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Psychopharmacology AccessScience from McGraw-Hill Education Page 1 of 6 www.accessscience.com Psychopharmacology Contributed by: David J. Nutt, Peter L. Carlton Publication year: 2014 A discipline that merges psychology, which studies cognition, emotion, and behavior, and pharmacology, which characterizes the effects of drugs. In focusing on understanding drugs that affect brain processes, especially thinking, feeling, and action, with a particular emphasis on those drugs that affect abnormalities in thought, affect (mood), and behavior, psychopharmacology is closely related to psychiatry. Understanding the effects of drugs on psychological processes entails examining the regulation of these drugs by neurotransmitters, because drugs mediate their actions through changing these transmitters. See See also: PHARMACOLOGY See ; PHARMACY See ; PSYCHOLOGY . Psychopharmacology is concerned with four major classes of drugs that are of clinical significance in controlling four major categories of psychiatric disorders: anxiety, depression, mania (bipolar disorder), and schizophrenia. However, the scope of psychopharmacology is not limited to drugs and encompasses the study of other brain processes, including those that underlie medical conditions such as addiction and dementias, as well as those involved in sleep, attention, memory, and cognition. See See also: ADDICTIVE DISORDERS ; BRAIN ; COGNITION ; SLEEP AND DREAMING . Anxiety Anxiety is a normal, future-oriented emotional state with motivational value. However, if anxiety becomes excessive in magnitude or duration, it can interfere significantly with normal functioning and thus becomes a medical syndrome. It has been estimated that 2–4% of the general population suffers from an anxiety disorder at any time, with lifetime rates of up to 20%, and these may require psychiatric attention and treatment with an anxiolytic drug. There are two major groups of anxiolytics—those that act quickly (fast-acting, sedative drugs) and those that work more slowly. Of the fast-acting anxiolytics, the benzodiazepines [for example, diazepam ® (Valium, )] are the most commonly used because they are the safest; however, in the past, barbiturates and related drugs (for example, meprobamate) were used. A major advance in understanding the benzodiazepines was the identification of the cellular sites at which these drugs act—the so-called benzodiazepine receptors. These receptors are part of the receptor for the neurotransmitter gamma-aminobutyric acid (GABA), which is the main inhibitory chemical in the brain. The benzodiazepines and other related drugs share a biochemical property in that all augment the activity of GABA; however, this augmentation occurs in different ways, which explains why barbiturates are more toxic than AccessScience from McGraw-Hill Education Page 2 of 6 www.accessscience.com benzodiazepines. These drugs are sedatives, so they can be used to promote sleep. Other sedative drugs, such as antihistamines, are sometimes used to reduce anxiety. Slower-acting anxiolytics include drugs that are also antidepressants and others such as buspirone that act on the receptors for the neurotransmitter serotonin. A more recent approach to reducing anxiety is one that focuses on calcium channels to reduce neurotransmitter release, through the use of drugs such as pregabalin. See See also: ANXIETY DISORDERS See ; TRANQUILIZER . Depression The symptoms of depression can include sadness, hopelessness, despair, and irritability. Suicidal thoughts and attempts are common, and sometimes result in completed suicide. In addition, physical symptoms such as loss of appetite, sleep disturbances, and psychomotor agitation (for example, restlessness, hand wringing, and pacing) are often associated with depression. When depression becomes so pervasive and intense that normal functioning is impaired, antidepressant medication may be indicated. It has been estimated that as much as 15% of the population will require antidepressant medication at some time in their lives. There are two major groups of antidepressant drugs, which share the property of elevating the level of the neurotransmitter serotonin or norepinephrine (or both). The first group comprises drugs that act to block the reuptake of these neurotransmitters into nerve cells—if they work on serotonin, they are called selective ® serotonin reuptake inhibitors [SSRIs, for example, fluoxetine (Prozac, )]; if they work on norepinephrine, then they are called nor- epinephrine reuptake inhibitors (NRIs, for example, reboxetine). Some antidepressant drugs (for example, venlafaxine and older tricyclic antidepressants) block the uptake of both neurotransmitters, and this may result in somewhat greater clinical efficacy. Bupropion is an antidepressant that is effective in increasing norepinephrine as well as increasing dopamine (a neurotransmitter in the brain); this latter effect probably explains why it is also useful in quitting smoking, because dopamine deficiency may lead to withdrawal symptoms. The antidepressant drugs in the second group, which are less often prescribed, are called monoamine oxidase inhibitors because their major biochemical effect is to inhibit an enzyme called monoamine oxidase, which breaks down serotonin and norepinephrine. Therefore, by inhibiting monoamine oxidase, the levels of serotonin and norepinephrine are increased. The antidepressants typically require at least several weeks of chronic administration before they become effective in alleviating depression, which is thought to reflect the need for adaptive changes in neurotransmitter receptors and second messengers to occur. When used properly over time, they can maintain efficacy for many years, and their main role is now to prevent further episodes of depression from occurring. They also work in alleviation of the anxiety disorders, probably by the same mechanisms of changing neurotransmitter levels, but AccessScience from McGraw-Hill Education Page 3 of 6 www.accessscience.com they affect other brain regions rather than the ones involved in depression. See See also: AFFECTIVE DISORDERS ; NORADRENERGIC SYSTEM . Mania (bipolar disorder) Manic episodes are characterized by hyperactivity, grandiosity, flight of ideas, and irritability. Some affected patients may be euphoric, whereas others have racing thoughts, delusions of grandeur, and poor (if not self-destructive) judgment. Periods of depression follow these episodes of mania in the majority of patients. The cycles of this bipolar disorder are typically interspersed among periods of normality, which vary from many years to hardly any time at all. Mania can be life-threatening and needs urgent medical involvement. It can be brought under control by using mood stabilizers, such as lithium or sodium valproate, or by antipsychotic drugs because they block dopamine, which is thought to be elevated in mania. Prevention of further episodes is the key requirement of treatment because of the damage that both manic and depressive episodes cause to family and work life; thus, maintenance therapy with mood stabilizers such as those already mentioned or lamotrigine (which may be better at preventing depressive relapse) is necessary. See See also: BIPOLAR DISORDER ; PSYCHOTHERAPY . Schizophrenia Schizophrenia is the most common form of psychosis; it incorporates a broad range of symptoms that can include bizarre delusions, hallucinations, incoherence of thought processes, and inappropriate affect (the so-called positive symptoms), as well as major impairments of cognitive social and work functions (the negative symptoms). It affects about 1% of the population in all countries and ethnic groups. The positive symptoms of schizophrenia are thought to be a result of excessive dopamine release in the limbic system and can be controlled, to varying degrees, by a large group of drugs called antipsychotics. Symptom management requires chronic medication and can be expected in about 80% or more of the people treated for schizophrenia. However, treatment is only partially successful, because normal functioning is not completely restored in most patients. In general, the negative symptoms are less responsive to treatment and tend to dominate the long-term outcome. Antipsychotic drugs fall into three main classes: typical, atypical, and dopamine partial agonists. Typical drugs include haloperidol, atypicals include clozapine and olanzapine, and the only partial agonist currently in clinical practice is aripiprazole. Although different antipsychotic drugs have different kinds and degrees of side effects, all share a common biochemical action, which is to attenuate the activity of dopamine. The reduction in dopamine activity produced by the antipsychotics is thought necessary for their antipsychotic effects and accounts directly for their adverse effects on motor behavior. This occurs because dopamine is known to be present in high concentrations in the nigrostriatal system, which is an anatomically defined dopamine system of the brain that is AccessScience from McGraw-Hill Education Page 4 of 6 www.accessscience.com intimately involved in the regulation of movement. The motoric side effects fall into two general classes. The first class includes motor restlessness (akathisia) and symptoms that are very similar to those of Parkinson’s disease. In general, these disturbances can be managed by adjunctive medication with other drugs. Such control is not yet possible for the second class of movement disorder, called tardive dyskinesia, which is a disturbance typically including involuntary
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