TREATMENT-RESISTANT DEPRESSION IN CHILDREN AND ADOLESCENTS

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DEFINITION OF TREATMENT RESISTANCE IN

CHILDHOOD DEPRESSION

As there are virtually hundreds of psychopharmacology studies and numerous psychotherapy investigations reported in the literature in which adults with depression have significantly better improvements on active versus placebo interventions, there is a data-based foundation for categorizing treatment-resistant subjects. Thus, for older age groups (i.e., adults and geriatric populations), the definition of treatment resistance depends only on where to draw the cut-off point

Should Pharmacotherapy Investigations Have Preceded Psychotherapy Studies for Depressed Children?

Given the great care that must be exercised when prescribing catecholamine receptor–altering agents to children, it is seemingly incongruous that systematic, federally funded studies of tricyclic antidepressant (TCA) and selective serotonin reuptake inhibitor (SSRI) drugs for 6- to 12-year old children with major depressive disorder (MDD) preceded investigation of nonpharmacologic modalities.23, 32, 64 From an historical perspective, when the first drug studies for depressed children were

IMPLICATIONS OF FAMILY STUDIES FOR THE TREATMENT RESPONSE OF MDD IN CHILDREN

As discussed in earlier sections of this article, the poor treatment response for childhood-onset MDD to pharmacologic treatment has been proposed to be secondary to interference with critical psychodevelopmental stages48, 49 to neurodevelopmental differences that do not allow treatment response59, 61 or to the presence of etiologically distinct forms of early-onset illness.84 Family studies using affected children as probands can illuminate the involvement of all these possible factors that

PSYCHOSOCIAL IMPAIRMENTS IN CHILDHOOD DEPRESSION

During the last decade, investigations have shown that MDD in adults is associated with pervasive impairments in psychosocial functioning. Depressed adults experience difficulty in a variety of interpersonal and social areas at baseline assessment of their mood disorder. The importance of psychosocial functioning at baseline for long-term disease course is suggested by follow-up studies showing that these deficits at baseline are predictive of poor disease outcome.8, 69, 78 Further, follow-up

NEUROIMAGING STUDIES IN CHILDHOOD AFFECTIVE DISORDERS

Knowledge of the structural and functional pathophysiology associated with childhood affective disorders has the potential to advance significantly our understanding of these disorders in developing populations and further elucidate biologic factors associated with treatment resistance. There have been very few neuroimaging investigations, however, of children and adolescents with affective disorders. In contrast, numerous CT, MR imaging, and positron-emission tomography (PET) studies have

SUMMARY

Treatment resistance in depressed children and adolescents cannot yet be defined fully because of the paucity of controlled studies that demonstrate efficacy. Therefore, this article addresses several of the age-specific, developmental considerations that may impinge upon treatment response. Areas covered include familial-genetic, psychosocial, and neuroimaging studies in addition to a review of controlled studies to date.

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References (89)

  • S. Kutcher et al.

    Response to desipramine treatment in adolescent depression: A fixed-dose, placebo-controlled trial

    J Am Acad Child Adolesc Psychiatry

    (1994)
  • W. Maier et al.

    The relationship between alcoholism and unipolar depression

    J Psychiatr Res

    (1994)
  • H.A. Nasrallah

    Neurodevelopmental aspects of bipolar affective disorder

    Biol Psychiatry

    (1991)
  • J. Puig-Antich

    Affective disorders in childhood: A review and perspective

    Psychiatr Clin North Am

    (1980)
  • U. Rao et al.

    Childhood depression and risk of suicide: A preliminary report of a longitudinal study

    J Am Acad Child Adolesc Psychiatry

    (1993)
  • M.A. Riddle et al.

    Another sudden death in a child treated with desipramine: Case description and commentary

    J Am Acad Child Adolesc Psychiatry

    (1993)
  • J.G. Simeon et al.

    Adolescent depression: A placebo-controlled fluoxetine treatment study and follow-up

    Prog Neuropsychopharmacol Biol Psychiatry

    (1990)
  • M. Strober et al.

    A family study of bipolar I disorder in adolescence: Early onset of symptoms linked to increased familial loading and lithium resistance

    J Affect Disord

    (1988)
  • V.W. Swayze et al.

    Subcortical and temporal structures in affective disorder and schizophrenia: A magnetic resonance imaging study

    Biol Psychiatry

    (1992)
  • N.K. Tancer et al.

    Rate of atypical depression and tricyclic drug response in adolescents [abstract]

    J Am Acad Child Adolesc Psychiatry

    (1992)
  • M. Target et al.

    Efficacy of psychoanalysis for children with emotional disorders

    J Am Acad Child Adolesc Psychiatry

    (1994)
  • R.D. Todd et al.

    Genetic studies of affective disorders: Should we be starting with childhood onset probands?

    J Am Acad Child Adolesc Psychiatry

    (1993)
  • B.T. Walsh et al.

    Effects of desipramine on autonomic control of the heart

    J Am Acad Child Adolesc Psychiatry

    (1994)
  • R.A. Weller et al.

    Psychopathology in families of children with major depressive disorders

    J Affect Disord

    (1994)
  • L.L. Altschuler et al.

    Reduction of temporal lobe volume in bipolar disorder: A preliminary report of magnetic resonance imaging

    Arch Gen Psychiatry

    (1992)
  • C.A. Anderson et al.

    Psychosocial outcomes of children of unipolar depressed, bipolar, medically ill and normal women: A longitudinal study

    J Consult Clin Psychol

    (1993)
  • N.C. Andreasen et al.

    The family history method using diagnostic criteria

    Arch Gen Psychiatry

    (1977)
  • P.A. Barnett et al.

    Psychosocial functioning and depression: Distinguishing among antecedents, concomitants, and consequences

    Psychol Bull

    (1988)
  • L.R. Baxter et al.

    Cerebral metabolic rates for glucose in mood disorders

    Arch Gen Psychiatry

    (1985)
  • L.R. Baxter et al.

    Reduction of prefrontal cortex glucose metabolism common to three types of depression

    Arch Gen Psychiatry

    (1989)
  • L.R. Baxter et al.

    Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder

    Arch Gen Psychiatry

    (1992)
  • A.G. Billings et al.

    Life stressors and social resources affect posttreatment outcomes among depressed patients

    J Abnorm Psychol

    (1985)
  • K.N. Botteron

    Neuroimaging in child psychiatry

    Current Opinion in Psychiatry

    (1994)
  • E. Caine et al.

    Psychiatric syndromes in Huntington's disease

    Am J Psychiatry

    (1983)
  • S.E. Chua et al.

    Schizophrenia—A brain disease?

    Br J Psychiatry

    (1995)
  • C.E. Coffey et al.

    White matter hyperintensity on magnetic resonance imaging: Clinical and neuroanatomic correlates in the depressed elderly

    J Neuropsychiatry Clin Neurosci

    (1989)
  • C.E. Coffey et al.

    Quantitative cerebral anatomy in depression

    Arch Gen Psychiatry

    (1993)
  • J.L. Cummings

    Frontal-subcortical circuits and human behavior

    Arch Neurol

    (1993)
  • A.R. Damasio et al.

    Emotional disturbances associated with focal lesions of the limbic frontal lobe

  • W.C. Drevets et al.

    A functional anatomical study of unipolar depression

    J Neurosci

    (1992)
  • R.M. Dupont et al.

    Subcortical abnormalities detected in bipolar affective disorder using magnetic resonance imaging

    Arch Gen Psychiatry

    (1990)
  • I. Elkin et al.

    National Institute of Mental Health Treatment of Depression Collaborative Research Program

    Arch Gen Psychiatry

    (1989)
  • Emslie G, Weinberg WA, Kowatch RA, et al: Fluoxetine treatment of depressed children and adolescents. Presented at the...
  • FigielG.S. et al.

    Subcortical hyperintensities on brain magnetic resonance imaging: A comparison of normal and bipolar subjects

    J Neuropsychiatry

    (1991)
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    Address reprint requests to Barbara Geller, MD, Washington University School of Medicine, 4940 Children's Place, St. Louis, MO 63110

    This work was supported by grants R01–MH40646, R01–MH40273, and R01–MH45486 to Dr. Geller and by grant P50–MH30381 from the National Institute of Mental Health.

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