Apatia multimodal iatrogênica

Oliveira-Souza, Ricardo de; Figueiredo, Wagner Martignoni de

doi:10.1590/S0004-282X1996000200007

Resumos

O presente trabalho documenta um efeito peculiar dos antidepressivos em 5 pacientes - a apatia -, definida pela incapacidade de experimentar emoções. O reconhecimento da apatia no curso de tratamento antidepressivo deve levantar a possibilidade de iatrogenia e suspensão do antidepressivo em uso. Frizamos que a apatia deve ser diferenciada da abulia e da avolição, com as quais é comumente contundida. Documentamos que a indiferença emocional pode se confinar a um domínio sensorial ("apatia unimodal") ou, como em nossos casos, a mais de uma modalidade ("apatia multimodal"). Circuitos anterobasais, centrados na amígdala e no pólo temporal, são fortes candidatos para integrar a experiência emocional às imagens mentais e percepções multimodais do ambiente, uma vez que para eles convergem os principais sistemas de projeção do prosencéfalo, ao mesmo tempo em que se situam em pontos estratégicos para modular o córtex pré-frontal e parieto-têmporo-occipital. O fato de que a apatia foi produzida por classes quimicamente distintas, como ISRSs (inibidores seletivos de recaptação da serotonina), IMAOs (inibidores reversíveis da monoamino oxidase) e tricíclicos, indica que a fisiopatologia em jogo se deve a alguma ação compartilhada por essas drogas no plano subneuronal. A intervenção em circuitos serotoninérgicos cerebrais parece o mecanismo mais adequado para explicar tal efeito.

antidepressivos; apatia; sistema límbico; abulia; avolição

The present paper reports on five patients who developed apathy as a peculiar side effect of antidepressants. Their behavioral and psychopathological changes were primarily due to the near-absence of emotional experience, a key characteristic that distinguishes apathy from avolition and abulia. The emergence of apathy in the course of an antidepressant treatment should raise the suspicion of an adverse effect of the drug and lead to its prompt withdrawal. A sample of the relevant clinical evidence favoring the distinction of apathy confined to a single sensory domain ("unimodal apathy") from apathy confined to more than one sensory realm ("multimodal apathy") is reviewed. From a pathophysiological standpoint, it would appear that neural nets centered in the amygdala-temporo polar cortex are critical for the integration of sensory perceptions and mental imagery with appropriate emotional tone and quality as well as with their accompanying somatic markers, as they receive afferents from the major projection systems of the prosencephalon and lie in nodes strategic to modify the ongoing activity of multiple parallel brain systems. The fact that one common symptom can be produced by such a heterogeneous family of substances points to a shared neurochemical mechanism of action. At present, discrete cerebral serotoninergic circuits would appear to be suitable candidates for such a role. Cases as these may be critical for the understanding of the cerebral organization of emotions in man, lending support to the notion that distinct neurochemical systems mediate discrete psychopathological symptoms.

antidepressants; apathy; limbic system; abulia; avolition

Apatia multimodal iatrogênica

Multimodal apathy: a unique effect of antidepressant therapy at the neurological-psychiatric interface

Ricardo de Oliveira-Souza^I; Wagner Martignoni de Figueiredo^II

^IProfessor Assistente, Serviço de Clínica Médica C (Prof. Omar da Rosa Santos) do Hospital Universitário Gaffrée e Guinle (HUGG,UNI-RIO), Rio de Janeiro

^IIProfessor Adjunto, Serviço de Clínica Médica C (Prof. Omar da Rosa Santos) do HUGG,UNI-RIO, Rio de Janeiro

RESUMO

O presente trabalho documenta um efeito peculiar dos antidepressivos em 5 pacientes - a apatia -, definida pela incapacidade de experimentar emoções. O reconhecimento da apatia no curso de tratamento antidepressivo deve levantar a possibilidade de iatrogenia e suspensão do antidepressivo em uso. Frizamos que a apatia deve ser diferenciada da abulia e da avolição, com as quais é comumente contundida. Documentamos que a indiferença emocional pode se confinar a um domínio sensorial ("apatia unimodal") ou, como em nossos casos, a mais de uma modalidade ("apatia multimodal"). Circuitos anterobasais, centrados na amígdala e no pólo temporal, são fortes candidatos para integrar a experiência emocional às imagens mentais e percepções multimodais do ambiente, uma vez que para eles convergem os principais sistemas de projeção do prosencéfalo, ao mesmo tempo em que se situam em pontos estratégicos para modular o córtex pré-frontal e parieto-têmporo-occipital. O fato de que a apatia foi produzida por classes quimicamente distintas, como ISRSs (inibidores seletivos de recaptação da serotonina), IMAOs (inibidores reversíveis da monoamino oxidase) e tricíclicos, indica que a fisiopatologia em jogo se deve a alguma ação compartilhada por essas drogas no plano subneuronal. A intervenção em circuitos serotoninérgicos cerebrais parece o mecanismo mais adequado para explicar tal efeito.

Palavras-chave: antidepressivos, apatia, sistema límbico, abulia, avolição.

ABSTRACT

The present paper reports on five patients who developed apathy as a peculiar side effect of antidepressants. Their behavioral and psychopathological changes were primarily due to the near-absence of emotional experience, a key characteristic that distinguishes apathy from avolition and abulia. The emergence of apathy in the course of an antidepressant treatment should raise the suspicion of an adverse effect of the drug and lead to its prompt withdrawal. A sample of the relevant clinical evidence favoring the distinction of apathy confined to a single sensory domain ("unimodal apathy") from apathy confined to more than one sensory realm ("multimodal apathy") is reviewed. From a pathophysiological standpoint, it would appear that neural nets centered in the amygdala-temporo polar cortex are critical for the integration of sensory perceptions and mental imagery with appropriate emotional tone and quality as well as with their accompanying somatic markers, as they receive afferents from the major projection systems of the prosencephalon and lie in nodes strategic to modify the ongoing activity of multiple parallel brain systems. The fact that one common symptom can be produced by such a heterogeneous family of substances points to a shared neurochemical mechanism of action. At present, discrete cerebral serotoninergic circuits would appear to be suitable candidates for such a role. Cases as these may be critical for the understanding of the cerebral organization of emotions in man, lending support to the notion that distinct neurochemical systems mediate discrete psychopathological symptoms.

Key words: antidepressants, apathy, limbic system, abulia, avolition.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 11-janeiro-1996.

Dr. Ricardo de Oliveira Souza - Rua General Belford 226 - 20961-000 Rio de Janeiro RJ - Brasil.

1. Andreasen NC, Black DW. Introductory textbook of psychiatry, Ed2. Washington DC: American Psychiatric Press, 1995.
2. Bauer RM. Visual hypoemotionality as a symptom of visual-limbic disconnection in man. Arch Neurol, 1982;39:702-708.
3. Bech P, Kastrup M, Rafaelsen OJ. Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM-III syndromes. Acta Psychiat Scand 1986;73(Suppl 326): 1-37.
4. Costello CG. Research on symptoms versus research on syndromes: arguments in favour of allocating more research time to the study of symptoms. Br J Psychiatry 1992;160:304-308.
5. Damasio AR. Descartes' error, emotion, reason, and the human brain. New York: Avon Books, 1994.
6. Downer JDC. Changes in visual gnostic function and emotional behavior following unilateral temporal damage in the "split-brain" monkey. Nature 1961;191:50-51.
7. Fedoroff JP, Starkstein SE, Price T, Leiguarda R. Apathy following cerebrovascular lesions. Neurology 1994;44(Suppl 2): A376.
8. Fisher CM. Abulia minor vs agitated behavior. Clin Neurosurg 1984;31:9-31.
9. George MS, Trimble MR. A fluvoxamine-induced frontal lobe syndrome in a patient with comorbid Gilles de la Tourette's syndrome and obsessive compulsive disorder (letter). J Clin Psychiatry 1992;53:379.
10. Heilman KM, Scholes R, Watson RT. Auditory affective agnosia: disturbed comprehension of affective speech. J Neurol Neurosurg Psychiatry 1975;38:69-72.
11. Hoehn-Saric R, Harris GJ, Pearlson GD, Cox CS, Machlin SR, Camargo EE. A fluoxetine-induced frontal lobe syndrome in an obsessive compulsive patient. J Clin Psychiatry 1991;52:131-133.
12. Hoehn-Saric R, Lipsey JR, McLeod DR. Apathy and indifference in patients on fluvoxamine and fluoxetine. J Clin Psychopharmacol 1990;10:343-345.
13. Lilly R, Cummings JL, Benson DF, Frankel M. The human Klüver-Bucy syndrome. Neurology 1983;33:1141-1145.
14. Marin RS. Differential diagnosis and classification of apathy. Am J Psychiatry 1990; 147:22-30.
15. Mesulam M-M, Perry J. The diagnosis of love-sickness: experimental psychophysiology without the polygraph. Psychophysiology 1972;9:546-551.
16. Murphy DL. Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 1990;3:457-471.
17. Mun-ay EA, Mishkin M. Amygdalectomy impairs crossmodal associations in monkeys. Science 1985;228:604-606.
18. Pandya DN, Yeterian EH. Hodology of limbic and related structures: cortical and commissural connections. In: Wieser HG, EIgerCE(eds). Presurgical evaluation of epileptics. Berlin: Springer-Verlag, 1987:3-14.
19. Poeck K. The Klüver-Bucy syndrome in man. In Vinken PJ, Bruyn GW (eds). Handbook of clinical neurology, Vol. 1 (45) {Fredericks JAM (ed) Clinical neuropsychology]. Amsterdam: Elsevier, 1985:257-263.
20. Ross ED, Rush AJ. Diagnosis and neuroanatomical correlates of depression in brain-damaged patients: implications for a neurology of depression. Arch Gen Psychiatry, 1981 ;38:1344-1354.
21. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci 1992;4:47-50.
22. Tranel D, Hyman BT. Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990;47:349-355.
23. Turner BH, Mishkin M, Knapp M. Organization of the amygdalopetal projections from modality-specific cortical association areas in the monkey. J Comp Neurol 1980; 191:515-543.
24. Tusa RJ, Ungerleider LG. The inferior longitudinal fasciculus: a reexamination in humans and monkeys. Ann Neurol 1985;18:583-591.
25. Zilbovicius M, Rancurel G, Samson Y, Leder S, Brack B, Raynaud C. Apathy and disinhibition are related to different patterns of frontal hypoperfusion in Pick's disease. Neurology 1992;42(SuppI 3): 347.

Datas de Publicação

Publicação nesta coleção
06 Dez 2010
Data do Fascículo
Jun 1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Andreasen NC, Black DW. Introductory textbook of psychiatry, Ed2. Washington DC: American Psychiatric Press, 1995.

[2] 2. Bauer RM. Visual hypoemotionality as a symptom of visual-limbic disconnection in man. Arch Neurol, 1982;39:702-708.

[3] 3. Bech P, Kastrup M, Rafaelsen OJ. Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM-III syndromes. Acta Psychiat Scand 1986;73(Suppl 326): 1-37.

[4] 4. Costello CG. Research on symptoms versus research on syndromes: arguments in favour of allocating more research time to the study of symptoms. Br J Psychiatry 1992;160:304-308.

[5] 5. Damasio AR. Descartes' error, emotion, reason, and the human brain. New York: Avon Books, 1994.

[6] 6. Downer JDC. Changes in visual gnostic function and emotional behavior following unilateral temporal damage in the "split-brain" monkey. Nature 1961;191:50-51.

[7] 7. Fedoroff JP, Starkstein SE, Price T, Leiguarda R. Apathy following cerebrovascular lesions. Neurology 1994;44(Suppl 2): A376.

[8] 8. Fisher CM. Abulia minor vs agitated behavior. Clin Neurosurg 1984;31:9-31.

[9] 9. George MS, Trimble MR. A fluvoxamine-induced frontal lobe syndrome in a patient with comorbid Gilles de la Tourette's syndrome and obsessive compulsive disorder (letter). J Clin Psychiatry 1992;53:379.

[10] 10. Heilman KM, Scholes R, Watson RT. Auditory affective agnosia: disturbed comprehension of affective speech. J Neurol Neurosurg Psychiatry 1975;38:69-72.

[11] 11. Hoehn-Saric R, Harris GJ, Pearlson GD, Cox CS, Machlin SR, Camargo EE. A fluoxetine-induced frontal lobe syndrome in an obsessive compulsive patient. J Clin Psychiatry 1991;52:131-133.

[12] 12. Hoehn-Saric R, Lipsey JR, McLeod DR. Apathy and indifference in patients on fluvoxamine and fluoxetine. J Clin Psychopharmacol 1990;10:343-345.

[13] 13. Lilly R, Cummings JL, Benson DF, Frankel M. The human Klüver-Bucy syndrome. Neurology 1983;33:1141-1145.

[14] 14. Marin RS. Differential diagnosis and classification of apathy. Am J Psychiatry 1990; 147:22-30.

[15] 15. Mesulam M-M, Perry J. The diagnosis of love-sickness: experimental psychophysiology without the polygraph. Psychophysiology 1972;9:546-551.

[16] 16. Murphy DL. Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 1990;3:457-471.

[17] 17. Mun-ay EA, Mishkin M. Amygdalectomy impairs crossmodal associations in monkeys. Science 1985;228:604-606.

[18] 18. Pandya DN, Yeterian EH. Hodology of limbic and related structures: cortical and commissural connections. In: Wieser HG, EIgerCE(eds). Presurgical evaluation of epileptics. Berlin: Springer-Verlag, 1987:3-14.

[19] 19. Poeck K. The Klüver-Bucy syndrome in man. In Vinken PJ, Bruyn GW (eds). Handbook of clinical neurology, Vol. 1 (45) {Fredericks JAM (ed) Clinical neuropsychology]. Amsterdam: Elsevier, 1985:257-263.

[20] 20. Ross ED, Rush AJ. Diagnosis and neuroanatomical correlates of depression in brain-damaged patients: implications for a neurology of depression. Arch Gen Psychiatry, 1981 ;38:1344-1354.

[21] 21. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci 1992;4:47-50.

[22] 22. Tranel D, Hyman BT. Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990;47:349-355.

[23] 23. Turner BH, Mishkin M, Knapp M. Organization of the amygdalopetal projections from modality-specific cortical association areas in the monkey. J Comp Neurol 1980; 191:515-543.

[24] 24. Tusa RJ, Ungerleider LG. The inferior longitudinal fasciculus: a reexamination in humans and monkeys. Ann Neurol 1985;18:583-591.

[25] 25. Zilbovicius M, Rancurel G, Samson Y, Leder S, Brack B, Raynaud C. Apathy and disinhibition are related to different patterns of frontal hypoperfusion in Pick's disease. Neurology 1992;42(SuppI 3): 347.