The EU paediatric regulation:: Effects on paediatric psychopharmacology in Europe

Child and adolescent psychiatry is a relatively young field and the recognition, classification, and treatment of disorders in children and adolescents lag behind those in adults. In recent years there is an increasing awareness of the differences between children and adults in psychopathology and pharmacology. Related to this new paediatric regulations have been introduced. This article reviews the regulatory and legislative measures that were adopted in the EU in 2007 and the subsequent impact of these measures on the field of paediatric psychopharmacology.The consequences of the paediatric regulation in the EU are reflected in several domains: regulatory, research aimed at drug development and clinical practices. In the regulatory domain, the consequences include: new paediatric indications, inclusion of special (class) warnings, specification of dose regimens, and information on safety specific to children and adolescents, and development of new medicinal formulations.The paediatric regulation leads to timely development of paediatric friendly formulations and better quality of the clinical evidence. In clinical practices, an increased awareness of the uniqueness of paediatric pharmacology is emerging among medical professionals, and subsequent improvement of medical care (i.e. correct doses, appropriate formulation, monitoring for expected adverse events). In addition, clinical guidelines will have to be revised more frequently in order to integrate the recently acquired knowledge.The new regulations stimulate transparency and discussions between academia, pharmaceutical industry, and regulators. The purpose is to optimize clinical research and obtain evidence for paediatric psychopharmacology, thereby providing adequate support for treatment.     

Delineation of the clinical picture of Dysphoric/Mixed Hypomania

BACKGROUND: While Mixed Depression (i.e. depression plus subthreshold concurrent manic/hypomanic symptoms) has recently seen a wave of studies, little is known about Dysphoric/Mixed Hypomania (i.e. combination of syndromal hypomania and depression) compared to Bipolar I Disorder Mixed State (i.e. combination of syndromal mania and depression). STUDY AIM: To delineate the clinical picture of Dysphoric/Mixed Hypomania. METHODS: Consecutive 441 Bipolar II Disorder (BP-II) Major Depressive Episode (MDE) outpatients were cross-sectionally assessed for depression and concurrent hypomanic symptoms when presenting for treatment of depression, by a mood disorder specialist psychiatrist (FB), using the Structured Clinical Interview for DSM-IV, in a private practice. Consecutive 275 remitted BP-II were also assessed for the clinical picture of past (recalled) Hypomania. Dysphoric Hypomania was defined as the co-occurrence of DSM-IV irritable mood Hypomania and MDE. RESULTS: Frequency of Dysphoric Hypomania was 17.0%, and it was 66.4% for Mixed Depression. Irritable mood, always present by definition in Dysphoric Hypomania, was present in 65.9% of recalled Hypomania and elevated mood in 81.4%. Dysphoric Hypomania had significantly more racing/crowded thoughts, and much less increased goal-directed activity. Functioning was always impaired in Dysphoric Hypomania (by definition), while it was improved in most recalled Hypomanias. Factor structure was different: recalled Hypomania had three factors ('elevated mood', 'irritability and racing/crowded thoughts', 'goal-directed and risky overactivity'), Dysphoric Hypomania had five factors ('depressive vegetative symptoms', 'low mood and psychomotor agitation', 'risky activities', 'loss of interest', 'racing/crowded thoughts and suicidality'). DISCUSSION: Dysphoric Hypomania was uncommon among depressed outpatients (while Mixed Depression was common). Its clinical picture was closer to depression than to hypomania. If it were seen as a simple depression, antidepressants could be used alone (i.e. not protected by mood stabilising agents), risking the worsening of intra-depression irritable hypomania (which was related to suicidality). Systematic assessment of intra-depression hypomanic symptoms is supported.     

“There are always two sides to these things”: Managing the dilemma of serious adverse effects from SSRIs

Over the past two decades, evidence and regulatory responses have surfaced regarding associations between selective serotonin reuptake inhibitors (SSRIs) and serious adverse effects, especially akathisia, aggression and suicidality. Given increasing concern about depression prevalence and harm, the dominance of biomedical approaches, and the normalisation of antidepressant use, reports about the potential for serious adverse effects from SSRIs present a dilemma for people working in depression intervention: the drugs are linked to “two conflicting claims” that they may either decrease or increase harm. We present data from in-depth semi-structured interviews with nine professionals in New Zealand working in fields relating to depression and supportive of SSRIs, to investigate the negotiation of this dilemma. We analysed participants’ talk about akathisia, aggression and suicidality associated with SSRIs, and found the use of rhetorical strategies that minimised the significance of risks, countered risks with notions of benefit and/or questioned the validity of risks. These discursive resources provided ways of mitigating the dilemma otherwise posed by evidence of adverse drug effects. However in doing so they referenced notions of SSRI benefit that relied upon assumptions about the efficacy of the drugs, risks of untreated depression, and the impact of adverse effects. Overall, our analysis highlights ways in which evidence of serious adverse effects from SSRIs can be rhetorically contained and undermined.     

The use of antidepressants and introduction of new types in different socio-economic groups: A Danish registry-based cross-sectional study

Background: Danish registry-based studies have found socio-economic differences in drug use. The extent to which the use of antidepressants differs between socio-economic groups is unknown. Aim: 1) to examine the association between socio-economic status (SES) and use of antidepressants 2) to evaluate the introduction of new types of antidepressants. Methods: A registry-based cross-sectional study linking information from administrative registries in North Jutland County, Denmark, 1995–99. Main outcome measures: 1) the prevalence proportion for use of antidepressants in different SES groups and by sex, and the estimated prevalence proportion ratio; 2) the proportion using the new drugs in different socio-economic groups through the study period. Results: Women used antidepressants more than twice as often as men with an increasing tendency for both men and women. The use of antidepressants was highest in persons outside the labour market. Among employees, the proportion using new types of antidepressants increased from 1% to 18%. High SES seemed to correlate to higher use of new antidepressants. The new antidepressants were introduced faster among men compared with women. Conclusion: The study showed differences in purchase of antidepressants in different SES groups. Furthermore, it showed faster introduction of new antidepressants among men and employees with high SES.     

Antidepressant‐Induced Suicidality: An Update

Evidence suggests that antidepressant treatment may in some cases result in worsening depression and increased risk of suicidality in pediatric and adolescent patients. The United States Food and Drug Administration requires that antidepressants carry a black box warning regarding such a risk in patients up to age 24. Many studies of antidepressant‐induced suicidality among adults have also reported an increased risk, while several other investigations involving that population have not supported such a finding. This article provides an update of the controversy surrounding antidepressants as a potential cause of suicidal ideations or behavior. Antidepressant‐induced suicidality appears to be an uncommon occurrence but also a legitimate phenomenon. Close monitoring and a follow‐up care should be provided for patients after initiation of a new antidepressant.