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Psychopharmacology refers to the study of drugs as they relate to mind and behavior. This topic includes several different aspects of this relationship. It includes the study, development, and administration of drugs or medications to treat psychological and psychiatric disorders, such as anxiety disorders, mood disorders, and psychoses. It includes the study and development of drugs that affect behaviors in psychologically normal people, such as sleeping, feeding, and sexual functioning. It includes the study and development of drugs that affect cognitions and perceptions, such as attention, memory, learning, hunger, sensory perception, and pain. It includes the study of drugs that are addictive or abused and the study and development of drugs to treat drug addiction, to help alleviate withdrawal from addictive drugs, and to help maintain abstinence from addictive drugs. In addition, psychopharmacology includes the investigation of psychological, pharmacological, biological, neuroscientific, and molecular biologic mechanisms that underlie the actions of psychopharmacologic agents to help understand how these drugs work, underlying particular psychological disorders, and more general aspects of psychology and behavior.
Outline
I. Introduction
II. Principles and Paradigms of Psychopharmacology
A. Psychopharmacology versus Behavioral Pharmacology
B. Conditional and Unconditional Behaviors
C. Human and Animal Subjects
D. Pharmacokinetics and Pharmacodynamics
E. Toxicity and Adverse Side Effects
III. Mechanisms of Action of Psychopharmacologic Agents
A. Neuroanatomy
B. Neurophysiology and Electrophysiology
C. Neurochemistry
IV. Clinical Psychopharmacology
A. Anxiety Disorders
B. Eating Disorders
C. Learning, Memory, Attention, and Related Cognitive Disorders
D. Mood Disorders
E. Pain
F. Psychoses
G. Sexual Dysfunction
H. Sleep Disorders
I. Substance-Related Disorders
1. Alcohol-Related Disorders
2. Amphetamine-Related Disorders
3. Caffeine-Related Disorders
4. Cannabis-Related Disorders
5. Cocaine-Related Disorders
6. Hallucinogen-Related Disorders
7. Inhalant-Related Disorders
8. Nicotine-Related Disorders
9. Opioid-Related Disorders
10. Phencyclidine (or Phencyclidine-like)-Related Disorders
11. Sedative-, Hypnotic-, or Anxiolytic-Related Disorders
V. Special Populations
A. Pediatric
B. Geriatric
C. Individual Differences
I. Introduction
Psychopharmacology can be traced back to the use of botanically derived medicinal agents, particularly alcohol and opium, in Greek culture and throughout the world by shamans or medicine men to achieve particular psychological states and to alter mood, anxiety, hunger, and pain. Psychopharmacology developed markedly in the twentieth century, especially after World War II. Sedative-hypnotics (e.g., barbiturates) and stimulants (e.g., amphetamines) were introduced at the beginning of this century, but it was the dramatic actions of antipsychotic medications (e.g., phenothiazines) that grabbed professional, public, and media attention. The pharmaceutical industry realized the potential market and profitability of psychopharmacologic agents beginning in the middle of this century and the development of psychopharmacologic medications became a major thrust. With cultural changes in the 1960s also came an explosion in popular, recreational use of a wide variety of mind-altering drugs, including marijuana, LSD, amphetamines, and opiates. This societal change also led to debates and discussions about addictive drugs, including drugs used for medicinal and nonmedicinal reasons. Technological and conceptual developments in behavioral sciences, neurosciences, and molecular biology from the 1960s to the present further added to interest in psychopharmacology. Today, it is taken as a given that drugs can alter mind and behavior, that drugs can be developed to treat psychological problems, that drugs not intended primarily as psychopharmacologic agents also can affect mind and behavior, and that psychopharmacology is a diverse and active discipline to study drugs and to help understand mind and behavior. The present research paper addresses major issues in psychopharmacology. This research paper discusses principles and paradigms of psychopharmacology; mechanisms of action of psychopharmacologic agents; clinical psychopharmacology; and issues related to special populations
II. Principles and Paradigms of Psychopharmacology
A. Psychopharmacology versus Behavioral Pharmacology
Within any field different camps develop for a variety of reasons, some historical, some conceptual, some methodologic, and some personal. The study of drugs and psychology is no exception to this truism. Whereas psychopharmacology has come to refer to a broad rubric of issues, methods, and topics, behavioral pharmacology has a narrower focus. This particular subfield is mentioned here because it is so important to the broader topic and it has made so many contributions to knowledge of drugs and behavior. It is singled out because scientists studying drugs and behavior either identify themselves as behavioral pharmacologists or psychopharmacologists. Behavioral pharmacology developed as behaviorists—that is, experimental psychologists who focused on behavior rather than on mind, perception, or motivations—began to study drugs. In addition, behavioral pharmacology refers to a series of techniques (especially operant techniques) that are used to examine drug effects on behavior and the actions of environmental or other variables on behavioral responses to drug actions. The behaviors of interest are operant (responses elicited by the environment) and conditioned behaviors, rather than unconditioned, naturally occurring behaviors. Traditional behavioral pharmacologists are primarily interested in the actions of drugs, the biological and behavioral mechanisms that underlie drug actions, and the identification and development of new drugs that alter behavior.
B. Conditional and Unconditional Behaviors
Conditional behaviors, also called conditioned behaviors, are behaviors that have come under the control of environmental stimuli or under the control of other external stimuli that in and of themselves do not elicit the given response. These conditional behaviors are either classically conditioned (Pavlovian conditioning) or instrumentally conditioned (operant or Skinnerian conditioning). Classical conditioning refers to the phenomenon in which a conditional stimulus (CS) (e.g., tone) is presented with an unconditional stimulus (UCS) (e.g., meat powder to a dog) that leads to an unconditional response (UCR) (e.g., salivation). After repeated pairings of the CS and UCS, the CS comes to elicit a similar response, which is known as the conditional response (CR). Operant conditioning refers to the phenomenon in which the behaviors emitted are shaped by the consequence (e.g., reward or punishment) of the behavior. This approach is typically studied in operant chambers (Skinner boxes). Psychopharmacologists, especially behavioral pharmacologists, use variations of these learning principles and paradigms to study drug actions on behaviors.
Unconditional behaviors refer to innate, or naturally occurring, behaviors. These behaviors include: feeding, drinking, sleeping, moving, exploring, jumping, startling, touching, grabbing, grooming, playing, fighting, nesting, and copulating. Psychopharmacologists examine effects of drugs on these and other unconditional behaviors in order to learn about drug actions, to compare different drugs, and to understand various behaviors.
Together, the study of drugs on unconditional and conditional behaviors offers a more complete picture of behavioral effects of drugs. The conditional behaviors offer the advantage of exquisite control and sensitive measure of drug effects. The unconditional behaviors offer the advantage of information that is of direct clinical relevance as well as information about basic, everyday behaviors.
C. Human and Animal Subjects
Psychopharmacology uses human and animal subjects. Human subjects include patients with particular disorders, conditions, or injuries, and healthy, normal volunteers. It is relevant and important to stipulate and consider the age, gender, race, ethnicity, genotype, and other major demographics of the patients or subjects. Animal subjects are taken from a wide variety of species, including monkeys, rabbits, rats, mice, gerbils, hamsters, and pigeons. Age, sex, and genotype are important variables to consider when examining effects of drugs on animal subjects.
D. Pharmacokinetics and Pharmacodynamics
Pharmacokinetics refers to the actions of the body on drugs (e.g., distribution, metabolism, reabsorption, elimination of a drug). Pharmacodynamics refers to the actions of drugs on the body (e.g., binding to a particular receptor, stimulation of a chemical or electrical response, stimulation of a physiologic or organ response, stimulation of a behavioral or psychological response). Both of these principles are important when studying psychopharmacologic agents. They are relevant to the characterization of the relationship between drugs and the body. In addition, particular situations or stimuli (e.g., stressors, other drugs, history of exposure to the drug of interest, individual difference variables) can alter pharmacokinetics or pharmacodynamics or both types of processes. Identification of the contribution of these mechanisms of action are relevant to the prescription of appropriate drugs and dosages and to elucidate the mechanisms underlying a given drug or condition.
E. Toxicity and Adverse Side Effects
As with all drugs, psychopharmacologic agents have an effective dose range. Outside this range, the drugs either are ineffective or have toxic and adverse side effects. For example, stimulants used to treat attentional problems, to regulate hunger, or to control asthmatic attacks, can cause anxiety, shakiness, dizziness, and panic. Antibiotics used to kill or to control infectious diseases can lead to psychotic-like episodes and hallucinations. Analgesics can result in respiratory distress. The combination of various drugs, especially when used with alcohol, can potentiate these toxic and adverse side effects. It is relevant to consider this issue in the present context because drugs that are not normally considered to be psychopharmacologic agents can cause psychological effects in high dosages or in combination with other drugs. In addition, drugs can have a range of behavioral effects (e.g., discomfort, headache, dizziness, nausea, sedation, altered appetite, sexual impotence) that decrease the likelihood of adherence to prescribed medication regimens. The study of these effects also contributes to psychopharmacologic knowledge.
III. Mechanisms of Action of Psychopharmacologic Agents
A. Neuroanatomy
The brain, central nervous system, and peripheral nervous system all are relevant to the actions of psychopharmacologic agents. The vast array of effects of these drugs is reflected in the range of relevant neuroanatomical sites affected by these drugs. The specific loci of action reveal information about the underlying mechanisms of drug action and also reveal information about the anatomical substrates of specific psychological and behavioral responses. Brain regions that are relevant to the present discussion include the reticular activating system (for arousal and consciousness), pons and medulla (for autonomic control), cerebellum (for motor function and locomotion), pituitary (for hormonal regulation), hypothalamus (for body weight and hunger regulation), amygdala (for aggression), limbic system (for emotions and mood), hippocampus (for memory and learning), ventral tegmental area and nucleus accumbens (for reward), occipital lobe (for vision), parietal lobe (for somatosensory perception), temporal lobe (for audition), and the cortex (for higher cognitive and sensory-motor processing). Increasingly, psychopharmacologists are investigating neuroanatomical structures and loci via electrophysiological (e.g., single cell recording), surgical (e.g., ablation), and pharmacological (e.g., specific agonists and antagonists, radioactively labeled drugs) techniques in conjunction with functional assessment of drug effects. This work can be done on a molecular and cytoarchitectural level in animal subjects. Developments in receptor biology, structure and function, allow for detailed analyses of the cellular bases for psychopharmacologic drug actions. In addition, brain imaging techniques (including positron emission tomography [PET], magnetic resonance imaging [MRI], computed tomography [CT], single photon emission computed tomography [SPECT], and magnetoencephalography [MEG]) allow for the examination of structural and functional information relevant to psychopharmacologic agents in humans.
B. Neurophysiology and Electrophysiology
The function and actions of neurons, nerves, neural tracts, and neural tissue can be evaluated by invasive and noninvasive techniques and are included in psychopharmacologic investigations. In animal subjects, current technology allows for single cell recording of electrical activity relevant to neurophysiologic function. Action potentials, excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), long-term potentiation (LTP), and kindling all are studied in response to psychopharmacologic agents. Sensory and motor nerve recording, in animal subjects and in human patients, also provide useful information in this context. Electromyography (EMG) can be used in human patients to evaluate muscular responses, for example, to muscle relaxants and in cases of anxiety and pain. Electrocardiography (ECG or EKG) is used to assess heart function and is relevant in the present context to evaluate side effects of psychopharmacologic agents, as an index of stress responses, and to evaluate effects of psychopharmacologic drugs that may be revealed in cardiovascular arousal (e.g., anxiety, general arousal). Electroencephalography (EEG) is a noninvasive technique used to evaluate electrophysiologic activity of the brain. Detailed analyses of this information (e.g., contingent negative variation [CNV], auditory evoked potentials [AEP], visual evoked potentials [VEP], somatosensory evoked potentials [SEP], and positive or negative deflections in these responses) reveal the relay of information through specific brain regions and, thereby, can be used to evaluate the actions and to suggest mechanisms of psychopharmacologic agents.
C. Neurochemistry
The chemical bases of communication among neurons and the chemical regulation or modulation of this communication are affected by psychopharmacologic agents. These drugs can alter all of the known chemical neurotransmitters, including: amino acid transmitters (e.g., g-amino-butyric acid [GABA], glycine, taurine, beta-alanine, glutamate, aspartate, cysteic acid), acetylcholine, catecholamines (e.g., norepinephrine, epinephrine, dopamine), indoleamines (e.g., serotonin), histamine, and neuroactive peptides (e.g., pro-opiomelanocortin [POMC], b-endorphin, leucine-enkephalin, methionine-enkephalin, dynorphin, neuropeptide-Y). Psychopharmacologic agents also can alter neuromodulators and chemicals that affect body functions, including: adrenocorticotrophin hormone (ACTH), corticotropin releasing factor (CRF), corticosteroids, and many peptides (e.g., Substance P, galanin, cholecystokinin [CCK], neurotensin, vasopressin, antidiuretic hormone [ADH], thyrotropin releasing hormone [TRH]). In addition to these relatively large molecules, psychopharmacologic agents can affect chemical ions (charged particles) that alter neuronal transmission. Further, psychopharmacologic agents can affect second messengers (e.g., cyclic adenosine monophosphate [cAMP], guanine diphosphate [GDP],nerve growth factor [NGF]) and G-proteins that act to modulate neuronal communication. Genes with altered expression after drug exposure also are under investigation. Evaluations of these actions are active topics of research.
IV. Clinical Psychopharmacology
Psychopharmacologically active agents (e.g., alcohol, opium) have been used for millennia to alter psychological state. Over the past 200 years, specific gases and chemicals have been identified (e.g., nitrous oxide, barbituric acid) that also alter consciousness and psychological state. It was not until the 1950s, however, that use of drugs to treat mental disorders and conditions became formalized and a focus of research and clinical attention. The dramatic reports in the early 1950s of chlorpromazine (Thorazine) to treat psychoses was a breakthrough that allowed previously uncontrollable patients to be cared for in a humane manner. This important development proved to be the genesis of clinical psychopharmacology as a central element in modern psychiatry and as a valuable adjunct to psychotherapy. No single pharmacological class is the panacea for the treatment of mental disorders. In fact, the identification and distinction among mental health disorders continues to be accompanied by the development of many different psychopharmacological agents that either treat the mental health condition or the symptoms associated with the condition. This section addresses the available psychopharmacologic treatments of the major categorizations of mental health disorders presented by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV) of the American Psychiatric Association and of other important psychological conditions.
A. Anxiety Disorders
Psychopharmacologic treatment of anxiety disorders began with the use of sedative-hypnotics (e.g., bromide salts, alcohol, chlorol hydrate) at the turn of the twentieth century. Barbiturates (e.g., phenobarbital, pentobarbital) were introduced early in the twentieth century but their adverse side effects, including addiction liability and toxic overdose, limited the use of these agents. The development of the benzodiazepines (e.g., chlordiazepoxide, diazepam) in the 1960s as general anxiolytics (separate from the muscle relaxant properties) was a major breakthrough because of the wide effective dose range and the limited adverse side effects. Subsequently, beta-adrenergic receptor antagonists (e.g., propranolol), antihistamines (e.g., hydroxyzine), and anticholinergic agents were used to treat specific cases of anxiety disorders (e.g., speech anxiety, posttraumatic stress disorder [PTSD]). More recently, azapirones (e.g., buspirone) that act via serotonergic antagonism and some dopaminergic antagonism have proven useful for mild forms of generalized anxiety. In the late 1980s, selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine [Prozac], sertraline [Zoloft], paraxetine [Paxil]) were introduced and, in the 1990s, were approved for treatment of specific anxiety disorders (e.g., panic, agoraphobia, PTSD). In addition, tricyclic drugs (e.g., clomipramine, imipramine, amitriptyline) and monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine) are used in the treatment of some anxiety disorders (e.g., panic, agoraphobia, PTSD).
B. Eating Disorders
Eating disorders usually are characterized by a morbid fear of becoming fat and a preoccupation with body weight, food, and body image. Eating disorders include anorexia nervosa (restricting type and eating/ purging type) and bulimia nervosa (purging and nonpurging type) and occur more commonly among females than among males. Anorexia nervosa is associated with a 5 to 18% premature mortality rate. In addition, these individuals are at risk for comorbid depression, mood disorders, and an increased risk of physical health problems as a result of poor nutrition. Given the serious implications of this illness, hospitalization can become necessary in an effort to restore the patient’s nutritional status, electrolyte balance, and hydration. Unfortunately, no psychopharmacologic agent or class of agents cures the primary symptoms of anorexia nervosa. Various drugs are used to treat secondary symptoms associated with these eating disorders. For example, amitriptyline (i.e., the tricyclic antidepressant Elavil) has been used effectively in some patients with this disorder, and cyproheptadine, a drug with antiserotonergic and antihistaminic effects, is effective with some restrictive-type anorexia patients. Some studies suggest that fluoxetine (i.e., an SSRI) administration may result in weight gain, but most studies indicate that antidepressants provide little benefit to these patients. There are risks (e.g., hypotension, cardiac arrhythmias, dehydration) associated with the use of tricyclic antidepressants in these patients and, therefore, it is not recommended that they be used. There are no data on the use of other SSRIs in patients with anorexia nervosa. MAOIs (phenelzine or tranylcypromine) may be useful, but few data are available to establish their value unequivocally. Antidepressant medications seem to be particularly useful with bulimic patients. Imipramine, desipramine, trazodone, fluoxetine, and MAOIs have been successful in treating binge–purge cycles. Antidepressants are effective when used in dosages suggested for the treatment of depressive disorders. However, higher dosages of fluoxetine usually are needed to alleviate binge episodes than those dosages suggested for treating depression. Carbamazepine and lithium are useful in bulimic patients with comorbid mood disorders but are not useful in treating binge episodes alone. Bupropion is contraindicated in patients with a history of anorexia nervosa and bulimia nervosa because it may result in seizures.
Although not usually defined as classical eating disorders, there certainly are many cases of overeating that lead to obesity and excessive body weight. Some people overeat in response to psychological or environmental conditions; others are night-eaters (i.e., they get up and eat excessively after they have gone to bed); and others eat to the point of obesity and excessive body weight as a result of biological variables. Appetite suppressant medications (e.g., dexfenfluramine, diethylpropion, fenfluramine, mazindol, phendimetrazine, phentermine) are useful for some people but the effects are modest. Other appetite suppressant medications (e.g., amphetamines) are not recommended for use because they are addictive. Various antidepressants are used in some cases of overeating.
C. Learning, Memory, Attention, and Related Cognitive Disorders
There is a wide variety of cognitive conditions that deleteriously affect learning, memory, and attention but that do not involve other psychopathology. For example, Attentional Deficit Disorder with and without hyperactivity (ADHD and ADD), senile dementia, and Alzheimer’s disease are familiar to the public. Each of these conditions can have profound negative effects on daily living and quality of life. Psychopharmacologic treatment for these conditions is an active, current topic of interest with modest success to date. For example, ADHD is treated with stimulants (including dextroamphetamine, methylphenidate [Ritalin], and pemoline), antidepressants (including imipramine, desipramine, and nortriptyline), and clonidine. Memory deficit-related conditions are an area of great interest and experimental investigations areexamining various medications, including drugs that act as: dopaminergic agonists, a-2 adrenergic agonists, cholinergic agonists, general cerebral metabolic enhancers, calcium channel blockers, and serotonergic agents.
D. Mood Disorders
Mood disorders are manifested as either depressive or manic episodes. Among the most serious of the mood disorders are major depressive disorder or unipolar depression, in which a patient only experiences depressive episodes, and bipolar disorder, in which a patient experiences both manic and depressive episodes or only manic episodes. The history and current use of pharmacological agents to treat these separate mood disorders differ. With regard to unipolar depression, amphetamines were first used in the late 1930s. In the 1950s, the tricyclic and tetracyclic antidepressants (TCAs) (e.g., imipramine, amoxapine) and MAOIs (e.g., phenelzine) were serendipitously discovered to elevate depressive moods. These prototypal compounds, however, affect many systems indiscriminately, have a slow action of onset, and produce numerous unwanted side effects that deter patient compliance. The largest new drug class of antidepressants includes SSRIs (e.g., fluoxetine). In general, the SSRIs are no more effective than TCAs but cause limited and more tolerated side effects and have a reduced risk of overdose. Two new antidepressants, with pharmacologic actions and side effects profiles that differ from those of SSRIs, are nefazodone and venlafaxine which inhibit serotonin reuptake and also either exhibit 5-HT2A/5-HT2C antagonism or inhibit the reuptake of norepinephrine, respectively. Other nonuptake- inhibiting serotonergic drugs that increase serotonin release and function through partial agonism of the 5-HT1A (e.g., buspirone) and 5-HT2C (e.g., m-chlorophenylpiperazine) receptors are being investigated. Manipulation of the serotonergic system is the most common, current approach in antidepressant drug therapy, but new selective and reversibleMAO-A inhibitors (e.g., moclobemide) are being tested and have been reported as effective to treat unipolar and bipolar patients with no anticholinergic or cardiovascular side effects and minimal dietary restrictions. With regard to bipolar disorder, lithium remains the major pharmacological treatment since its discovery as a calming agent in 1949. Only 60 to 80% of bipolar patients, however, respond to lithium treatment alone. Patients who do not respond to lithium are often given antidepressants in combination with antipsychotics despite the higher risk of developing tardive dyskinesia. Over the past few years, a variety of other drugs, including anticonvulsants (e.g., carbamazepine) and calcium channel blockers (e.g., verapamil), have been used to treat bipolar disorder. Mania also can be treated with benzodiazepines, anticonvulsants, antipsychotics, or calcium channel blockers. In mostcasesof bipolar disorders, patients receive a combined pharmacotherapeutic treatment during the course of their illness.
E. Pain
Pain is the unpleasant psychological experience associated with actual or potential tissue damage. Pain may be acute, periodic, or continuous; sharp, dull /aching, or burning; annoying, uncomfortable, or unbearable. Pain occurs in response to readily identifiable accidents, injury, or medical treatments (e.g., surgery); to ambiguous or mixed causes (e.g., weather conditions, disturbed sleep, work environment); and to unknown immediate causes (e.g., undiagnosed pathology, forgotten injury). Pain is treated by a variety of pharmacologic agents including: opiates (e.g., morphine, meperidine, fentanyl, codeine), nonsteroidal anti-inflammatory agents (e.g., salicylic acid derivatives such as aspirin; para-aminophenol derivatives such as acetaminophen; indole and indene acetic acids such as indomethacin) and drugs that are selectively used to treat specific pain-related disorders (e.g., the 5- HT1D agonist, sumatriptan, to treat migraine headaches). With regard to pain of known cause, pharmacologic treatments are relatively effective for the vast majority of people. With regard to pain of ambiguous or unknown origin and with regard to continuous pain, pharmacologic treatments have mixed results. For example, opiate medications alter how chronic pain patients perceive and cope with pain but do not completely alleviate the pain.
Unfortunately, currently available analgesics have many undesirable side effects including sedation, respiratory depression, gastrointestinal upset or constipation, pruritus, and addiction. Ongoing investigations are attempting to develop analgesic medications with greater efficacy and few side effects.
F. Psychoses
Psychotic disorders are characterized by delusions, hallucinations, disorganized speech, or disorganized or catatonic behavior. The major psychotic disorders include schizophrenia, schizophreniform disorder, schizoaffective disorder, or delusional disorder. The most widely prescribed antipsychotic drugs are referred to as neuroleptics. The major antipsychotics are: tricyclic phenothiazines, thioxanthenes, dibenzepines, butyrophenones, benzamides, clozapines, and risperidone. Most drugs of these types block D2 dopaminergic receptors and inactivate dopamine neurotransmitters in the forebrain. Some of these medications also affect D1 dopaminergic, 5-HT2 serotonergic, and a-adrenergic receptors. Unfortunately, none of these medications cures psychoses, each one helps only some patients, and there are deleterious side effects, including: akathisia, rigidity, tremors, and other neuromuscular effects. In addition to these major drugs, lithium, anticonvulsants, and benzodiazipenes are prescribed.
G. Sexual Dysfunction
DSM-IV distinguishes among sexual dysfunctions as: Sexual Desire Disorder, Sexual Arousal Disorder, Orgasmic Disorder, Sexual Pain Disorders, Sexual Dysfunction Due to a General Medical Condition, Substance-Induced Sexual Dysfunction, and Sexual Dysfunction Not Otherwise Specified. These conditions are different from Paraphilias (e.g., intense sexual urges to unusual objects, Exhibitionism, Voyeurism). Psychopharmacology has played a relatively small role in the treatment of these conditions but that role is increasing. Antianxiety agents and antidepressants are helpful in some patients. Other medications (e.g., methohexital sodium) have been used in conjunction with desensitization therapy. Sex hormones (e.g., estrogen, testosterone) have been used in specific cases. With changes in societal attitudes to the discussion of these types of problems also may come increased attention to the development and study of treatment for these conditions. [See Research Paper on Sexual Dysfunction Therapy.]
H. Sleep Disorders
Humans spend one-quarter to one-third of their lives sleeping and roughly one-third of all adults experience some type of sleep disorder during their lives. Sleep disorders are categorized by the DSM-IV as: Primary Sleep Disorders (including Dyssomnias and Parasomnias), Sleep Disorder Related to Another Mental Disorder, Sleep Disorder Due to a General Medical Condition, and Substance-Induced Sleep Disorder. The most common Sleep Disorder is Insomnia, but other Dyssomnias include: Hypersomnia, Narcolepsy, Breathing-Related Sleep Disorder, and Circadian Rhythm Sleep Disorder. Parasomnias include: Nightmare Disorder, Sleep Terror Disorder, and Sleepwalking Disorder. Primary Insomnia is treated with benzodiazepines or sedative-hypnotics. Primary Hypersomnia is treated with stimulants, such as amphetamines, or SSRIs. Narcolepsy is treated with stimulants, antidepressants, and sometimes with a1 agonists. Benzodiazepines and other anti-anxiety medications are used selectively to treat other sleep disorders.
I. Substance-Related Disorders
In the DSM-IV, Substance-Related Disorders include taking drugs of abuse, side effects of medication, and toxic exposure. Substance-Related Disorders are categorized as Substance Use Disorders (Substance Dependence and Substance Abuse) or as Substance- Induced Disorders (Substance Intoxication, Substance Withdrawal, any Substance-Induced adverse psychological or behavioral effect). A wide variety of psychopharmacologic agents are used in conjunction with psychological approaches to treat the varied aspects of Substance-Related Disorders. This section provides a brief synopsis of this expansive aspect of psychopharmacology.
Alcohol and nicotine (e.g., in cigarettes, cigars, and other tobacco products) are the most commonly used and abused substances in our culture. Other drugs also are used recreationally and have deleterious effects. Psychopharmacologic treatments can be used to discourage drug use, to decrease withdrawal symptoms, or to treat comorbid psychological conditions. The major Substance-Related Disorders and their Treatments are:
1. Alcohol-Related Disorders
Psychopharmacologic agents used for the treatment of alcohol abuse include disulfiram (i.e., Antabuse). When ingested, disulfiram inhibits the enzyme aldehyde dehydrogenase so that consumption of alcohol results in a toxic reaction to the accumulation of acetaldehyde in the blood. Consumption of alcohol while taking disulfiram leads to flushing, feelings of heat and numbness in the limbs and upper chest, nausea, dizziness, malaise, blurred vision, air hunger, and palpitations. Psychotropic medications that are used to treat anxiety and depressive symptoms in these patients are useful. Recently, these drugs and SSRIs have been used to control craving for alcohol. Specifically, trazodone, serotonin type 3 (5HT3) antagonists, and dopaminergic agonists (e.g., apomorphine, bromocriptine) may be effective in decreasing cravings. Naltrexone, an opioid antagonist, also has shown promise as a possible treatment for alcohol dependence. Benzodiazepines are the primary medications for controlling alcohol withdrawal symptoms (seizures, delirium, anxiety, tachycardia, hypertension). Carbamazepine, b-adrenergic receptor antagonists, and clonidine also have been used to treat sympathetic activity associated with alcohol withdrawal. However, these drugs are not effective in the treatment of seizures or delirium.
2. Amphetamine-Related Disorders
The pharmacologic treatment for amphetamine-induced psychotic disorder and amphetamine-induced anxiety disorder is usually antipsychotics (phenothiazine, haloperidol) and anxiolytics (diazepam), respectively, on a short-term basis. Chronic lithium treatment to attenuate the euphoria associated with amphetamine use, thereby decreasing the likelihood of continued use, is not recommended.
3. Caffeine-Related Disorders
Analgesics such as aspirin, ibuprofen, and acetaminophen usually are sufficient for treating headaches and muscle aches associated with caffeine withdrawal. Benzodiazepines rarely are needed and should only be prescribed for a short period of time (less than 7 days).
4. Cannabis-Related Disorders
Psychopharmacologic treatment for these disorders is less clear, but some patients may respond to anxiolytics for the treatment of withdrawal symptoms. In addition, antidepressants may be useful in treating any underlying depressive disorder associated with cannabis abuse.
5. Cocaine-Related Disorders
Several pharmacologic agents have been used to decrease cocaine craving in cocaine abusers. Dopaminergic agonists, amantadine and bromocriptine, and TCAs such as desipramine and imipramine seem to decrease drug cravings, increase energy, and improve sleep. Carbamazepine also decreases cravings, but not in patients with antisocial personality disorder.
6. Hallucinogen-Related Disorders
Pharmacologic agents such as dopaminergic antagonists are often used to treat psychotic symptoms associated with withdrawal and benzodiazepines can be used to treat anxiety symptoms on a short-term basis.
7. Inhalant-Related Disorders
There are no prescribed methods of psychopharmacologic treatments for these disorders.
8. Nicotine-Related Disorders
Administration of nicotine through a transdermal patch is a useful approach to help individuals quit smoking because it curbs withdrawal symptoms associated with nicotine cessation (e.g., hunger, irritability, inattention). Nicotine also can be administered via chewing gum or in a nasal spray. Clonidine and antidepressants (fluoxetine and buspirone in particular) have been used to help some people who abstain from tobacco use.
9. Opioid-Related Disorders
Methadone, a synthetic opioid agonist that is administered orally, is used as a substitute for heroin to help the patient move away from injectable opiates, maintain a steady job, and reintegrate into a daily lifestyle that is not associated with drug-taking. Levo-alpha-acetyl-methadol (LAAM) is a longer acting opioid agonist that is similar to methadone and only needs to be administered about three times a week. Buprenorphine is a mixed opioid agonist-antagonist that has shown promise as an opioid substitute in the treatment of opioid addiction. Naltrexone can be used to block the pharmacologic actions of opioids, including the subjective high, and, possibly the subsequent drug craving and physical dependence. Clonidine is administered during the initial stages of opiate withdrawal and naltrexone is administered to treat opioid overdose.
10. Phencyclidine (or Phencyclidine-like)-Related Disorders
Benzodiazepines and dopamine receptor antagonists (haloperidol) are used for controlling behavioral disorders associated with phencyclidine intoxication.
11. Sedative-, Hypnotic-, or Anxiolytic-Related Disorders
Carbamazepine may be useful in the treatment of benzodiazepine withdrawal. The treatment for barbiturate abuse is far more complicated than benzodiazepine withdrawal because sudden death can occur during withdrawal. It is recommended that phenobarbital be substituted in the withdrawal procedure and the dosages gradually decreased over a long period of time. Once complete withdrawal has occurred, nonbarbiturate sedative-hypnotics should be used as a substitute for the barbiturate. However, this substitution typically translates the drug dependence to a new substance and does not cure the addiction.
V. Special Populations
A. Pediatric
Age influences pharmacokinetic and pharmacodynamic responses. With regard to psychopharmacology, it is generally assumed that children are small adults and, therefore, adjustments in psychopharmacologic treatments simply need to be made based on body weight. This assumption, however, may be wrong. There are rapid, age-related biological and psychological changes that begin in the newborn and continue throughout childhood and adolescence. These changes demand a psychopharmacologic treatment approach that differs from adults and is sensitive to developmental stages, both physical and psychological. As of now, our understanding of pediatric psychopharmacology is limited and many important investigations of drug actions across developmental periods have yet to be conducted.
B. Geriatric
Aging is a highly individualized process that results in various changes over time that can alter significantly the actions of psychotropic medications in the body and how the body affects the drugs. In elderly patients there are changes in: organ system function, drug distribution, drug action, drug metabolism, and drug elimination. In addition, cumulative drug actions are common among elderly persons who take many prescription medications, over-the-counter medications, and other substances (e.g., alcohol, nicotine, caffeine). Psychopharmacologic treatments in the elderly require coordinated, integrated medical care that captures a complete picture of functioning within each individual. Quality of life in elderly patients can be greatly improved and prolonged by thoughtful use of medications and medical interventions. However, there are several obstacles to compliance that the prescriber should consider, including the expense of medications and treatment, the forgetfulness of some patients, and the deliberate choice by a patient not to take a particular treatment. The same sets of medical advances that offer improved quality of life for some, may represent threats to autonomy if thoughtfulness is not included in the clinical decision-making for each patient.
C. Individual Differences
Besides age, many factors can influence interindividual variability in drug responsivity, susceptibility to negative side effects, and potential drug abuse liability. These factors include biological (e.g, genetics, gender, ethnicity, disease state), environmental (e.g., stress, culture), and behavioral (e.g., diet, drug use, drug history) influences as well as the interactions of any two or more of these variables. The mechanisms by which these variables influence the actions of drugs can be molecular, biological, pharmacokinetic, pharmacodynamic, psychological, or social in nature. The identification of individual difference variables and their contribution to drug action are relevant to the clinical administration of medications as well as to our understanding of the mechanisms underlying drug addiction.
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See also:
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