Pick Disease 

Updated: Jun 06, 2014
Author: A M Barrett, MD, FAAN, FANA, FASNR; Chief Editor: Jasvinder Chawla, MD, MBA 

Overview

Background

Pick disease (named after Arnold Pick) is a progressive dementia defined by clinical and pathologic criteria. Unlike Alzheimer disease, which typically presents with impairment of recent memory associated with entorhinal cortex and hippocampal dysfunction, Pick disease typically affects the frontal and/or anterolateral temporal lobes. (See Etiology.)

First described in 1892, with the defining pathologic characteristics first reported by Alois Alzheimer in 1911, Pick disease is now considered by some to be part of a complex of neurodegenerative disorders with similar or related histopathologic and clinical features. (See Presentation and Workup.)[1, 2]

Frontotemporal dementia

Pick disease is one of the disorders classified under the term frontotemporal dementia (FTD). Almost all instances can be pathologically classified by the following abnormal deposited proteins in cells:

  • FTLD-tau, marked by abnormal accumulation of three microtubule-binding repeats (3R tau), as contrasted with isoforms of cerebral tau with four microtubule-binding repeats (4R tau), found in other neurodegenerative conditions

  • Associated with progranulin (FTD-TDP), marked by neuronal cytoplasmic inclusions and, frequently, intranuclear inclusions, as well as variable dystrophic neurites, in the frontotemporal cortex

  • Associated with fused-in-sarcoma (FUS) protein (neuronal intermediate filament inclusion disease, basophilic inclusion body disease, or atypical, with ubiquitin-only immunoreactive changes)[3]

  • FTLD-UPS NOS: Ubiquitin or P62-positive only immunoreactive inclusions

  • FTLD-IF NOS: Intermediate filament immunoreactive inclusions

  • BIBD NOS: Basophilic inclusion body disease

  • FTLD-niNOS without any immunoreactive inclusions

See Etiology and Workup.

FTD with abnormal tau protein accumulation has been associated with mutations at chromosome 17; TDP-43 associations are linked to band 9p; ubiquinated FUS accumulation is still under intense investigation; other mutations (CHMP-2B) are also identified in rarer cases.

Primary progressive aphasia is a focal atrophy syndrome that may be associated with Pick disease, Alzheimer disease, or other pathology. Two types of primary progressive aphasia are identified: (1) semantic dementia, in which meaning systems are lost from language, and (2) nonfluent primary progressive aphasia. Clinically, the deficit appears restricted to the frontal and/or temporal lobes.[4] Behavioral-variant FTD is the other major FTD syndrome; in this disorder, deficits are nonverbal and primarily affect social, emotional, and self-regulatory skills.

See Figure 1 in Boxer et al (2013) for an illustration of the neuropathologic subtypes of Pick disease/FTD.[5]

Images of neurodegenerative findings can be viewed online at Internet Pathology Laboratory, University of Utah, CNS Degenerative Diseases.

Cellular characteristics

Pick disease is defined pathologically by severe atrophy, neuronal loss, and gliosis. Frequently, Pick disease is accompanied by the occurrence of tau-positive inclusions.[6] Swollen (ballooned) neurons (Pick cells) and argentophilic neuronal inclusions, known as Pick bodies,[7] can disproportionally affect the frontal and temporal cortical regions. (See Workup.)

Fewer Pick bodies may be present in these regions if the primary symptoms are behavioral (behavioral variant), compared with the primary symptoms of aphasia.[8, 9]

In a clinicopathologic series, only 5% of patients with clinically diagnosed frontotemporal dementia had classic Pick disease with Pick bodies at postmortem evaluation. (See Epidemiology.)[10]

Patient education

For patient education information, see the Brain and Nervous System Center, as well as Pick Disease and Dementia Medication Overview.

Etiology

The specific cause of Pick disease is unknown. As many as 50% of patients with frontotemporal dementia have a positive family history of dementia and inherit frontotemporal dementia as an autosomal dominant trait with high penetrance.[3]

In families with an inherited frontal lobe dementia (some of which have been found to be pathologically or clinically indistinguishable from Pick disease), linkage to markers on chromosomes 17, 9, and 3 have been reported. The links between risk factor genes and causative factors is still not fully explored.

These familial disorders are heterogenous in different family members. Some members may present primarily with amyotrophy, and others may present with primary supranuclear gaze palsy, parkinsonism, schizophrenialike thought disorder, or progressive aphasia and/or apraxia.

People with learning disabilities such as dyslexia may be at higher risk of FTD, but it is not known whether this is generally true or if it is true only for certain patterns of learning disability and, whether only certain types of symptoms, such as the syndrome complex of primary progressive aphasia, may be more common in people with a learning disability history.

Epidemiology

Occurrence in the United States

Frontotemporal dementias as a group are the fourth most common cause of dementia. In most parts of the United States, among patients younger than 60 years, the frontotemporal dementias are the first or second most common cause of dementia. In patients older than 60 years, the incidence and prevalence of Alzheimer disease begins to take off, with Alzheimer disease becoming by far the most prevalent form of dementia.[10]

Pick disease is sometimes used to refer to the clinical phenotype of the frontotemporal dementias. This group of disorders has a variety of pathologic substrates, the most prevalent of which is frontotemporal lobar degeneration with ubiquitin inclusions. In one pathologic series, Pick disease itself (as defined by the presence of tau-positive, silver staining, cytoplasmic inclusions) accounted for only 5% of all cases of frontotemporal dementias.[10]

International occurrence

Familial forms of Pick disease may occur more frequently in Europe (particularly in Scandinavian nations). The estimated frequency ranges from 7-43 cases per 100,000 population.[11] In a study in the Netherlands, the prevalence was 28 per 100,000 persons.[3]

Race-, sex-, and age-related demographics

Familial forms of Pick-complex dementias, linked to chromosome arm 17q, may be particularly common in people of Scandinavian origin/descent. It may represent as many as 17% of dementias in this population.

More men than women may be affected by Pick disease.

Pick disease occurs in a younger age group than dementia of the Alzheimer type, with peak incidence occurring in individuals aged 55-65 years.[12, 13]

Prognosis

Like most dementias, Pick disease is slowly progressive, leading to increased vocational and personal disability. However, a small number of people who have behavioral disturbance consistent with the behavioral variant of FTD may not progress—this has been called the phenocopy variant. In past studies, slow or no progression occurs only in patients with nonlinguistic symptoms—none had primary progressive aphasia.

Some patients can progress slowly over extremely long periods. Some may develop artistic or other talents during the course of their dementia, a phenomenon that is perhaps related to disinhibition of "creative" brain areas. Musical or artistic tastes also may change (eg, the patient may develop a sudden interest in music intended for much younger listeners).

Some patients may be capable of acquiring new knowledge or skills, such as the use of a computer-assisted, simple communication system. This relative sparing of ability to “do things” (process-oriented rather than content-oriented memory) may be helpful in implementing behavioral training techniques to optimize social and daily activity competence.

Mortality and morbidity

Pick disease runs a shorter course than Alzheimer disease, on average about 6 years.[12, 14] In some individuals whose main symptoms are a disturbance of speech and language (primary progressive aphasia), the clinical course can be slow. In one small series, these patients survived an average of 5 years longer than patients with behavioral symptoms (behavioral variant).[8] A patient with primary progressive aphasia may preserve the ability to function at home for 10 or more years after onset.

 

Presentation

History

The onset of behavioral and cognitive dysfunction in individuals with Pick disease can be difficult to identify.

The primary impairment in cognition normally does not involve an abnormal level of consciousness or distractibility. Such a finding is more consistent with an attentional dementia[15] or a confusional state and/or dementia. In many cases, individuals with Pick disease perform well on quick cognitive screening tests, such as the Mini-Mental Status Examination (MMSE).[11] However, these studies omit assessment of behavioral and social judgment or response inhibition, and, thus, this kind of quick screening is not sensitive to early Pick disease impairment that can still be disabling.

Clinical course during the first 2 years

Behavioral variant

Psychiatric abnormalities that seem to respect the pattern of the classic frontal lobe syndromes are present.[16] Patients with orbitofrontal dysfunction can become aggressive and socially inappropriate. They may steal or demonstrate obsessive or repetitive stereotyped behaviors. Patients with dorsomedial or dorsolateral frontal dysfunction may demonstrate a lack of concern, apathy, or decreased spontaneity. Patients can demonstrate an absence of self-monitoring, abnormal self-awareness, and an inability to appreciate meaning.[16] Patients with gray matter loss in the bilateral posterolateral orbitofrontal cortex and right anterior insula may demonstrate changes in eating behaviors, such as a pathologic sweet tooth. Patients with more focal gray matter loss in the anterolateral orbitofrontal cortex may develop hyperphagia.[17]

Primary progressive aphasia

Speech and language abnormalities often begin early and progress rapidly. Memory impairment is relatively less severe than speech/language and behavioral changes.

Across subtypes of FTD, including Pick disease, patients can demonstrate apathy, irritability, and agitation.[18] Patients may be depressed early in the disease. These mood changes can predate amnesia.

Patients usually have relatively little limb apraxia and/or visuospatial dysfunction, thus distinguishing them from patients with diffuse, bihemispheric impairment.

Incontinence can occur early. In contrast, continence generally is preserved in mild-to-moderate Alzheimer disease.

Parkinsonism, with its concomitant history of rigidity and gait impairment, can occur. Severe parkinsonism suggests an alternate diagnosis, such as corticobasal ganglionic degeneration, diffuse Lewy body disease, or progressive supranuclear palsy.

Physical Examination

The general physical examination often shows the patient to be unkempt at an earlier stage than in comparably impaired patients with Alzheimer disease.

Abnormal spontaneous behaviors observed during examination may include the following:

  • Witzelsucht or inappropriate jocularity

  • Echolalia (repeating the examiner's words), echopraxia (imitating the examiner's gestures),[19, 20] and other disinhibited approach or utilization behaviors

A general neurologic examination may include some of the following abnormalities:

  • Primitive reflexes, such as grasp, suck, and snout (not the palmomental reflex, which is often present in healthy individuals[18] )

  • Akinesia, plastic rigidity, or paratonia on motor examination[21]

  • Resting tremor - Uncommon; its presence suggests Parkinson disease or a Parkinson-plus syndrome

Mental status/neuropsychological examination may reveal the following:

  • Verbal output that is often nonfluent - Most patients have difficulty in naming common objects or pictures (anomia); spontaneous speech can be sparse, yet fluent, in character, with preserved grammar (logopenia)

  • Perseveration - Cognitive and motor (see the image below)

    Motor perseveration in a patient with Pick disease Motor perseveration in a patient with Pick disease. The patient was asked to copy loops (as demonstrated by the examiner in the first line).
  • Relatively preserved visuospatial and visual orientation skills

 

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of Pick disease include the following:

  • Rarely, subcortical stroke, for example affecting the striatum

  • Primary brain tumors of the frontal lobe, pituitary, or related regions

  • Adult polyglucosan body disease

  • Chronic meningitis

  • Hashimoto encephalopathy

  • Hemochromatosis (controversial)

  • Creutzfeldt-Jakob disease

  • Olfactory groove meningioma

  • Sequential bilateral thalamic strokes

  • Herpes simplex encephalitis

Differential Diagnoses

 

Workup

Approach Considerations

As in any dementia evaluation, initial workup includes a vitamin B-12 level, thyroid function studies, antinuclear antibodies,[15] and, possibly, fluorescent treponemal antibody testing for syphilis. The American Academy of Neurology, in their practice guidelines for the evaluation of dementia, indicates that the incidence of syphilis as a cause of dementia is so low in the typical American patient that routine screening for syphilis is not necessary.[22] However, the index of suspicion should be high in patients with human immunodeficiency virus (HIV) and in patients from geographic regions where the prevalence of syphilis is high.

If prominent inattention is observed, the patient may have a toxic and/or metabolic encephalopathy rather than a true dementia. In such patients, obtain a urine toxicology screen, serum chemistry panel, complete blood count (CBC) and differential count, liver function tests, ammonia level, and erythrocyte sedimentation rate.

If the patient has parkinsonism or a movement disorder, the following tests can be added:

  • Ceruloplasmin (serum) and serum or urinary copper to exclude Wilson disease

  • Manual peripheral blood smear for acanthocytes

  • Genetic testing - Not commercially available for screening for mutations associated with frontotemporal dementias, but genetic testing may be obtained from research laboratories.

Second-line workup

A second-line workup includes cerebrospinal fluid (CSF) examination (for chronic meningitis or elevated pressure) and HIV serology. As Alzheimer disease is almost always in the differential diagnosis, CSF analysis for Abeta1-42 may be indicated.

If prominent inattention is present, obtain a metastatic cancer workup, electroencephalogram (EEG), and Lyme disease serology. Consider consultation with a social worker, geriatric case manager, or nurse practitioner.

Third-line workup

A third-line workup includes the following:

  • Evaluation by a neuropsychologist, behavioral neurologist, or neuropsychiatrist

  • Consideration and discussion of genetic counseling and testing if a familial syndrome is suspected-- excellent information is available at Association for FTD

  • Consideration of a brain biopsy in very select patients

CT Scanning, MRI, and PET Scanning

Brain CT scanning and MRI

Order a computed tomography (CT) scan if magnetic resonance imaging (MRI) is contraindicated in the patient (eg, if the patient has a pacemaker or metallic ocular implants).

If not contraindicated, an MRI scan is preferred. Metastatic lesions and subcortical infarction (eg, caudate, thalamic) can easily be missed on a CT scan. Frontal lobe atrophy out of proportion to atrophy in other brain regions can sometimes be detected. Some patients with frontotemporal dementia may have increased T2 signal in frontal lobe white matter, especially on fluid-attenuated inversion recovery (FLAIR) sequences.[10]

Functional brain and physiologic imaging

Functional brain imaging, eg, with single-photon emission CT (SPECT) scanning, or physiologic imaging with positron emission tomography (PET) scanning may be appropriate in some patients.

In some patients with relatively isolated social-behavioral dysfunction, employers or others may require evidence of a medical disorder. Such patients may appear cognitively normal on objective neuropsychological tests, yet may be unable to function due to acquired brain disease. A SPECT scan may demonstrate relative hypometabolism in frontal and temporal areas (when other neuroimaging is normal), thus providing evidence of brain dysfunction.

Lumbar Puncture

Lumbar puncture (CSF examination) may be appropriate. Some memory disorder specialists perform this examination in every patient with frontal lobe or atypical dementia.

Check pressure, cultures, cryptococcal antigen, and large-volume tap for cytology or acid-fast bacillus (AFB) if the clinical situation warrants such testing. Elevated levels of phosphorylated tau protein and low levels of Abeta1-42 are found in the CSF of patients with Alzheimer disease. Data on levels of tau and beta-amyloid in CSF from patients with frontotemporal dementias has been inconsistent.[23, 24]

Markers for Creutzfeldt-Jakob disease, central nervous system (CNS) Whipple disease, progressive multifocal leukoencephalopathy, and herpes encephalitis also can be ordered from the spinal fluid.

Complications

After diagnostic lumbar puncture, some patients with Pick disease and cerebral atrophy can develop a subdural hematoma.

Observe the patient for headache or change in mental status for several days after this procedure (some physicians admit the patient for 23 h observation). If a subdural hematoma is suspected, perform a CT scan with and without contrast or an MRI scan with contrast.

Brain Biopsy

Brain biopsy may be considered in exceptional circumstances if the diagnosis is in doubt and use of a treatment depends on the results. Occasionally, spinal fluid markers can obviate the need for a brain biopsy, even in these patients. Some of the factors mitigating for a brain biopsy include the following:

  • If the diagnosis is in doubt (eg, faced with second- or third-line autoimmune therapy for neurosarcoidosis)

  • If a familial frontotemporal dementia is suspected

  • If the family desires

  • If a treatment that has significant adverse effects is being considered

Histologic findings

Neuropathological analysis involves inspecting the morphology of neuronal or glial inclusions and their anatomical distribution. In the future, it may be important to detect FTD-tau pathology in order to administer tau-directed therapeutics. However, since FTLD-TDP is more common (about half the cases), histologic analysis is not projected to result in specific clinical decisions for most patients. Almost all cases of FTLD can be categorized as one of the above categories (FTLD-tau and FTLD-TDP) or to the molecular subgroup FTLD-FUS.

 

Treatment

Approach Considerations

On first evaluation, discontinue medications that can impair memory or cause confusion (eg, anticholinergic drugs, sedatives, benzodiazepines). Consider empiric treatment for symptoms that are consistent with depression and/or sleep disorders. Consider administering thiamine empirically (100-300 mg intravenous [IV]/intramuscular [IM]).

Because dysfunction of cortical cholinergic systems does not occur in Pick disease, the use of acetyltransferase inhibitors in this condition makes less sense than it does in the treatment of Alzheimer disease or dementia with Lewy bodies. Nonetheless, class II studies have suggested that they might be of some benefit. The few published studies assessing the efficacy of memantine in frontotemporal dementias have had equivocal results. Some research has indicated that drugs that modulate the serotonergic system may be helpful for treating behavioral symptoms in frontotemporal dementias.

On second evaluation, treat any systemic conditions that were identified and discuss performing a lumbar puncture and HIV testing with the patient and family. If prominent inattention is present and epilepsy is considered, consider further second-line workup, including electroencephalography or an empiric trial of an anticonvulsant. Consider referral to a case manager, geriatric nurse practitioner, or other dementia resource person or group for social-family issues. Discuss the potential utility of lumbar puncture to identify rare treatable conditions.

On third evaluation, perform a lumbar puncture if elected by patient and family. Treat any conditions identified on testing, and consider consultation with a behavioral neurologist or geriatric psychiatrist. Share dementia information and reading material with the family. Consider a brain biopsy if the diagnosis is in doubt or if substantial benefit will result for the patient and/or family with a tissue diagnosis.

Diet and activity

High-sugar–content foods may need to be restricted in some patients with carbohydrate craving, which may indicate Klüver-Bucy syndrome.

It is not clear whether a diet relatively low in carbohydrates, especially refined carbohydrates and sugar, and relatively high in fats and protein (a ketogenic diet), may be associated with improved cognition in Pick disease and FTDs. Such a diet has been associated with symptomatic improvement of both Alzheimer disease and Parkinson disease, but the results are very preliminary and should not outweigh a doctor's advice about an appropriate heart-healthy diet.

A regimen of appropriate therapeutic exercise (eg, brisk walking with a partner) can be helpful in these patients to help regulate mood and reduce akathisia. It is also possible exercise may have beneficial effects on cognitive function.

Inpatient care

Most of the dementia workup above is now recommended as outpatient management. However, a one-day hospital stay may accomplish the second and third steps above under rare conditions (eg, potential need for epilepsy monitoring, if the diagnosis might include chronic meningitis or encephalitis, or if the need for brain biopsy is suspected). However, think carefully about the high risk of hospital-acquired delirium, with potential sundowning and agitation; this complication (see below) is associated with increased mortality and poor quality of life.

Outpatient care

Periodic follow-up care is indicated to manage problem behaviors or clinical problems of the patient, to support the caregiver, or to reevaluate the diagnosis if it is in doubt.

If paranoia, depression, or other behavioral problems manifest, pharmacologic treatments can be tailored to address these problems.

Decompensation/risk of hospital-acquired delirium

Like all people with dementia, people with Pick disease who are relatively high functioning are at very high risk of hospital-acquired delirium. If they decompensate while in a hospital or other unfamiliar setting during illness or medical intervention, this medical complication may adversely affect the outcome of the hospitalization as well as their general health. This should be considered when contemplating elective surgery or other nonessential interventions (eg, cataract removal).

Medicolegal concerns

Loss of social-emotional abilities must be taken into account when making recommendations about continuing work, especially when responsibility for others is part of the work role. People with FTD may retain intellectual capability of performing tasks, but they may make social or interpersonal errors that are unacceptable or even dangerous to themselves or others.

Surgical care

At this time, surgical treatments are not demonstrated to benefit people with frontotemporal dementias or Pick disease.

Consultations

Neuropsychologist, behavioral neurologist, geriatric psychiatrist, or neuropsychiatrist

Patient care can include consultations with a neuropsychologist, behavioral neurologist, geriatric psychiatrist, or neuropsychiatrist. For patients with progressive aphasia, consultation with a speech pathologist for family and patient education and, in rare cases, referral for a computerized communication assistive device, can be beneficial.

Consultation with a nurse practitioner or a geriatric or psychiatric case manager (social worker) experienced with dementia is indicated. If needed, such professionals can be located through a local chapter of the Alzheimer's Association or the state Department of Aging. While the patient is able to participate, a family contact (eg, durable power of attorney) can be designated to decide care-giving and/or end-of-life issues.

The nurse or case manager also can assist caregivers with stress management, teach behavioral techniques, provide referral to day programs, and assess a patient who may need to be admitted for short- or long-term management of behavioral problems.

Genetic counselor

In situations in which a strong family history of frontotemporal dementia or Pick disease is present, unaffected family members may desire genetic testing. It cannot be overstressed that this should be performed only after informed genetic counseling, preferably in a specialty center familiar with the genetics of dementing disorders. In this setting, testing may be of benefit.[25]

Brain injury specialist

If the patient and family have difficulty accepting the idea of social-emotional dysfunction and disability, and, for example, continue to assign the patient responsibility such as caring for small children, it can be helpful to consult with a job coach, cognitive specialist, or psychologist or social worker experienced with people with traumatic brain injury. Such specialists are experienced with recognizing and explaining the deficits encountered in people with FTD, because of the frequency of orbital-frontal cortical deficits after traumatic brain injury.

 

Medication

Medication Summary

Unfortunately, no available drugs arrest or reverse Pick disease. Currently, practitioners use a combination of neuroprotective and symptomatic therapies—including the administration of vitamins, antidepressants, cholinergic agents, and/or dopaminergic agents—in patients with the disorder.

Research studies suggest that a number of agents may actively inhibit neurodegeneration in animals, cellular models, or other disorders (see Scott and Barrett for a review[26] ), but none of these drugs are currently standard for use in Pick disease.

Vitamins

Class Summary

These are cofactors that are needed in metabolic reactions and that are essential for normal deoxyribonucleic acid (DNA) synthesis, with some vitamins providing antioxidant effects.

Vitamin E (E-Gem, Gamma-E-Gems, Aqua Gem-E, Aquasol E)

Vitamin E may protect polyunsaturated acid in membranes from attack by free radicals.

Thiamine

Thiamine is an essential coenzyme that combines with adenosine triphosphate (ATP) to form thiamine pyrophosphate.

Antidepressants

Class Summary

Although selective serotonin reuptake inhibitors (SSRIs) have been suggested for behavioral symptoms (eg, a craving for sweets, hypersexual behavior) in these patients,[27, 28] exercise care in using these agents in patients with parkinsonism, who may develop adverse effects of akathisia or dyskinesias.

Agents with mixed noradrenergic and serotonergic action may be helpful in treating patients with depression and frontal cognitive disorder.

Mirtazapine (Remeron)

Mirtazapine may be sedating, especially at the lower 15mg dose, and may be useful for patients with agitation or disinhibition and depression.

Venlafaxine (Effexor, Effexor XR)

Venlafaxine may be helpful for abulic patients who also have symptoms of depression or decreased initiative.

Trazodone (Oleptro)

Trazodone is a 5-HT2–receptor antagonist that inhibits the reuptake of 5-HT. It has a negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Trazodone has good hypnotic properties and is effective in reducing agitation in patients with head trauma or dementia. This agent is also useful for sleep disturbances. It is structurally unrelated to tricyclic antidepressants (TCAs), tetracyclics, or monoamine oxidase inhibitors (MAOIs). The cardiac conduction effects of trazodone are qualitatively dissimilar to and quantitatively less pronounced than those of TCAs and so are less toxic in cases of trazodone overdose.[29]

Acetylcholinesterase Inhibitors, Central

Class Summary

Cholinergic therapy may be helpful for patients with aphasia,[30] and preliminary studies indicate that cholinesterase inhibitors may be useful for aphasia in Pick disease,[31] as well as for other dementia-related symptoms in this disorder.[32]

Donepezil (Aricept)

Donepezil is an acetylcholinesterase inhibitor that is used in dementia of the Alzheimer type. Cholinergic stimulation may improve naming[30] and increase neuronal plasticity[33] ; thus, it is reasonable to attempt therapy in patients with primary progressive aphasia. Unfortunately, no clinical studies are available on the effect of donepezil in patients with Pick disease.

Ergot Derivatives

Class Summary

Although these agents may worsen sexual or behavioral disinhibition, they may improve executive function, perseveration, and abulia.[34, 35, 36]

Bromocriptine (Parlodel, Cycloset)

Bromocriptine is a semisynthetic ergot alkaloid derivative. It is a strong dopamine D2-receptor agonist and a partial dopamine D1-receptor agonist. Bromocriptine inhibits prolactin secretion, with no effect on other pituitary hormones. It may be given with food to minimize the possibility of gastrointestinal (GI) irritation.

Approximately 28% of this agent is absorbed from the GI tract and metabolized in liver. Bromocriptine's approximate elimination half-life is 50 hours, with 85% excreted in feces and 3-6% eliminated in urine.

Initiate this drug at a low dosage; slowly increase the dosage to individualize therapy. Assess the dosage titration every 2 weeks. Gradually reduce the dose in 2.5-mg decrements if severe adverse reactions occur.

Antiparkinson Agents, Dopamine Agonists

Class Summary

Although these agents may worsen sexual or behavioral disinhibition, they may improve executive function, perseveration, and abulia.

Amantadine

Amantadine inhibits N-methyl-D-aspartic acid (NMDA) receptor–mediated stimulation of acetylcholine release in rat striatum. It may enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.