Chapter 11 - Changes in Behavior

Family Medicine Perspective

Section 4

By Dale C. Moquist, MD

Family Physicians frequently see people with changes in behavior or they "are not normal." In a Family Physician's practice the major diagnoses we think of are delirium, dementia, and depression. As a family physician you need to have the tools to approach this problem in the midst of a busy office. This article will not cover cerebrovascular disease.

The first step is taking a history. A good place to start is with these crucial questions:

  • How long has this been going on?
  • How abruptly did this start?
  • Are the symptoms progressing?
  • If so, how fast?

The chart below helps to differentiate the characteristics of these three common medical problems seen in Family Medicine.

Characteristic Delirium Dementia Depression
Onset Abrupt Gradual Mood Changes
Duration Acute Illness Chronic Illness Sub acute
Disorientation Early in Course Late Intact
Attention Span Short Stable Stable
Cognition Variable Hourly Stable Day-to-day Fluctuating
Sleep Wake Disturbed Day-Night Reversal Disturbed
Prognosis Reversible Irreversible Reversible
Disabilities Unaware Concealed Highlighted
Performance Unable Tries Hard Does Not Try
Depressive SX Variable Present Present

Delirium has had numerous other names including altered mental status, acute confusional state, reversible dementia, acute organic brain syndrome, and toxic metabolic encephalopathy. It is characterized by disturbance of consciousness, change in cognition, development over a short time, and a consequence of a medical condition. To help make the diagnosis you can use the Confusion Assessment Method which requires the first two items and either the third or fourth item to make the diagnosis of delirium:

  • Acute change in mental status and fluctuating course
  • Inattention
  • Disorganized thinking
  • Altered level of consciousness

To help determine the medical source and workup, you can use the following mnemonic:

  • Drugs
  • Electrolytes
  • Lack of Drugs
  • Infection
  • Reduced sensory
  • Intracranial
  • Urinary retention
  • Myocardial

Appropriate lab work includes CBC, Electrolytes, renal function, UA, blood cultures, chest x-ray, ECG, and liver functions. It is appropriate to order serum drug levels for the patient on chronic drugs. Do not forget about doing a urine drug screen in this population.

Treatment of Delirium is treating the underlying cause. To help the patient recover, avoid sedative use unless absolutely necessary. Remove indwelling devices such as central lines and indwelling catheters. Actively treat constipation and urinary retention. To encourage proper sleep hygiene establish a consistent bedtime in a comfortable setting, a soft night light, providing daytime activity, and treating depression and delusions. While avoiding benzodiazepines and antihistamines, you could consider the use of trazodone and zolpidem. In the hospital setting it is important to re-orient the patient. Softly touching these patients can be very effective.

Depression can be mimicked by thyroid disease or any condition that promotes apathy. Dementia has overlapping symptoms with depression in the form of impaired concentration, lack of motivation, psychomotor retardation, and disrupted sleep. Many older people report somatic symptoms and less often report depressed mood. Side effects of drugs may be confusing in the elderly. Do not forget the elderly has the highest rate of successful suicide.

The U.S. Preventive Services Task Force recommends screening adults for depression in clinical practice that have systems in place to assure accurate diagnosis, effective treatment, and follow up. In a busy family medicine office using an efficient screening tool is welcomed to help identify depression. One such method is to use the Five-item Geriatric Depression Scale:

  • Are you basically satisfied with your life?
  • Do you often get bored?
  • Do you often feel helpless?
  • Do you prefer to stay home rather than going out and doing new things?
  • Do you feel pretty worthless the way you are now?
  • If 2 or more answers are positive for depression then a more thorough evaluation for depression is indicated.

Another method is to use the Periodic Health Questionaire-2 (PHQ-2). This is done by asking the patient if during the past month you have often been bothered by:

  • Little interest or pleasure in doing things?
  • Feeling down, depressed, or hopeless?
  • If the answer is no to BOTH questions then the screen is negative
  • If EITHER answer is yes, then proceed with a more in-depth evaluation

The Patient Health Questionnaire-9 can be used to further evaluate patients with a positive screen. This has been designed to correspond with the criteria in the DSM-IV for making the diagnosis of major depression. The PHQ-9 can also be used to follow the severity of depressive symptoms and assessing the response of treatment in these patients. The problematic areas assessed by the PHQ-9 are:

  • Little interest or pleasure in doing things
  • Feeling down, depressed or hopeless
  • Trouble falling asleep, staying asleep, or sleeping too much
  • Feeling tire or having little energy
  • Poor appetite or overeating
  • Feeling bad about yourself, feeling that your are a failure, or feeling that you have let yourself or your family down
  • Trouble concentrating on things such as reading the newspaper or watching television
  • Moving or speaking so slowly that other people could have notice. Or being so fidgety or restless that you have been moving around a lot more than usual
  • Thinking that you would be better off dead or that you want to hurt yourself in some way

Major Depression is a treatable illness. Psychotherapy can include cognitive-behavioral therapy, interpersonal psychotherapy, and problem-solving therapy. Problem-solving therapy helps the patient to identify practical life difficulties and patient-defined solutions. Cognitive-behavioral therapy has been shown to be helpful as the sole treatment of mild and moderate depression and in conjunction with antidepressants in severe depression.

In considering pharmacotherapy, there is no one antidepressant considered superior in treatment. The duration of therapy should be at least 6-12 months. Older patients with major depression will be more likely to require maintenance therapy. The recurrence rate after the first episode of major depression is felt to 50% and 90% after the third episode. The choice of medication can be based on the side effect profile of the medication. The Selective Serotonin-reuptake Inhibitors (SSRIs) are the medication class of first choice because of their favorable side effect profile. Common side effects are gastrointestinal, insomnia, tremor, agitation, hyponatremia, and occasional sedation. Based on the side effect profile, sertraline, citalopram, and escitalopram would be considered the medications of first choice in treating the elderly.

Drug Initial Dose Usual Dosage
Citalopram 10 mg 20-40 mgm
Fluoxetine 10 mgm 20-40 mgm
Paroxetine 10 mgm 20-40 mgm
Paroxetine CR 12.5 mgm 12.5-37.5 mgm
Sertraline 25 mgm 100-200 mgm
Escitalopram 10 mgm 10-20 mgm

Tricyclic antidepressants can be used if patients do not respond to SSRIs. Blood levels are available to ensure proper dosing. The prominent side effects are anticholinergic and include drowsiness, constipation, dry mouth, blurry vision, orthostatic hypotension and urinary hesitancy. With these side effects, nortriptyline and desipramine are more appropriate for use in the elderly.

Drug Initial Dose Usual Dosage
Amitriptyline 10-25 mgm hs 25-200 mgm hs
Desipramine 10-25 mgm hs 25-150 mgm hs
Nortriptyline 10-25 mgm hs 25-100 mgm hs

Other antidepressants include bupropion, venlafaxine, duloxetine, and mirtazapine. Bupropion is usually well tolerated and free of sexual side effects. In doses greater than 300 mgm there is a slight risk of seizures. Therefore it is contraindicated in patients with a seizure disorder. Venlafaxine acts as an SSRI at lower doses while inhibiting the reuptake of norepinephrine at higher doses. Side effects include nausea at low dose and hypertension at higher doses. Duloxetine has been approved for treatment of depression and neuropathic pain. This drug is similar to venlafaxine and has been shown to reduce stress incontinence in women. Mirtazapine is given at bedtime because of its sedative properties. This drug is associated with increased appetite and weight gain. This drug is used frequently in the nursing-home residents.

Drug Initial Dose Usual Dosage
Bupropion 75 mgm 150-300 mgm
Venlafaxine 37.5 mgm 75-225 mgm
Duloxetine 20 mgm 30-60 mgm
Mirtazapine 7.5 mgm hs 15-45 mgm hs

Dementia is chronic irreversible cognitive decline. In lay terms it is "brain failure." The real issue is how to detect mild dementia to help maintain the functional state of the patient in the community. There is no blood test or radiographic test to make an early diagnosis of dementia. The traditional history and physical does not detect the early stages of dementia.

There are a number of reliable and valid cognitive screening tools for use in Family Medicine. The Mini-Cog has been validated in the elderly. You ask the patient to remember three items and then have the patient do the clock drawing test. This is simply done by asking the patient to draw a circle and put the numbers in the correct sequence and position. You ask the patient to draw a short and long hand to a designated time such as 11:10. This test is not affected by language skill and education level. After the clock drawing test you ask the patient to recall the previous three items. If this is normal you can be reassured they do not have a major cognitive problem. If either one of these items is abnormal a more thorough evaluation is needed.

The Mini-Mental State Exam is the most widely used cognitive screening tool in the United States. This measures orientation, registration, attention and calculation, recall, language and constructional skill to help detect dementia. Besides being a valid tool for detection it is useful in tracking and quantifying changes over time. The MMSE is easy to administer. A total score of less than 24 out of a maximum of 30 points is suggestive of dementia. Factors other than cognitive function influencing the MMSE are age, educational level, deficits in language skills, and motor or visual impairment. Therefore the cut level of 24 may be adjusted by the population being tested. It is not sensitive to mild dementia and not specific to Alzheimer's disease. The MMSE can be found here.

When considering dementia a workup would include a complete blood count, a comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, and neuroimaging. When considering dementia you must consider depression. This workup is done to improve the function of these patients.

The dementia workup brings up a question, what about reversible dementia? The concept of reversible dementia was discussed when certain illness were treated the cognitive function of these patients improved. However, Knopmanreported on a review of 560 consecutive patients newly diagnosed with dementia. In this review at the Mayo Clinic no cases of reversible dementia due to normal pressure hydrocephalus, subdural hematoma, vitamin B12 deficiency, hypothyroidism, or neurosyphilis were found. Knopman said, "none of the patients with dementia reverted to normal with treatment of the putative reversible cause." This means reversible dementia is a rare occurrence.

Many preventive measures for dementia have been discussed. These include vitamin E, NSAIDS, gingko biloba. The Alzheimer's disease Anti-inflammatory Prevention Trial was a randomized, double masked study using celecoxib and naproxen compared to placebo. This study showed these medications did not prevent development of dementia. Another study showed gingko biloba did not prevent the onset of dementia. Some studies have suggested physical activity and participation in leisure activities are associated with decreased risk of dementia.

The treatment of patients with dementia can be frustrating for the caregivers. Many times this falls on the shoulders of the spouse or one of the children. It is important to have consistent caregivers, a consistent daily routine, adequate daytime stimulation, adequate levels of light, scheduled toileting, and particularly a familiar safe environment. Sundowning can be a big problem for caregivers and lead to caregiver fatigue. Behavioral approaches for sundowning should include giving diuretics and laxatives early in the day, clean glasses, working hearing aids, providing personal care at the same time, monitor amount of sensory stimulation, regular dosing of medications, and having familiar objects at the bedside. To help caregiver fatigue, consider respite care for the caregiver.

At times these patients become delusional and have hallucinations. In approaching this problem, first determine if these symptoms are having harmful effects for these patients. If there are no harmful effects, no medication is needed but careful observation. If these symptoms are interfering with care and causing potential harm, then medication should be considered. Quetiapine, olanzapine, and Risperidone reduce agitation and behavioral disturbances for people with dementia. The medications and the doses used for these problems are:

Drug Starting Dose Peak Dose
Quetiapine 25-50 mg 200 mgm daily
Clozapine 12.5-25 mgm BID 100 mgm daily
Haloperidol 0.25 mgm HS 3-5 mgm daily
Olanzapine 1.25-2.5 mgm HS 5 mgm daily
Risperidone .25-0.5 mgm HS 1-1.5 mgm daily

The above medications are used for delusions and hallucinations, not for wandering and confusion. Haloperidol has a higher incidence of extrapyramidal symptoms and tardive Dyskinesia. Other potential side effects include lethargy, dry mouth, weight gain, and sexual side effects. All of these medications have black box warnings for increased cardiovascular events and death.

Medications are now available for treatment of dementia. These are cholinesterase inhibitors and NMDA receptors. Many of the early studies showed a delay in nursing home placement, an improvement in functional ability, a slight improvement in cognitive ability, and may decrease behavioral problems. Side effects for these meds include nausea, anorexia, vomiting, diarrhea, headache or nightmares. Contraindications include uncontrolled asthma, angle-closure glaucoma, sick sinus syndrome and left bundle branch block.

The medications available and the doses used are listed below:

Drug Dosing Interval Titration Labs
Donepezil 5-10 mgm Daily Yes No
Rivastigmine 8-24 mgm Daily Yes No
Galantamine 1.5-6.0 mgm BID Yes No
Memantine 5-10 mgm BID Yes No
Galantamine Patch 4.6-9.5 mgm Daily Yes No

We have now have these multiple drug regimens available for treatment of dementia. The real question is what is the evidence? The American College of Physicians and the American Academy of Family Physicians issued guidelines on the use of these meds:

  • Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or Memantine on individualized assessment.
  • Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia.
  • There is an urgent need for further research on the clinical effectiveness of pharmacologic management of dementia.

We have tried to outline an approach for a busy family medicine office to screen for and approach these problems.

Bibliography:

  1. Rinaldi, Patrizia. Validation of the Five-Item Geriatric Depression scale in elderly Subjects in three Different Settings. J Am Ger Soc 2003; 51:694-698.
  2. Thibault JM. Efficient Identification of Adults with Depression and Dementia. Am Fam Phy September 15, 2004; 70:1101-1110.
  3. Depression Screen and PHQ-9 Symptom Checklist www.americangeriatricsl.org/education/depression. Accessed February 5, 2009.
  4. Seigerschmidt, Eva. The clock drawing test and questionable dementia: reliability and validity. International Journal of Geriatric Psychiatry 2002; 16:1048-1054.
  5. Knopman D. Incidence and causes of nondegenerative nonvascular dementia. Arch Neurol 2006; 63:218-221.
  6. ADAPT Research Group. Cognitive function over time in the Alzheimer's disease anti-inflammatory Prevention Trial (ADAPT). Arch of Neurology 2008; 65:E1-E10
  7. KeKosky S. Ginkgo biloba for prevention of dementia a randomized Controlled Trial. JAMA November 19, 2008; 300:2253-2262.
  8. Off Label use of Atypical Antipsychotic Drugs. www.effectivehealthcae.ahrq.gov. July 2007

References:

  • Cognitive Assessment. Geriatrics Review Syllabus 6th Edition 2006:pp47-48.
  • Chapter 30 Dementia. Geriatrics Review Syllabus 6th Edition 2006; pp221-230.
  • Chapter 32 Delirium. Geriatrics Review Syllabus 6th Edition 2006: pp239-248.
  • Adelman A. Initial Evaluation of the Patient with suspected Dementia. Am Fam Phy May 1, 2005; 71:1745-1750
  • Kerwin D. How to prevent a delayed Alzheimer's diagnosis. Journal of Family Practice. January 2009; 58:9-15.

Links:

  • www.aan.com. Accessed Practice Parameters on 2-02-2009.
    • Detection of Dementia and Mild Cognitive Impairment
    • Diagnosis of Dementia
    • Management of Dementia