Psychopharmacology PDF

11/27/23, 3:35 AM Realizeit for Student Psychopharmacology Pharmacologic treatment of clients with personality disorders focuses on the client’s symptoms rather than the particular subtype. The four symptom categories that underlie personality disorders are cognitive–perceptual distortions, includ...

11/27/23, 3:35 AM Realizeit for Student Psychopharmacology Pharmacologic treatment of clients with personality disorders focuses on the client’s symptoms rather than the particular subtype. The four symptom categories that underlie personality disorders are cognitive–perceptual distortions, including psychotic symptoms; affective symptoms and mood dysregulation; aggression and behavioral dysfunction; and anxiety. These four symptom categories relate to the underlying temperaments associated with personality disorders: Low reward dependence corresponds to the categories of affective dysregulation, detachment, and cognitive disturbances. High novelty seeking corresponds to the target symptoms of impulsiveness and aggression. High harm avoidance corresponds to the categories of anxiety and depression symptoms. Cognitive–perceptual disturbances include magical thinking, odd beliefs, illusions, suspiciousness, ideas of reference, and low-grade psychotic symptoms. These chronic symptoms usually respond to low-dose antipsychotic medications (Koch et al., 2016). Several types of aggression have been described in people with personality disorders. Aggression may occur in impulsive people (some with a normal electroencephalogram and some with an abnormal one); people who exhibit predatory or cruel behavior; or people with organic-like impulsivity, poor social judgment, and emotional lability. Lithium, anticonvulsant mood stabilizers, and benzodiazepines are used most often to treat aggression. Low-dose neuroleptics may be useful in modifying predatory aggression (Black & Andreasen, 2016). Mood dysregulation symptoms include emotional instability, emotional detachment, depression, and dysphoria (Garofalo et al., 2018). Emotional instability and mood swings respond favorably to lithium, carbamazepine (Tegretol), valproate (Depakote), or low-dose neuroleptics such as haloperidol (Haldol). Emotional detachment, cold and aloof emotions, and disinterest in social relations often respond to selective serotonin reuptake inhibitors (SSRIs) or atypical antipsychotics such as risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel). Atypical depression is often treated with SSRIs, monoamine oxidase inhibitor (MAOI) antidepressants, or low-dose antipsychotic medications. Anxiety seen with personality disorders may be chronic cognitive anxiety, chronic somatic anxiety, or severe acute anxiety. Chronic cognitive anxiety responds to SSRIs and MAOIs, as does chronic somatic anxiety or anxiety manifested as multiple physical complaints. Episodes of severe acute anxiety are best treated with MAOIs or low-dose antipsychotic medications. Antidepressant Drugs Antidepressant drugs are primarily used in the treatment of major depressive illness, anxiety disorders, the depressed phase of bipolar disorder, and psychotic depression. Off-label uses of antidepressants include the treatment of chronic pain, migraine headaches, peripheral and diabetic neuropathies, 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: 1. Tricyclic and the related cyclic antidepressants 2. Selective serotonin reuptake inhibitors (SSRIs) 3. MAO inhibitors (MAOIs) 4. Other antidepressants such as desvenlafaxine (Pristiq), venlafaxine (Effexor), bupropion (Wellbutrin), duloxetine (Cymbalta), trazodone (Desyrel), and nefazodone (Serzone) 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 effects. In addition, cyclic antidepressants are potentially lethal if taken in an overdose. During that same period, the MAOIs were discovered to have a positive effect on people with depression. Although the MAOIs have a low incidence of sedation and anticholinergic effects, they must be used with extreme caution for several reasons: A life-threatening side effect, 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 selective serotonin reuptake inhibitors (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 efficacy and produce fewer troublesome side effects. The SSRIs and clomipramine are effective 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 https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVtCtaoun4KMdegul%2fePt%2bh9MMaIFoYvxFjmrRvhyUR… 1/5 11/27/23, 3:35 AM Realizeit for Student MAOIs. However, SSRIs are effective 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 effect, 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 effects 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 effective until taken for several weeks. The cyclic compounds may take 4 to 6 weeks to be effective, MAOIs need 2 to 4 weeks for effectiveness, and SSRIs may be effective in 2 to 3 weeks. Researchers believe that the actions of these drugs are an “initiating event” and that eventual therapeutic effectiveness results when neurons respond more slowly, making serotonin available at the synapses (Burchum & Rosenthal, 2018). Side Effects of Selective Serotonin Reuptake Inhibitors SSRIs have fewer side effects compared to the cyclic compounds. Enhanced serotonin transmission can lead to several common side effects such as anxiety, agitation, akathisia (motor restlessness), nausea, insomnia, and sexual dysfunction, specifically diminished sexual drive or difficulty 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 effects 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 Effects of Cyclic Antidepressants Cyclic compounds have more side effects than do SSRIs and the newer miscellaneous compounds. The individual medications in this category vary in terms of the intensity of side effects, but generally, side effects fall into the same categories. The cyclic antidepressants block cholinergic receptors, resulting in anticholinergic effects such as dry mouth, constipation, urinary hesitancy or retention, dry nasal passages, and blurred near vision. More severe anticholinergic effects such as agitation, delirium, and ileus may occur, particularly in older adults. Other common side effects include orthostatic hypotension, sedation, weight gain, and tachycardia. Clients may develop tolerance to anticholinergic effects, but these side effects are common reasons that clients discontinue drug therapy. Clients taking cyclic compounds frequently report sexual dysfunction similar to problems experienced with SSRIs. Both weight gain and sexual dysfunction are cited as common reasons for noncompliance (Stahl, 2017). Side Effects of Monoamine Oxidase Inhibitors The most common side effects of MAOIs include daytime sedation, insomnia, weight gain, dry mouth, orthostatic hypotension, and sexual dysfunction. The sedation and insomnia are difficult to treat and may necessitate a change in medication. Of particular concern with MAOIs is the potential for a lifethreatening hypertensive crisis if the client ingests food that contains tyramine or takes sympathomimetic drugs. Because the enzyme MAO is necessary to break down the tyramine in certain foods, its inhibition results in increased serum tyramine levels, causing severe hypertension, hyperpyrexia, tachycardia, diaphoresis, tremulousness, and cardiac dysrhythmias. Drugs that may cause potentially fatal interactions with MAOIs include SSRIs, certain cyclic compounds, buspirone (BuSpar), dextromethorphan, and opiate derivatives such as meperidine. The client must be able to follow a tyramine-free diet; Box 2.1 lists the foods to avoid. Studies are currently underway to determine whether a selegiline transdermal patch would be effective in treating depression without the risks of dietary tyramine and orally ingested MAOIs. 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, ri cheese slices. Aged meats such as pepperoni, salami, mortadella, summer sausage, beef logs, meat extracts, and similar products. Make sure meat and chicken are f 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). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVtCtaoun4KMdegul%2fePt%2bh9MMaIFoYvxFjmrRvhyUR… 2/5 11/27/23, 3:35 AM Realizeit for Student Adapted from Ohio State University Wexner Medical Center, Columbus, OH (2018) Side Effects of Other Antidepressants Of the other or novel antidepressant medications, nefazodone, trazodone, and mirtazapine commonly cause sedation. Both nefazodone and trazodone commonly cause headaches. Nefazodone can also cause dry mouth and nausea. Bupropion, venlafaxine, and desvenlafaxine may cause loss of appetite, nausea, agitation, and insomnia. Venlafaxine may also cause dizziness, sweating, or sedation. Sexual dysfunction is much less common with the novel antidepressants, with one notable exception: Trazodone can cause priapism (a sustained and painful erection that necessitates immediate treatment and discontinuation of the drug). Priapism may also result in impotence. WARNING - Nefazodone May cause rare but potentially life-threatening liver damage, which could lead to liver failure. WARNING - Bupropion Can cause seizures at a rate four times that of other antidepressants. The risk for seizures increases when doses exceed 450 mg/day (400 mg SR); dose i increments; the client has a history of seizures, cranial trauma, excessive use of or withdrawal from alcohol, or addiction to opiates, cocaine, or stimulants (OTC) stimulants or anorectics; or the client has diabetes being treated with oral hypoglycemics or insulin. Drug Interactions An uncommon but potentially serious drug interaction called serotonin syndrome (or 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 (Burchum & Rosenthal, 2018). These symptoms are similar to those seen with an SSRI overdose. 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, he or she can take it up to 8 hours after the missed dose. To minimize side effects, 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, he or she 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 effects 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 effective 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 f children younger than 16 years. Mechanism of Action Although lithium has many neurobiologic effects, 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 https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVtCtaoun4KMdegul%2fePt%2bh9MMaIFoYvxFjmrRvhyUR… 3/5 11/27/23, 3:35 AM Realizeit for Student competition with calcium and produces its effects 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, 2017). The mechanism of action for anticonvulsants is not clear because it relates to their off-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 effect 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 effective 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 effective 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. 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 the 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 Effects Common side effects of lithium therapy include mild nausea or diarrhea, anorexia, fine hand tremor, polydipsia, polyuria, a metallic taste in the mouth, and fatigue or lethargy. Weight gain and acne are side effects that occur later in lithium therapy; both are distressing for clients. Taking the medication with food may help with nausea, and the use of propranolol often improves the fine tremor. Lethargy and weight gain are difficult to manage or minimize and frequently lead to noncompliance. Toxic effects of lithium are severe diarrhea, vomiting, drowsiness, muscle weakness, and lack of coordination. Untreated, these symptoms worsen and can lead to renal failure, coma, and death. When toxic signs occur, the drug should be discontinued immediately. If lithium levels exceed 3 mEq/L, dialysis may be indicated. Side effects of carbamazepine and valproic acid include drowsiness, sedation, dry mouth, and blurred vision. In addition, carbamazepine may cause rashes and orthostatic hypotension, and valproic acid may cause weight gain, alopecia, and hand tremor. Topiramate causes dizziness, sedation, weight loss (rather than gain), and increased incidence of renal calculi (Burchum & Rosenthal, 2018). WARNING - Valproic Acid and Its Derivatives Can cause hepatic failure, resulting in fatality. Liver function tests should be performed before therapy and at frequent intervals thereafter, especially for th teratogenic effects such as neural tube defects (e.g., spina bifida). Can cause life-threatening pancreatitis in both children and adults. Can occur shortly af therapy. WARNING - Carbamazepine Can cause aplastic anemia and agranulocytosis at a rate five to eight times greater than the general population. Pretreatment hematologic baseline data s periodically throughout therapy to discover lowered WBC or platelet counts. Client Teaching https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVtCtaoun4KMdegul%2fePt%2bh9MMaIFoYvxFjmrRvhyUR… 4/5 11/27/23, 3:35 AM Realizeit for Student For clients taking lithium and the anticonvulsants, monitoring blood levels periodically is important. The time of the last dose must be accurate so that plasma levels can be checked 12 hours after the last dose has been taken. Taking these medications with meals minimizes nausea. The client should not attempt to drive until dizziness, lethargy, fatigue, or blurred vision has subsided. Antianxiety Drugs (Anxiolytics) Antianxiety drugs, or anxiolytic drugs, are used to treat anxiety and anxiety disorders, insomnia, obsessive-compulsive disorder (OCD), depression, posttraumatic stress disorder, and alcohol withdrawal. Antianxiety drugs are among the most widely prescribed medications today. A wide variety of drugs from different classifications have been used in the treatment of anxiety and insomnia. Benzodiazepines have proved to be the most effective in relieving anxiety and are the drugs most frequently prescribed. Benzodiazepines may also be prescribed for their anticonvulsant and muscle relaxant effects. Buspirone is a nonbenzodiazepine often used for the relief of anxiety and therefore is included in this section. Other drugs such as propranolol, clonidine (Catapres), and hydroxyzine (Vistaril) that may be used to relieve anxiety are much less effective. Mechanism of Action Benzodiazepines mediate the actions of the amino acid GABA, the major inhibitory neurotransmitter in the brain. Because GABA receptor channels selectively admit the anion chloride into neurons, activation of GABA receptors hyperpolarizes neurons and thus is inhibitory. Benzodiazepines produce their effects by binding to a specific site on the GABA receptor. Buspirone is believed to exert its anxiolytic effect by acting as a partial agonist at serotonin receptors, which decreases serotonin turnover (Stahl, 2017). The benzodiazepines vary in terms of their half-lives, the means by which they are metabolized, and their effectiveness in treating anxiety and insomnia. Drugs with a longer half-life require less frequent dosing and produce fewer rebound effects between doses; however, they can accumulate in the body and produce “next-day sedation” effects. Conversely, drugs with shorter half-lives do not accumulate in the body or cause next-day sedation, but they do have rebound effects and require more frequent dosing. Temazepam (Restoril), triazolam (Halcion), and flurazepam (Dalmane) are most often prescribed for sleep rather than for relief of anxiety. Diazepam (Valium), chlordiazepoxide (Librium), and clonazepam are often used to manage alcohol withdrawal as well as to relieve anxiety. Side Effects Although not a side effect in the true sense, one chief problem encountered with the use of benzodiazepines is their tendency to cause physical dependence. Significant discontinuation symptoms occur when the drug is stopped; these symptoms often resemble the original symptoms for which the client sought treatment. This is especially a problem for clients with long-term benzodiazepine use, such as those with panic disorder or generalized anxiety disorder. Psychological dependence on benzodiazepines is common; clients fear the return of anxiety symptoms or believe they are incapable of handling anxiety without the drugs. This can lead to overuse or abuse of these drugs. Buspirone does not cause this type of physical dependence. The side effects most commonly reported with benzodiazepines are those associated with CNS depression, such as drowsiness, sedation, poor coordination, and impaired memory or clouded sensorium. When used for sleep, clients may complain of next-day sedation or a hangover effect. Clients often develop a tolerance to these symptoms, and they generally decrease in intensity. Common side effects from buspirone include dizziness, sedation, nausea, and headache (Stahl, 2017). Elderly clients may have more difficulty managing the effects of CNS depression. They may be more prone to falls from the effects on coordination and sedation. They may also have more pronounced memory deficits and may have problems with urinary incontinence, particularly at night. Client Teaching Clients need to know that antianxiety agents are aimed at relieving symptoms such as anxiety or insomnia but do not treat the underlying problems that cause the anxiety. Benzodiazepines strongly potentiate the effects of alcohol; one drink while on a benzodiazepine may have the effect of three drinks. Therefore, clients should not drink alcohol while taking benzodiazepines. Clients should be aware of decreased response time, slower reflexes, and possible sedative effects of these drugs when attempting activities such as driving or going to work. Benzodiazepine withdrawal can be fatal. After the client has started a course of therapy, he or she should never discontinue benzodiazepines abruptly or without the supervision of the physician (Burchum & Rosenthal, 2018). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVtCtaoun4KMdegul%2fePt%2bh9MMaIFoYvxFjmrRvhyUR… 5/5