New-generation antidepressants, suicide and depressed adolescents: how should clinicians respond to changing evidence?

Adolescent Service, Prince of Wales Hospital, Randwick, Australia. m.dud
Australian and New Zealand Journal of Psychiatry (Impact Factor: 3.77). 07/2008; 42(6):456-66. DOI: 10.1080/00048670802050538
Source: PubMed

ABSTRACT The purpose of the present paper was to identify, from the voluminous literature on efficacy and safety in new-generation antidepressants (NGAs) with depressed children and adolescents, practical clinical strategies for acute phase treatment. To this end a pragmatic survey of studies and reviews was undertaken. Meta-analyses of randomized controlled trials of NGAs in depressed children and adolescents have noted a comparative lack of efficacy, and a weak but statistically significant increased risk of self-harm and suicidal thoughts. But NGA prescription rates and youth suicide rates are generally inversely related, and ensuing 'black box' warnings about NGAs, by deterring NGA prescribing, have possibly contributed to rising youth suicide rates. In moderate-severe depression, benefits for fluoxetine and possibly other NGAs demonstrably outweigh risks. NGAs are not present in adolescents who die by suicide. Concern about NGA risks must be balanced against risks of non-treatment. While mild depression entails regular review, psychoeducation, self-care strategies and psychological interventions, NGAs should be administered concurrently with psychological treatments if depression is moderate- to severe, or if mild depression persists. Patients should be warned about off-label status of NGAs in depression, serious side-effects such as 'activation', suicidality, emotional blunting and manic switches, the need for adherence and avoiding abrupt discontinuation. They should be monitored early and regularly. Better evidence is required regarding psychological treatments, clinical course, and clinical practice trends. In moderate-severe depression the risk of suicide if NGAs are not used may outweigh any risk of self-harm associated with them.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing community and government recognition of the magnitude and impact of adolescent depression. Family based interventions have significant potential to address known risk factors for adolescent depression and could be an effective way of engaging adolescents in treatment. The evidence for family based treatments of adolescent depression is not well developed. The objective of this clinical trial is to determine whether a family based intervention can reduce rates of unipolar depressive disorders in adolescents, improve family functioning and engage adolescents who are reluctant to access mental health services. The Family Options study will determine whether a manualized family based intervention designed to target both individual and family based factors in adolescent depression (BEST MOOD) will be more effective in reducing unipolar depressive disorders than an active (standard practice) control condition consisting of a parenting group using supportive techniques (PAST). The study is a multicenter effectiveness randomized controlled trial. Both interventions are delivered in group format over eight weekly sessions, of two hours per session. We will recruit 160 adolescents (12 to 18 years old) and their families, randomized equally to each treatment condition. Participants will be assessed at baseline, eight weeks and 20 weeks. Assessment of eligibility and primary outcome will be conducted using the KID-SCID structured clinical interview via adolescent and parent self-report. Assessments of family mental health, functioning and therapeutic processes will also be conducted. Data will be analyzed using Multilevel Mixed Modeling accounting for time x treatment effects and random effects for group and family characteristics. This trial is currently recruiting. Challenges in design and implementation to-date are discussed. These include diagnosis and differential diagnosis of mental disorders in the context of adolescent development, non-compliance of adolescents with requirements of assessment, questionnaire completion and treatment attendance, breaking randomization, and measuring the complexity of change in the context of a family-based intervention.Trial registration: Australia and New Zealand Clinical Trials Registry Title: engaging youth with high prevalence mental health problems using family based interventions; number 12612000398808. Prospectively registered on 10 April 2012.
    Trials 11/2013; 14(1):384. · 2.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment. Methods: The MEDLINE/PubMed, EMBASE and electronic databases were searched from inception to October 1, 2013, for randomized controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing trials of pharmacological and psychotherapeutic approaches to treatment-resistant depression (TRD). Results: Switching to a different antidepressant is a useful option following nonresponse to a first-line agent. Although widely used in clinical practice, there is limited evidence to support antidepressant combination for TRD. Notwithstanding evidence for lithium or T3 augmentation to be successful in TRD, most studies were carried out when participants were treated with tricyclic antidepressants (TCA). Of the available strategies to augment the response to new-generation antidepressants, the use of some atypical antipsychotics is best supported by evidence. Several novel therapeutic options are currently discussed. Evidence suggests that cognitive therapy (CT) is an effective strategy for TRD. Conclusions: The success of switching to a different antidepressant following a first-line agent is supported by evidence, but there is limited evidence for effective combination strategies. Lithium and T3 augmentation of TCA have the strongest evidence base for successful treatment of TRD. The use of augmentation of newer-generation antidepressants with atypical antipsychotics is supported by a growing evidence base. Current evidence supports CT as an effective strategy for TRD. There is a need for additional large-scale RCT of TRD. The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD. © 2014 S. Karger AG, Basel.
    Psychotherapy and Psychosomatics 01/2014; 83(2):70-88. · 9.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We sought to examine potential barriers to the use of evidence-based guidelines for youth depression in a tertiary specialist mental health service, as part of an initiative to implement evidence based practice within the service. This was a qualitative study adopting a social constructionist perspective using focus groups. The focus groups, conducted with all clinicians (medical and allied health), were audiotaped, transcribed and thematic analysis was undertaken. Clinicians were asked about the barriers to implementing four key recommendations from the National Institute for Health and Clinical Excellence (NICE) guidelines. Barriers existed at (i) the individual clinician level; (ii) the clinical level in terms of the presentation of young people; and (iii) the service level. The key individual clinician level barrier was a stated belief that the guidelines were not relevant to the young people presenting to the service, with little evidence to guide practice. Related, the main barrier with regard to the clinical presentation was the severity and complexity of this presentation, often making the delivery of interventions like cognitive behavioural therapy (CBT) difficult. At the service level, a lack of integration with primary and secondary level care meant sequencing interventions according to guideline recommendations was difficult. There is a clear imperative to develop the evidence base to ensure that effective treatments for young people aged up to 25 years with severe and complex disorders that include comorbid conditions, suicide risk and psychosocial difficulties are investigated and disseminated. Furthermore, this work has highlighted the need for greater investment in models of care that ensure integration between existing primary and secondary care and enhanced specialist early intervention mental health services for young people.
    Australian and New Zealand Journal of Psychiatry 11/2011; 45(11):993-1001. · 3.77 Impact Factor