PMID- 10674194
OWN - NLM
STAT- MEDLINE
DCOM- 20000229
LR  - 20221207
IS  - 1056-4993 (Print)
IS  - 1056-4993 (Linking)
VI  - 9
IP  - 1
DP  - 2000 Jan
TI  - Pharmacotherapy of early-onset depression. Update and new directions.
PG  - 135-57
AB  - Although an increased recognition of depressive disorders in youth represents a 
      positive conceptual change over the past decades, there still is a very limited 
      amount of research on useful treatment interventions. The paucity of data is 
      particularly keen for the use of psychotropic drugs. For example, by applying the 
      criteria suggested by the International Psychopharmacology Algorithm Project, 
      there barely are enough first-grade ("Level A," meaning at least two RCTs) data 
      supporting the short-term efficacy of antidepressants (the SSRIs) in the 
      treatment of juvenile depression. And yet, limited data have not translated into 
      limited use in routine clinical practice. In fact, the use of antidepressant 
      medications has increased exponentially over the last decade, a change that is 
      especially conspicuous for individuals less than 18 years of age. The perceived 
      safety of the SSRIs and other novel antidepressants is partly at the root of 
      their increased popularity. Data regarding their safety are likewise quite 
      limited, however, and essentially are nonexistent for longer-term use. Based on 
      the reviewed data, a medication algorithm for the treatment of early-onset 
      depression can be suggested (Fig. 1). The algorithm underscores the need for 
      adequate evaluation and diagnostic assessment, with particular attention to 
      comorbid conditions (such as a bipolar diathesis) that may dictate alternative 
      treatment strategies. In general, psychotherapy is the initial approach to 
      juvenile MDD, with medication use reserved for more severe cases or those not 
      responding to psychotherapy alone. Given that only two types of psychotherapy and 
      two SSRIs have adequate controlled short-term efficacy data, all but the initial 
      steps must be undertaken guided by clinical judgment and an individualized 
      risk-benefit analysis. An algorithm such as this one, based on the very limited 
      efficacy and safety data available, may be viewed as setting priorities for a 
      comprehensive research agenda, more than dictating rigid treatment guidelines. In 
      closing, it can be suggested that future research on the pharmacotherapy of 
      early-onset depressive disorder pay particular attention to the following three 
      aspects: 1. Too many drugs, too few data: Rapid advances in drug development have 
      led to a plethora of available antidepressant agents. It is clear that there are 
      many more agents available than can be adequately studied at present. Because 
      many such agents are mechanistically similar, if not identical, it may be wise to 
      focus research efforts on truly novel agents, particularly those (such as the CRH 
      receptor antagonists, or those affecting neurosteroidogenesis) whose action is 
      based on preclinical and clinical pathophysiologic disease paradigms. 2. 
      Longitudinal follow-up and maintenance studies: Essentially all reviewed 
      treatment studies have been short-term trials. There is a marked paucity of 
      longer-term follow-up data, or of naturalistic and "real-world" effectiveness 
      studies. For example, one of the few studies addressing maintenance 
      pharmacotherapy for early-onset depression has demonstrated surprisingly high 
      recurrence rates, even for those subjects actively on maintenance medication. 3. 
      Long-term safety: Clinicians and parents alike often face difficult decisions 
      regarding the long-term exposure of antidepressant drugs on the developing brain. 
      Although no definitive long-term safety data are likely to become available 
      anytime soon, real risks, such as suicide, and potential sequelae of long-term 
      exposure to the underlying illness itself need all to be part of any 
      decision-making process. Preclinical studies have shown that brain-derived 
      neurotrophic factor (BDNF) levels can be upregulated by antidepressants, and low 
      BDNF factors have been associated with atrophic brain changes in recurrent forms 
      of adult MDD. Although these observations require specific application to 
      juvenile forms of the disorder, they raise the exciting prospect that the natural 
      course of the illne
FAU - Martin, A
AU  - Martin A
AD  - Yale Child Study Center, Yale University School of Medicine, New Haven, 
      Connecticut, USA. Andres.Martin@Yale.Edu
FAU - Kaufman, J
AU  - Kaufman J
FAU - Charney, D
AU  - Charney D
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Child Adolesc Psychiatr Clin N Am
JT  - Child and adolescent psychiatric clinics of North America
JID - 9313451
RN  - 0 (Antidepressive Agents)
RN  - 0 (Serotonin Uptake Inhibitors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Algorithms
MH  - Antidepressive Agents/adverse effects/*therapeutic use
MH  - Brain/drug effects
MH  - Child
MH  - Clinical Trials as Topic
MH  - Combined Modality Therapy
MH  - Depressive Disorder/diagnosis/*drug therapy/psychology
MH  - Humans
MH  - Selective Serotonin Reuptake Inhibitors/adverse effects/therapeutic use
MH  - Treatment Outcome
RF  - 125
EDAT- 2000/02/16 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/16 09:00
PHST- 2000/02/16 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/16 09:00 [entrez]
PST - ppublish
SO  - Child Adolesc Psychiatr Clin N Am. 2000 Jan;9(1):135-57.