1 de noviembre de 2012

A consensus statement for safety monitoring guidelines of treatments for major depressive disorder

A consensus statement for safety monitoring guidelines of treatments for major depressive disorder

Seetal Dodd, Clinical Senior Lecturer; Senior Fellow,1 Gin S Malhi, Professor and Head,2 John Tiller, Professor,3 Isaac Schweitzer, Professor, Ian Hickie, Executive Director,4 Jon Paul Khoo, Consultant Psychiatrist,5 Darryl L Bassett, Adjunct Professor,6 Bill Lyndon, Clinical Senior Lecturer, Philip B Mitchell, Head,7 Gordon Parker, Scientia Professor,7 Paul B Fitzgerald, Professor,8 Marc Udina, Psychiatrist,9 Ajeet Singh, Consultant Psychiatrist & Clinical Senior Lecturer,1 Steven Moylan, Clinical Lecturer,10 Francesco Giorlando, Psychiatry Registrar,3 Carolyn Doughty, Psychologist; Clinical Lecturer,11 Christopher G Davey, Consultant Psychiatrist,12 Michael Theodoras, Director,13 and Michael Berk, Professor14



This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring.


Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content.


Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment.


The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.

Major depressive disorder (MDD) afflicts an estimated 16% to 20% of the population during their lifetime [1-3]. In Australia 3.1% of men and 5.1% of women are affected in any 12-month period [4]. Current treatments include pharmacological, psychological and physical therapies. Antidepressants are amongst the most commonly prescribed classes of drugs [5] and their use continues to grow [6]. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice.
The adverse effects of antidepressants vary between individual drugs and drug classes and have been extensively documented [7-9]. In general tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are associated with more severe adverse effect profiles than the newer antidepressants. MAOIs interact with dietary tyramine necessitating patient counselling about dietary risks [10]. While there is substantial intra-variation in tolerability, MAOIs and TCAs retain an important place in the management of refractory depression [10] and the more putatively biological depressive disorders such as melancholia [11]. The selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs) broadly have lower toxicity than older agents [12], but have also been associated with significant adverse effects including cardiovascular effects, sexual dysfunction [8], weight gain [13], electrolyte disturbances, haematological effects [8] and hepatic damage [14]. A possible increase in suicidal thoughts and self-destructive behaviour in paediatric patients prescribed antidepressants has been documented [15] and regulatory warnings have been extended for young people up to the age of 25 years [16]. Most treatment guidelines recommend clinician vigilance for adverse symptoms or caution when administering antidepressants to people from high risk populations, including those with a prior history of medication sensitivity, the medically unwell [17], the elderly [18], adolescents [19] and pregnant or breastfeeding women [20]. Specific recommendations are, however, not widely available.

MDD is frequently comorbid with physical problems and illnesses including obesity [21], cardiovascular disease and diabetes mellitus [22], substance misuse and other mental disorders, reflecting both antecedent and consequence pathways [23]. This may affect the efficacy of treatments for MDD as well as increasing the vulnerability of patients to adverse effects and risk of harmful drug interactions.

Non-pharmacological treatments for MDD including psychotherapy [24] have also been associated with adverse events. Such adverse effects are, however, less frequently reported. Complementary and alternative treatments can be associated with adverse events [25] and pharmacological interactions. Even exercise, which has an established evidence base in depression treatment [26], may be associated with adverse effects in individuals with comorbid cardiovascular disease, prolonged QT interval or who attempt strenuous activity without a period of adjustment [27]. However, gradual exercise training for rehabilitation following a major cardiac event in depressed individuals is associated with 73% reduced mortality when compared to depressed individuals who did not participate in exercise training [28].
Guidelines exist for safety monitoring of treatments for schizophrenia [29], bipolar disorder [30] and for specific medications (e.g. clozapine) [31], but there are none for clinical depression. Previous Australian guidelines focus on treatment algorithms [32]. Guidelines for baseline screening and safety monitoring of antidepressant treatments may significantly reduce risks of adverse events.
FUENTE: http://anp.sagepub.com/content/45/9/712.full