TREATMENT-RESISTANT DEPRESSION IN CHILDREN AND ADOLESCENTS
Section snippets
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.
References (89)
- et al.
Aggregating data from multiple informants in child psychiatry epidemiological research
J Am Acad Child Adolesc Psychiatry
(1992) - et al.
Magnetic resonance imaging in childhood and adolescent bipolar affective disorder: A pilot investigation
J Am Acad Child Adolesc Psychiatry
(1995) - et al.
Frontal cortex and basal ganglia metabolic rates assessed by position emission tomography with [18F] 2 deoxyglucose in affective illness
J Affect Disord
(1986) The epidemiology of bipolar affective disorder
Compr Psychiatry
(1981)Commentary on unexplained deaths of children on Norpramin
J Am Acad Child Adolesc Psychiatry
(1991)- et al.
Rate and predictors of prepubertal bipolarity during follow-up of 6 to 12 year old depressed children
J Am Acad Child Adolesc Psychiatry
(1994) - et al.
Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6 to 12 year olds with major depressive disorder
J Am Acad Child Adolesc Psychiatry
(1992) - et al.
Baseline and two to three year follow-up characteristics of placebo-washout responders from the nortriptyline study of depressed 6 to 12 year olds
J Am Acad Child Adolesc Psychiatry
(1992) - et al.
A magnetic resonance imaging study of putamen nuclei in major depression
Psychiatry Res
(1991) - et al.
Prediction of response of chronic depression to imipramine
J Affect Disord
(1989)
Response to desipramine treatment in adolescent depression: A fixed-dose, placebo-controlled trial
J Am Acad Child Adolesc Psychiatry
The relationship between alcoholism and unipolar depression
J Psychiatr Res
Neurodevelopmental aspects of bipolar affective disorder
Biol Psychiatry
Affective disorders in childhood: A review and perspective
Psychiatr Clin North Am
Childhood depression and risk of suicide: A preliminary report of a longitudinal study
J Am Acad Child Adolesc Psychiatry
Another sudden death in a child treated with desipramine: Case description and commentary
J Am Acad Child Adolesc Psychiatry
Adolescent depression: A placebo-controlled fluoxetine treatment study and follow-up
Prog Neuropsychopharmacol Biol Psychiatry
A family study of bipolar I disorder in adolescence: Early onset of symptoms linked to increased familial loading and lithium resistance
J Affect Disord
Subcortical and temporal structures in affective disorder and schizophrenia: A magnetic resonance imaging study
Biol Psychiatry
Rate of atypical depression and tricyclic drug response in adolescents [abstract]
J Am Acad Child Adolesc Psychiatry
Efficacy of psychoanalysis for children with emotional disorders
J Am Acad Child Adolesc Psychiatry
Genetic studies of affective disorders: Should we be starting with childhood onset probands?
J Am Acad Child Adolesc Psychiatry
Effects of desipramine on autonomic control of the heart
J Am Acad Child Adolesc Psychiatry
Psychopathology in families of children with major depressive disorders
J Affect Disord
Reduction of temporal lobe volume in bipolar disorder: A preliminary report of magnetic resonance imaging
Arch Gen Psychiatry
Psychosocial outcomes of children of unipolar depressed, bipolar, medically ill and normal women: A longitudinal study
J Consult Clin Psychol
The family history method using diagnostic criteria
Arch Gen Psychiatry
Psychosocial functioning and depression: Distinguishing among antecedents, concomitants, and consequences
Psychol Bull
Cerebral metabolic rates for glucose in mood disorders
Arch Gen Psychiatry
Reduction of prefrontal cortex glucose metabolism common to three types of depression
Arch Gen Psychiatry
Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder
Arch Gen Psychiatry
Life stressors and social resources affect posttreatment outcomes among depressed patients
J Abnorm Psychol
Neuroimaging in child psychiatry
Current Opinion in Psychiatry
Psychiatric syndromes in Huntington's disease
Am J Psychiatry
Schizophrenia—A brain disease?
Br J Psychiatry
White matter hyperintensity on magnetic resonance imaging: Clinical and neuroanatomic correlates in the depressed elderly
J Neuropsychiatry Clin Neurosci
Quantitative cerebral anatomy in depression
Arch Gen Psychiatry
Frontal-subcortical circuits and human behavior
Arch Neurol
Emotional disturbances associated with focal lesions of the limbic frontal lobe
A functional anatomical study of unipolar depression
J Neurosci
Subcortical abnormalities detected in bipolar affective disorder using magnetic resonance imaging
Arch Gen Psychiatry
National Institute of Mental Health Treatment of Depression Collaborative Research Program
Arch Gen Psychiatry
Subcortical hyperintensities on brain magnetic resonance imaging: A comparison of normal and bipolar subjects
J Neuropsychiatry
Cited by (18)
Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder
2011, Psychiatry Research - NeuroimagingNoradrenergic and Serotonergic Neuroendocrine Responses in Prepubertal, Peripubertal, and Postpubertal Rats Pretreated with Desipramine and Sertraline
2002, Journal of the American Academy of Child and Adolescent PsychiatryPreschool Major Depressive Disorder: Preliminary Validation for Developmentally Modified DSM-IV Criteria
2002, Journal of the American Academy of Child and Adolescent PsychiatryPractice parameters for the assessment and treatment of children and adolescents with depressive disorders
1998, Journal of the American Academy of Child and Adolescent PsychiatryRandomized, controlled trial of amitriptyline versus placebo for adolescents with 'treatment-resistant' major depression
1998, Journal of the American Academy of Child and Adolescent PsychiatryChild and adolescent bipolar disorder: A review of the past 10 years
1997, Journal of the American Academy of Child and Adolescent Psychiatry
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.