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DOI: 10.1055/s-0041-1742144
Medication Management of Neuropsychiatric Symptoms in Neurological Conditions: A Dimensional Transdiagnostic Approach
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Abstract
Neuropsychiatric symptoms are prevalent in neurologic practice, but their complexity makes them challenging to manage. Many cognitive, affective, behavioral, and perceptual symptoms span multiple neurologic diagnoses—and there is prominent variability in neuropsychiatric symptom burden for a given condition. There is also a relative lack of robust controlled clinical trial evidence and expert consensus recommendations for a range of neuropsychiatric symptom presentations. Thus, the categorical approach (e.g., a discrete diagnosis equals a specific set of medication interventions) used in many other medical conditions can sometimes have limited utility in commonly encountered neuropsychiatric clinical scenarios. In this review, we explore medication management for a range of neuropsychiatric symptoms using a dimensional transdiagnostic approach applied to the neurological patient. This approach allows the clinician to think beyond the boundaries of a discrete diagnosis and treat specific symptom domains (e.g., apathy, impulsivity). Pharmacologic considerations, including mechanisms of action and their application to various neurotransmitter systems and brain networks, are discussed, as well as general recommendations to optimize medication adherence and rapport with the patient. The dimensional, transdiagnostic approach to pharmacological management of patients with neurological conditions will help the clinician treat neuropsychiatric symptoms safely, effectively, and confidently.
Publication History
Article published online:
09 February 2022
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References
- 1 Arciniegas DB, Kaufer DI. Joint Advisory Committee on Subspecialty Certification of the American Neuropsychiatric Association, Society for Behavioral and Cognitive Neurology. Core curriculum for training in behavioral neurology and neuropsychiatry. J Neuropsychiatry Clin Neurosci 2006; 18 (01) 6-13
- 2 Perez DL, Keshavan MS, Scharf JM, Boes AD, Price BH. Bridging the great divide: What can neurology learn from psychiatry?. J Neuropsychiatry Clin Neurosci 2018; 30 (04) 271-278
- 3 Agüera-Ortiz L, García-Ramos R, Grandas Pérez FJ. et al. Depression in Alzheimer's disease: a Delphi consensus on etiology, risk factors, and clinical management. Front Psychiatry 2021; 12: 638651
- 4 Anderson KE, van Duijn E, Craufurd D. et al. Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders. J Huntingtons Dis 2018; 7 (03) 355-366
- 5 Warden DL, Gordon B, McAllister TW. et al; Neurobehavioral Guidelines Working Group. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma 2006; 23 (10) 1468-1501
- 6 Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 1997; 48 (5, Suppl 6): S10-S16
- 7 Neylan TC. Physiology of arousal: Moruzzi and Magoun's ascending reticular activating system. J Neuropsychiatry Clin Neurosci 1995; 7 (02) 250
- 8 Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem coma. Brain 2003; 126 (Pt 7): 1524-1536
- 9 Meythaler JM, Brunner RC, Johnson A, Novack TA. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. J Head Trauma Rehabil 2002; 17 (04) 300-313
- 10 Giacino JT, Whyte J. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. J Head Trauma Rehabil 2003; 18 (01) 4-5 , author reply 5–6
- 11 Ma HM, Zafonte RD. Amantadine and memantine: a comprehensive review for acquired brain injury. Brain Inj 2020; 34 (03) 299-315
- 12 Passler MA, Riggs RV. Positive outcomes in traumatic brain injury-vegetative state: patients treated with bromocriptine. Arch Phys Med Rehabil 2001; 82 (03) 311-315
- 13 Ishizuka T, Murakami M, Yamatodani A. Involvement of central histaminergic systems in modafinil-induced but not methylphenidate-induced increases in locomotor activity in rats. Eur J Pharmacol 2008; 578 (2-3): 209-215
- 14 Zolkowska D, Jain R, Rothman RB. et al. Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. J Pharmacol Exp Ther 2009; 329 (02) 738-746
- 15 Aboitiz F, Ossandón T, Zamorano F, Palma B, Carrasco X. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks. Front Psychol 2014; 5: 183
- 16 Arciniegas DB, Silver JM. Pharmacotherapy of posttraumatic cognitive impairments. Behav Neurol 2006; 17 (01) 25-42
- 17 Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006; 166 (10) 1092-1097
- 18 Quinn TJ, Richard E, Teuschl Y. et al. European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment. Eur J Neurol 2021; 28 (12) 3883-3920
- 19 Sagvolden T. The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Funct 2006; 2: 41
- 20 Cortese S. Pharmacologic treatment of attention deficit-hyperactivity disorder. N Engl J Med 2020; 383 (11) 1050-1056
- 21 Southwick SM, Morgan III CA, Bremner AD. et al. Noradrenergic alterations in posttraumatic stress disorder. Ann N Y Acad Sci 1997; 821: 125-141
- 22 Guina J, Merrill B. Benzodiazepines I: upping the care on downers: the evidence of risks, benefits and alternatives. J Clin Med 2018; 7 (02) E17
- 23 Mendelson WB. Clinical distinctions between long-acting and short-acting benzodiazepines. J Clin Psychiatry 1992; 53 (Suppl): discussion 8–9 4-7
- 24 Boyce TG, Ballone NT, Certa KM, Becker MA. The use of β-adrenergic receptor antagonists in psychiatry: a review. J Acad Consult Liaison Psychiatry 2021; 62 (04) 404-412
- 25 Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev 2010; (12) CD006815
- 26 Sawantdesai NS, Kale PP, Savai J. Evaluation of anxiolytic effects of aripiprazole and hydroxyzine as a combination in mice. J Basic Clin Pharm 2016; 7 (04) 97-104
- 27 Werner FM, Coveñas R. Safety of antipsychotic drugs: focus on therapeutic and adverse effects. Expert Opin Drug Saf 2014; 13 (08) 1031-1042
- 28 Olten B, Bloch MH. Meta regression: relationship between antipsychotic receptor binding profiles and side-effects. Prog Neuropsychopharmacol Biol Psychiatry 2018; 84 (Pt A): 272-281
- 29 Williamson D, Frenette AJ, Burry LD. et al. Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review. BMJ Open 2019; 9 (07) e029604
- 30 Polich G, Iaccarino MA, Zafonte R. Psychopharmacology of traumatic brain injury. Handb Clin Neurol 2019; 165: 253-267
- 31 Raskind MA, Peskind ER. Alzheimer's disease and related disorders. Med Clin North Am 2001; 85 (03) 803-817
- 32 Wang LY, Shofer JB, Rohde K. et al. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry 2009; 17 (09) 744-751
- 33 Antonsdottir IM, Smith J, Keltz M, Porsteinsson AP. Advancements in the treatment of agitation in Alzheimer's disease. Expert Opin Pharmacother 2015; 16 (11) 1649-1656
- 34 Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer's disease. Expert Opin Pharmacother 2017; 18 (06) 611-620
- 35 Marin RS. Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 1991; 3 (03) 243-254
- 36 Mulin E, Leone E, Dujardin K. et al. Diagnostic criteria for apathy in clinical practice. Int J Geriatr Psychiatry 2011; 26 (02) 158-165
- 37 Jorge RE, Starkstein SE, Robinson RG. Apathy following stroke. Can J Psychiatry 2010; 55 (06) 350-354
- 38 van Duijn E, Reedeker N, Giltay EJ, Roos RA, van der Mast RC. Correlates of apathy in Huntington's disease. J Neuropsychiatry Clin Neurosci 2010; 22 (03) 287-294
- 39 Kant R, Duffy JD, Pivovarnik A. Prevalence of apathy following head injury. Brain Inj 1998; 12 (01) 87-92
- 40 Andersson S, Krogstad JM, Finset A. Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity. Psychol Med 1999; 29 (02) 447-456
- 41 Arnts H, van Erp WS, Lavrijsen JCM, van Gaal S, Groenewegen HJ, van den Munckhof P. On the pathophysiology and treatment of akinetic mutism. Neurosci Biobehav Rev 2020; 112: 270-278
- 42 Marin RS, Wilkosz PA. Disorders of diminished motivation. J Head Trauma Rehabil 2005; 20 (04) 377-388
- 43 Harrison F, Aerts L, Brodaty H. Apathy in dementia: systematic review of recent evidence on pharmacological treatments. Curr Psychiatry Rep 2016; 18 (11) 103
- 44 Sepehry AA, Sarai M, Hsiung GR. Pharmacological therapy for apathy in Alzheimer's disease: a systematic review and meta-analysis. Can J Neurol Sci 2017; 44 (03) 267-275
- 45 Mintzer J, Lanctôt KL, Scherer RW. et al; ADMET 2 Research Group. Effect of methylphenidate on apathy in patients with Alzheimer disease: the ADMET 2 randomized clinical trial. JAMA Neurol 2021; 78 (11) 1324-1332
- 46 Walther S, Stegmayer K, Wilson JE, Heckers S. Structure and neural mechanisms of catatonia. Lancet Psychiatry 2019; 6 (07) 610-619
- 47 Oldham MA. The probability that catatonia in the hospital has a medical cause and the relative proportions of its causes: a systematic review. Psychosomatics 2018; 59 (04) 333-340
- 48 Denysenko L, Sica N, Penders TM. et al; The Academy of Consultation-Liaison Psychiatry Evidence-Based Medicine Subcommittee Monograph. Catatonia in the medically ill: etiology, diagnosis, and treatment. Ann Clin Psychiatry 2018; 30 (02) 140-155
- 49 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry 2006; 19 (03) 294-298
- 50 Cuijpers P, van Straten A, Warmerdam L, Andersson G. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety 2009; 26 (03) 279-288
- 51 DeRubeis RJ, Siegle GJ, Hollon SD. Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nat Rev Neurosci 2008; 9 (10) 788-796
- 52 Posner K, Brown GK, Stanley B. et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 2011; 168 (12) 1266-1277
- 53 Sinyor M, Schaffer A, Levitt A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review. Can J Psychiatry 2010; 55 (03) 126-135
- 54 Bixby AL, VandenBerg A, Bostwick JR. Clinical management of bleeding risk with antidepressants. Ann Pharmacother 2019; 53 (02) 186-194
- 55 Starkstein SE, Mizrahi R, Power BD. Antidepressant therapy in post-stroke depression. Expert Opin Pharmacother 2008; 9 (08) 1291-1298
- 56 Sun Y, Liang Y, Jiao Y. et al. Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis. BMJ Open 2017; 7 (08) e016499
- 57 Brittner M, Micoulaud-Franchi JA, Richieri R. et al. Ketamine in acute and severe major depressive disorder [in French]. Presse Med 2014; 43 (05) 492-500
- 58 Fond G, Loundou A, Rabu C. et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 2014; 231 (18) 3663-3676
- 59 Haq AU, Sitzmann AF, Goldman ML, Maixner DF, Mickey BJ. Response of depression to electroconvulsive therapy: a meta-analysis of clinical predictors. J Clin Psychiatry 2015; 76 (10) 1374-1384
- 60 Gálvez V, Ho KA, Alonzo A, Martin D, George D, Loo CK. Neuromodulation therapies for geriatric depression. Curr Psychiatry Rep 2015; 17 (07) 59
- 61 Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus review and treatment recommendations for TMS therapy for major depressive disorder. Brain Stimul 2016; 9 (03) 336-346
- 62 Kisely S, Li A, Warren N, Siskind D. A systematic review and meta-analysis of deep brain stimulation for depression. Depress Anxiety 2018; 35 (05) 468-480
- 63 Bottomley JM, LeReun C, Diamantopoulos A, Mitchell S, Gaynes BN. Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: A systematic review and meta-analysis. Compr Psychiatry 2019; 98: 152156
- 64 Kaltenboeck A, Winkler D, Kasper S. Bipolar and related disorders in DSM-5 and ICD-10. CNS Spectr 2016; 21 (04) 318-323
- 65 Dubovsky SL. Mania. Continuum (Minneap Minn) 2015; 21 (3 behavioral neurology and neuropsychiatry): 737-755
- 66 Guo C, Stretz C, Anderson JR. et al. Psychiatric sequelae of stroke affecting the non-dominant cerebral hemisphere. J Neurol Sci 2021; 430: 120007
- 67 Yatham LN, Kennedy SH, Parikh SV. et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord 2018; 20 (02) 97-170
- 68 Hollander E, Kim S, Braun A, Simeon D, Zohar J. Cross-cutting issues and future directions for the OCD spectrum. Psychiatry Res 2009; 170 (01) 3-6
- 69 Mega MS, Cummings JL. Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci 1994; 6 (04) 358-370
- 70 Richter PMA, Ramos RT. Obsessive-compulsive disorder. Continuum (Minneap Minn) 2018; 24 (3, behavioral neurology and psychiatry): 828-844
- 71 Price BH, Perez DL, Rapalino O, Oakley DH. Case 41-2020: a 62-year-old man with memory loss and odd behavior. N Engl J Med 2020; 383 (27) 2666-2675
- 72 Scahill L. Alpha-2 adrenergic agonists in children with inattention, hyperactivity and impulsiveness. CNS Drugs 2009; 23 (Suppl. 01) 43-49
- 73 McAllister TW. Neurobehavioral sequelae of traumatic brain injury: evaluation and management. World Psychiatry 2008; 7 (01) 3-10
- 74 Swartz JR, Miller BL, Lesser IM, Darby AL. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997; 58 (05) 212-216
- 75 By the American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics Society 2019 Updated AGS Beers Criteria(R) for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019; 67 (04) 674-694
- 76 Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007; 76 (03) 391-396