Exploring psychotropic drug efficacy

Leucht et al (pp. ) argue that the perceived benefit of prescribing psychotropic medications has been undermined by a number of recent studies and reports, in both the academic and lay literature. The authors also contend that as clinical practice has become more highly specialised, psychiatrists may have lost touch with the evidence base for medicines outside their own field and thus are unable to judge the comparative efficacy of psychiatric drugs. In a review of meta-analyses for 48 drugs in 20 medical diseases and 16 drugs for the treatment of 8 psychiatric disorders, Leucht et al found that the latter were not generally less efficacious than the former. The authors caution, however, that any comparison of outcomes in different diseases can only be undertaken from a qualitative perspective given that any improvement in outcome over placebo must be considered in the context of the specific disease concerned.

Although prescribing of antidepressants is widespread, studies of antidepressant efficacy indicate that response is highly variable and unpredictable. Wiles et al (pp. ) considered the role of depression severity in relation to likelihood of response to either a selective serotonin reuptake inhibitor (SSRI) or a noradrenaline reuptake inhibitor (NARI), in the context of a randomised trial conducted in primary care. Six weeks after randomisation, little evidence for interaction between antidepressant type and depression severity was found.

Mental disorders and mortality

The raised mortality rates consistently found among those with mental disorders have long been a source of concern. Two studies focus on this issue in the Journal this month, one based in Finland and a second in the USA. In a population-based sample, Markkula et al (pp. ) found a post-adjustment elevation in the hazard ratio for death for those diagnosed at baseline with depressive and alcohol use disorders. They also found an elevation in risk of unnatural death for those diagnosed with anxiety disorders or alcohol dependence. Looking specifically at mortality associated with depression among those who have suffered acute myocardial infarction, Scherrer et al (pp. ) found that risk was greatest for patients with insufficiently treated depression and that risk was also present for those with treatment-resistant depression. The authors note that in the latter group, increased risk of mortality was partly explained by the presence of comorbid disorders.

Impact of early-life experiences

Read & Bentall (pp. ) regard as highly promising the emerging interest among researchers in considering negative childhood experiences in relation to the development of mental health problems in later life, and call for more research to be directed towards understanding the biological and psychological mechanisms involved. They also remind us of the importance of asking about childhood events in the clinical setting in order to optimise formulations and treatment plans.

Keyes et al (pp. ) address the question of whether childhood maltreatment increases vulnerability to a range of specific mental disorders through different specific mechanisms or through giving rise to a general liability to dimensions of psychopathology. Using a latent variable approach to analyse data obtained from a nationally representative sample of US adults, the authors found that the association between childhood maltreatment and common psychiatric disorders was mediated through liability to develop internalising and externalising psychopathology. Gender-specific effects were also found in relation to specific types of abuse: physical abuse was associated with externalising liability in men and internalising liability in women.

Children of depressed mothers are known to be at elevated risk of a range of developmental and mental health problems. Data from the ALSPAC sample were utilised by Barker et al (pp. ) to investigate the relative impact of exposure to maternal psychopathology compared with associated risk factors (such as having a single caregiver, being of low socioeconomic status and being born to a young mother). In addition to the effects of exposure to maternal depression, exposure to each additional risk factor increased the odds for internalising and externalising disorders in boys and girls by at least 20%. The authors conclude that preventive strategies need to be aimed at the treatment of maternal depression, as well as targeting associated risk factors.