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Home , Serotonin syndrome

Psychiatric Options in the Treatment of Seniors Leo J. Borrell, MD

lzheimer’s is an incurable but treatable . The A use of is in- creasing, and clinicians and health- care organizations should realize that supportive care must extend beyond prescriptions. Caregiver ed- ucation and emotional support are essential elements of the treatment package. Medications can be com- bined with behavioral and environ- mental interventions. Treatment goals that set realistic expectations and treatments that enhance cogni- tion and improve behavior lead to symptomatic improvement. One can expect initial improvement and rotransmitter acetylcholine (ACh) as improvements in secondary out- the progression of the disease to be well as the enzyme that synthesizes comes such as on the Mini-Mental slowed, but should not anticipate ACh. This is an essential finding in State Examination (MMSE) and the arrest. Stabilization or a temporary the cholinergic hypothesis, which Clinical Rating Scale Sum delay in progression is the most no- states that cognitive function may of the Boxes. table outcome of treatment for be preserved if levels of ACh are Rivastigmine is the second selec- Alzheimer’s Disease (AD). maintained, although increasing the tive AChE inhibitor. Its duration It is ideal to start anti-dementia level of ACh is not yet possible. lasts about 10 hours and is adminis- medications as soon as the diagnosis The main cognitive enhancement tered twice daily; unlike donepezil, of dementia is made. This is particu- therapies today are cholinesterase which is administered only once. larly important since recent research (AChE) inhibitors donepezil and ri- The side effects (usually transient shows that donepezil (Aricept) be- vastigmine (Exelon). These medica- and generally mild) from this treat- gun early is beneficial in preventing tions and AChE inhibitors, such as ment are similar to donepezil. frontal lobe cortical atrophy. Also, galantamine (Razadyne), are the Galantamine, an AChE inhibitor it is important to use both anti- most thoroughly studied medica- has shown improved cognitive func- cholinesterase inhibitors and me- tions used to treat AD. Tacrine tion. Early initiation of treatment is mantine (Namenda) since each im- (Cognex) is an older, less selective beneficial and has been shown to proves functioning in a different part agent in that class, but is now modulate nicotinic cholinergic activi- of the brain. Anti-cholinesrase in- rarely used. Stabilization from treat- ty. How this relates to the efficacy of hibitors in general improve cognitive ment with AChE inhibitors may per- the drug is unknown. The use of function, including memory, where- sist for up to a year. AChE inhibitors can provide a signif- as memantine improves social and Donepezil was first marketed in icant improvement in cognitive and emotional functioning. 1997 and is the preeminent drug in functional performance of persons its class. During a half-year trial, with AD. The drugs are well tolerat- Cognition Enhancers more than 4 of 5 patients receiving ed; and though the target is a sec- The brain of a person suffering treatment showed improvement or ondary degenerative effect of the from (AD) exhibits damaged neu- no decline in cognitive function. disease, they are one of the few rons and reduced levels of the neu- Treatment with donepezil produced pharmacologic tools for delaying

September/October 2006 Assisted Living Consult 39 the cognitive decline of persons with AD. Figure 1. Causes of Psychiatric Symptoms and Behavior Can Overlap Memantine is approved by the FDA for the treatment of moderate to severe dementia. A nonpharma- cologic 6-week study evaluated im- Frontal Lobe Major provements in mental ability and Impairment Depression daily functioning in elderly, inde- pendent-living adults who were randomized to memory training, Impulsivity Anxiety Irritability reasoning training, speed of pro- Hyperactivity Dysphoria Agitation Restlessness cessing training, or a control group. Verbal Of those evaluated, 87% who were Aggression speed-trained, 74% who were rea- soning-trained, and 26% who were Physical memory-trained demonstrated reli- Aggression Withdrawal able cognitive improvement imme- diately after the intervention period. Delusions Thus, older patients may benefit from keeping mentally active. Re- cent research suggests that taking Psychotic memantine has a positive effect on Disorder cognition, mood, behavior, and the ability to perform activities of daily living in persons with moderate to severe AD. The review also demon- strated a small reduction in the inci- of in patients with AD. gree with medications. dence of agitation in patients with Patients that have bleeding prob- Classes of that have moderate to severe dementia. lems or are taking heparin must use been used in the management of Vitamin E with caution. specific symptom clusters in pa- Antioxidants In addition to its potential antiox- tients have been reviewed and Other therapeutic strategies also idant properties, estrogen is thought summarized in Table 1. have been used in the treatment of to possess other properties that pos- (Risperdal): Despite AD through reduction of oxidative sibly could inhibit the progression of a lack of formal sanction, com- stress within the brain. Agents in AD although it did not improve cog- pelling evidence now supports the various antioxidant neuroprotective nitive or functional outcomes. use of risperidone or strategies for the treatment of AD Prednisone has been of particu- (Zyprexa) in patients with AD who have included vitamin E; lar interest as a potential agent, but exhibit significant delusions, hallu- (Emsam), a selective monoamine recent published results involving cinations, or aggressive behavior. oxidase inhibitor; ascorbic acid; its use as a treatment of AD also Olanzapine: A key study evaluat- coenzyme Q; ginkgo biloba; and were negative. AChE inhibitors will ing the efficacy of olanzapine for estrogen. continue to offer early-stage pa- the treatment of psychosis and agi- Vitamin E and selegiline current- tients the best hope for slowing the tation in patients with AD recently ly are used by many clinicians, progression. indicated results similar to those of based partly on the results of a risperidone. The main side effects large . The administra- Managing the Behavioral of treatment were somnolence and tion of selegiline or Vitamin E de- Problems Associated with AD change in gait. layed progression in all endpoints. Behavioral disabilities are closely Quetiapine (Seroquel) has been The most interesting finding of the linked to the functional impair- introduced recently. Because of seda- study was that Vitamin E delayed ments of AD. Figure 1 illustrates the tive effects, it is preferred for agita- the placement of patients into long- ways in which psychiatric symp- tion. Other atypical anti-psychotics term-care facilities by approximate- toms and behavior can overlap, and are expected to be available soon. ly 7 months. Because Vitamin E is caregivers need to monitor symp- Ziprasidone (Geodon) should be safer and usually less expensive toms closely and adjust medications used with caution because of the than selegiline, that finding has as needed. Some behavioral impair- risk of cardiac arrhythmias. prompted widespread clinical use ments can be ameliorated to a de- Ariprazole (Abilify) is a recently

40 Assisted Living Consult September/October 2006 thy. The use of the selective sero- Table 1. Preferred Medication tonin reuptake inhibitor (SSRI) for Subtypes of Agitation (Celexa) in patients with dementia reported significant effica- Subtype Treatment cy. (Zoloft) had positive results after administration to pa- (other than Treat underlying medical condition. If tients with AD who had dysphonic medication ) medication is needed, consider typical affect and agitation. Among the an- tidepressants, excitalopram oxalate Depression Without psychosis: (Lexapro) or citalopram often are excitalopram (Lexapro), (Effexor), chosen first because they have few- or (Cymbalta) for retarded er side effects (occasionally insom- depression nia or ) and are usually safe With psychosis: plus to combine with other medications antipsychotic, or electroconvulsive therapy an older person is likely to be tak- Psychosis Acute: , primary ing. They are given once a day risperidone (Risperdal) or quetiapine (Seroquel) (usually in the morning). Long-term: atypical antipsychotic If these do not work, an alterna- tive tailored to the needs of the in- Anxiety Acute: such as lorazepam dividual can be chosen. For exam- (Ativan) or oxazepam (Serax) ple, (Remeron), Long-term: (Buspar) or excitalopram (Lexapro) bupropion (Wellbutrin), duloxetine hydrochloride (Cymbalta), and ven- Acute: (Desyrel); consider zolpidem lafaxin (Effexor) tend to be energiz- (Ambien), eszopiclone (Lunesta), or ramelteon ing and might be chosen for some- (Rozerem) one who is very withdrawn or Long-term: trazodone (Desyrel) apathetic. Care must be exercised “Sundowning” Acute: trazodone (Desyrel) in the use of duloxetine hydro- Long-term: trazodone (Desyrel); consider choloride in persons with substan- typical or atypical antipsychotic. tial use and those with chronic liver disease. The tricylic Aggression or anger Severe Acute: typical or atypical antipsychotic antidepressants tend to have more Long-term: divalproex sodium (Depakote) or troublesome side effects, such as atypical antipsychotic dry mouth, constipation, and dizzi- Mild ness if a person stands up too Acute: trazodone (Desyrel) quickly. When used by experienced Long-term: divalproex sodium (Depakote), doctors and carefully monitored, SSRI, trazodon (Desyrel), or buspirone (Buspar) they are sometimes quite effective in severe depression, but should be Osteoarthritic pain Long-term: , SSRI, or trazodone (Desyrel), venlafaxine (Effexor), used with caution because of the duloxetine (Cymbalta) for neuropathy risk of cardiac arrhythmia. associated with diabetes Bupropion should not be used in individuals with central nervous sys- Weight Loss mirtazapine (Remeron) and psychotherapy tem problems because of a high rate of . Clearly, there are many antidepressants to choose from. approved atypical anti-psychotic. (Prozac). The main side effects are There often is a need to try several The primary advantages of aripra- , insomnia, anxiety, se- medications before finding the best zole are that it does not cause vere agitation, and assaultive or ag- one. Patience is important since it weight gain and it lowers triglyc- gressive behaviors. often takes several weeks to tell if a erides by 30-40 mgs. It does not medicine is working. During the create a risk for diabetes. In addi- Antidepressants waiting period, a person’s spirits can tion, it is effective with the negative These psychotropics are of some be kept up with activities, a day symptoms of schizophrenia. It is in- value in treating patients with AD program, or a support group. hibited by carbamazepine (Tegre- who have depression, dysphonic People with depression also can tal), , and agitation, anxiety, and maybe apa- have delusions, such as a fear that

September/October 2006 Assisted Living Consult 41 body organs are not working, that cognitive disturbances. In addition, proved for neuropathic pain. they have been abandoned by mirtazpine has a relatively high safe- Persons failing to respond to ini- everyone, or that they have no ty margin in case of overdose and a tial conservative pain management more money (when in fact they low tendency to cause seizures. It measures may exhibit depressive have). Delusional depression can causes no significant changes in vital symptoms, including associated be life threatening because of the signs although in some people mir- sleep disturbance, loss of appetite, possibility of suicide, or because of tazpine tends to raise cholesterol weight loss, and effective distress. refusal to eat and drink, which can levels. Mirtazpine should be used Early interventions should include cause severe weight loss and dehy- with caution if the patient has active the use of antidepressant medica- dration. Agitation and trouble sleep- liver or kidney disease, or heart or tions for mood and sleep. Low- ing also often are very prominent. problems. The doc- dose TCAs and tricyclic-like antide- Although these symptoms can be tor should be alert to any history of pressants may help augment very upsetting to witness, there are seizures, mania, , drug levels in the brain and effective treatments. Usually, the use, or any other physical or emo- improve the quality of sleep. These first strategy is to combine the anti- tional problems. dual mechanisms of action may be depressant with an anti-psychotic Antidepressants also can be used more efficacious than short-acting medication. If severe depression or in conditions other than depression. sleep medications, including over- delusional depression does not re- the-counter preparations. Tricyclics spond to medications, electro con- should be used only in low vulsive therapy can be lifesaving. dosages or not at all with geriatric Although there are many negative patients because of the high inci- myths surrounding treatment, dents of arrhythmias. it is very safe when given by ex- Antidepressants Those who fail to respond to perts and is an important tool for also can be used in medication and individual physical the severely depressed person. therapy may be candidates for mul- conditions other than tidisciplinary rehabilitation pain Mirtazpine depression. treatment. Multidisciplinary pro- Mirtazpine is the first drug in a new grams may include rehabilitation class of antidepressants with a specialists; physical, occupational, unique ability to target specific and therapeutic recreational special- serotonin receptors. Along with its ists; pain psychologists; biofeed- efficacy in the treatment of moder- Some antidepressants, especially back specialists; and nursing and ate to severe depression, mirtaxap- the SSRIs, can help with anxiety. vocational counselors. This interdis- ine has proven to be effective for Tricyclics and SSRIs also are used ciplinary team approach relies treating anxiety, motor retardation, for pain relief in arthritis and cer- heavily on coordinated services and cognitive and sleep distur- tain types of nerve pain if over-the- with the goal of improving psy- bances associated with depression. counter medicines like Tylenol or chosocial functioning. Mirtazpine has a tetracyclic chem- Advil haven’t worked. Trazodone ical structure that causes it to act dif- (Desryel), a relative of Trazodone ferently from other common antide- (Serzone), is sold as an antidepres- If zolpidem tartrate (Ambien) is pressants such as SSRIs, monoamine sant but usually is too sedating for used, it should be alternated with oxidase inhibitors (MAOIs) and tri- this purpose. We discuss it later as trazadone. Trazodone is a relatively cyclics. While stimulating norepi- a sleeping aide. safe, non-habit-forming medication nephrine and serotonin release, mir- that technically is considered to be tazpine also has the unique ability Use of Antidepressants with an antidepressant, but actually is to block two specific serotonin re- Medical Problems used more often simply to help the ceptors, thus causing fewer sero- Pain Management individual get a good night’s sleep. togergic side effects (decreased in- and Depression It also is a good short-term alterna- terest in sex, nausea, nervousness, Although significant literature sup- tive treatment for anxiety or when a insomnia, and ). In studies, ports the effects of tradi- mild sedative is needed. It should the use of mirtazpine, compared tional tricyclic antidepressant (TCA) be started in very small amounts at with tricyclic antidepressants, also medications in chronic pain, studies first and adjusted upward until the resulted in fewer of the analgesic response to SSRIs right dose is found. To help with symptoms (blurred vision, dry have demonstrated conflicting re- sleep it should he given about 1 mouth, indigestion, and constipa- sults. Recently, duloxetine hy- hour before bedtime. The main side tion), cardiovascular symptoms, and drochloride has been FDA-ap- effect is drowsiness if the dose is

42 Assisted Living Consult September/October 2006 in treatment, prominent limitations Essential Steps in Managing of conventional antidepressant thera- Psychiatric Behavior Disturbance py remain. They include the delayed onset of therapeutic response and 1. Help the caregiver recognize and characterize the psychiatric the partial or lack of response in as symptoms of AD many as 50% of patients who com- 2. Help the caregiver recognize what triggers these symptoms plete an adequate trial. Examples of 3. Know what can be done to relieve symptoms include modafinil (Provig- 4. Use simple, clear terminology when describing symptoms to clinicians il) and (Ritalin). 5. Design a treatment plan after a behavior has been recognized 6. Include in treatment plan: Anticonvulsants Divalproex (Depakote) is best a. medication known as a treatment for brain dis- b. behavioral techniques orders such as and c. environmental changes seizures, and as a mood stabilizer for bipolar disorder. It also can help with behavioral symptoms in too high. Other side effects include older persons with dementia, espe- dizziness when standing up and, cially in a person showing aggres- very rarely, painful erections in sion, anger, or hypersexual behav- men. In addition, sun exposure ior. It is often combined with an may help with sleep problems and anti-psychotic. The side effects of light therapy should be considered. Sun exposure may help divalproex are nausea and sedation, with sleep problems which usually can be controlled by Toxic Effects-Serotonin and light therapy starting at small doses, making Syndrome gradual adjustments, and monitor- Residents with depression and pain should be considered. ing the level of medication in the frequently benefit from dual treat- bloodstream. ment with serotogenic antidepres- sants and . How- Managing Psychosis in the ever, these drugs can sometimes Treatment of Parkinson’s interact and cause serotonin syn- syndrome symptoms within weeks and drome, a potentially fatal condition of having those medications altered. Parkinson’s Disease caused by excess serotonin at post- Each resident exhibited symptoms Typical work by synaptic serotonin receptors. It is a including hallucinations, my- blocking the D2 subtype of severe systemic reaction to sero- oclonus, and , al- receptors. Atypical tonin excess, with symptoms of though none had symptoms in all agents act differently because of a , hypertension, restless- three clinical criteria categories. In different pattern of dopamine re- ness, agitation, muscle rigidity, my- all cases the symptoms resolved ceptor-binding, with reduced activi- oclonus, increased deep tendon re- when at least one of the two med- ty on receptors that influence motor flexes, diaphoresis, , and ications was stopped, and resolu- function. Sertonergic blockade is al- . It can result from the com- tion generally occurred within a so believed to be important for pro- bination of an MAOI with an SSRI, day or two. ducing an antipsychotic effect. the combination of an MAOI with Among the atypicals, risperidone is , and less commonly Stimulants the most potent dopamine blocker with other drug combinations such The diagnosis and treatment of de- and, thus, has been shown fre- as paroxetine (Paxil) and dex- pression may be more difficult in quently to worsen motor function tromethorphan (Touro), or with older people, who usually present in PD. augmentation of SSRI or with somatic complaints rather than MAOI antidepressants. dysphoric mood and who, due to Lewy Body Disease In a recent case report, 4 long- altered metabolism, experience a Dementia with Lewy body disease term care residents with possible more brittle course on antidepres- (LBD) is a variant of Parkinson’s serotonin syndrome were exam- sants. Once treated, older patients disease that is significantly associat- ined. All were taking still have a higher and more rapid ed with psychosis. Visual hallucina- antidepressants and opioid anal- rate of recurrence. tions, fluctuating level of conscious- gesics, and all developed serotonin Despite significant improvements ness, and Parkinsonism are typical

September/October 2006 Assisted Living Consult 43 Buspirone (Buspar) RELATED DISCUSSION: Buspirone is an anti-anxiety med- The Role of Psychotherapy ication that is not habit-forming and does not cause sedation. Bus- Research conducted on the outcome of paranoia, delusions, and halluci- pirone is an excellent choice for of mental health services delivered nations. someone who is very nervous or by specialists who are not full-time These symptoms can be con- worried but does not have psy- staff in nursing homes has shown trolled with a combination of med- chotic delusions. It can be helpful improved clinical outcomes and less ications in the form of mood stabiliz- for someone who gets angry too use of acute services. ers, anti-psychotic, anti-anxiety, and easily. It also is very safe to com- The preferred practice includes anti-depressants as well as psy- bine with other medications that an the routine presence of qualified chotherapy, behavioral manage- older person may be taking. Side mental health clinicians in the facili- ment, and frequent (rather than less) effects of , dizziness, or ty. Optimal services are interdiscipli- family contact. nary and multidimensional, with the Research shows that psychothera- nausea can occur if the dose is too most effective interventions blending py reduces the use of medications strong: once in a while it also can innovative approaches to training by 50% and 100% of those who re- cause over stimulation. Buspirone and education with consultation and ceived psychotherapy (counseling) works gradually, and the dose usu- feedback on clinical practices. did better than those who received ally needs to be adjusted over 2 to Psychiatric symptoms secondary medication alone. They also had a 6 weeks before beneficial effects to dementia usually begin in the first significant decrease in behavioral can be judged. year of the disease, and progression, problems sooner and a better quality while gradual, is erratic. The level of of life for longer. Psychotherapy Treatment of Panic Disorder agitation suggests the more severe should be recommended for all pa- Selective Serotonin symptoms. This usually occurs after tients with psychiatric problems if Reuptake Inhibitors 5 years, and is related to more se- they have the cognitive ability to vere psychiatric symptoms benefit from it. Systematic reviews and randomized clinical trials have found that selec- tive serotonin reuptake inhibitors improve symptoms in panic disor- symptoms. Use of risperidone is ferred by for use in older people der compared with placebo. One recommended. Typical anti-psy- because they are cleared from the subsequent review found the dis- chotics make the symptoms worse. body relatively quickly. Those in- continuation of sertraline in people The atypical anti-psychotics in clude lorazepam (Ativan), the pri- with a good response increased ex- widest use now are risperidone and mary choice because of its short acerbation of symptoms. A second olanzapine. There is a high risk of half life; temazepam (Restoril); subsequent review found that diabetes and glucose must be mon- and oxazepam (Serax). The effects paroxetine plus cognitive behav- itored closely. of others, such as flurazepam (Dal- ioral therapy improved symptoms mane) and clonazepam (Klono- compared with placebo plus cogni- Treatment of Anxiety pin), can last 24 hours or longer; tive behavioral therapy. Divalproex and Panic Disorder these longer-acting agents usually has been found effective in the Antianxiety Medication are best avoided because they may geriatric population when SSRIs are a group of cause daytime sedation or falling. and lorazepam are not effective. about a dozen medications that Benzodiazepines are habit-form- In closing, increased initial data cause sedation and can relieve anx- ing if used steadily for more than a collection, documentation, ongoing iety. They are best used only in few weeks; even single doses can observation and assessment, and temporary situations—once in a cause unsteady gait and can inter- enhanced communication among while for sleep or for a daytime cri- fere with memory. Fall precautions treatment professionals can all re- sis of anxiety or agitation when or a wheelchair should be consid- sult in less frustration in our respec- someone needs to be calmed down ered for the first 48 hours. tive jobs working with geriatric pa- quickly. In an emergency, benzodi- Because of the disadvantages of tients. More importantly, we can azepines sometimes are combined benzodiazepines, it usually is best optimize the effective level of care with an anti-psychotic; they also to avoid using them for the long- for our patients and, consequently, can be combined for a week or term treatment of insomnia, anxi- their quality of life. ALC more with other medicines that ety, or agitation unless other choic- may take longer to start working, es have failed. See Better Ways to Leo J. Borrell, MD, is Senior Psychiatric such as divalproex. Fall Asleep: The Danger of Benzodi- Consultant and founder of SeniorPsy- Some benzodiazepines are pre- azepines on page 29. chCare (SPC) of Houston, TX.

44 Assisted Living Consult September/October 2006