium, and Thyroid hormone may produce added results in depression. There are numerous drugs, some new to the market, that have been used for Mania. These include Depakote, Lithium, Tegretol, and Neurontin. Also, mood stabilizer drugs may make a dramatic difference in the elevated, expansive, or irritable mood. They may correct the grandiosity, not sleeping, poor judgment, rapid speech, and racing thoughts. The older antipsychotic drugs such as Haldol, Mellaril, Moban, Navane, and Thorazine may still be effective in depression with a possible psychotic element, but may have undesirable side effects. In recent years, there has been a wave of new antipsychotic drugs such as Zyprexa (Olanzapine), Risperdal (Risperidone), Seroquel (Quetiapine fumarate), and Clozaril (Clozapine) that are more specific at the site of action, may have less undesirable side effects, and may have a potential for more desirable results (although any drug may potentially have almost any side effect). Paul Ehrlich, a German scientist in the early 1900s, made a prediction that is coming closer to reality. He stated there will be a drug "aimed precisely at a disease site and wouldn't harm healthy tissue." B. Antianxiety Medications for Anxiety and Related Disorders (panic, phobias, insomnia, etc.). 1. Benzodiazepines. Benzodiazepines such as Librium (Chlordiazepoxide), Paxipam (Halazepam), Valium (Diazepam), Klonopin (Clonazepam), Xanax (Alprazolam), Serax (Oxazepam), and Ativan (Lorazepam) are perhaps the best known group of drugs for anxiety relief. This group of drugs has also been used for anxiety associated with seizures, withdrawal syndromes, insomnia, restless legs, agitation, bipolar disorder, panic, and PMS. Of course, tolerance can be a concern. These drugs are often effective within minutes. 2. Antidepressants. Some of the antidepressants which have been used in depression with anxiety include Remeron (Mirtazapine), Effexor (Venlafaxine), Serzone (Nefazodone), the SSRI drugs such as Paxil (Paroxetine), and the old Tricyclic drugs such as Elavil (Amitriptyline). The newer drugs, in general, have less potential side effects and may have a quicker onset of action within two weeks as opposed to four to six weeks. 3. BuSpar (Buspirone). This drug is especially interesting in that, unlike the Benzodiazepines that work on a neurotransmitter called GABA, it augments a subdivision of serotonin (5-HT1). Also, it produces intolerance. It may take a month or so to be effective. 4. Antihistamines. Antihistamines have been used for years for mild anxiety. Vistaril (Hydroxyzine) and Benadryl (Diphenhydramine) may be the best known. 5. Beta Blockers. ß-adrenergic receptor antagonists (Inderal [Propranolol], Visken [Pindolol], Tenormin [Atenolol], Lopressor [Metoprolol], and Corgard [Nadolol]) have been used for the somatic (physical) symptoms of anxiety. They have been used primarily for hypertension, but have also been used in aggressive behaviors and phobias. Pindolol, in particular, may help boost antidepressant response. 6. Major Tranquilizers (Neuroleptics). This group of drugs has often been used when anxiety is severe enough to begin to cause a disorganization of thoughts, hallucinations, delusions, or bizarre behaviors with social withdrawal. Thus, they have been used in Schizophrenia, Bipolar Disorder, Paranoid Disorder, and Autism. They work on various neurotransmitters (Dopamine, Histamine, Norepinephrine, and Acetylcholine). This class of medication includes some newer ones that, in general, may have less side effects and may be more effective overall (Zyprexa [Olanzapine], Risperdal [Risperidone], and Seroquel [Quetiapine]). These newer drugs block dopamine reuptake like the old major tranquilizers (Thorazine [Chlorpromazine], Mellaril [Thioridazine], Navane [Thiothixene], Moban [Molindone], Haldol [Haloperidol], Prolixin [Fluphenazine], and Stelazine [Trifluoperazine]). However, the newer ones also affect a subdivision of Serotonin (5-HT2 antagonist) on the postsynaptic side. The newer ones seem to not only help the positive symptoms of schizophrenia (hallucinations and delusions), but the negative symptoms (social withdrawal, poverty of thoughts, lack of facial expression, and anhedonia) as well. Thus, most major tranquilizers help special kinds of severe anxieties but the newer ones may have added benefits with fewer overall side effects, as a class. The agent Clozaril (Clozepine) was the first of the newer dopamine agents but it can have troublesome side effects, and is not used in pure anxiety disorders. Olanzapine will soon be available in a sublingual form (Zydis).
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