J Head Trauma Rehabil Focus on Clinical Practice and Research Vol. 20, No. 4, pp. 377–388 c 2005 Lippincott Williams & Wilkins, Inc. Disorders of Diminished Motivation

Robert S. Marin, MD; Patricia A. Wilkosz, MD, PhD

Disorders of diminished motivation occur frequently in individuals with traumatic injury. Motivation is an ever-present, essential determinant of behavior and adaptation. The major syn- dromes of diminished motivation are apathy, , and akinetic mutism. Depending on their etiology, disorders of diminished motivation may be a primary clinical disturbance, a symptom of another disorder, or a coexisting second disorder. This article presents a biopsychosocial ap- proach to the assessment and management of motivational impairments in patients with traumatic brain injury. The recognition and differential diagnosis of disorders of diminished motivation, as well as the mechanism and clinical pathogenesis, are discussed. Key words: abulia, akinetic mutism, anterior cingulum, apathy, cholinesterase inhibitor, disorders of diminished motiva- tion, , methylphenidate, traumatic brain injury, ventral pallidum

OTIVATION is essential to adaptive This article presents an approach to the as- Mfunctioning and quality of life. This is sessment and management of motivational im- as true for individuals with traumatic brain pairments in patients with TBI. It introduces injury (TBI) as it is for those with stroke, de- definitions of motivation and of the 3 major mentia, or any other neuropsychiatric illness. disorders of diminished motivation (DDM): Clinicians understand intuitively the impor- akinetic mutism, abulia, and apathy. Diagno- tance of motivation. Without motivation, in- sis of DDM is further clarified in terms of dividuals with TBI will fail to keep appoint- behavior, thought content, and affective ments, stay on their medications, devote symptoms. Assessment and management themselves to friends and family, or return to of DDM are then described on the basis of their jobs. Motivational loss handicaps phys- a biopsychosocial approach to the causes ical rehabilitation and coping skills,1 and it of motivational loss.3 Investigators from is a major source of burden for families of the fields of ,4 neuropsychology,5 individuals with TBI.2 rehabilitative ,6 and occupational Motivation is an ever-present, essential de- therapy7 agree that DDM are a major source terminant of behavior and adaptation. Like at- of disability for patients with TBI. Diminished tention, emotion, and other state variables, motivation in patients with TBI contributes motivation is not a single function of the to loss of social autonomy,6 financial and brain. Psychologically and biologically, moti- vocational loss, and family burden.2 Given vation is a complex of capacities; the neu- the frequency of diminished motivation in ral systems subserving it are themselves patients with TBI—estimates vary from 5% to delimited and distributed, integrated and 67%4,8,9—properly diagnosing and treating interdependent. DDM has enormous potential to alleviate the resultant personal and social burden.

From the Western Psychiatric Institute and Clinic, DISORDERS OF DIMINISHED Department of Psychiatry, University of Pittsburgh MOTIVATION: RECOGNITION School of Medicine, Pa. Corresponding author: Patricia A. Wilkosz, MD, PhD, Motivation refers to the characteristics and Western Psychiatric Institute and Clinic, 3811 O’Hara St, Pittsburgh, PA 15213 (e-mail: [email protected]. determinants of goal-directed behavior. The- edu). ories of motivation are intended to account 377 378 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY–AUGUST 2005 for the “direction, vigor, and persistence of an behavior. Thus, the recognition of diminished individual’s actions,”10 that is, for how behav- motivation requires examining goal-related ior “gets started, is energized, is sustained, is aspects of overt behavior, thought content, directed, is stopped, and what kind of subjec- and emotion. Disorders of diminished moti- tive reaction is present in the organism when vation are recognized by the simultaneous all this is going on.”11 diminution in each of these 3 aspects of Disorders of diminished motivation include behavior: akinetic mutism, abulia, and apathy. Recent Diminished overt behavior may range literature12–15 places DDM on a continuum from a subtle attenuation in social or oc- of motivational loss, with apathy at the mi- cupational functioning, for example, apathy, nor pole of severity and akinetic mutism to profound deficits in the capacity to initi- at the major pole of severity. The 3 result ate any movement whatsoever, as with aki- from dysfunction of the neural machinery that netic mutism. Symptoms of diminished overt mediates motivation. behavior include diminished productivity, Akinetic mutism is essentially character- diminished effort, and diminished initiative. ized by a total absence of spontaneous behav- Diminished goal-related thought content, ior and speech occurring in the presence of if mild, is indicated by decreased interests, preserved visual tracking.12 Traumatic brain plans, or goals for the future. If severe, there is injury may cause akinetic mutism, although a virtual absence of goal-related thought con- few cases have been reported in the TBI tent. The latter would characterize abulia and literature.16 akinetic mutism. Abulia,originally denoting a disorder of Diminished emotional responses to goal- will (bul in Latin),17,13,15 characterizes pa- related events mean emotionally indifferent, tients with symptoms less severe than but shallow, or restricted responses to important qualitatively identical to akinetic mutism: life events. Clinically, this usually means flat- poverty of behavior and speech output, lack tened, labile, or shallow affect and emotional of initiative, loss of emotional responses, psy- indifference. chomotor slowing, and prolonged speech la- To summarize, diminished motivation is tency. Abulia evolves into akinetic mutism present if a patient with an intact level when it worsens and into apathy when it of consciousness, attention, language, and improves. sensorimotor capacity presents with a si- Apathy is a state of diminished motiva- multaneous decrease in goal-related aspects tion in the presence of normal conscious- of overt behavior, thought content, and ness, attention, cognitive capacity, and mood. emotion. This operational definition of DDM Patients with apathy are generally able to initi- leads to a clinical approach for differentiating ate and sustain behavior, describe their plans, between DDM and other disorders. goals, and interests, and react emotionally to significant events and experiences. However, DIFFERENTIAL DIAGNOSIS these features are less extensive, less com- mon, less intense, and shorter in duration than Differential diagnosis of DDM depends on they are in individuals who are not apathetic. the acuity and severity of the TBI. For se- In other words, apathy differs from normality vere cases, differential diagnosis focuses on quantitatively rather than qualitatively. TBI complications that produce profound To further clarify the diagnosis of DDM, it is impairment in level of consciousness, atten- helpful to relate them to the changes in overt tion, speech, or motor capacity, for example, behavior, thought content, and emotion that vegetative states, and stupor, locked- contribute to the clinical recognition of dimin- in syndrome, or quadriparesis. Patients who ished motivation. Motivation is the psycho- have chronic and less severe impairment must logical domain concerned with goal-directed be evaluated for and dementia Disorders of Diminished Motivation 379 as well as frontal-subcortical syndromes that viewed as a pathognomonic feature of affect personality and executive cognitive depression or any other diagnosis.19,20 function. Akinesia, though it may be associated Differential diagnosis requires awareness with apathy, is a disorder of movement, that if DDM are overdiagnosed, reversible not motivation. or more readily treated causes of inactivity 2. Those in which diminished activity is such as stupor or delirium are overlooked. associated with diminished motivation Underdiagnosis leads to premature attempts but both are due to some other disor- at physical rehabilitation or other interven- der: Depression is a disorder of mood. tions whose success depends on strong moti- By definition, it is a dysphoric state. vation. treatment may also fail, Negative thoughts about the self, the not because a reversible mood disorder is ab- present, and the future (Beck’s triad of sent but because it is overshadowed by a DDM depression) are characteristic. Conse- that requires treatment first. quently, one suffers from depression. Patients with diminished motivation all By contrast, one does not suffer from show diminished activity. Inactivity, whether apathy or other DDM as DDM are not motor, cognitive, or emotional, may result dysphoric states. Although motivational from changes in virtually any domain of men- symptoms are common in depression, tal status. Therefore, differential diagnosis it is dysphoria and negative thought of DDM is simplified by considering these content that distinguish depression. different aspects of mental status. Demoralization, like depression, is There are 2 groups of disorders to distin- adysphoric state. Demoralization is guish in differential diagnosis: distinguished by a sense of futility, 1. Those in which diminished activity is resignation, or powerlessness to realize actually due to another impairment: In some goal that is still desired. Dementia stupor and coma, diminished activity is by definition a disorder of cognition, and the appearance of apathy are due and cognitive impairments are essential to the diminished level of consciousness. to diagnosis. Apathy is a common and Similarly, a person in a state of delir- disabling aspect of dementia, although ium may show diminished activity but it is not the defining feature of the it is primarily a disorder of attention (im- syndrome. paired ability to establish, shift, or main- tain attention). Aprosodia is a disorder MECHANISM AND CLINICAL of emotional processing in which the PATHOGENESIS ability to understand or express emo- tion is impaired.18 Aprosodia may be mis- The motivational deficits in patients with taken for apathy because both may be TBI result from complex mechanical and associated with truncated emotional re- physiological processes affecting the neural sponses. Diminished motivation is not systems that mediate motivation. These sys- afeature of aprosodia, however.3 Cata- tems may be affected by gross pathology, such tonia and psychomotor retardation re- as contusion and hemorrhage, or by more semble DDM because of reduced motor subtle changes, such as diffuse axonal injury, and speech activity. Executive cognitive hypoxia, and microvascular changes. Neuro- impairments and waxy flexibility may be logical dysfunction causing diminished mo- seen in . Slowing of thought tivation may be approached in anatomical, and activity, the essential features of psy- physiological, and chemical terms. Anatomi- chomotor retardation, occur in many cally, the anterior cingulum (AC), nucleus ac- disorders, including DDM. Therefore, cumbens (NA), ventral pallidum (VP), medial psychomotor retardation should not be dorsal nucleus of the (MD), and the 380 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY–AUGUST 2005

Figure 1. Motivational circuitry. The core circuit (shaded) consists of the anterior cingulum, the nucleus accumbens, the ventral pallidum, and the ventral tegmental area. Nucleus accumbens and the ventral pallidum are divided into (1) more medial portions that are associated with limbic input from the amygdala and the hippocampus and (2) more lateral portions associated with output circuits. Output is via the motor cortex, the basal ganglia, the reticulospinal tract, and the pedunculopontine nucleus. The amygdala and the hippocampus, as well as the prefrontal cortex, modulate information in the core circuit on the basis of the current environment and the drive state of the organism. The ventral pallidum output reaches the prefrontal cortex via the mediodorsal nucleus of the thalamus. The current motivational state is represented by the pattern of activity distributed within the core circuit. The flow of information within and through the core circuit permits the translation of motivation into action. Adapted with permission from Kalivas et al.21 ventral tegmental area (VTA) are the most A separate aspect of motivation is mod- important structures for establishing and ifying the current motivational state on maintaining the current motivational state. the basis of the reward value of the cur- The anterior cingulum, NA, VP, and MD rent environment. The reward significance comprise a cortico-striatal-pallidal-thalamic of the environment is signaled by neurons circuit21,22 thought to mediate motivation in several forebrain regions, including VTA, (Fig 1). Disruption of this core circuit pro- striatum, ventral striatum, NA, dorsolateral duces akinetic mutism, abulia, or apathy de- and orbital prefrontal cortex, anterior cingu- pending on the severity of the dysfunction.3,15 late cortex, and amygdala.26 Modifying the Clinical effects of core circuit dysfunction cor- current motivational state depends on the respond to animal research showing that the amygdala, the hippocampus, the prefrontal “initiation and maintenance of behavioral re- cortex,21 and the greater limbic lobe.27 This sponses”depends on the circuit composed of may explain why disease states affecting these NA, VP, and VTA.23 Clinical arguments for in- structures present as apathy: if unable to reg- cluding AC in the core circuit3 are supported ister changes in the reward significance of by experimental evidence24,25 that AC has an the environment, the organism will be “ap- essential role to play in motivational aspects athetic” to these stimuli. This formulation of decision making. may account for the apathy associated with Disorders of Diminished Motivation 381 hippocampal dysfunction (amnestic disorder, given in Table 1 implies that assessment of Alzheimer’s disease), the apathy and placid- patients with diminished motivation requires ity seen with amygdala injury (Kluver-Bucy a comprehensive and systematic neuropsychi- syndrome28), and the “background of apa- atric evaluation, including evaluation of the thy and abulia”29 associated with orbitofrontal patient’s social and physical environment. dysfunction. Similarly, inability to develop a The psychosocial history will indicate the motivational map of the external environment patient’s baseline level of motivation3 and is postulated to account for the indifference coping skills1 that characterize adult person- associated with right hemisphere injury.30 ality. It is also important to keep in mind Pathogenesis of TBI symptoms may also the enormous variability in individuals’ ac- be understood in terms of the neurochem- complishments, interests, and goals and the istry of the motivational circuitry, for ex- way these are influenced by personal experi- ample, dopaminergic or glutamatergic path- ence, education, social class, culture, and age ways. Dopaminergic activity is of particular cohort. importance for motivational deficits because Personal loss, psychological trauma, and of the central role that it plays in reward, phase-of-life events may alter motivation. novelty seeking, and response to unexpected Occasionally, apathy is the primary symptom events.31,26 There is some evidence32,33 that of an adjustment disorder, for example, the dopaminergic activity is affected in TBI.34 Sev- empty nest syndrome or a retirement reac- eral other biochemical changes have been de- tion. Apathy can also be a defense mechanism scribed in TBI, including changes in levels of when it is the primary means for dealing with glutamate, acetylcholine, neuropeptides, and anxiety. The social withdrawal or emotional oxygen-free radicals. Their direct and indirect distance seen in Cluster A personality disor- participation in the motivational circuitry pro- ders may mistakenly be interpreted as neuro- vides a rationale for the use of pharmacologi- genic motivational loss. Conversely, one can cal therapies in DDM, including glutamatergic err by attributing subtle motivation loss to and cholinergic agents.10 Cluster A personality disorder when, in fact, one has encountered the first symptoms of neurogenic apathy.3 ASSESSMENT Interactions of medical, psychological, and neurological variables are particularly rele- The assessment of patients with diminished vant in elderly patients because they of- motivation depends on the etiology of dimin- ten have multiple clinical problems. Many ished motivation and the interaction of bio- drugs may alter motivation. Dopaminergic logical, psychosocial, and socioenvironmen- agents, or antagonists, are most famil- tal factors that control motivated behavior. iar as mediators of motivational change. But Table1lists conditions associated with apa- equally important are serotinergic, choliner- thy, abulia, and akinetic mutism.3,35 The con- gic, and adrenergic agents because of their ditions that cause akinetic mutism may also interaction with dopamine systems. Pharma- cause abulia and apathy because all 3 may cokinetic variables have an independent in- result from dysfunction of the AC-NA-VP-MD fluence on motivation. For example, there circuit mediating motivation. In other words, are case reports suggesting that selective when less severe, the diseases that cause serotonin reuptake inhibitors (SSRIs) may akinetic mutism cause abulia and apathy. In dispose to apathy.36 Furthermore, SSRIs, par- addition, there are many neurological and ticularly fluoxetine and paroxetine, are po- psychiatric disorders and psychosocial condi- tent 2D6 inhibitors. If an irritable patient with tions that produce apathy but do not cause TBI is treated with haloperidol and then, be- abulia and akinetic mutism because the core cause apathy is misdiagnosed as depression, circuit structures are spared. The information treated with one of these SSRIs, motivation 382 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY–AUGUST 2005

Table 1. Conditions associated with apathy, abulia, and akinetic mutism

Neurological disorders∗ Medical disorders Apathetic hyperthyroidism Frontotemporal dementia Hypothyroidism Anterior cerebral artery infarction Pseudohypoparathyroidism Tumor Lyme disease Chronic fatigue syndrome Trauma Testosterone deficiency Right hemisphere Debilitating medical conditions, for example, Right middle cerebral artery infarction malignancy, congestive heart failure, renal or heart Cerebral white matter failure Ischemic white matter disease Drug induced Multiple sclerosis Neuroleptics, especially “typical”neuroleptics Binswanger’s encephalopathy Selective serotonin reuptake inhibitors HIV Marijuana dependence Basal ganglia Amphetamine or cocaine withdrawal Parkinson’s disease Socioenvironmental (lack of reward, loss of Huntington’s disease incentive, lack of perceived control) Progressive supranuclear palsy Role change Carbon monoxide poisoning Institutionalism Diencephalon Degeneration or infarction of thalamus Wernicke-Korsakoff disease ∗Akinetic mutism results from bilateral dysfunction of Amygdala the cortico-striatal-pallidal-thalamic circuit, which Kluver-Bucy syndrome consists of anterior cingulum, nucleus accumbens, Multifocal disease ventral pallidum, and mediodorsal nucleus of Alzheimer’s disease (apathy may be thalamus. When improving or less severe, such cases mediated by damage to the present as abulia or apathy. Etiology may be vascular, prefrontal cortex, the parietal trauma, tumor, degeneration, or toxin (eg, carbon cortex, and the amygdala) monoxide poisoning).

may worsen for 2 reasons. The SSRI may in- ciated movements, or conjugate eye move- duce apathy directly and haloperidol-induced ment abnormalities suggest that diminished motor apathy may worsen because the SSRI motivation may be due to Huntington’s increases levels of haloperidol. disease, Parkinson’s disease, or progressive Neurological disorders affecting motivation supranuclear palsy. and its neural machinery should direct the Neuropsychological assessment clarifies clinician’s attention to several aspects of the the cognitive context of motivational loss. neurological examination. Since frontal and Executive cognitive assessment may suggest diencephalic diseases figure prominently in that lack of activity in one patient reflects differential diagnosis of DDM, it is important impairment in sequencing while in another it to know whether olfactory function, visual reflects loss of verbal fluency and initiation. acuity, and visual fields are intact. Frontal re- Each will benefit from a different type of lease signs and paratonic rigidity (gegenhal- “psychological prosthesis.” ten) are relevant for the same reason. Clinicians, especially those unfamiliar with Extrapyramidal motor signs clarify the DDM, may find it helpful to rate the sever- evaluation of motor subtypes of DDM. For ity of motivational loss with formal rating example, chorea, micrographia, loss of asso- scales. The rating process can familiarize one Disorders of Diminished Motivation 383 with the clinical signs of motivation and its Several rating methods are available for loss as well as aid differential diagnosis. For quantifying loss of motivation. Construct va- example, if a clinician is unsure whether a lidity is strongest for the Apathy Evaluation psychomotor-retarded patient is apathetic or Scale (AES),37 an 18-item scale that can be depressed, it may be helpful for the clini- administered as a self-rated scale, a care- cian to discover that the apathy rating is high giver pencil-and-paper test, or a clinician- whereas the depression score is unexpectedly rated semistructured inventory (Table 2).38,39 low. This would suggest that the psychomotor Several articles document the feasibility of rat- retardation is better characterized as bradyki- ing apathy with the Apathy Scale,40,41 which nesia and akinesia. If so, the next clinical step is derived from a preliminary version of the may be to perform a neurological examina- AES. The Children’s Motivation Scale,42 also tion and obtain a magnetic resonance image of derived from the AES, uses developmentally the head rather than to have the patient start appropriate behavioral anchors to permit rat- taking an antidepressant. ing of apathy in children and adolescents. The

Table 2. Apathy Evaluation Scale (clinician version)

Name: Date: / / Rater: Rate each item on an interview at the subject. The interview should begin with a description of the subject’s interests, activities, and daily routine. Base your ratings on both verbal and nonverbal information. Rating should be based on the past 4 weeks. For each item, ratings should be judged: Not at All Slightly Somewhat A Lot Characteristic Characteristic Characteristic Characteristic (1) (2) (3) (4)

1. She/he is interested in things. 2. She/he gets things done during the day. 3. Getting things started on his/her own is important to him/her. 4. She/he is interested in having new experiences. 5. She/he is interested in learning new things. 6. She/he puts little effort into anything. 7. She/he approaches life with intensity. 8. Seeing a job through to the end is important to her/him. 9. She/he spends time doing things that interest her/him. 10. Someone has to tell her/him what to do each day. 11. She/he is less concerned about her/his problems than she/he should be. 12. She/he has friends. 13. Getting together with friends is important to him/her. 14. When something good happens, she/he gets excited. 15. She/he has an accurate understanding of her/his problems. 16. Getting things done during the day is important to her/him. 17. She/he has initiative. 18. She/he has motivation.

The Apathy Evaluation Scale was developed by Robert S. Marin, MD. Development and validation studies are described in Marin et al.38 Scoring instructions and administrations guidelines are available from Robert S. Martin, MD, Western Psychiatric Institute and Clinic, 3811 O’Hara St, Pittsburgh, PA 15213. 384 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY–AUGUST 2005

Neuropsychiatric Inventory43 is a multidimen- ment must consider the physical and psy- sional instrument administered to caregivers. chosocial environment. Modifying the overall It is widely used to assess noncognitive symp- environment and attending to family and pro- toms of dementia and devotes 1 of 10 item fessional caregivers is an elementary but cru- domains to apathy. cial dimension of treatment for DDM. Preliminary evaluation requires optimizing the patient’s general medical condition. This TREATMENT may mean controlling seizures or headaches, arranging physical or cognitive rehabilitation The growing interest in DDM is leading to for cognitive and sensorimotor loss, or en- novel approaches to understand the coping suring optimal hearing, vision, and speech. impairments1 or neuropsychological losses5 These elementary steps also increase motiva- of patients with TBI. These and other new tion because improved physical status may en- approaches are likely to lead to new thera- hance functional capacity, drive, and energy pies for DDM. Psychological and socioenvi- and thereby increase the patient’s expectation ronmental approaches to DDM apply primar- that initiative and effort will be successful. ily to apathy and abulia. Their relevance to The aim of environmental interventions is akinetic mutism arises once patients begin to to increase the reward potential of the envi- respond to pharmacological therapies. ronment. Adaptive devices, such as motorized Some of the psychological treatments are wheel chairs or voice-activated computers, also appropriate for patients with depression, compensate directly for the sensorimotor often because patients with depression are and neurological impairments that deny the suffering in part from diminished motivation. patient full benefit of the environment. In im- The applicability of such psychological ap- poverished environments, either at home or proaches to depression and to DDM leads institutions, it is important to introduce new some to wonder if it is necessary to consider sources of pleasure, interest, and stimulation. them for DDM. Actually, these interventions Increasing opportunities for socialization is have a specific role for DDM. Once a clinician also helpful. For many, returning to the fa- diagnoses a patient as apathetic and not de- miliar personal and physical circumstances of pressed, the question becomes what kind of their homes may be the fastest way to a health- psychological therapies are indicated. If these ier physical or social environment. treatments are viewed as treatments for de- General psychological status contributes pression, the clinician may fail to offer them to motivation in the same way that gen- to the patient with apathy. Clearly, this would eral medical condition does. Goal-directed be inappropriate. behavior depends not only on motivation Treatment of akinetic mutism and abulia is but also on other state variables: arousal, at- primarily pharmacological. Patients with ap- tention, mood, and cognition. Psychological athy may require pharmacological interven- treatments may include a variety of behav- tions, but the preservation of cognitive and ioral techniques7,16,44 or specialized cogni- communicative capacity calls increasingly for tive rehabilitative approaches, for example, psychological and social interventions. Such enhancing attention or performance speed.45 interventions are based on careful character- Psycho-education, vocational counseling, and ization of the patient’s motivational and neu- psychotherapy should not be overlooked. Psy- ropsychological status. The general principle chotherapy may focus on injury-related loss, is to define the patient’s losses and resid- interpersonal problems, or family stressors. ual capacities and then design a “psycho- Behavioral interventions should be intro- logical prosthesis” that compensates for the duced methodically, making clear the tasks deficits and makes the best possible use of and skills required of the patient. Goals should residual abilities. Regardless of severity, treat- be defined collaboratively to strengthen Disorders of Diminished Motivation 385 engagement and enhance the patient’s sense like home, for example, by bringing in family of control and expectation of success. Once photographs or favorite books. goals are defined, staff should be careful to There are 5 steps to pharmacological treat- follow through with the treatment plan. ment: (1) Optimize medical status. (2) Diag- Finally, there is the integration of neuropsy- nose and treat other conditions more specif- chological assessment with the treatment of ically associated with diminished motivation motivational loss. Accurate assessment pro- (eg, apathetic hyperthyroidism, Parkinson’s vides the template for developing an individ- disease). (3) Eliminate or reduce doses of ualized plan for psychological treatment. The psychotropics and other agents that aggravate treatment can be thought of as a “psycholog- motivational loss (eg, SSRIs, dopamine an- ical prosthesis”because it is precisely molded tagonists). (4) Treat depression efficaciously to the pattern of abilities lost and retained as a when both DDM and depression are present. result of injury. Thus, for deficits in initiation When depression is associated with apathy, and perseveration, the psychological prosthe- consider using more activating antidepres- sis requires the caregiver to prompt the pa- sants (eg, sertraline, bupropion, venlafaxine). tient when to begin or end a particular task. If (5) Increase motivation through use of stimu- patients are able to initiate behavior but fail to lants, dopamine agonists, or other agents such act because they are unable to sequence, plan, as cholinesterase inhibitors (Table 3). These and monitor behavior, their motivational pros- agents have been used for treating a variety of thesis requires the caregiver to tell the patient, behavioral and cognitive impairments in pa- “go into the kitchen ...now open the refriger- tients with TBI.32–34 Cholinesterase inhibitors ator door ...now take out the sour cream on (donepezil, galantamine, rivastigmine) may the top shelf ...bring the sour cream into the also benefit apathy in TBI. 46,47 dining room ... thank you very much.” Here With and dopamine agonists, the motivational prosthesis is a specific sub- treatment is initiated with minimal doses stitute for the impairments in planning and and slowly titrated upward once improve- sequencing. ment begins. Some patients respond to small Similar psychological prostheses aid doses, but when impairment is significant DDM patients with other neurobehavioral and risk factors few, higher doses should be impairments. Of particular importance is the considered. association of diminished motivation with en- There is significant and sometimes dra- vironmental dependency or stimulus-bound matic benefit of in abulia and behavior. A bland or unfamiliar environment akinetic mutism.16 Presumably, other and will aggravate this condition because there less toxic dopamine agonists have compara- is nothing to trigger the “old” behaviors. ble potential. Pramipexole may have some Families complain, “All he does is sit around advantage for DDM because it has selectiv- here and do nothing.” Professional caregivers ity for D3 dopamine receptors that are pref- may have the same complaint. A variety of erentially distributed in the limbic forebrain. neuropsychological impairments contribute All of the dopaminergic drugs dispose to to environmental dependency. For example, behavioral toxicity, including , mo- the patient may be unable to generate an tor activation and restlessness, sleep distur- idea or a goal for behavior. The psychological bance, and delirium. Caution should be taken prosthesis in this instance uses the pathology with the stimulants to monitor pulse and itself to treat the problem. Instead of trying blood pressure, although serious problems to create new habits, the caregiver returns are unusual. alters both dopamin- the person to an environment that habitually ergic and glutamatergic receptors, which may elicits the desired behavior. In most cases, actually be a clinical advantage48 since DDM this means returning the patient home or are not due only to lack of dopaminergic activ- at least creating an environment that looks ity. In older patients, amantadine dosage must 386 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY–AUGUST 2005

Table 3. Drugs used in the treatment of apathy, abulia, and akinetic mutism

Agent Usual total daily dosage, mg∗ Stimulants Dextroamphetamine 20 (5–60) Methylphenidate 20 (10–60) Activating Bupropion 200 (100–400) Parnate 45 (30–90) Protriptyline 40 (20–60) Venlafaxine 150 (100–450) Dopamine agonists (selective and mixed) Amantadine 200 (100–300) Bromocriptine 10 (5–90) Selegiline 10 (5–40)† L-DOPA/carbidopa 25/100 TID –25/250 QID Pergolide 2 (1–5) Pramipexole 5 TID (0.375–4.5) Other psychotropics Modafinil (Provigil) 200 (100–400) Donepezil (Aricept) 5 (5–10) Galantamine (Reminyl) 8 BID (4–8) Rivastigmine (Exelon) 3 BID (1.5–6)

∗Values in parentheses represent range. †Requires diet low in tyramine, especially at doses above 10 mg; lower doses may produce serotonin syndrome if administered with agents that slow selegiline metabolism. be adjusted to account for decreased creati- glutamatergic agents may prove useful as nine clearance. well.49 Disorders of diminished motivation asso- ciated with extrapyramidal motor symptoms CONCLUSION are treated with the same agents, including amantadine. The goal of treatment is to ma- Motivation is fundamental for adaptive be- nipulate dopaminergic function for the sake havior. The major DDM are apathy, abulia, and of motivation, not just to improve motor abil- akinetic mutism. Depending on their etiology, ity. Overlooking this may compromise out- DDM may be the primary clinical disturbance, come in the end because the benefit of a symptom of some other disorder, or a coex- improved mobility will be undercut by lack of isting second disorder requiring independent motivation. diagnosis and management. Differential diag- Newer psychotropic medications may be nosis usually focuses on delirium, dementia, helpful for treating DDM. Modafinil, intro- depression, demoralization, akinesia, catato- duced recently for the treatment of nar- nia, and aprosodia. In recent years, the neuro- colepsy, has stimulating or arousing effects logical model for DDM has been based on the that may prove useful in some patients. cortico-subcortical circuit involving AC-NA- Modafinil may cause headache and gastroin- VP-MD and the modification of current mo- testinal symptoms, but it is relatively free of tivational state by the prefrontal cortex, the major toxicity. The growing knowledge of amygdala, the hippocampus, and the greater glutamate systems raises the possibility that limbic lobe. Current knowledge permits Disorders of Diminished Motivation 387 us to approach assessment and treatment of socioenvironmental approaches available in DDM on the basis of our understanding of neuropsychiatry. By treating DDM, we offer these systems. Treatment of DDM includes the individuals with TBI a way to improve their full range of biomedical, psychological, and functional abilities and quality of life.

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