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Accreditation Information
ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
This home study web activity has been assigned 2.25 credit hours. ACPE UPN: 0203-0000-10-096-H01-P Release Date: 6/16/2010 Expiration Date: 7/1/2013
To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the online assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.
Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.
Kevin Chamberlin, PharmD Assistant Clinical Professor University of Connecticut Health Center
Casey K Gardner, PharmD Clinical Assistant Professor of Pharmacy Practice College of Pharmacy & Health Services Campbell University
Jonathan P. Lacro, Pharm.D., FASHP, BCPS, BCPP Program Manager and Clinical Pharmacist in Psychiatry VA San Diego Healthcare System & Associate Clinical Professor of Psychiatry University of California, San Diego & Research Scientist Veterans Medical Research Foundation
Sean M. Jeffery, PharmD, CGP, FASCP Assistant Clinical Professor & Clinical Pharmcy Specialist, Geriatrics VA Connecticut Healthcare System
Faculty Disclosures
Kevin W. Chamberlin has no relevant financial relationships to disclose. Casey K Gardner, PharmD, has no relevant financial relationships to disclose. Sean M. Jeffery has no relevant financial relationships to disclose. Jonathan P. Lacro has no relevant financial relationships to disclose. Kristen Meyer, PharmD, has no relevant financial relationships to disclose. Christopher J. Thomas, PharmD, has no relevant financial relationships to disclose.
Anxiety
By the end of this review concept, you will be able to: Differentiate different types of anxiety disorders. Describe the epidemiology and etiology of generalized anxiety disorder. List drugs that can cause anxiety. Describe signs and symptoms of generalized anxiety disorder. Describe diagnostic and treatment protocols for patients with anxiety disorders. Identify pharmacological treatment options for patients with anxiety disorders. Describe indications, contraindications, dosing, adverse effects, and drug-drug interactions for agents commonly
Anxiety disorders are among the most common diagnosable conditions in older adults. Yet the prevalence of anxiety disorders is lower for the elderly than for other age groups. Despite these differences, anxiety disorders continue to be the most prevalent of psychiatric disorders in the elderly. In community samples, the 6-month prevalence of all anxiety disorders was 19.7% and the lifetime prevalence was 34.1%. Panic disorder involves sudden extreme fear, striking without warning. Symptoms generally reach a peak within ten minutes. Panic disorders affect about 6 million American adults and twice as many women as men are affected. Phobias are many and varied. Two phobias that are of particular interest in the elderly population are the disabling fear associated with something that presents no real danger, and the fear of embarrassment or humiliation in social settings. With both phobias, increased avoidance behavior is observed. Obsessive-compulsive disorder involves unwanted thoughts or obsessions and compulsive behaviors that are difficult to stop or control. Obsessive-compulsive disorder is often a chronic, relapsing illness. It affects about 2.2 million Americans. Post-traumatic stress disorder can occur three months or more after the traumatic event. Symptoms must last more than one month to be considered a post-traumatic stress disorder. It affects abut 7.7 million Americans
The most common anxiety disorder in the elderly population is generalized anxiety disorder. This disorder affects more women than men, and is characterized by excessive worrisome thoughts and tensions that persist for at least six months. Estimates of the prevalence of generalized anxiety disorder in the older population ranges from 1% to 9%, with some references identifying as high as 20%. There is a general consensus that generalized anxiety disorder, like other anxiety disorders, is less common in the elderly population than in the adult population. Like most anxiety disorders, generalized anxiety disorder results in higher than normal levels of serotonin and norepinephrine in the brain. It can be caused by a number of factors such as psychiatric illness, traumatic events, loss of freedom, loss of support systems, social isolation and a variety of cardiovascular, pulmonary, endocrine and neurologic disorders. Various medications can also induce anxiety, worsening the underlying medical condition.
On your screen you see a partial list of common agents and general medical conditions associated with anxiety. Many agents like the sympathomimetics and methylxanthine derivatives like theophylline are very stimulating and can exacerbate underlying anxiety disorder. In addition, some of these medications are used in conditions already associated with anxiety, for example the use of theophylline in patients with COPD or digitalis in heart failure patients.
Signs and symptoms of generalized anxiety disorder include fatigue, muscle tension, and nausea. Many of these symptoms may last for more than six months. These signs and symptoms are similar to what patients might experience during a panic attack. The difference resides in the intensity and rapid onset of the symptoms during the panic attack. Additionally, panic attacks appear less common in the elderly. Determining whether the patient is experiencing generalized anxiety disorder or major depressive disorder is difficult because both of these disorders share symptoms (e.g. fatigue, difficulty concentration and sleep disturbances) and depression and generalized anxiety are frequently co-occurring. Generalized anxiety will not present with anhedonia, which is a core feature of major depressive disorder. Typically a patient with generalized anxiety will be seen by a primary care physician and present with unexplained physical symptoms (e.g. aches, pains, fatigue, gastrointestinal symptoms).
Physical exam Anxiety assessment scales include: Hamilton Anxiety Scale Anxiety Status Inventory Sheehan Patient Rated Anxiety Scale Zung Self-rating Anxiety Scale Beck Anxiety Inventory
In diagnosing anxiety disorders, symptoms should be confirmed and the duration of symptoms identified. The patient should be thoroughly examined, and relevant laboratory tests performed to rule out the common medical causes of anxiety or other medical conditions. A thorough history should be obtained from both the patient and caregivers. Appropriate treatment of underlying physiologic illness may eliminate or significantly decrease anxiety symptoms. Both anxiety and depression assessment scales are helpful in determining the severity of these disorders. Anxiety assessment scales include the Hamilton Anxiety Scale and Anxiety Status Inventory, which are clinician rated, and the Sheehan Patient Rated Anxiety Scale, Zung Self-rating Anxiety Scale and Beck Anxiety Inventory,, which are all patientrated. Clinician-rated scales are preferred in long-term care settings.
Copyright 2011 American Society of Consultant Pharmacists
Benzodiazepines with short and intermediate half-lives can effectively treat symptoms associated with generalized anxiety disorder. Usual geriatric dosing ranges are shown on your screen; lower maximum doses are recommended when using these agents to treat anxiety associated with dementia syndromes. Recommended duration of therapy is no longer than four months, although some patients may require longer-term therapy. For those patients with dementia who are manifesting anxiety symptoms, it is recommended to stop the medication as soon as possible because the anxiety symptoms may be transient. Benzodiazepines should be used cautiously in the elderly because of their increased sensitivity to adverse effects such as sedation, short-term memory impairment, dysarthria, ataxia and falls as well as their decreased pulmonary reserve and potential tendency towards hypoxia.
Copyright 2011 American Society of Consultant Pharmacists
The most common pharmacodynamic interaction is potentiation of sedation and respiratory depression in combination with other sedating agents like alcohol, antidepressants, and antipsychotics. In overdose, the benzodiazepine - alcohol combination has often resulted in death. Pharmacokinetic drug interactions are more commonly observed with alprazolam since it is metabolized by the CYP-450 -3A4 hepatic isoenzyme system. Patients receiving alprazolam and a metabolic inhibitor or inducer should be closely monitored for adverse effects or therapeutic failure. Drugs that inhibit CYP-450-3A4 and decrease alprazolam clearance are shown in the table along with those that increase the agents clearance. Lorazepam and oxazepam are eliminated by conjugation and are not implicated in significant pharmacokinetic drug interactions.
Buspirone is an alternative treatment for general anxiety disorder in patients who cannot tolerate the adverse effects associated with benzodiazepines. The agent lacks the sedative, anticonvulsant, muscle relaxant and dependence properties of the benzodiazepines. Buspirone is not effective in panic disorder and may cause worsening of symptoms. Also, it is not cross-tolerant with benzodiazepines and will not block benzodiazepine withdrawal. It has a slow onset of action, and may be dosed at fifteen to forty-five milligrams per day. The elderly may have a reduced risk of falls with buspirone, but should be monitored for adverse effects such as dizziness, nausea, and headaches.
Pharmacodynamic Interactions: Contraindicated with MAO inhibitors Caution with serotonergic antidepressants Monitor for potentiation of adverse effects Pharmacokinetic Interactions: Increases bioavailability of haloperidol
Buspirone is contraindicated in combination with MAO inhibitors, and should be used with caution in combination with serotonergic antidepressants. Monitoring for potentiation of adverse effects such as nausea and restlessness is essential. Pharmacokinetically, buspirone has been noted to increase the bioavailability of haloperidol.
Paroxetine: Other drugs that can increase serotonin as at risk for serotonin syndrome, anticoagulants/antiplatelets for increased risk of bleeding, CYP2B6 substrates, CYP2D6 inhibitors/substrates, When to consider: Patients taking benzodiazepines or buspirone who may benefit from adjunct therapy Except for TCAs, first line agents for Panic disorder Comorbid depression Obsessive-compulsive disorder Social phobia Nerve pain
Antidepressants are an alternative first line therapy for general anxiety disorders in patients who cannot tolerate or poorly respond to benzodiazepines or buspirone or who have another reason to not take them (such as increased risk for falls). Antidepressants can also be used to augment treatment in patients who partially respond to benzodiazepines or buspirone. Antidepressants, excluding TCAs, are first line agents in patients with panic disorder, comorbid depression with anxiety, obsessive-compulsive disorder, and social phobia.
Non-benzodiazepines Buspirone SSRIs: Citalopram Escitalopram no yes data no data data ? no ? no yes ? ? ? data
The table on your screen shows various agents and their indications for anxiety disorders. A yes signifies an FDA approved indication; a no signifies no approved use of the drug for that disorder. The term data indicates that there is evidence to support the drugs use, but it is not an FDA approved indication at this time.
Other Antidepressants: Bupropion Mirtazapine Nefazodone Duloxetine Venlafaxine Other Medications: Gabapentin Pregabalin Tiagabine no data data no no no no no no no no data data ? no no data no data yes no data no no no no data data no data ? ? data no no no no data data data
No = not an FDA approved indication Yes = FDA approved indication Data = not FDA approved, but evidence supports use ? = inconclusive data
Copyright 2011 American Society of Consultant Pharmacists
Anxiety disorders are diagnosed in many geriatric patients. In selecting the appropriate drug therapy, one should consider the following patient-specific factors: presence of cognitive impairment and comorbid medical illnesses, history of falls, adverse effect profiles, the risk of drug interactions, and the type of anxiety disorder being treated. Primary therapeutic outcomes are amelioration of anxious symptoms and functional improvement.
Alcohol Abuse
Learning Objectives:
By the end of this review concept, you will be able to: Describe the prevalence and morbidity/mortality associated with alcohol abuse in the elderly. Compare the etiology of early-onset and late-onset alcohol abuse. Describe the physiological changes that occur as a result of alcohol abuse, and the resulting clinical signs and symptoms. Explain the difficulties in diagnosing alcohol abuse in the elderly, and describe tests and metabolic markers that may be useful in confirming diagnosis. Describe the process and some of the therapeutic options available for treating alcohol abuse. Describe drugs commonly used in the pharmacotherapy of alcohol abuse, including their use, effects, dosing, adverse reactions, monitoring protocols and drug-drug interactions. Explain the risks associated with combining alcohol with prescription medications.
Very few studies have focused on the incidence or prevalence of substance abuse among older adults, but the perception is that problems are more often associated with the improper use of alcohol and prescription drugs, as opposed to abuse of illicit drugs. Although older adults are believed to have the lowest rates of alcohol abuse as an age cohort, the prevalence of alcohol use and abuse in this group is clearly underestimated. As a group, elderly adults tend to drink less and have fewer alcohol-related problems than younger people do. However, because drinking patterns are relatively stable over time, persons who develop alcoholism early in life tend to carry the problem into late life unless treated. As the proportion of the aging population increases, the number of older people with alcohol related problems will increase, even if the prevalence remains the same. Also contributing to the increasing number of older adults with alcohol-related problems is the observation that approximately one-third of older adults will experience alcohol-use problems after the age of 60 years. Older adults with alcohol-related problems are at greater risk for morbidity and mortality. One reason for the higher morbidity and mortality associated with the disorder is that older adults who drink at high-risk levels have not been recognized as atrisk or as problem drinkers by health care personnel. Symptoms of alcohol abuse are often mistaken for other medical conditions such as depression, insomnia, and poor nutrition. Alcohol abuse can obscure the diagnosis of transient ischemic attacks and Alzheimers disease, often leaving these comorbid conditions undetected and untreated.
Clinicians distinguish between two elderly alcoholic populations-- those with early-onset alcohol problems and those with late onset alcohol problems that occur after the age of sixty. It has been suggested, but not substantiated, that a number of people develop later-onset alcoholism after they retire, due to feelings of depression, boredom, and social isolation. Alcoholrelated disabilities may play an important role in admitting a patient to a nursing home or psychiatric facility.
Excessive alcohol use is associated with several adverse health effects including greater risk for harmful drug interactions, injury, depression, memory problems, liver disease, cardiovascular disease, cognitive changes and sleep disturbances. Physiologically, alcohol decreases alertness, judgment, coordination and reaction time. It also increases the risk of falls and accidents, leading to a higher incidence of hip fractures and associated mortality in the elderly. Drinking heavily can result in irreversible cognitive impairment, and affect the heart, liver, kidneys and stomach. Moderate to heavy drinkers are approximately nine times more likely to die by suicide than by natural causes or injury.
Since older adults have an increased sensitivity to alcohol compared to younger adults, alcohol use recommendations for older adults are generally lower than those set for adults under 65 years. The recommended amount of alcohol that persons over the age of 65 may consume is provided on the screen. Exceeding these recommendations by the National Institute of Alcohol Abuse and Alcoholism and the Center for Substance Abuse Treatments Treatment Improvement Protocol for older adults increases the risk of alcohol-related problems. Psychosocial tests and metabolic indicators help identify alcohol abuse and dependence. The Short Michigan Alcohol Screening Test-Geriatric version (SMAST-G) was developed specifically for older adults and is useful both as a screening tool and to track progress in treatment. The CAGE test, a widely used alcohol screening test, may not detect earlier stages of alcoholism. Metabolic indicators of alcohol abuse include liver function tests, which can detect hepatic injury, hypoalbuminemia which occurs secondary to increased alcohol consumption at the expense of proper nutrition, increased clotting time as a result of decreased intake of vitamin K containing foods and hepatic impairment and macrocytic anemia that is most often due to folic acid deficiency. Despite the numerous metabolic indicators suggesting alcohol abuse, it is important to remember that these tests have poor positive predictive ability.
The success rate for elderly adults being treated for alcohol abuse is not significantly different from that of the general population. Long term improvement can be seen in twenty-five percent of all alcoholics abstaining from alcohol for at least one year. The treatment process involves nonjudgmental confrontation and detoxification, followed by intense educational and therapeutic activities, such as an introduction to Alcoholics Anonymous. Treatment options include total abstinence, abstinence with improved functioning, overall improved functioning but no abstinence, and pharmacotherapy.
Psychosocial therapy can help treat alcohol abuse. Counseling, individually or in a group, tends to be behavior oriented, and addresses the defense mechanism of denial. Individual counseling can be costly, and is usually not covered by many insurance companies. Group therapy through Alcoholics Anonymous and other addiction-related support groups reinforces abstinent behavior and are especially effective if the settings are age-segregated.
Disulfiram is useful in abstinence programs because it produces severely unpleasant reactions when alcohol is ingested. These reactions, which include severe nausea, vomiting, flushing, and palpitations, may persist for two weeks after cessation of therapy. Disulfiram is contraindicated in cardiovascular disease, diabetes, epilepsy, and hepatic failure. It should be used with extreme caution in elderly, since adverse effects include hepatitis, peripheral neuropathy, and heart failure. Liver function tests, bilirubin, and complete blood count should be assessed at baseline, re-assessed in ten days, and monitored every six months thereafter. It is important to counsel patient to remain abstinent throughout this period and avoid any product containing alcohol.
Disulfiram interacts with other drugs and can cause central nervous system toxicity with metronidazole. Other drugs such as phenytoin and warfarin can increase serum levels of disulfiram.
Alcohol-Drug Interactions
Alcohol induces hepatic metabolic enzymes, causing: Increased clearance of concurrent drugs Decreased serum drug levels Therapeutic failure Possible death
Alcohol and drug interactions can profoundly influence the effectiveness of medications which are taken concurrently. Alcohol induces hepatic metabolic enzymes, which causes the increased clearance of some drugs and may result in decreased serum levels of medications that share metabolic pathways. Therapeutic failure may result as well. When alcohol is mixed with prescription medications, such as barbiturates, benzodiazepines, narcotics, and other medications, the results may be fatal.
Sleep Disorders
Learning Objectives:
By the end of this review concept, you will be able to: Describe typical age-related changes in the sleep cycle. Describe the epidemiology of sleep disorders in the elderly population. Differentiate transient and chronic sleep disorders. Differentiate primary and secondary sleep disorders. List common primary sleep disorders. List psychiatric, medical and pharmacological causes of secondary sleep disorders. Describe procedures for assessing and diagnosing sleep disorders in the elderly. Describe nonpharmacological therapies for the treatment of insomnia. Describe pharmacological options for the treatment of insomnia. Describe effects, dosing, side effects and contraindications for common agents used in the treatment of insomnia in the elderly. Describe pharmacological and nonpharmacological options for the treatment of apnea and other sleep disorders.
Stage 1 Period between sleep and wakefulness Initiates sleep Stage 2 Light sleep Muscle and brain activity shutdown Stage 3 Deep sleep 5% of total sleep time Occurs 1 to 3 hours after falling asleep Rebuilding stage for body Lessens with age Stage 4 Deep sleep 10 15% of total sleep time Rebuilding stage for body Lessens with age
REM Rapid eye movement stage Occurs in 90 minute cycles Longer during first half of sleep time Characterized by: Irregular breathing Increased heart rate Increased blood pressure Decreased core body temperature Decreased muscle tone Associated with dreaming
From: Neubauer DN. Sleep problems in the elderly. Amer Fam Phys. 1999;59(9):2551.
Agings Influence on Sleep More time spent in bed More time trying to fall asleep Less time sleeping Sleep tends to be lighter Stages 3 and 4 and REM sleep decreases More frequent awakenings Less time for restorative functions
The most deep sleep an average adjult gets is within the first 4 hours of falling asleep. The longer one sleeps, the less deep sleep that occurs and the more REM sleep that is experienced. As adults get older, they experience a number of changes in their sleep patterns. They tend to go to bed earlier, spending more time in bed trying to fall asleep and less time sleeping. Their sleep tends to be lighter, as stages three and four, and REM sleep decreases, as illustrated on the comparison graph of young adults sleep cycles compared with that of the elderly. This means that less time is spent in restorative sleep, and the person frequently awakens without feeling rested. While these changes result in more fragmented sleep, they are more or a less a natural consequence of the aging process.
When these changes in sleep patterns threaten the health and well being of the individual, the person is said to have a sleep disorder. Up to 66% of residents in long-term care facilities have some type of sleep disturbance related to a primary sleep disorder, a mental or medical condition, or substance abuse. In the general geriatric population, 23 to 34% of older adults report symptoms of insomnia, such as difficulty falling and staying asleep, and early morning awakenings. Untreated and severe insomnia may lead to increased mortality.
Insomnia may be either transient, lasting only a couple of days; short-term, lasting several days to weeks; or, chronic. Sleep disorders are generally considered chronic if they persist longer than three weeks. Transient and short-term insomnia is usually associated with an acute stressor, such as jet lag or work-related stress, whereas chronic insomnia is typically caused by one or more long-term contributing factors, such as a medical condition.
Audio Transcript Primary sleep disorders include dyssomnias, hypersomnias, and parasomnias. Secondary sleep disorders may be caused by other psychiatric disorders, medical conditions, medications, and/or substances of abuse.
Dyssomnias are disorders in initiating or maintaining sleep, or of excessive sleepiness. They include primary insomnia that is not secondary to another disorder or use of drugs, and narcolepsy, which is rather infrequent in the elderly. Dyssomnias also include breathing-related disorders such as sleep apnea. The three patterns of apnea include central sleep apnea, obstructive sleep apnea, and mixed apnea. Apneas may be lethal if associated with hypoxemia and cardiac arrhythmias. They also contribute to sudden nocturnal death in the early morning hours. Circadian-rhythm disorder is another type of dyssomnia that involves changes in the duration of circadian cycles with age. Such changes can affect other homeostatic rhythms and reduce total sleep time. Other dyssomnias include restless leg syndrome, which can cause repeated awakenings.
Hypersomnias are a more severe problem than insomnia. Sleep apnea, as mentioned before, is characterized by cessation of breathing for about 10 seconds for at least 30 episodes during the night. Narcolepsy consists of a tetrad of symptoms. One of these symptoms is sudden, brief (approximately 15 minutes) sleep attacks that can occur during any type of activity. Another symptom is cataplexy, or sudden loss of muscle tone that may cause the patient to slump to the floor, unable to move. A third symptom is sleep paralysis, characterized by a generalized flaccidity of muscles with full consciousness in the transition zone between sleep and walking. The fourth symptom of narcolepsy is hypnagogic hallucinationsvisual or auditorywhich may precede sleep or occur during the sleep attack. The attacks are characterized by an abrupt transition into REM sleep, a necessary criterion for diagnosis. Kleine-Levin syndrome predominates in young men and is characterized by hypersomnic attacks three or four times a year. These attacks can last up to 2 days, and typically are associated with hyperphagia, hypersexuality, and mental status changes upon awakening. This syndrome typically remits after the age of 40. Nocturnal myoclonus is characterized by periodic lower leg movements that occur during sleep with subsequent daytime sleepiness, anxiety, depression, and cognitive impairment.
Parasomnias typically begin in childhood and resolve with age. Sleep terror tends to affect preadolescents, but can also affect adults, and is characterized by an abrupt awakening from stage 3 or 4 sleep. Symptoms include: fear, sweating, tachycardia, and confusion for several minutes, with amnesia for the event. Nightmares may occur during REM sleep. Sleepwalking, or somnambulism, includes ambulation or other fine behaviors while still asleep, and again with amnesia for the event. Sleepwalking in the elderly (as it predominates in children), can be a feature of dementia. Enuresis is involuntary micturition during sleep in a person who has voluntary control while awake. Again, this parasomnia predominiates in children and this section is included for complete review of sleep disorders.
Secondary insomnia in the elderly is commonly due to general mental conditions that disrupt sleep and increase sleep latency and early morning awakenings. Depression, anxiety, and psychosis are examples of such conditions. Medical illnesses that can induce insomnia include: Parkinsons disease, dementia, pulmonary disease, and pain. Finally, substance use and abuse can influence sleep disturbances in the elderly.
Drugs that contribute to the development of insomnia are listed on your screen. Although alcohol initially causes drowsiness, it disrupts sleep later in the evening, decreases REM sleep, and increases awakenings.
The elderly who complain about insomnia generally admit to excessive daytime sleepiness and unrefreshing sleep. Again, this is due to the fact that restorative sleep in stage 3 and 4 is reduced. As a result, patients will tend to nap more in the day, which contributes to the vicious cycle of increased sleep latency at bedtime. If left untreated, this sleep deficit can lead to cognitive impairment, resulting in a greater risk of accidents and falls, and an inability to carry out daily tasks.
To diagnose insomnia, a complete medical and psychiatric history should be obtained. Sleep habits of the patient should be documented every twenty-four hours for several days to weeks. Long-term care staff, the patient, or family caregivers can keep a sleep diary of the patients sleeping habits. The diary should note the duration of sleep, type of sleep problem(s), daily functioning, and level of daytime alertness. The diary should reveal signs and symptoms of a major primary sleep disorder, and their duration. A complete physical exam should be conducted, and lab tests assessed for occult conditions that may be contributors. All medical conditions and treatment that disrupt sleep should be ruled out. Besides observation, occurrence of nocturnal wheezing and repetitive stereotypic leg movements should be noted. If apnea is likely, polysomnography should be ordered.
If a secondary sleep disorder is highly suspected, the clinician should consider discontinuing any offending drugs and substituting less problematic alternatives. The clinician should also take steps to optimize treatment of chronic diseases known to disrupt sleep. Establishing consistent sleep hygiene practices, such as those listed here, can help alleviate the disorder. Patients with obstructive sleep apnea should lose weight if necessary, and avoid alcohol and sedative-hypnotics. If the patient does not respond to treatment, mechanical and surgical measures can be taken such as nasal continuous positive airway pressure, or in extremely severe cases a tracheotomy may need to be performed. It is essential to monitor all therapeutic responses to these treatment measures.
In a study published in JAMA in 1999, subjects receiving cognitive-behavior therapy attended 8 weekly 90-minute therapy sessions conducted in small groups of 4 to 6 individuals. Treatment consisted of a structured, multifaceted intervention involving behavioral, cognitive, and educational components that targeted different facets of late-life insomnia. The behavioral component used sleep restriction therapy and stimulus control procedures. Sleep restriction consisted of curtailing time in bed to the actual sleep time, like step 2 on your screen. Daytime napping was made optional during this study, as long as it was limited to less than 1 hour and prior to 3:00 PM. Overall, behavioral interventions into sleep hygiene had the most sustained effect over the 2 years of the study.
From: Morin CM, et al. Behavioral and Pharmacological Therapies for Late-Life Insomnia: A Randomized Controlled Trial. JAMA. 1999;281:991-999.
The figure on the left side of your screen is a post hoc comparison showing subjects in the cognitive-behavior therapy group and combined conditions rating themselves as significantly more improved and less impaired than subjects in either the pharmacotherapy or placebo groups. The bar graph on the right of your screen shows changes in wake after sleep onset (WASO), as measured by patients sleep diaries. For the cognitive-behavior therapy condition, there was no significant change on any of the dependent variables at any follow-up, suggesting that treatment gains achieved by post-treatment assessment were well maintained. The pharmacotherapy intervention showed significant worsening from the post-treatment period, especially noted at the 24-month follow-up, for total wake time, sleep efficiency, and wake after sleep onset. For the combined interventions, statistically significant changes were obtained at all 3 follow-up periods (3, 12, and 24 months) on measures of total wake time, sleep efficiency, and wake after sleep onset, which may indicate significant worsening of sleep pattern over time.
Copyright 2011 American Society of Consultant Pharmacists
The medication classes listed on your screen have replaced barbiturates as preferred hypnotic agents because of their greater safety profile in overdose situations and their reduced effects on hepatic enzyme induction. Today, hypnotic sedatives such as benzodiazepines and nonbenzodiazepines are often prescribed for insomnia, particularly in the community-dwelling elderly. However, these drugs also have their drawbacks. In addition to being the largest underrecognized cause of hypersomnolence, long-term use of agents such as benzodiazepines and tricyclic antidepressants often causes adverse effects and is associated with morbidity incurred with falls. Sedating antidepressants, such as mirtazipine, are also used for dual treatment of insomnia, depression, and/or appetite stimulation. In general, it is generally appropriate to use medications for short courses of 1 2 weeks.
Benzodiazepines are still the most widely prescribed medication for insomnia. The shorter acting agents induce sleep and decrease sleep latency, and all benzodiazepines suppress stages three, four, and REM sleep. Benzodiazepines include short- and intermediate-acting agents such as triazolam and temazepam. Long-acting agents such as flurazepam, diazepam, and chlordiazepoxide form active metabolites and should not be used in the elderly due their greatly prolonged elimination half-lives. These agents have also been associated with cognitive impairment and increased risk of hip fractures. All benzodiazepines are associated with similar adverse effects such as impaired motor coordination, daytime sedation with cognitive impairment, and dizziness. Because they decrease respiratory drive and worsen obstructive breathing disorders, all benzodiazepines are contraindicated in the treatment of sleep apnea. The use of benzodiazepines needs to be closely monitored to ensure appropriateness of indication, dose, and duration, especially when using unnecessary and potentially hazardous agents as defined in the Health Care Financing Administration guidelines.
Triazolam, a short-acting benzodiazepine, does not have active metabolites, and is helpful in reducing sleep latency. However, rebound insomnia and amnesia may result, especially at higher doses. The usual geriatric starting dose is 0.125 mg and should only be used for very short periods of time because of its increased association with dependency, transient psychotic reactions, and rebound anxiety.
Temazepam, estazolam, and quazepam are intermediate-acting benzodiazepines. These agents are useful for sleep maintenance, and should be taken an hour to an hour and a half before bedtime. Because they form no active metabolites, temazepam and estazolam improve sleep maintenance without causing significant daytime residual effects and may be preferred in the elderly. Quazepam is metabolized to at least one active metabolite with a potential half-life up to 8 days and should be avoided in the elderly population.
Copyright 2011 American Society of Consultant Pharmacists
Antihistamines like diphenhydramine induce sleep with a low sedative potency. Disadvantages of antihistamines include the quick development of tolerance and significant anticholinergic side effects. Consensus panel recommendations from experts on geriatric prescribing suggest that antihistamines not be utilized in the older adult, and are contraindicated for patients with dementia, prostatic hypertrophy, glaucoma, and chronic constipation due to their potent anticholinergic properties. This also correlates with restrictions placed on antihistamine use in the elderly by the Health Care Financing Administration (HCFA). Antihistamines, including diphenhydramine, chlorpheniramine, and brompheniramine, are in a large number of both combination and non-combination products available direct to the consumer over-the-counter. It is important to recognize these agents and counsel patients with regard to their potential harm.
Zaleplon (Sonata) Member of the pyrazolopyrimidine class Half-life is about 1 hour Start at 5 10 mg qHS, immediately before bedtime May repeat dose if desired wake time is greater than 4 hours from time sleep is interrupted Minimal residual daytime effects Avoid giving near / with high fat foods Delayed time to maximum concentration by up to 2 hours Reduced maximum concentration by up to 35%
Copyright 2011 American Society of Consultant Pharmacists
Sedating antidepressants are effective for insomnia caused by depression, an example of treating the cause rather than the symptom. However, the tricyclic antidepressants are not preferred therapy in the elderly due to their anticholinergic side effects, orthostatic hypotension, cardiac-conduction effects, and daytime sedation.
The first hypnotic agent with a new mechanism of action approved in over 35 years, ramelteon is a melatonin receptor agonist with a high affinity for melatonin MT1 and MT2 receptors over the MT3 receptor. Endogenous melatonin acts on MT1 and MT2 receptors, which is thought to contribute to ramelteons sleep promoting properties. Ramelteon is designed for use in accordance with the maintenance of the circadian rhythm underlying the sleep-wake cycle. The major metabolite, MII [M-two], is active with approximately one-tenth to one-fifth the binding affinity of the parent molecule for the MT1 and MT2 receptors, respectively, and is 17- to 25-fold less potent in in vitro functional assays. However, MII circulates at higher concentrations than the parent compound, producing a 20- to 100-fold mean systemic exposure when compared to ramelteon. The metabolite also has a slight affinity for the serotonin 5-HT2B receptor.
Treatment Ropinirole (Requip) (currently only FDA-approved option) Carbamazepine Levodopa Clonazepam Bromocriptine Narcotic analgesics
For obstructive sleep apnea, continuous positive airway pressure, or CPAP, is the current treatment of choice. CPAP is effective in increasing oxygenation, consolidating sleep, and improving daytime cognition and alertness. Biphasic positive airway pressure may be used for patients intolerant or having incomplete satisfaction with CPAP treatment. BiPAP can decrease respiratory exertion on the patient, allowing the patient to exhale more easily by having a reduced pressure to expire against. Treatment for severe sleep apnea includes continuous positive airway pressure and otolaryngologic surgery. Nocturnal myoclonus may improve with benzodiazepines such as clonazepam; however, geriatric patients should be monitored closely for adverse effects. There is currently no approved treatment for Kleine-Levin syndrome.
Psychoses
Learning Objectives:
Describe the epidemiology ofpsychosis in the elderly. Differentiate between early-onset and late-onset schizophrenia List the signs and symptoms of schizophrenia and other psychotic disorders. Summarize guidelines for diagnosing psychotic disorders in the elderly. Differentiate between conventional and atypical antipsychotic medications used to treat psychosis in elderly patients. Summarize guidelines for the administration of antipsychotic therapy in the elderly. Describe mechanism of action, clinical benefits, dosing, adverse effects and monitoring protocols for conventional agents used to treat psychosis in elderly patients. Describe clinical presentation, management and monitoring guidelines associated with extrapyramidal effects of antipsychotic therapy. Describe mechanism of action, clinical benefits, dosing, adverse effects and monitoring protocols for atypicalagents used to treat psychosis in elderly patients. Describe pharmacokinetic and pharmacodynamic interactions associated with the use of antipsychotic therapy.
Late-life psychosis is a common and pathologically heterogeneous disorder. The condition accounts for up to ten percent of psychiatric hospital admissions for patients over the age of sixty. Psychotic symptoms in the elderly can be classified into primary psychotic disorders, including schizophrenia and secondary psychotic disorders, for which psychotic symptoms are associated with dementias such as Alzheimers disease and medical conditions such as delirium.
Schizophrenia is among the most expensive disorders in terms of treatment costs and need for public assistance. It is a chronic and severe psychiatric disorder with a lifetime prevalence of 1%. Onset of the illness typically begins in early adulthood. This type of schizophrenia is termed early onset schizophrenia, and those that develop it may stabilize and even symptomatically improve with age. A small, but distinct group experience their first onset of symptoms later in life. Late-onset schizophrenia presents after the age of forty-five. Persons with late-onset schizophrenia typically require lower doses than their early-onset counterparts. Late-onset schizophrenia affects more women than men.
Signs and symptoms of schizophrenia are commonly classified as positive, negative, and thought disorder. Positive symptoms include delusions and hallucinations, and generally respond better to pharmacotherapy than negative symptoms which include emotional flatness, limited speech and loss of initiative. Symptoms characteristic of thought disorder include confused thinking which is less severe with late onset schizophrenia, and disorganized speech, behavior and perceptions.
Diagnosing Psychosis
medical history physical examination laboratory tests - blood or urine samples
As with any new onset of psychiatric symptoms in the elderly, patients must be thoroughly evaluated to determine if the cause of their symptoms is reversible. Medical history, physical examination and laboratory tests can help rule out medical causes of psychotic symptoms.
Antipsychotic drugs are often utilized in the treatment of all types of psychotic disorders. These medications do not affect the course of the illness or treat the underlying cause, but they do provide symptomatic relief. Resolution of psychotic symptoms often greatly improves the patient's overall level of functioning. Conventional antipsychotic medications have been available since the 1950s and include low, intermediate, and high-potency agents. These antipsychotic agents are considered by many to be second line therapy for the treatment of late life psychosis due to their disabling adverse effects in the elderly population. Atypical antipsychotics, available since the 1990s, are more effective in treating negative symptoms of schizophrenia. Due to decreased incidence of significant adverse effects, atypical antipsychotics are preferred agents for the treatment of psychosis in the elderly population. However, the higher costs of these agents may be problematic.
The general principles for treating the elderly with both conventional and atypical antipsychotics are listed on your screen. First, always start low and go slow. Select an agent that is least likely to exacerbate pre-existing conditions. For example, low potency agents are preferred over high potency agents for Parkinson's disease. Increase doses at intervals no less than one week apart. If utilizing a sedating agent, give the largest portion of the dose at bedtime. For behavioral disorders associated with dementia syndromes, use lower doses. Re-evaluate patients at a minimum of every six months. If the patient is stable, attempt to reduce the dose. Monitor the frequency and severity of psychotic symptoms and the adverse effects of medications.
There is little published information regarding the use of newer atypical agents ziprasidone or aripiprazole in the elderly. Both compounds are nearly void of anticholinergic properties which should be beneficial in disorders of cholinergic dysfunction, including Alzheimers disease. A potential problem with ziprasidone use in the elderly may be QTc prolongation which has been observed in younger adults.
Clozapine is often poorly tolerated in the elderly due to severe sedation and anticholinergic effects. Other problematic adverse effects include confusion, orthostatic hypotension, and seizures. The risk of agranulocytosis requires the regular monitoring of hematologic parameters such as complete blood count and differential. Patients blood counts must be monitored closely. Seizures and falls should be assessed at that time along with therapeutic outcomes. Orthostatic blood pressure should be checked before each dose during the titration phase to prevent falls. Constipation should be monitored and aggressively treated to avoid bowel obstruction.
All the newer atypical antipsychotic agents have an improved EPS profile over conventional agents; however, risperidone can cause dose-related extrapyramidal symptoms. By restricting the maximum dose to less than two milligrams per day, these symptoms may be minimized. Adverse effects of risperidone include sedation, orthostatic hypotension, and peripheral edema. Patients on risperidone should be monitored for falls, and orthostatic blood pressure should be checked daily during the titration phase. Parkinsonian effects and tardive dyskinesia should be assessed using either the AIMS or DISCUS tests at baseline and every six months. Although the risk of tardive dyskinesia with risperidone is thought to be low, some cases have been reported. Therapeutic outcomes should be assessed by noting the frequency and severity of psychotic symptoms.
Olanzapine tends to be more sedating than risperidone, but does not appear to produce dose-related extrapyramidal symptoms within the usual geriatric therapeutic dose range. For patients especially sensitive to such symptoms, olanzapine or quetiapine may be preferred agents. The adverse effects of olanzapine include moderate somnolence, confusion, dizziness, and significant weight gain. A low incidence of extrapyramidal symptoms has been reported with this agent. Patients on olanzapine should be monitored for falls, weight gain, and pseudo parkinsonism. Orthostatic blood pressure should be checked daily during titration, as sedation tends to be the most severe during initial titration. Patients should be assessed for tardive dyskinesia with theAIMS or DISCUS instruments at baseline and every six months.
Another atypical antipsychotic, quetiapine, is metabolized by cytochrome P450 3A4.Initial and typical dosing guidelines are listed on your screen. Quetiapines adverse effects include moderate to severe somnolence during the initial titration period, confusion, dizziness, and orthostatic hypotension. Quetiapine can produce significant initial sedation, but has a very low potential for extrapyramidal symptoms. It may be an alternative to clozapine in psychoses associated with Parkinson's disease. Patients taking quetiapine should be monitored for adverse effects commonly associated with the newer atypical agents. The incidence of hypothyroidism associated with this drug may be increased in elderly women.
All antipsychotic medications undergo extensive hepatic metabolism mediated by the cytochrome P450 system. Concurrent use of an antipsychotic with an inhibitor may lead to increased adverse effects such as extrapyramidal symptoms. In combination with an enzyme inducer, lower than anticipated serum levels may occur with consequent therapeutic failure. Pharmacodynamic drug interactions are also common in the elderly. The additive sedative effects of an antipsychotic and a benzodiazepine, for example, can lead to confusion and falls while additive anticholinergic effects may contribute to the development of a drug-induced delirium.
Neuroleptic malignant syndrome or NMS is a rare but potentially fatal complication of antipsychotic drug therapy. If suspected, medical attention should be sought and the antipsychotic drug should be discontinued. Because some of the symptoms of neuroleptic malignant syndrome may mimic flu-like illness in the elderly, NMS may be difficult to diagnose. Any geriatric patient receiving an antipsychotic drug that suddenly develops a fever and rigidity should be promptly assessed for this condition.
Resources
For additional information, see: Bullock R, Saharan A (2002). Atypical antipsychotics: Experience and use in the elderly. Int J Clin Pract 56:515-525. Caligiuri MR, Jeste DV, Lacro JP (2000). Antipsychotic-Induced movement disorders in the elderly: epidemiology and treatment recommendations. Drugs Aging. 17: 363-84. Dolder CR and Jeste DV (2003). Incidence of tardive dyskinesia with typical versus atypical antipsychotics in very high risk patients. Biol Psychiatry 53:1142-1145. Ereshefsky, L. (1996). Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry:57[suppl 11]:12-25. Jeste, D. V., Eastham, J. H., Lacro, J. P., Gierz, M., Field, M. G. & Harris, M. J. (1996). Management of late-life psychosis. Clin Psychiatry; 57 (suppl 3):39-45. Katz IR, Jeste DV, Mintzer JE et al (1999). Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: A randomized, double-blind trial. J Clin Psychiatry 60:107-115. Kindermann SS, Dolder CR, Bailey A, et al (2002). Pharmacological treatment of psychosis and agitation in elderly patients with dementia: four decades of experience. Drugs Aging 19: 257-76. Kumar, V. (1997). Use of atypical antipsychotic agents in geriatric patients: a review. International Journal of Geriatric Psychopharmacology; 1:15-24.
Resources
Howard R, Rabins PV, Seeman MV, Jeste DV (2000).Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international consensus. The International Late-Onset Schizophrenia Group. Am J Psychiatry. 157: 172-8. Sernyak MJ, Leslie DL, Alarcon RD, et al (2002). Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 159:561-56. Snowden M, Sato K and Roy-Byrne P (2003). Assessment and treatment of nursing home residents with depression or behavioral symptoms associated with dementia: a review of the literature. J Am Geriatr Soc 51:1305-1317. Sweet JS, Clark WS, Gannon KS et al (2000). Olanzapine treatment of psychotic and behavioral symptoms in patients with alzheimer disease in nursing care facilities: A double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 57:968-976. Tariot PN, Salzman C, Yeung PP, et al (2000). Long-term use of quetipine in older patients with psychotic disorders. Clin Ther 22:1068-1084. Tune LE, Salzman C (2003). Schizophrenia in late life. Psychiatr Clin North Am. 26: 103-13 Woerner, M. G., Alvir, J. M., Saltz, B. L., et al. (1998). Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry; 155:1521-1528.
Resources
Woo BKP, Daly JW, Allen ED, et al (2003). Unrecognized medical disorders in older psychiatric inpatients in a senior behavioral health unit in a university hospital. J Geriatr Psychiatry Neurol 16:121-125. Zayas, E. M. & Grossberg, G. T. (1998). The treatment of psychosis in late life. J Clin Psychiatry;59[suppl 1]:5-10. Organizations The National Alliance for the Mentally Ill (NAMI) Colonial Place Three National Mental Health Association (NMHA) National Mental Health Consumers' Self-Help Clearinghouse
Depression
Learning Objectives: By the end of this review concept, you will be able to: Describe the epidemiology of depression in the elderly. List the common etiologies of major depression and agents that can cause drug-induced depression. List the signs and symptoms of major depression. Differentiate the clinical presentation of dementia with that of depression. Describe procedures and criteria for diagnosing depression in the elderly. Describe pharmacological and nonpharmacological options for the treatment of depression. Describe mechanism of action, clinical benefits, dosing, adverse effects and monitoring protocols for agents used in the treatment of depression in the elderly. Describe pharmacokinetic and pharmacodynamic interactions associated with the use of antipsychotic therapy. Summarize guidelines for the selection, implementation, and discontinuation of antidepressant therapy.
Depression is a treatable, cyclic disorder that can impair a persons ability to function socially, cognitively and physically. Unfortunately, in the elderly, depression is commonly untreated and misdiagnosed because it is commonly mistaken for other comorbid disorders, such as dementia. Many professionals and family members may consider symptoms of depression as a normal result of aging, and do not recognize the condition. Community-based studies have found 1 to 2 percent of the elderly meet the strict criteria for major depressive disorder. However, as many as 15 to 25 percent may experience depressive symptoms. These rates rise dramatically in the long term care setting where as many as 30 to 40 percent experience depressive symptoms and as many as 12 to 16 percent fulfill diagnostic criteria for major depression. Major depression is more common in elderly women than in elderly men. Among the thirty-one percent of long term care residents who report new episodes and symptoms, the presence of depression can increase the risk of death by almost sixty percent within the first year in the facility. Depressed elderly, particularly elderly males have higher rates of suicide than the general population. If left untreated, depression can also worsen comorbid conditions, contributing ultimately to death.
Major depression can be caused by psychological, psychosocial, medical and pharmacological factors. Psychological factors that can bring on major depression include experiencing the loss of a partner, home or daily functioning. Psychosocial factors can also trigger major depression in the elderly, especially in those individuals that lack adequate support systems. Two of the most common causes of depression in the elderly are comorbid medical conditions and pharmacological agents. Diseases that can lead to depression are listed on your screen. Depression can be a presenting symptom of many disorders, as it is in more than half the cases of Parkinsons disease.
Drug-Induced Depression
H2 Antagonists Cimetidine Ranitidine Anti-inflammatory Agents/Analgesics Opioids Phenylbutazone Indomethacin Cardiovascular Agents Guanethidine Methyldopa Reserpine Hydralazine Propranolol Prazosin Clonidine Digitalis Calcium channel blockers Thiazide Diuretics
Steroids Corticosteroids Anabolic Steroids Estrogen ?? Antiparkinsonian Agents Levodopa Sedative-hypnotic agents Alcohol Barbiturates Chloral hydrate Benzodiazepines Meprobamate Others Amphetamine Withdrawal Baclofen Metoclopramide Conventional antipsychotics
Symptoms of depression may also appear as an adverse effect of pharmacotherapy for many medical conditions. A list of the drugs that have been linked to depressive symptoms is displayed. It is important to realize that not everyone receiving one of these medications will develop major depression. The cause of depression in a person receiving treatment is not always causally related to a particular medication. This list indicates some medications that have been associated with the development of depressive symptoms and should be considered when evaluating the possible causes of depression.
Depression can significantly impair an individuals level of functioning. In addition to a decrease in physical and cognitive performance, the person is often unable to manage basic activities of daily living. Specific symptoms include those listed here as noted in the Diagnostic and Statistical Manual. At least five or more of these symptoms must be present all or most of the day for at least two weeks to be considered diagnostic of major depressive disorder.
Depressed patients often experience problems with memory of recent events and difficulties with tasks requiring concentration. In the elderly, these symptoms are also characteristic of dementia. "Pseudodementia" describes depressionrelated memory impairment. In patients with no underlying cognitive impairment, pseudodementia is fully reversible with effective treatment of the depressive illness.
Clinical Interview: medical history history of depressive episode substance abuse drug regimen Physical Examination: blood pressure mental status neurological evaluation
Lab Tests: CBC with differential folate, B12 serum electrolytes urinalysis chest x-ray ECG TSH Psychological Tests: Geriatric Depression Scale Hamilton Rating Scale for Depression Cornell Scale for Depression in Dementia Mini-Mental State Examination (MMSE)
In diagnosing depression, substance use or abuse, and underlying medical problems should be ruled out first. The clinical interview is fundamental to determining not only functional status and medical history, but also length of the depressive episode, history of previous episodes, family history of depression, and history of drug and alcohol abuse. Response to previous treatment for depression, suicidal ideation or attempts, and level of physical functioning should be also documented at this time. A review of the current drug regimen is essential. The physical exam should include a mini-mental state examination to assess impairment of cognitive functioning. Lab tests should include complete blood count with differential, urinalysis, and chest x-ray. Psychological screening tests such as the Geriatric Depression Scale, Hamilton Rating scale for Depression, or Cornell Scale for Depression in Dementia are also necessary for accurate assessment.
Depression can be treated with a variety of therapies including pharmacotherapy, psychotherapy, and electroconvulsive therapy. Cognitive-behavioral psychotherapy includes changing the behavior and thoughts of the depressed person. The objective of therapy is to generate new interpretations for ones life. Psychotherapy is most effective when used with pharmacotherapy, which is generally the cornerstone of treatment for the majority of depressed elderly. Antidepressants can promote the remission of symptoms and prevent recurrences. However, antidepressants may also contribute to pharmacokinetic or pharmacodynamic interactions that lead to significant adverse effects. For those severely depressed who do not respond to antidepressant drug therapy, electroconvulsive therapy is considered to be a safe and effective means of treating severe geriatric depression. Refinement of the procedure, with unilateral treatments, has been found to decrease the occurrence of severe irreversible memory impairment.
Antidepressants yield about a sixty percent remission rate in the depressed elderly, as compared to thirteen percent with placebo treatment. They can be categorized by their effects on various neurotransmitters and receptors, as shown here. The tricyclic antidepressants and monoamine oxidase inhibitors are effective antidepressants, but due to significant side effects at therapeutic dosages and narrow therapeutic index, they are considered to be second line therapy for geriatric patients. Conservative dosing and slow titration of antidepressants is recommended. Generally, patients should be treated for at least six months after their initial response to antidepressant therapy.
Safer and better tolerated than earlier agents, the selective serotonin reuptake inhibitors are considered first line therapy for many elderly patients. S-S-R-Is act by blocking the reuptake of serotonin, and cause fewer cardiovascular, anticholinergic and sedative effects than tricyclic antidepressants. Commonly used agents include fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram. Geriatric dosage requirements and adverse effects are listed for each drug. Doses must be individualized to optimize response and minimize adverse effects. Due to decreases in clearance related to age and organ function, actual geriatric maintenance dosages may be less than the usual adult maximum dosage. Adverse effects of selective serotonin reuptake inhibitors include headache, nausea, and diarrhea. These agents may also exacerbate insomnia, but are less likely to cause severe cognitive impairment. The potential for extrapyramidal adverse effects, druginduced SIADH, and drug-drug interactions should be considered.
Serotonin reuptake inhibitors and 5-H-T-2 antagonists include trazodone and nefazodone. Trazodone is rarely used to treat elderly depression. It is primarily used as a hypnotic, often added to S-S-R-I therapy in patients with severe sleep disturbances. The usual geriatric dose range is twenty-five to one hundred milligrams per day, and the most common adverse effects include sedation, confusion and orthostatic hypotension. Ventricular arrhythmias have resulted from use in some patients with preexisting cardiac disease. Nefazodone has a better tolerability profile. It selectively inhibits presynaptic reuptake of serotonin, and antagonizes postsynaptic 5-H-T-2 receptors. Nefazodone can be successfully utilized in the treatment of depression with severe anxiety symptoms. It modestly reduces resting pulse and supine blood pressure, and has low anticholinergic and cardiovascular effects. Adverse effects include somnolence, dry mouth, and nausea. It has also received a black box warning of life threatening hepatic failure.
Tricyclic antidepressants include both tertiary and secondary amines.The secondary amines, desipramine and nortriptyline, are the active metabolites of the tertiary amines imipramine, and amitriptyline, respectively. This is why they both have less anticholinergic side effects when compared to the tertiary amines. Since elderly patients are susceptible to anticholinergic side effects, it is recommended that only the secondary amines be used. Because these drugs can be very dangerous if the patient overdoses, they should never be given to suicidal patients. Desipramine and nortriptyline should be started at low doses and slowly titrated up.The usual dose for desipramine is 25-100mg per day and the usual dose for notriptyline is 30-50mg per day. Adverse effects include minimal anticholinergic side effects, photosensitivity, and orthostasis. Nortriptyline is the least likely to cause orthostasis. Also, desipramine may impart a blue-green color to urine.
Venlafaxine (Effexor) a norepinephrine, serotonin, and dopamine reuptake inhibitor short half-life: IR formulation is given bid, SR formulation allows qd dosing Dosing: Initial: 12.5-25 mg qd Usual adult range: 50-225 mg/day bid SR dosages include Effexor XR 37.5 mg, 75 mg, 150mg Active metabolite is renally eliminated; decrease dose 50% for CLCr < 30 mL/min
Dopamine and norepinephrine reuptake inhibitors include bupropion and venlafaxine. Bupropion does not cause orthostatic hypotension or arrhythmias, and has minimal anticholinergic effects. Furthermore, the risk of seizures with sustained release bupropion is less than the IR formulation and thought to be no greater than the risk seen with the selective serotonin reuptake inhibitors. Bupropion can cause insomnia and central nervous system stimulation; hence the last dose should be given no later than five pm. The immediate release formulation must be administered three times day in doses no greater than one hundred fifty milligrams. Like bupropion, venlafaxine comes in immediate release and sustained release formulations. Because of its short half-life, immediate release venlafaxine requires multiple daily dosing. The sustained release formulations are dosed once daily. This agent has side effects similar to SSRI's, and the potential for adverse cardiovascular effects such as dose-related increase in diastolic blood pressure. The most common adverse effect is doserelated nausea, which may be minimized if given with food. Like venlafaxine, duloxetine is a norepinephrine and serotonin reuptake inhibitor. Duloxetine can be given twice a day or once daily based on indication for utilization. Besides treating major depression, duloxetine also has the approval to treat diabetic neuropathy. Most adverse events are similar to that of venlafaxine, however, monitoring of the LFT must be done periodically. Duloxetine should be avoided in patients with known renal and hepatic insufficiency.
Copyright 2011 American Society of Consultant Pharmacists
Treatment of Depression with Alpha-2 Antagonist, Serotonin-2 Antagonist (5-HT2), and Serotonin-3 (5-HT3) Antagonist
Mirtazapine (Remeron) early improvement in depression-associated anxiety long half-life of 20-40 h allows qd dosing metabolized by, but does not inhibit CYP450 system Dosing: Initial: 7.5-15mg qhs Usual adult range: 15-45 mg/day ADRs: sedation, dizziness, significant weight gain (due to histamine blockade), agranulocytosis(rare) Do not combine with MAOIs
Mirtazapines blockade of 5-HT3 receptors mitigates the nausea often observed with drugs that inhibit serotonin reuptake such as selective serotonin uptake inhibitors and venlafaxine. Mirtazapine exhibits early onset of anxolytic and hypnotic effects; patients with anxiety or severe sleep disturbance may benefit. Due to mirtazapine's long half-life, dosage increases should be made at no less than one week intervals. Mirtazapines blockade of histamine is responsible for adverse effects such as sedation and weight gain.
Copyright 2011 American Society of Consultant Pharmacists
Discontinuation of antidepressant therapy abruptly can cause discontinuation syndrome. If tricyclic antidepressants are discontinued abruptly, symptoms of "cholinergic rebound" such as nausea, anxiety, sleep disturbance and flu-like symptoms often occur. When selective serotonin reuptake inhibitors are discontinued abruptly, anxiety, dizziness, and paresthesias may result. Generally, antidepressants should be slowly discontinued, tapering off over two to four weeks Following discontinuation of antidepressant therapy, patients should be monitored closely for recurrence of depressive symptoms.
Interactions of antidepressants occur by pharmacokinetic or pharmacodynamic mechanisms. Pharmacokinetic interactions involve the induction or inhibition of hepatic drug metabolizing enzymes, specifically cytochrome P-450 enzymes. Significant drug-drug interactions may involve 1A2, 2C19, 2D6, and 3A4 isoenzymes. Hepatic enzyme inhibition is largely an effect of selective serotonin reuptake inhibitors, however, potency of inhibition varies among agents. Of the S-S-R-Is, sertraline and citalopram are less likely to be implicated in significant interactions. In addition, bupropion, venlafaxine, and mirtazapine do not significantly inhibit major metabolic pathways. In many cases, concurrent use of an inhibitor and a substrate is not contraindicated; however, patients should be observed for toxicity or other negative outcomes of combination therapy. The most dangerous adverse reaction involving the serotonergic antidepressants is the serotonin syndrome. Caused by serotonergic hyperstimulation, symptoms may include tremor, myoclonus, seizures, agitation, fever, shivering, diarrhea and abdominal pain. If suspected, all serotonergic agents must be discontinued immediately and supportive measures employed, if necessary.
Close monitoring of antidepressants through serial clinical interviews and depression inventories is essential in elderly patients. An adequate dosage must be provided for a specific duration to assess the effectiveness of any given agent. Drug therapy should continue for six months after remission of symptoms. Adverse effects occurring during long-term administration should be monitored and addressed. Lifetime therapy is generally recommended for those with the onset of depression after age fifty. Depression tends to be cyclical. Fifty percent of patients experience recurrent symptoms within the first two years, and eighty to ninety percent experience recurrent depression after a second episode.
Several factors will influence the type of therapy used to treat depression. Such factors include the severity of the depressive episode and symptoms. Since comorbid medical conditions can increase susceptibility to adverse effects of certain drugs, they should be considered as well. Drugs that cause orthostatic hypotension are dangerous in the elderly due to risk of fractures and falls and should not be utilized in this population. Cost is a factor that influences selected therapy, but previous response to an antidepressant agent, the adverse effect profile of the agent, and dosing regimen complexity should also be considered.
Resources
For additional information, see: Alexopoulos GS, Bruce ML, Hull J, et al (1999). Clinical determinants of suicidal ideation and behavior in geriatric depression. Arch Gen Psychiatry 56:1048-1053. Blazer D, Hughes DC, George LK (1987). The epidemiology of depression in an elderly community population. Gerontologist 27:281-287. Beers, MH & Berkow, R. (2000). Depression The Merck Manual of Geriatrics. 3nd edition Section 4, Psychiatric Disorders. Whitehouse Station, NJ: Merck Research Laboratories: 310-321. Feinberg, M., Dinwiddie, J. & Wells, B. G.(1997). Depression in the elderly. American Society of Consultant Pharmacists. Finkel, S. I. (1996).Efficacy and tolerability of antidepressants therapy in the old-old. J Clin Psychiatry; 57 (suppl 5): 23-8. Lebowitz BD, Pearson JL, Schneider LS et al (1997). Diagnosis and treatment of depression in late life. Consensus statement update. JAMA 278:1186-1190. Mittmann N, Herrmann N, Einarson TR et al (1997). The efficacy, safety and tolerability of antidepressants in late life depression. J Affect Disord 46:191-217. Montgomery SA (2002). Late-life depression: Rationalizing pharmacological treatment options. Gerontology 48:392-400. Montgomery SA, Beckman ATF, Sadavoy J, et al (2000). Consensus statement on depression in the elderly. J Clin Psychiatry 2000;2:46-52.
Resources
NIH Consensus Development Panel on Depression in late life. (1992). Diagnosis and treatment of depression in later life. JAMA; 268: 1018-24. Snowden M, Sato K and Roy-Byrne P (2003). Assessment and treatment of nursing home residents with depression or behavioral symptoms associated with dementia: A review of the literature. J Am Geriatr Soc 51:1305-1317. Streim JE, Oslin DW, Katz IR, et al (2000). Drug treatment of depression in frail elderly nursing home residents. Am J Geriatr Psychiatry 8:150-159. Zisook, S. & Downs, N. S. (1998). Diagnosis and treatment of depression in late life. J Clin Psychiatry; 59(suppl 4):80-91.
Bipolar
Learning Objectives:
By the end of this review concept, you will be able to: Describe the clinical characteristics and epidemiology of bipolar disorder. List the signs and symptoms of bipolar disorder, including both manic and depressive phases. Describe agents and approaches commonly used in the acute and prophylactic treatment of bipolar disorder in the elderly. Compare and contrast dosing, adverse reactions, drug-drug interactions and monitoring guidelines for agents commonly used to treat bipolar disorders in the elderly.
Of those affected, ten to fifteen percent commit suicide. For this reason, aggressive treatment and prophylactic therapy is required throughout the bipolar patient's lifetime.
Copyright 2011 American Society of Consultant Pharmacists
Bipolar disorder can be difficult to treat, especially in the manic phase, because elevated feelings of well being confuse patients about the severity of their illness. Agents used to treat bipolar disorder include mood stabilizers such as lithium carbonate, valproate, carbamazepine, lamotrigine and atypical antipsychotics. Monotherapy is preferred whenever possible, but combination therapy may be utilized for patients who remain symptomatic on monotherapy or who experience rapid cycling. To maintain euthymia, long term therapy for many patients consists of a combination of medications including a mood stabilizer with an antipsychotic or an antidepressant. Recent guidelines have recommended that antidepressants be used cautiously in bipolar disorder because of their risk of inducing mania. Because the natural history of the disorder involves recurrent episodes, lifetime therapy is the rule.
Lithium is an effective mood stabilizer for bipolar disorder in many elderly patients. Due to the high occurrence of comorbid medical diseases and multiple medications in this population, geriatric patients receiving lithium must be carefully monitored for signs of toxicity. Even minor changes in fluid balance, such as dehydration associated with a minor respiratory illness, can significantly decrease lithium clearance and result in toxicity. The elderly are especially sensitive to the numerous adverse effects of lithium, which include tremor, hypothyroidism, and nausea. The elderly may also be more susceptible to impaired cognition and delirium, with evidence of neurotoxicity that can last for weeks following discontinuation and undetectable serum levels. For many patients, the effective range for prophylaxis is zero-point-four to less than one-pointzero milliequivalents per liter. It is important to note that lithium's antimanic effect may not occur for one to two weeks after therapeutic serum levels are attained. During this period, benzodiazepines and/or antipsychotics may be used adjunctively to achieve symptom control. Drugs that decrease lithium clearance or increase serum levels of lithium carbonate are shown on your screen.
Carbamazepine is another alternative for the treatment of bipolar disorder. Plasma concentrations correlate poorly with response, but are used as a guideline. The elderly may not tolerate levels more than eight micrograms per milliliter. Carbamazepine induces the oxidative metabolism of many other medications, which may result in lower than expected levels of concurrent medications and subsequent treatment failure. Common adverse effects of carbamazepine include GI upset, sedation, and benign leucopenia. Carbamazepine induces the metabolism of many drugs, and is inhibited by CYP450 3A4 inhibitors. Levels of carbamazepine are increased by valproate. Patients should be monitored for therapeutic response and adverse effects.
Copyright 2011 American Society of Consultant Pharmacists
Antipsychotics have been shown to be effective as monotherapy or in combination with prototypical therapies such as lithium and divalproex for the acute treatment of mania. Certain agents, such as olanzapine and a combination product of olanzapine and fluoxetine have been shown to be an effective treatment in delaying relapse into either mania or depression in patients with bipolar disorder as well as for the acute depressive episodes of bipolar disorder. Atypical antipsychotics have essentially replaced the prescription of typical or conventional antipsychotics such as haloperidol due to fewer neurological adverse drug reactions such as extrapyramidal symptoms and tardive dyskinesia. Atypical antipsychotics, however, are not without side-effects. Metabolic side-effects associated with some of the atypical antipsychotics are a concern for both clinicians and patients. Adverse events related to central nervous system effects, weight gain, and alterations in glucose, lipid, and prolactin levels in patients treated with atypical antipsychotics have been observed. A significantly higher number of cerebrovascular adverse events, including stroke, have been observed in patients receiving risperidone or olanzapine compared to placebo in elderly patients with dementia. Because of the risk of agranulocytosis and other adverse effects such as somnolence and hypotension, clozapine is reserved for patients with treatment-refractory psychotic mania.
Sachs GS. (2003). Decision tree for the treatment of bipolar disorder. J Clin Psychiatry. 64(Suppl 8): 35-40. Suppes T, Dennehy EB, Hirschfeld RMA, et al. Texas Consensus Conference Panel on Medication Treatment of Bipolar Disorder. The Texas Implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66:870-886. National Depressive and Manic-Depressive Association