Advance Practice Nurse Pharmacology Credit – Atypical Antipsychotics
After finishing this module, the reader will be able to:
- Describe the mechanism of action of the atypical antipsychotics.
- Discuss labeled uses for the atypical antipsychotics.
- Identify significant adverse effects caused by the atypical antipsychotics.
- Discuss patient monitoring during use of an atypical antipsychotic.
- Discuss nursing care issues associated with the administration of the atypical antipsychotics.
The atypical antipsychotics are psychotropic medications that are used to treat patients who have serious psychological disorders such as schizophrenia and bipolar disorder. These medications are in common use and there are indications that their use is, and will be increasing.
The atypical antipsychotics are psychotropic medications that have Food and Drug Administration (FDA) approved indications for the treatment of adult patients who have bipolar disorder, major depressive disorder, schizophrenia, and schizo-affective disorder, and there are labeled uses for children and adolescents, as well. The atypical antipsychotics, which are sometimes referred to as second-generation antipsychotics, were developed in the late ’80s and the ’90s as an alternative to the first-generation antipsychotic, drugs such as chlorpromazine, haloperidol, and thioridazine. These drugs had been proven to be much more effective at controlling the signs and symptoms of these serious psychiatric illnesses than the medications that were commonly used at the time, e.g., barbiturates (Briles, Rosenberg, Brooks, et al, 2012).
However, these first-generation antipsychotics (sometimes called typical antipsychotics) can and often do, cause significant adverse effects – some that are irreversible and some that are life-threatening. Because of the serious, potential adverse effects caused by the typical antipsychotics and because they are dangerous when taken in overdose, a search was made for safer medications that could be used to treat patients who had psychiatric disorders such as schizophrenia. The first atypical antipsychotic to be marketed in the United States was Clozapine® in 1989, and there are now 11 atypical antipsychotics available.
These drugs have, to a degree, been shown to be a better alternative. Compared to haloperidol, thioridazine and the other typical antipsychotics, the second generation antipsychotics such as olanzapine and quetiapine are much safer when taken in overdose and the adverse effects they cause – especially the extrapyramidal syndromes – initially appeared to be less frequent and less harmful. They are as effective as the typical antipsychotics for treating people who have bipolar disorder, major depressive disorder, schizophrenia, schizo-affective disorder. But as clinical experience with the atypical antipsychotics has accumulated, several problems became clear.
These drugs have serious long-term safety issues, including but not limited to metabolic disorders, cerebrovascular events, and increased risk of death. The incidence of extrapyramidal syndromes was initially thought to be significantly lower with the atypical antipsychotics. This is a very important advantage as extrapyramidal syndromes are often the reason why people will stop taking an antipsychotic. The incidence of extrapyramidal syndromes is lower for the atypical antipsychotics, but there is evidence that it is higher than originally thought and that it is significant.
The atypical antipsychotics are being prescribed for off-label uses, and they are being prescribed for patient populations that appear to be particularly vulnerable to the adverse effects. Example: The number of children and adolescents who are being prescribed these drugs is increasing, and the incidence of extrapyramidal syndromes and metabolic adverse effects caused by the atypical antipsychotics is higher in children and adolescents than in adults.
A recent article suggested that nurses do not have an in depth knowledge of the antipsychotics: 779 direct care professionals were queried and only 12% of the RNs could identify one serious adverse effect associated with antipsychotics. (Lemay, 2013). The use of the atypical antipsychotics is increasing and off-label use is widespread. If these patterns continue nurses will be giving these medications more often, and they will be giving them to patients who are susceptible to the adverse effects. Knowledge of how these drugs work and what they can do will be essential for professional nurses.
Learning Break: The atypical antipsychotic drugs were given the name atypical because when they were initially developed and used, it was thought that they were far less likely to cause the extrapyramidal syndromes that were “typically” associated with the original antipsychotic medications. The terms first-generation and second generation are informal and simply refer to the timeline of the development of these drugs.
Pharmacology of the atypical antipsychotics
There are 11 drugs currently available that are classified as atypical antipsychotics. They are listed here with the generic name first followed by the American brand name.
Olanzapine and fluoxetine: Symbyax®
The atypical antipsychotics are antagonists at the D2 receptors in the mesolimbic pathway, and they also antagonists at serotonin receptors, particularly the 5-HT2A receptors. The clinical effectiveness of these drugs is thought to be mediated through this receptor blockade. The differences between the first-generation antipsychotics and the atypical antipsychotics are: 1) The degree and duration of the D2 blockade is far less, and; 2) The serotonin receptor blockade (Rasimas, Lebelt, 2012; Pringsheim, Doja, Belanger, et al, 2011). The lower degree and decreased duration of D2 receptor antagonism and the serotonin receptor antagonism is thought to account for: 1) the decreased risk of developing extrapyramidal symptoms, and; 2) the antipsychotic effects of these drugs.
The therapeutic effect of the atypical antipsychotics is mediated through the dopaminergic and serotonergic systems, but these drugs have complex pharmacology and they also act as antagonists of the a1-adrenergic, histaminic, and muscarinic receptors (Gareri, De Fazio, Manfredi, et al, 2014; Rasimas, Lebelt, 2012; Minns, Clark, 2012; Meltzer, 2012). Antagonism of these receptors accounts for some of the common side effects, e.g., drowsiness caused by muscarinic receptor blockade and orthostatic hypotension caused by a1 adrenergic receptor blockade. The degree to which these receptors are affected is different for each drug, and the amount of receptor blockade can also be affected by the dose, e.g., the higher the dose of risperidone the greater the degree of D2 receptor blockade (Gareri, De Fazio, Manfredi, et al, 2014).
Example: Olanzapine is a strong antagonist of the 5-HT2A, 5-HT2C, D1-4, H1, and a1-adrenergic receptors. Olanzapine is a moderate antagonist of 5-HT3 and muscarinic receptors, and a weak antagonist of beta-adrenergic receptors.
Example: Risperidone is a serotonin and dopamine receptor antagonist 2 receptor is 20 times lower than the 5-HT2 affinity. Risperidone is also a potent antagonist of the a1 and a2 adrenergic receptors and histamine receptors. Risperidone is a low to moderate antagonist for 5-HT1C, 5-HT1D, and 5-HT1A receptors, a weak antagonist for D1 receptors, and it has no effect on the muscarinic and beta1 and beta2 adrenergic receptors.
The atypical antipsychotics are available as oral and sublingual tablets, oral liquid preparations, and parenteral preparations. The parenteral preparations are given as long-acting intramuscular IM) injections, one injection every two weeks or more, depending on the drug. Administering the atypical antipsychotics as long-acting injections has been found to increase patients’ adherence to the medication regimen and may cause fewer side effects (De Berardis, Marini, Carano, et al, 2013).
Indications for Use
It is beyond the scope of this module to list all of the indications for all of the atypical antipsychotics. Most of these drugs have labeled indications for the treatment of adult patients who have bipolar disorder, major depressive disorder, schizophrenia, or schizo-affective disorder. Aripiprazole, clozaril, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone have labeled indications for the treatment of children and adolescents who have an autism spectrum disorder, disruptive behavior disorders, pervasive development disorders, or Tourette syndrome. Some of the atypical antipsychotics can be used, depending on age, to treat children and adolescents who have bipolar disorder, major depressive disorder, or schizophrenia.
Example: Aripirazole has a labeled use for acute and maintenance treatment of adolescents 13 years or older who have schizophrenia, and it has a labeled use for acute and maintenance treatment of children 10 years and older who have bipolar disorder with acute manic or mixed episodes.
These labeled indications have specific limits; not all of the atypical antipsychotics can be used for all of the psychiatric conditions that are listed above and each one has restrictions. For example, some of the atypical antipsychotics can be prescribed for acute symptoms of certain psychiatric disorder but not as a maintenance therapy, and when they are used for the treatment of a patient who has major depressive disorder they should be used as adjunctive therapies. There are also age limits for the prescribing of these drugs, and the indications for use are also specific for the form of the drugs, e.g., oral versus IM injection.
Example: The oral form of olanzapine can be used for maintenance therapy for patients who have bipolar disorder. Short-acting parenteral olanzapine can be used to treat acute agitation in patients who have schizophrenia or bipolar I disorder. Long-acting olanzapine can be used to treat patients who have schizophrenia.
Example: Risperidone can be used to treat schizophrenia. It can also be used to treat acute mania or mixed episodes associated with bipolar I disorder.
The atypical antipsychotics must be prescribed with some caution. Before starting an atypical antipsychotic, the patient should be assessed for the presence of (Gareri, De Fazio, Manfredi, et al, 2014):
- congenital long QT syndrome;
- cardiovascular, hepatic, or renal disease;
- electrolyte abnormalities;
- medical conditions that might cause electrolyte abnormalities;
- medications that would affect the metabolism of the atypical antipsychotic;
- family history of torsades de pointes, and
- a prolonged QTc.
The 2005 and 2008 FDA warnings should be also be reviewed. These are available on-line and they can be summarized as follows: The use of atypical antipsychotics for the treatment of behavioral disorders in elderly patients with dementia is associated with increased mortality, and this risk applies to the use of the typical antipsychotics in this patient population, as well.
Adverse Effects Caused by Atypical Antipsychotics
Behavioral and psychological problems such as agitation, aggression, hallucinations, psychosis, and wandering are common in elderly patients who have dementia (Schulze, van de Bussche, Glaeske, et al, 2013; Desai, Heaton, Kelton, 2012). Non-pharmacologic treatment is preferred for controlling the behavioral and psychological problems of dementia (Huybrechts, Gerhard, Crystal, et al, 2012), but the typical and the atypical antipsychotics have been, and still are used to treat patients who have dementia and who have these behavioral problems (Steinberg, Lyketsos, 2012). However, this is an off-label use of these drugs and there are two significant issues concerning the use of the atypical antipsychotics in this clinical situation.
First, there is conflicting information about their efficacy for this purpose. Some clinical trials have indicated that the atypical antipsychotics can be effective at controlling behavioral and psychological problems associated with dementia (Maher, Maglione, Bagely, et al, 2011), but some researchers feel there is little evidence that they are effective (Rafaniello, Lombardo, Ferrajollo, et al, 2013), or that the therapeutic effect is at best modest (Gareri, De Fazio, Manfredi, et al, 2014; Schulze, van de Bussche, Glaeske, et al, 2013; Smith, Schultz, Seydel, et al, 2013; Steinberg, Lyketsos, 2012). Other researchers (Sulzter, Davis, Tariot, et al, 2008) found that the atypical antipsychotics were effective at controlling some behavioral and psychological problems associated with dementia such as anger and aggression, but other signs and symptoms were not positively affected or were made worse.
Second, there is evidence that the use of atypical antipsychotics in elderly patients with dementia increases the risk of suffering a stroke or other cerebrovascular event, or sudden death. In 2005 a meta-analysis of 17 randomized, placebo-controlled studies showed that patients who had dementia and were prescribed risperidone had a risk of death that was 1.6-1.7 times that of patients who were prescribed a placebo (Schneider, Dagerman, Insel, 2005). In response to this, the FDA issued a black box warning in 2005 for risperidone and the other atypical antipsychotics (FDA, 2005), and this warning was repeated in 2008 to include the conventional antipsychotics (FDA 2008). Subsequent research also indicated that elderly patients with dementia who are treated with atypical antipsychotics are more likely to suffer a stroke or other cerebrovascular event than those who do not receive one of these drugs.
Numerous studies and reviews examining these issues have been published, and some authors have seemingly confirmed these risks (Gareri, De Fazio, Manfredi, et al, 2014; Jibson, 2013; Shin, Choi, Jung, et al, 2013; Pratt, Roughhead, Salter, et al, 2012; Steinberg, Lyketsos, 2012; Gardette, Lapeyre-Mestre, Coley, et al, 2012; Maher, Maglione, Bagley, et al, 2011; Rossom, Rector, Lederle, et al, 2010; Kales, Valentine, Kim, 2007; Gill, Bronskill, Normand, 2007). Other researchers have found that the atypical antipsychotics are not especially dangerous for this patient population (Franchi, Sequi, Tettamanti, et al, 2013; Kiviniemi, Suvisaari, Koivumaa-Honkanen, et al, 2013; Lopez, Becker, Chang, et al, 2013; Rafaniello, Lombardo, Ferrajolo, et al, 2013; Raivio, Lavrial, Strandberg, et al, 2007) or for other elderly patient populations (Barak, Baruch, Mazeh, et al, 2007). And there is some evidence that it is the symptoms of the patients’ dementia, e.g., agitation, psychosis, or patient characteristics such as age and gender that account for the increased risk of mortality and other severe adverse events, not the drugs. (Lopez, Becker, Chang, et al, 2013; Gardette, Lapeyre-Mestre, Coley, et al, 2012).
Differing study designs, differing patient populations, differing duration of the studies, and other variables account for these disparate conclusions, and the issue is still unresolved. But the FDA warnings are still required to be included in the prescribing information for the atypical antipsychotics. And although the incidence of use of these drugs in patients who have dementia has declined, there are still large numbers of elderly patients who have dementia that are prescribed an atypical antipsychotic. (Schulze, van de Bussche, Glaeske, et al, 2013; Smith, Schultz, Seydel, et al, 2013; Desai, Heaton, Kelton, 2012; Kamble, Sherer, Chen, et al, 2010). Given that the number of people with dementia is expected to increase this is a worrisome trend.
Learning Break: Why are the atypical antipsychotics associated with an increased incidence of death and cerebrovascular events? The causes have not been clearly identified but possibilities include: (Shin, Choi, Jung, et al, 2013; Gill, Bronskill, Normand, et al, 2007):
- arrhythmias caused by prolonged QT interval;
- complications of excessive sedation such as aspiration and falls;
- orthostatic hypotension; 4) an increased incidence of venous thromboembolism, and;
Extrapyramidal syndromes are well known, well described, and very troublesome side effects of both the typical and atypical antipsychotics. Extrapyramidal syndromes are movement disorders that are thought to be caused by D2 receptor blockade in the mesocortical, tuberoinfundibular, and nigrostriatal pathways, more likely the nigostriatal pathway (Briles, Rosenberg, Brooks, et al, 2012). This receptor blockade causes an imbalance in the balance between dopaminergic and cholinergic tone and can result in an extrapyramidal syndrome. (Kowalski, 2012; Robottom, Weinberg, Shuler, 2012). Extrapyramidal syndromes include:
- Neuroleptic malignant syndrome
- Parkinsonism, and
- Tardive dyskinesia
Akathisia is motor restlessness, an urge to constantly move. Patients who have akathisia will usually have one of the following: 1) fidgeting or swinging movements of the legs; 2) moving from one foot to the other while standing; 3) pacing; 4) inability to sit still, and; 5) subjective complaints of restlessness. Akathisia usually develops hours or days after starting drug therapy,.
Dystonias are abnormal, involuntary muscle movements caused by synchronous contraction of agonist and antagonist muscles. Dystonias present as rhythmic, repetitive contractions and are characterized by twisting of body parts, abnormal movements, and abnormal postures. There are several different types of dystonias that can be caused by atypical antipsychotics, e.g., cervical dystonia, choreoathetoid motion, laryngeal dystonia, oculogyric crisis, and opisthotonis. Dystonias occur hours to days after administration of a drug. Dystonias develop hours to days after starting drug therapy.
Neuroleptic malignant syndrome (NMS) is rare, idiosyncratic reaction to antipsychotic medications. The exact incidence of NMS caused by the atypical antipsychotics is not known, but it has been reported to be caused by most of these medications (Troller, Chen, Sachdec, 2007). Neuroleptic malignant syndrome is a medical emergency characterized by extremely high body temperature, muscular rigidity, significant alterations in consciousness (e.g., confusion, coma, delirium, or stupor), and elevations of blood pressure and heart rate. Neuroleptic malignant syndrome typically occurs 2-10 days after administration of a drug, and it is thought to be caused by an abrupt blockade of the D2 receptors. Neuroleptic malignant syndrome develops 2-10 days after starting drug therapy.
Parkinsonism is a dose-dependent adverse effect. It is most often characterized by: 1) A coarse, rhythmic resting tremor that affects the head, limbs, mouth, or tongue; 2) cogwheel rigidity, and; 3) akinesia, and; 4) bradykinesia. Parkinsonism will usually start within several weeks of either starting an antipsychotic medication or increasing the dose.
Tardive dyskinesia is an extrapyramidal symptom that is characterized by rhythmic, repetitive movements, most notably (and most noticeable) in and around the face, lips, and tongue: repetitive tongue protruding and lip smacking are very common to this disorder. Blepharospasms, chorea, myoclonus, and tics are common to this disorder, as well. The term tardive is used because the onset of this extrapyramidal syndrome can be months or years after starting therapy with an antipsychotic. Tardive dyskinesia is notoriously resistant to treatment and it can become permanent, so early detection is crucially important. The incidence of tardive dyskinesia associated with the atypical antipsychotics is not known. But high doses of these drugs, especially it seems of risperidone, have been shown to cause tardive dyskinesia at rates that are equivalent to some of the typical antipsychotics (Tarsy, 2013). Children may be at a higher risk than adults (Correll, 2007).
Extrapyramidal syndromes are a significant reason for non-adherence to, and/or discontinuation of therapy with the typical antipsychotics (Briles, Rosenberg, Brooks, et al, 2012; Cha, McIntyre, 2012), and it was long thought that compared to the typical antipsychotics the atypical antipsychotics presented very little risk for extrapyramidal syndromes, thus offering a major advantage (Coplan, Gugger, Tasleem, 2013).
Time and clinical experience have confirmed that the incidence of extrapyramidal symptoms caused by the atypical antipsychotic is lower that of the first-generation drugs. But time and clinical experience have also shown that this level of risk for developing extrapyramidal syndromes is higher than initially thought, the level is not insignificant (Coplan, Gugger, Tasleem, 2013; Tarsy, 2013; Pringsheim, Doja, Bealnger, et al, 2011; Woods, Morganstern, Saska, et al, 2010, and it appears that the level of risk is higher for children and adolescents treated with atypical antipsychotics than it is for adults (Briles, Rosenberg, Brooks, et al, 2012; Rasimas, Lebelt, 2012; Pringsheim, Doja, Bealnger, et al, 2011).
The atypical antipsychotics can cause many metabolic disorders (Bobo, Cooper, Stein, et al, 2013; Deng, 2013; Ko, Soh, Kang, et al, 2013; Kumar, Datta, Wright, et al, 2013; Volpato, 2013; Cha, McIntyre, 2012, De Hert, Dobblelaere, Sheridan, et al, 2011);
- insulin resistance,
- intra-abdominal obesity,
- metabolic syndrome,
- substantial weight gain, and
- type 2 diabetes mellitus.
In many cases these risks are significant. Bobo, Cooper, Stein, et al (2013) found that the risk of developing type 2 diabetes mellitus increased three-fold in children and adolescents taking an atypical antipsychotic. Citrome, Holt, Walker, et al (2011) reported that patients who were prescribed olanzapine often gained significant amounts of weight: 7%, 15%, and 25% weight gain in 64%, 32%, and 12%, respectively, of the patients studied. And DelBello et al (2009) found that those patients with depression and type I bipolar disorder that were treated with quetiapine had markedly elevated serum triglycerides, a finding confirmed by Correll et al (2009) in patients treated with risperidone.
Learning Break: Prolactin is a hormone that is produced by the pituitary gland. Elevated levels of prolactin – hyperprolactinemia – may increase platelet aggregation, thus increasing the risk of ischemic stroke.
These metabolic adverse effects have both short-term and long-term consequences. Short-term consequences such as weight gain can cause non-compliance with the medication regimen, and given that many patients who take these medications will need to do so as a life-long therapeutic regimen, hyperlipidemia, metabolic syndrome, type 2 diabetes, and the other metabolic adverse effects caused by the atypical antipsychotics have the potential to cause serious long-term health effects.
The risk of developing one or more of these metabolic problems differs with each drug, e.g., weight gain appears to be a significant risk for olanzapine (Caccia, 2013; Citrome, Holt, Walker, et al, 2011), and the risk also appears to differ with patient populations: in particular, children and adolescents may be especially susceptible to the metabolic adverse effects of the atypical antipsychotics. (Caccia, 2013; Bobo, Cooper, Stein, et al, 2013; Kumar, Datta, Wright, et al, 2013; Briles, Rosenberg, Brooks, et al, 2012; De Hert, Dobblelaere, Sheridan, et al, 2011). Research in this area is ongoing, and some authors believe that the evidence for an increased risk for children and adolescents developing these metabolic abnormalities by therapy with the atypical antipsychotics is inconclusive (Almandil, Liu, Baseg, et al, 2013). However, given that atypical antipsychotics are being used more and more in this patient population (Bobo, Cooper, Stein, et al, 2013; Patten, Waheed, Brasee, 2012), caution with use and careful monitoring of children and adolescents receiving atypical antipsychotics would seem to be prudent.
Other Adverse Effects
Drowsiness and postural hypotension are common side effects caused by the atypical antipsychotics, and they have obvious relevance for nurses who administer these drugs.
QTc prolongation has been reported as adverse effect for all of the atypical antipsychotics, and QTc prolongation is recognized as a risk factor for the development of torsades de pointes. The incidence of torsades de pointes associated with the atypical antipsychotics is not known, but although prolonged QTc is a common adverse effect of this class of drugs, torsades de pointes caused by atypical antipsychotics is rare (Beach, Celano, Noseworthy, et al, 2013; Cha, McIntyre, 2012; Nielsen, 2011).
A detailed discussion of this issue is beyond the scope of this module. However, nurses who are administering the atypical antipsychotics should keep in mind that drug-induced torsades de pointes develops in people who have a prolonged QTc and other risk factors such as age, female gender, electrolyte abnormalities, and/or cardiac, hepatic, or renal disease. For a recent review of QTc prolongation, torsades de pointes, risk factors, and the atypical antipsychotics, readers are referred to the 2013 article by Beach, et al.
Drowsiness and orthostatic hypotension are adverse effects that are commonly caused by the atypical antipsychotics. These have obvious implications for patient safety. Patients who are receiving an atypical antipsychotic should have routine assessment of ambulatory status/ability, neurological status, and orthostatic vital signs.
Despite the warning in the prescribing information, the atypical antipsychotics are still used to control behavioral and psychological problems in elderly people who have dementia. It is preferable to use non-pharmacological interventions in this patient population. Patients who have dementia and have behavioral and psychological problems should be assessed for (Smith, 2013):
- unmet physical needs;
- unmet psychological needs, and;
- environmental and/or psychiatric causes of the behavioral and psychological problems.
If interventions in these areas are not successful, then careful use of an antipsychotic may be warranted after careful assessment of the risks and benefits.
Extrapyramidal syndromes cannot be completely prevented, but knowledge of the clinical signs and symptoms of these adverse effects and early detection of them can help lessen the consequences. Two important points to remember: 1) some of the signs and symptoms of an extrapyramidal syndrome may be subtle, and; 2) the onset is delayed, in some cases (tardive dyskinesia) by a very long period of time.
Weight, serum glucose, serum cholesterol, and serum lipids should be periodically checked.
QTc Prolongation and Torsades de Pointes
The physician should be notified if a patient who is receiving an atypical antipsychotic develops serum electrolyte abnormalities or cardiac conduction abnormalities. Low serum calcium, magnesium, and potassium increase the risk of developing torsades de pointes, as does a QTc that is > 500 msec or > 60 msec above the patient’s baseline.
If a new medication is prescribed, check to see if it may affect the phamacokinetics of the atypical antipsychotic, e.g., decrease metabolism or decrease excretion of the antipsychotic, as this is also an identified risk for the development of torsades de pointes.
Clarithromycin is a strong inhibitor of CYP450 enzymes, and ziprasidone is in part metabolized by these enzymes. Concurrent use of clarithromycin and ziprasidone could cause an elevated plasma concentration of ziprasidone. (Trinkley, 2013).
Patient education is a vital part of the safe use of the atypical antipsychotics. The patient who is receiving an atypical antipsychotic should be thoroughly informed of the adverse effects that can be caused by these drugs. In particular, the patient should be advised about the signs and symptoms of the metabolic disturbances, the extrapyramidal syndromes, drowsiness, and orthostatic hypotension. This is important for several reasons. First, the patient may be able to detect subtle, early symptoms of these adverse effects before they are noticed by the nurse. Second, these adverse effects are often the reason for non-compliance with and discontinuation of, the medication regimen as they are very distressing for the patient. Patients must be informed that the adverse effects can be managed and that abrupt stopping an atypical antipsychotic can cause a discontinuation syndrome and some these are quite serious in their clinical effects (Salomon, 2014).
Case Study #1
A 15-year-old male, S.L., has been diagnosed with type I bipolar disorder. The psychiatrist who is treating him prescribed lithium carbonate, 600 mg in divided doses. The patient’s symptoms of depression and mania were lessened, but not to the degree that he, his parents, and the psychiatrist felt were optimal. The dose of lithium was gradually increased to 1200 mg a day and this seemed to help, but the increased dose also caused nausea and anorexia, and the patient expressed considerable discomfort. In response, the psychiatrist decided to continue therapy with lithium at a reduced dose and to prescribe olanzapine, a starting dose of 2.5 mg a day and increasing to a target dose of 10 mg a day. After a month of taking lithium and olanzapine the patient reported that his feelings of depression and mania were much less frequent and less severe. However, he is concerned because he has gained 15 pounds, and the psychiatrist is concerned because there is an elevation in the patient’s serum glucose (125 mg/dL) and an elevation in his serum triglycerides (175 mg/dL). The psychiatrist is worried about the laboratory values and also about the possibility that the patient will stop taking the olanzapine (The patient has expressed considerable anxiety about and frustration with, the weight gain), worsening his bipolar disorder and possibly causing a discontinuation syndrome. The psychiatrist decided to slowly taper the dose of olanzapine and to prescribe aripiprazole; this drug is reported to be much less likely than olanzapine to cause weight gain and other metabolic derangements. After two months the patient’s serum glucose and serum triglycerides are within normal limits, as are all other blood studies, and he is back to his original weight. He is doing well socially and in school and objectively and subjectively his depression and mania are much less frequent and severe.
Case Study #2
M.B. is a 79-year-old female who was recently diagnosed with Alzheimer’s disease and Alzheimer’s related dementia. She has been a resident at a local nursing home for two months, and until recently she has seemed to be relatively content with her daily routine, but for the past week she has been noted to be, on occasion, very agitated, and she had several severe emotional outbursts. During one of these episodes she struck a staff member. A careful assessment was made to determine if changes in the environment or psychological or social interventions might be helpful. However, despite several weeks of non-pharmacological interventions, the patient’s behavioral and emotional status worsened. The decision was made to start the patient on risperidone. Prior to starting the drug, a physical examination was performed, a 12-lead ECG was done, serum glucose, calcium, magnesium, and potassium were measured and a lipid panel was done. Ambulatory status was assessed, body weight was measured, and orthostatic vital signs were checked. Her medication profile was carefully reviewed. After reviewing the data, the psychiatrist decided that it would be safe to begin therapy with risperidone. After several weeks of receiving the drug, the staff noted a significant improvement, but they continued to monitor the patient for adverse effects and routine ECG and laboratory and assessments were continued.