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INTRODUCTION Although much remains unknown about what causes mental illness, science in the past 40 years has made great strides in helping us understand how the brain works and in presenting possible causes of why some brains work diƯerently from others. Such advances in neurobiologic research are continually expanding the knowledge base in the field of psychiatry and are greatly influencing clinical practice. The psychiatric–mental health nurse must have a basic understanding of how the brain functions and of the current theories regarding mental illness. This chapter includes an overview of the major anatomic structures of the nervous system and how they work—the neurotransmission process. It presents the major current neurobiologic theories regarding what causes mental illness, including genetics and heredity, stress and the immune system, and infectious agents. The use of medications to treat mental illness (psychopharmacology) is related to these neurobiologic theories. These medications directly aƯect the central nervous system (CNS) and subsequently behavior, perceptions, thinking, and emotions. This chapter discusses five categories of drugs used to treat mental illness, including their mechanisms of action, their side eƯects, and the roles of the nurses in administration and client teaching. Although pharmacologic interventions are the most eƯective treatment for many psychiatric disorders, adjunctive therapies, such as cognitive and behavioral therapies, family therapy, and psychotherapy, can greatly enhance the success of treatment and the client’s outcome. Chapter 3 discusses these psychosocial modalities. THE NERVOUS SYSTEM AND HOW IT WORKS Central Nervous System The CNS comprises the brain, the spinal cord, and associated nerves that control voluntary acts. Structurally, the brain consists of the cerebrum, cerebellum, brain stem, and limbic system. Figures 2. and 2.2 show the locations of brain structures. FIGURE 2.1. Anatomy of the brain. Cerebrum The cerebrum is divided into two hemispheres; all lobes and structures are found in both halves except for the pineal body, or gland, which is located between the hemispheres. The pineal body is an endocrine gland that influences the activities of the pituitary gland, islets of Langerhans, parathyroids, adrenals, and gonads. The corpus callosum is a pathway connecting the two hemispheres and coordinating their functions. The left hemisphere controls the right side of the body and is the center for logical reasoning and analytic functions such as reading, writing, and mathematical tasks. The right hemisphere controls the left side of the body and is the center for creative thinking, intuition, and artistic abilities. The cerebral hemispheres are divided into four lobes: frontal, parietal, temporal, and occipital. Some functions of the lobes are distinct; others are integrated. The frontal lobes control the organization of thought, body movement, memories, emotions, and moral behavior. The integration of all this information regulates arousal, focuses attention, and enables problem-solving and decision-making. Abnormalities in the frontal lobes are associated with schizophrenia, attention-
deficit/hyperactivity disorder (ADHD), and dementia. The parietal lobes interpret sensations of taste and touch and assist in spatial orientation. The temporal lobes are centers for the senses of smell and hearing and for memory and emotional expression. The occipital lobes assist in coordinating language generation and visual interpretation, such as depth perception. Cerebellum The cerebellum is located below the cerebrum and is the center for coordination of movements and postural adjustments. It receives and integrates information from all areas of the body, such as the muscles, joints, organs, and other components of the CNS. Research has shown that inhibited transmission of dopamine, a neurotransmitter, in this area is associated with the lack of smooth coordinated movements in diseases such as Parkinson’s disease and dementia. FIGURE 2.2. The brain and its structures. Brain Stem The brain stem includes the midbrain, pons, and medulla oblongata and the nuclei for cranial nerves III through XII. The medulla, located at the top of the spinal cord, contains vital centers for respiration and cardiovascular functions. Above the medulla and in front of the cerebrum, the pons bridges the gap both structurally and functionally, serving as a primary motor pathway. The midbrain connects the pons and cerebellum with the cerebrum. It measures only 0.8 in (2 cm) length and includes most of the reticular activating system and the extrapyramidal system. The reticular activating system influences motor activity, sleep, consciousness, and awareness. The extrapyramidal system relays information about movement and coordination from the brain to the spinal nerves. The locus coeruleus, a small group of norepinephrine-producing neurons in the brain stem, is associated with stress, anxiety, and impulsive behavior. Limbic System The limbic system is an area of the brain located above the brain stem that includes the thalamus, hypothalamus, hippocampus, and amygdala (although some sources diƯer regarding the structures this system includes). The thalamus regulates activity, sensation, and emotion. The hypothalamus is involved in temperature regulation, appetite control, endocrine function, sexual drive, and impulsive behavior associated with feelings of anger, rage, or excitement. The hippocampus and amygdala are involved in emotional arousal and memory. Disturbances in the limbic system have been implicated in a variety of mental illnesses, such as the memory loss that accompanies dementia and the poorly controlled emotions and impulses seen with psychotic or manic behavior. Neurotransmitters Approximately 100 billion brain cells form groups of neurons, or nerve cells, that are arranged in networks. These neurons communicate information with one another by sending electrochemical messages from neuron to neuron, a process called neurotransmission. These electrochemical messages pass from the dendrites (projections from the cell body), through the soma or cell body, down the axon (long extended structures), and across the synapses (gaps between cells) to the dendrites of the next neuron. In the nervous system, the electrochemical messages cross the synapses between neural cells by way of special chemical messengers called neurotransmitters.
been found to contribute to the delusions, hallucinations, and withdrawn behavior seen in schizophrenia. Some antidepressants block serotonin reuptake, thus leaving it available longer in the synapse, which results in improved mood. TABLE 2.1 Major Neurotransmitters Type Mechanism of Action Physiological EƯects Dopamine Excitatory Controls complex movements, motivation, cognition; regulates emotional response Norepinephrine (noradrenaline) Excitatory Causes changes in attention, learning and memory, sleep and wakefulness, mood Epinephrine (adrenaline) Excitatory Controls fight-or-flight response Serotonin Inhibitory Controls food intake, sleep and wakefulness, temperature regulation, pain control, sexual behaviors, regulation of emotions Histamine Neuromodulator Controls alertness, gastric secretions, cardiac stimulation, peripheral allergic responses Acetylcholine Excitatory or inhibitory Controls sleep and wakefulness cycle; signals muscles to become alert Neuropeptides Neuromodulators Enhance, prolong, inhibit, or limit the eƯects of principal neurotransmitters Glutamate Excitatory Results in neurotoxicity if levels are too high Gamma-aminobutyric acid Inhibitory Modulates other neurotransmitters Histamine The role of histamine in mental illness is under investigation. It is involved in peripheral allergic responses, control of gastric secretions, cardiac stimulation, and alertness. Some psychotropic drugs block histamine, resulting in weight gain, sedation, and hypotension. Acetylcholine Acetylcholine is a neurotransmitter found in the brain, spinal cord, and peripheral nervous system, particularly at the neuromuscular junction of skeletal muscle. It can be excitatory or inhibitory. It is synthesized from dietary choline found in red meat and vegetables and has been found to aƯect the sleep–wake cycle and to signal muscles to become active. Studies have shown that people with Alzheimer’s disease have decreased acetylcholine-secreting neurons, and people with myasthenia gravis (a muscular disorder in which impulses fail to pass the myoneural junction, which causes muscle weakness) have reduced acetylcholine receptors. Glutamate Glutamate is an excitatory amino acid that can have major neurotoxic eƯects at high levels. It has been implicated in brain damage caused by stroke, hypoglycemia, sustained hypoxia or ischemia, and some degenerative diseases such as Huntington’s or Alzheimer’s. Gamma-Aminobutyric Acid Gamma-aminobutyric acid (GABA), an amino acid, is the major inhibitory neurotransmitter in the brain and has been found to modulate other neurotransmitter systems rather than to provide a direct stimulus. Drugs that increase GABA function, such as benzodiazepines, are used to treat anxiety and to induce sleep. BRAIN IMAGING TECHNIQUES At one time, the brain could be studied only through surgery or autopsy. Now, current brain imaging techniques allow visualization of the brain’s structure and function. These techniques are useful for diagnosing some disorders of the brain and have helped correlate certain areas of the brain with specific functions. Brain
imaging techniques are also useful in research to find the causes of mental disorders. Table 2.2 describes and compares several of these diagnostic techniques. Types of Brain Imaging Techniques Computed tomography (CT), also called computed axial tomography, is a procedure in which a precise x-ray beam takes cross-sectional images (slices) layer by layer. A computer reconstructs the images on a monitor and also stores the images on magnetic tape or film. CT can visualize the brain’s soft tissues, so it is used to diagnose primary tumors, metastases, and eƯusions and to determine the size of the ventricles of the brain. Some people with schizophrenia have been shown to have enlarged ventricles; this finding is associated with a poorer prognosis and marked negative symptoms (Fig. 2.5; see Chapter 16). The person undergoing CT must lie motionless on a stretcher-like table for about 20 to 40 minutes as the stretcher passes through a tunnel-like “ring” while the serial x-rays are taken. TABLE 2.2 Brain Imaging Technology Procedure Imaging Method Results Duration Computed tomography (CT) Serial x-rays of brain Structural image 20–40 minutes Magnetic resonance imaging (MRI) Radio waves from brain detected from magnet Structural image 45 minutes Positron emission tomography (PET) Radioactive tracer injected into bloodstream and monitored as client performs activities Functional 2–3 hours Single-photon emission computed tomography (SPECT) Same as PET Functional 1–2 hours In magnetic resonance imaging (MRI), a type of body scan, an energy field is created with a huge magnet and radio waves. The energy field is converted to a visual image or scan. MRI produces more tissue detail and contrast than CT and can show blood flow patterns and tissue changes such as edema. It can also be used to measure the size and thickness of brain structures; persons with schizophrenia can have as much as a 7% reduction in cortical thickness. The person undergoing an MRI must lie in a small, closed chamber and remain motionless during the procedure, which takes about 45 minutes. Those who feel claustrophobic or have increased anxiety may require sedation before the procedure. Clients with pacemakers or metal implants, such as heart valves or orthopedic devices, cannot undergo MRI. FIGURE 2.5. Example of computed tomography of the brain of a client with schizophrenia (right) compared with a normal control (left). More advanced imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), are used to examine the function of the brain. Radioactive substances are injected into the blood; the flow of those substances in the brain is monitored as the client performs cognitive activities as instructed by the operator. PET uses two photons simultaneously; SPECT uses a single photon. PET provides better resolution with sharper and clearer pictures and takes about 2 to 3 hours; SPECT takes 1 to 2 hours. These scans are used in oncology and brain disorders, such as tumors, and for cognitive problems. In psychiatry, PET and SPECT are used primarily for research, not for the diagnosis and treatment of clients with mental disorders (Schatzberg & DeBattista,
- (Fig. 2.6). A recent breakthrough is the use of the chemical marker FDDNP with PET
commonly conducted to investigate the genetic basis of mental illness: Twin studies are used to compare the rates of certain mental illnesses or traits in monozygotic (identical) twins, who have an identical genetic makeup, and dizygotic (fraternal) twins, who have a diƯerent genetic makeup. Fraternal twins have the same genetic similarities and diƯerences as nontwin siblings. Adoption studies are used to determine a trait among biologic versus adoptive family members. Family studies are used to compare whether a trait is more common among first-degree relatives (parents, siblings, and children) than among more distant relatives or the general population. Although some genetic links have been found in certain mental disorders, studies have not shown that these illnesses are solely genetically linked. Investigation continues about the influence of inherited traits versus the influence of the environment—the “nature versus nurture” debate. The influence of environmental or psychosocial factors is discussed in Chapter 3. Stress and the Immune System (Psychoimmunology) Researchers are following many avenues to discover possible causes of mental illness. Psychoimmunology, a relatively new field of study, examines the eƯect of psychosocial stressors on the body’s immune system. A compromised immune system could contribute to the development of a variety of illnesses, particularly in populations already genetically at risk. So far, eƯorts to link a specific stressor with a specific disease have been unsuccessful. However, the immune system and the brain can influence neurotransmitters. When the inflammatory response is critically involved in illnesses such as multiple sclerosis or lupus erythematosus, mood dysregulation and even depression are common. Current investigations have focused on the contribution of inflammation, such as mild encephalitis, in the causality of severe mental disorders (Bechter, 2020). Infection as a Possible Cause Some researchers are focusing on infection as a cause of mental illness. Most studies involving viral theories have focused on schizophrenia, but so far, none has provided specific or conclusive evidence. Theories that are being developed and tested include the existence of a virus that has an aƯinity for tissues of the CNS, the possibility that a virus may actually alter human genes, and maternal exposure to a virus during critical fetal development of the nervous system. Bacterial infections in pregnant women may impact the developing brain of the fetus and are associated with an elevated risk for psychosis in oƯspring (Lee et al., 2020). THE NURSE’S ROLE IN RESEARCH AND EDUCATION Amid all the reports of research in these areas of neurobiology, genetics, and heredity, the implications for clients and their families are still not clear or specific. Often, reports in the media regarding new research and studies are confusing, contradictory, or diƯicult for clients and their families to understand. The nurse must ensure that clients and families are well informed about progress in these areas and must also help them to distinguish between facts and
hypotheses. The nurse can explain if or how new research may aƯect a client’s treatment or prognosis. The nurse is a good resource for providing information and answering questions. PSYCHOPHARMACOLOGY Medication management is a crucial issue that greatly influences the outcomes of treatment for many clients with mental disorders. The following sections discuss several categories of drugs used to treat mental disorders (psychotropic drugs): antipsychotics, antidepressants, mood stabilizers, anxiolytics, and stimulants. Nurses should understand how these drugs work; their side eƯects, contraindications, and interactions; and the nursing interventions required to help clients manage medication regimens. Several terms used in discussions of drugs and drug therapy are important for nurses to know. EƯicacy refers to the maximal therapeutic eƯect that a drug can achieve. Potency describes the amount of the drug needed to achieve that maximum eƯect; low- potency drugs require higher dosages to achieve eƯicacy, while high-potency drugs achieve eƯicacy at lower dosages. Half-life is the time it takes for half of the drug to be removed from the bloodstream. Drugs with a shorter half-life may need to be given three or four times a day, but drugs with a longer half-life may be given once a day. The time that a drug needs to leave the body completely after it has been discontinued is about five times its half-life. Keeping clients informed The U.S. Food and Drug Administration (FDA) is responsible for supervising the testing and marketing of medications for public safety. These activities include clinical drug trials for new drugs and monitoring the eƯectiveness and side eƯects of medications. The FDA approves each drug for use in a particular population and for specific diseases. At times, a drug will prove eƯective for a disease that diƯers from the one involved in original testing and FDA approval. This is called oƯ-label use. An example is some anticonvulsant drugs (approved to prevent seizures) that are prescribed for their eƯects in stabilizing the moods of clients with bipolar disorder (oƯ- label use). The FDA also monitors the occurrence and severity of drug side eƯects. When a drug is found to have serious or life-threatening side eƯects, even if such side eƯects are rare, the FDA may issue a black box warning. This means that package inserts must have a highlighted box, separate from the text, which contains a warning about the serious or life- threatening side eƯects. Several psychotropic medications discussed later in this chapter carry black box warnings. When drugs have serious yet infrequent side eƯects, the FDA requires a Risk Evaluation and Mitigation Strategy (REMS), specific actions, and/or safeguards that govern the use of these drugs (FDA, 2021). REMS for specific drugs are discussed later in this chapter. Principles that Guide Pharmacologic Treatment The following are several principles that guide the use of medications to treat psychiatric disorders: A medication is selected based on its eƯect on the client’s target symptoms such as delusional thinking, panic attacks, or hallucinations. The medication’s eƯectiveness is evaluated largely by its ability to diminish or eliminate the target
side eƯects (discussion to follow) because of the blocking of the D2 receptors. Newer, atypical antipsychotic drugs, such as clozapine (Clozaril), are relatively weak blockers of D2, which may account for the lower incidence of extrapyramidal side eƯects. In addition, atypical antipsychotics inhibit the reuptake of serotonin, as do some of the antidepressants, increasing their eƯectiveness in treating the depressive aspects of schizophrenia. Paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurasidone (Latuda) are second-generation agents. Paliperidone (Invega) is chemically similar to risperidone (Risperdal); however, it is an extended-release preparation. This means the client can take one daily dose in most cases, which may be a factor in increased compliance. Asenapine (Saphris) is a sublingual tablet, so clients must avoid food or drink for 10 to 15 minutes after the medication dissolves. TABLE 2.3 Antipsychotic Drugs Other atypical antipsychotics, called dopamine system stabilizers, are being developed. These drugs are thought to stabilize dopamine output; that is, they preserve or enhance dopaminergic transmission when it is too low and reduce it when it is too high. This results in control of symptoms without some of the side eƯects of other antipsychotic medications. Aripiprazole (Abilify), the first drug of this type, was approved for use in 2002. Cariprazine (Vraylar), brexpiprazole (Rexulti), and Caplyta (lumateperone) are newer antipsychotics. These drugs are used for schizophrenia, manic episodes, and as adjunct medication in both bipolar disorder and depression. The most common side eƯects are sedation, weight gain, akathisia, headache, anxiety, and nausea (Stahl, 2021). Six antipsychotics are available in depot injection, a time-release form of intramuscular medication for maintenance therapy. Two first-generation antipsychotics use sesame oil as the vehicle for these injections, so the medication is absorbed slowly over time; thus, less frequent administration is needed to maintain the desired therapeutic eƯects. Decanoate fluphenazine (Prolixin) has a duration of 7 to 28 days, and decanoate haloperidol (Haldol) has a duration of 4 weeks. After the client’s condition is stabilized with oral doses of these medications, administration by depot injection is required every 2 to 4 weeks to maintain the therapeutic eƯect. Risperidone (Risperdal Consta), paliperidone (Invega Sustenna), and olanzapine pamoate (Zyprexa Relprevv), second-generation antipsychotics, encapsulate active medication into polymer-based microspheres that degrade slowly in the body, gradually releasing the drug at a controlled rate. Risperdal Consta, 25 mg, is given every 2 weeks. Invega Sustenna, 117 mg, is given every 4 weeks. Zyprexa Relprevv can be given 210 mg every 2 weeks or 405 mg every 4 weeks. Zyprexa Relprevv has the potential to cause postinjection delirium/sedation syndrome, including sedation, confusion, disorientation, agitation, and cognitive impairment that can progress to ataxia, convulsions, weakness, and hypertension, which can lead to arrest. For that reason, REMS require that the client must be directly observed by a health care professional for 3 hours after the injection and must be alert, oriented, and symptom-free before they can be
released (FDA, 2021). Aripiprazole (Abilify Maintena), a third-generation antipsychotic, is slowly absorbed into the bloodstream because of the insolubility of aripiprazole particles (Otsuka America Pharmaceuticals, 2020). After initiation with oral medication, Abilify Maintena 400 mg is given monthly. → WARNING - Atypical Antipsychotics Older clients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk for death. Causes of death are varied, but most appear to be either cardiovascular or infectious in nature. Side EƯects Extrapyramidal Side EƯects. Extrapyramidal symptoms (EPSs), serious neurologic symptoms, are the major side eƯects of antipsychotic drugs. They include acute dystonia, pseudoparkinsonism, and akathisia. Although often collectively referred to as EPSs, each of these reactions has distinct features. One client can experience all the reactions in the same course of therapy, which makes distinguishing among them diƯicult. Blockade of D2 receptors in the midbrain region of the brain stem is responsible for the development of EPSs. First-generation antipsychotic drugs cause a greater incidence of EPSs than do other antipsychotic drugs. → WARNING - Geodon Contraindicated in clients with a known history of QT prolongation, recent myocardial infarction, or uncompensated heart failure, it should not be used with other QT-prolonging drugs. Therapies for acute dystonia, pseudoparkinsonism, and akathisia are similar and include lowering the dosage of the antipsychotic, changing to a diƯerent antipsychotic, or administering anticholinergic medication (discussion to follow). While anticholinergic drugs also produce side eƯects, atypical antipsychotic medications are often prescribed because the incidence of EPSs associated with them is decreased. Acute dystonia includes acute muscular rigidity and cramping, a stiƯ or thick tongue with diƯiculty swallowing, and, in severe cases, laryngospasm and respiratory diƯiculties. Dystonia is most likely to occur in the first week of treatment, in clients younger than 40 years, in males, and in those receiving high-potency drugs such as haloperidol and thiothixene. Spasms or stiƯness in muscle groups can produce torticollis (twisted head and neck), opisthotonus (tightness in the entire body with the head back and an arched neck), or oculogyric crisis (eyes rolled back in a locked position). Acute dystonic reactions can be painful and frightening for the client. Immediate treatment with anticholinergic drugs, such as intramuscular benztropine mesylate (Cogentin) or intramuscular or intravenous diphenhydramine (Benadryl), usually brings rapid relief. TABLE 2.4 Drugs Used to Treat Extrapyramidal Side EƯects Generic (Trade) Name Oral Dosages (mg) IM/IV Doses (mg) Drug Class Amantadine (Symmetrel) 100 bid or tid – Dopaminergic agonist Benztropine (Cogentin) 1–3 bid 1–2 Anticholinergic Biperiden (Akineton) 2 tid–qid 2 Anticholinergic Diazepam (Valium) 5 tid 5–10 Benzodiazepine Diphenhydramine (Benadryl) 25–50 tid or qid 25–50 Antihistamine Lorazepam (Ativan) 1–2 tid – Benzodiazepine Procyclidine (Kemadrin) 2.5–5 tid – Anticholinergic Propranolol (Inderal) 10–20 tid; up to 40 qid – Beta-blocker Trihexyphenidyl (Artane) 2–5 tid – Anticholinergic bid, two times a day; IM, intramuscularly;
blinking, grimacing, and other excessive unnecessary facial movements are characteristic. After it has developed, TD is irreversible, although decreasing or discontinuing antipsychotic medications can arrest its progression. Unfortunately, antipsychotic medications can mask the beginning symptoms of TD; that is, increased dosages of the antipsychotic medication cause the initial symptoms to disappear temporarily. As the symptoms of TD worsen, however, they “break through” the eƯect of the antipsychotic drug. In 2017, the FDA approved valbenazine (Ingrezza) and deutetrabenazine (Austedo, Teva) as the first drugs to treat TD. These drugs are vesicular monoamine transporter 2 (VMAT2) inhibitors. It is believed that these drugs decrease the activity of monoamines, such as dopamine, serotonin, and norepinephrine, thereby decreasing the abnormal movements associated with Huntington’s chorea and TD. Valbenazine has a dosage range of 40 to 80 mg daily, and deutetrabenazine ranges from 12 to 48 mg daily. Both drugs cause somnolence, QT prolongation, akathisia, and restlessness. In addition, valbenazine can cause nausea, vomiting, headache, and balance disturbances. Deutetrabenazine can also cause NMS and increased depression and suicidality in clients with Huntington’s chorea (Schatzberg & DeBattista, 2019). These drugs are also quite expensive, as much as $ per day. Preventing TD is the primary goal when administering antipsychotics. This can be done by keeping maintenance dosages as low as possible, changing medications, and monitoring the client periodically for initial signs of TD using a standardized assessment tool such as the Abnormal Involuntary Movement Scale (see Chapter 16). Clients who have already developed signs of TD but still need to take an antipsychotic medication are often given one of the atypical antipsychotic drugs that have not yet been found to cause or therefore worsen TD. Anticholinergic Side EƯects. Anticholinergic side eƯects often occur with the use of antipsychotics and include orthostatic hypotension, dry mouth, constipation, urinary hesitance or retention, blurred near vision, dry eyes, photophobia, nasal congestion, and decreased memory. These side eƯects usually decrease within 3 to 4 weeks but do not entirely remit. The client taking anticholinergic agents for EPSs may have increased problems with anticholinergic side eƯects. Using calorie-free beverages or hard candy may alleviate dry mouth, and stool softeners, adequate fluid intake, and the inclusion of grains and fruit in the diet may prevent constipation. Other Side EƯects. Antipsychotic drugs also increase blood prolactin levels. Elevated prolactin may cause breast enlargement and tenderness in men and women; diminished libido, erectile and orgasmic dysfunction, and menstrual irregularities; and increased risk for breast cancer. It can also contribute to weight gain. Weight gain can accompany most antipsychotic medications, but it is most likely with the second-generation antipsychotic drugs, with ziprasidone (Geodon) being the exception. Weight increases are most significant with clozapine (Clozaril) and olanzapine (Zyprexa). Since 2004, the FDA has made it mandatory for drug manufacturers that atypical antipsychotics carry a warning of the increased risk for
hyperglycemia and diabetes. Though the exact mechanism of this weight gain is unknown, it is associated with increased appetite, binge eating, carbohydrate craving, food preference changes, and decreased satiety in some clients. Prolactin elevation may stimulate feeding centers, histamine antagonism stimulates appetite, and there may be an as yet undetermined interplay of multiple neurotransmitter and receptor interactions with resultant changes in appetite, energy intake, and feeding behavior. Penninx and Lange (2018) found that genetics can also make clients more prone to weight gain and metabolic syndrome. Metabolic syndrome is a cluster of conditions that increase the risk for heart disease, diabetes, and stroke. The syndrome is diagnosed when three or more of the following are present: Obesity—excess weight, increased body mass index (BMI), and increased abdominal girth because of fat deposits Increased blood pressure High blood sugar level High cholesterol—with at least 150 mg/dL of triglyceride; less than 40 mg/dL of high-density lipoprotein for women and 50 mg/dL for men Obesity is common in clients with schizophrenia, further increasing the risk for type 2 diabetes mellitus and cardiovascular disease. In addition, clients with severe, persistent mental illness are less likely to exercise or eat low-fat nutritionally balanced diets; this pattern decreases the likelihood that they can minimize potential weight gain or lose excess weight. The increased risk of heart disease results in a shorter life expectancy (Penninx & Lange, 2018). It is recommended that clients taking antipsychotics be involved in an educational program to control weight and decrease BMI. However, it can be a diƯicult task. Lifestyle changes, including diet and exercise, along with counseling and support, are common measures used to prevent or reduce weight gain. Research examining the use of anti-obesity medications seems to indicate they are more successful when combined with a comprehensive lifestyle program (Tham et al., 2021). Most antipsychotic drugs cause relatively minor cardiovascular adverse eƯects such as postural hypotension, palpitations, and tachycardia. Certain antipsychotic drugs, such as thioridazine (Mellaril), droperidol (Inapsine), and mesoridazine (Serentil), can also cause a lengthening of the QT interval. A QT interval longer than 500 ms is considered dangerous and is associated with life- threatening dysrhythmias and sudden death. Although rare, the lengthened QT interval can cause torsade de pointes, a rapid heart rhythm of 150 to 250 beats/minute, resulting in a “twisted” appearance on the electrocardiogram (hence the name “torsade de pointes”). Thioridazine and mesoridazine are used infrequently to treat psychosis; droperidol is most often used as an adjunct to anesthesia or to produce sedation. Sertindole (Serlect) was never approved in the United States to treat psychosis but was used in Europe and was subsequently withdrawn from the market because of the number of cardiac dysrhythmias and deaths that it caused.
sleep apnea, dermatologic disorders, panic disorder, and eating disorders. Although the mechanism of action is not completely understood, antidepressants somehow interact with the two neurotransmitters, norepinephrine and serotonin, that regulate mood, arousal, attention, sensory processing, and appetite. Antidepressants are divided into four groups: Tricyclic and the related cyclic antidepressants Selective serotonin reuptake inhibitors (SSRIs) MAO inhibitors (MAOIs) Other antidepressants such as desvenlafaxine (Pristiq), venlafaxine (EƯexor), bupropion (Wellbutrin), duloxetine (Cymbalta), trazodone (Desyrel), and nefazodone (Serzone) Table 2.5 lists the dosage forms, usual daily dosages, and extreme dosage ranges. The cyclic compounds became available in the 1950s and for years were the first choice of drugs to treat depression even though they cause varying degrees of sedation, orthostatic hypotension (drop in blood pressure on rising), and anticholinergic side eƯects. In addition, cyclic antidepressants are potentially lethal if taken in an overdose. During that same period, the MAOIs were discovered to have a positive eƯect on people with depression. Although the MAOIs have a low incidence of sedation and anticholinergic eƯects, they must be used with extreme caution for several reasons: A life-threatening side eƯect, hypertensive crisis, may occur if the client ingests foods containing tyramine (an amino acid) while taking MAOIs. Because of the risk of potentially fatal drug interactions, MAOIs cannot be given in combination with other MAOIs, tricyclic antidepressants, meperidine (Demerol), CNS depressants, many antihypertensives, or general anesthetics. MAOIs are potentially lethal in overdose and pose a potential risk in clients with depression who may be considering suicide. The SSRIs, first available in 1987 with the release of fluoxetine (Prozac), have replaced the cyclic drugs as the first choice in treating depression because they are equal in eƯicacy and produce fewer troublesome side eƯects. The SSRIs and clomipramine are eƯective in the treatment of obsessive-compulsive disorder (OCD) as well. Prozac Weekly is the first and only medication that can be given once a week as maintenance therapy for depression after the client has been stabilized on fluoxetine. It contains 90 mg of fluoxetine with an enteric coating that delays release into the bloodstream. Preferred Drugs for Clients at High Risk for Suicide Suicide is always a primary consideration when treating clients with depression. SSRIs, venlafaxine, nefazodone, and bupropion are often better choices for those who are potentially suicidal or highly impulsive because they carry no risk of lethal overdose in contrast to the cyclic compounds and the MAOIs. However, SSRIs are eƯective only for mild and moderate depression. Evaluation of the risk for suicide must continue even after treatment with antidepressants is initiated. The client may feel more energized but still have suicidal thoughts, which increases the likelihood of a suicide attempt. Also, because it often takes weeks before the medications have a full therapeutic eƯect, clients may become discouraged and tired of waiting to feel better, which can result in suicidal
behavior. There is an FDA-required warning for SSRIs and increased suicidal risk in children and adolescents. Mechanism of Action The precise mechanism by which antidepressants produce their therapeutic eƯects is not known, but much is known about their action on the CNS. The major interaction is with the monoamine neurotransmitter systems in the brain, particularly norepinephrine and serotonin. Both of these neurotransmitters are released throughout the brain and help regulate arousal, vigilance, attention, mood, sensory processing, and appetite. Norepinephrine, serotonin, and dopamine are removed from the synapses after release by reuptake into presynaptic neurons. After reuptake, these three neurotransmitters are reloaded for subsequent release or metabolized by the enzyme MAO. The SSRIs block the reuptake of serotonin, the cyclic antidepressants and venlafaxine block the reuptake of norepinephrine primarily and block serotonin to some degree, and the MAOIs interfere with enzyme metabolism. This is not the complete explanation, however; the blockade of serotonin and norepinephrine reuptake and the inhibition of MAO occur in a matter of hours, while antidepressants are rarely eƯective until taken for several weeks. The cyclic compounds may take 4 to 6 weeks to be eƯective, MAOIs need 2 to 4 weeks for eƯectiveness, and SSRIs may be eƯective in 2 to 3 weeks. Researchers believe that the actions of these drugs are an “initiating event” and that eventual therapeutic eƯectiveness results when neurons respond more slowly, making serotonin available at the synapses (Burchum & Rosenthal, 2022). Side EƯects of Selective Serotonin Reuptake Inhibitors SSRIs have fewer side eƯects compared to the cyclic compounds. Enhanced serotonin transmission can lead to several common side eƯects such as anxiety, agitation, akathisia (motor restlessness), nausea, insomnia, and sexual dysfunction, specifically diminished sexual drive or diƯiculty achieving an erection or orgasm. In addition, weight gain is both an initial and ongoing problem during antidepressant therapy, although SSRIs cause less weight gain than other antidepressants. Taking medications with food usually can minimize nausea. Akathisia is usually treated with a beta-blocker such as propranolol (Inderal) or a benzodiazepine. Insomnia may continue to be a problem even if the client takes the medication in the morning; a sedative– hypnotic or low-dosage trazodone may be needed. Less common side eƯects include sedation (particularly with paroxetine [Paxil]), sweating, diarrhea, hand tremor, and headaches. Diarrhea and headaches can usually be managed with symptomatic treatment. Sweating and continued sedation most likely indicate the need for a change to another antidepressant. Side EƯects of Cyclic Antidepressants Cyclic compounds have more side eƯects than do SSRIs and the newer miscellaneous compounds. The individual medications in this category vary in terms of the intensity of side eƯects, but generally side eƯects fall into the same categories. The cyclic antidepressants block cholinergic
serotonergic syndrome) can result from taking an MAOI and an SSRI at the same time. It can also occur if the client takes one of these drugs too close to the end of therapy with the other. In other words, one drug must clear the person’s system before initiation of therapy with the other. Symptoms include agitation, sweating, fever, tachycardia, hypotension, rigidity, hyperreflexia, and, in extreme reactions, even coma and death. These symptoms are similar to those seen with an SSRI overdose. p. 30 p. 31 BOX 2.1 Foods (Containing Tyramine) to Avoid When Taking Monoamine Oxidase Inhibitors Mature or aged cheeses or dishes made with cheese, such as lasagna or pizza. All cheese is considered aged except cottage cheese, cream cheese, ricotta cheese, and processed cheese slices. Aged meats such as pepperoni, salami, mortadella, summer sausage, beef logs, meat extracts, and similar products. Make sure meat and chicken are fresh and have been properly refrigerated. Italian broad beans (fava), bean curd (tofu), banana peel, overripe fruit, and avocado. All tap beers and microbrewery beer. Drink no more than two cans or bottles of beer (including nonalcoholic beer) or 4 oz of wine per day. Sauerkraut, soy sauce or soybean condiments, or marmite (concentrated yeast). Yogurt, sour cream, peanuts, brewer’s yeast, and monosodium glutamate (MSG). Adapted from Schatzberg, A. F., & DeBattista, C. (2019). Schatzberg’s manual of clinical psychopharmacology (9th ed.). American Psychiatric Association. Client Teaching Clients should take SSRIs first thing in the morning unless sedation is a problem; generally, paroxetine most often causes sedation. If the client forgets a dose of an SSRI, they can take it up to 8 hours after the missed dose. To minimize side eƯects, clients generally should take cyclic compounds at night in a single daily dose when possible. If the client forgets a dose of a cyclic compound, they should take it within 3 hours of the missed dose or omit the dose for that day. Clients should exercise caution when driving or performing activities requiring sharp, alert reflexes until sedative eƯects can be determined. Clients taking MAOIs need to be aware that a life- threatening hyperadrenergic crisis can occur if they do not observe certain dietary restrictions. They should receive a written list of foods to avoid while taking MAOIs. The nurse should make clients aware of the risk for serious or even fatal drug interactions when taking MAOIs and instruct them not to take any additional medication, including OTC preparations, without checking with the physician or pharmacist. Mood-Stabilizing Drugs Mood-stabilizing drugs are used to treat bipolar disorder by stabilizing the client’s mood, preventing or minimizing the highs and lows that characterize bipolar illness, and treating acute episodes of mania. Lithium is the most established mood stabilizer; some anticonvulsant drugs, particularly carbamazepine (Tegretol) and valproic acid (Depakote, Depakene), are eƯective mood stabilizers. Other anticonvulsants, such as gabapentin (Neurontin), topiramate (Topamax), oxcarbazepine (Trileptal), and lamotrigine (Lamictal), are also used for mood stabilization. Occasionally, clonazepam (Klonopin) is also used to treat acute mania. Clonazepam is included in the discussion of antianxiety agents. →
WARNING - Lamotrigine Can cause serious rashes requiring hospitalization, including Stevens-Johnson syndrome and, rarely, life-threatening toxic epidermal necrolysis. The risk for serious rashes is greater in children younger than 16 years. Mechanism of Action Although lithium has many neurobiologic eƯects, its mechanism of action in bipolar illness is poorly understood. Lithium normalizes the reuptake of certain neurotransmitters such as serotonin, norepinephrine, acetylcholine, and dopamine. It also reduces the release of norepinephrine through competition with calcium and produces its eƯects intracellularly rather than within neuronal synapses; it acts directly on G-proteins and certain enzyme subsystems such as cyclic adenosine monophosphates and phosphatidylinositol. Lithium is considered a first-line agent in the treatment of bipolar disorder (Stahl, 2021). The mechanism of action for anticonvulsants is not clear because it relates to their oƯ-label use as mood stabilizers. Valproic acid and topiramate are known to increase the levels of the inhibitory neurotransmitter GABA. Both valproic acid and carbamazepine are thought to stabilize mood by inhibiting the kindling process. This can be described as the snowball-like eƯect seen when minor seizure activity seems to build up into more frequent and severe seizures. In seizure management, anticonvulsants raise the level of the threshold to prevent these minor seizures. It is suspected that this same kindling process may also occur in the development of full-blown mania with stimulation by more frequent minor episodes. This may explain why anticonvulsants are eƯective in the treatment and prevention of mania as well. Dosage Lithium is available in tablet, capsule, liquid, and sustained-release forms; no parenteral forms are available. The eƯective dosage of lithium is determined by monitoring serum lithium levels and assessing the client’s clinical response to the drug. Daily dosages generally range from 900 to 3,600 mg; more importantly, the serum lithium level should be about 1 mEq/L. Serum lithium levels of less than 0.5 mEq/L are rarely therapeutic, and levels of more than 1.5 mEq/L are usually considered toxic. The lithium level should be monitored every 2 to 3 days while the therapeutic dosage is being determined; then, it should be monitored weekly. When the client’s condition is stable, the level may need to be checked once a month or less frequently. p. 31 p. 32 → WARNING - Lithium Toxicity is closely related to serum lithium levels and can occur at therapeutic doses. Facilities for serum lithium determinations are required to monitor therapy. Carbamazepine is available in liquid, tablet, and chewable tablet forms. Dosages usually range from 800 to 1,200 mg/day; the extreme dosage range is 200 to 2,000 mg/day. Valproic acid is available in liquid, tablet, and capsule forms and as sprinkles with dosages ranging from 1,000 to 1,500 mg/day; the extreme dosage range is 750 to 3,000 mg/day. Serum drug levels, obtained 12 hours after the last dose of the medication, are monitored for therapeutic levels of both these anticonvulsants. Side EƯects Common side eƯects of lithium therapy include mild nausea or diarrhea, anorexia,
