A piece of the puzzle: Does bipolarity partly explain the high prevalence of treatment resistance in depression?

In this cross-sectional study we examined whether the prevalence of treatment resistant depression (TRD) can be partly attributed to level of bipolarity. We included data of 201 patients with either episodic depression or TRD, who received treatment for their depression at either an outpatient or 2nd opinion/daytime setting, within a specialised mental healthcare department in the Netherlands. Whether level of TRD, assessed by the 'Dutch Measure for quantification of Treatment Resistance in Depression', can be partly explained by level of bipolarity, assessed by 'the Bipolarity Index', was examined using linear regression. We found no direct association between level of TRD and level of bipolarity, nor did comorbid anxiety disorders obscure an existing association. In this study we found no evidence for overlooked bipolarity contributing to the high prevalence of TRD. If replicated, we could state that additional screening on bipolarity with an instrument such as the 'Bipolarity Index' in the specialised mental health care is unnecessary.

The Additional Effect of Individualized Prescriber-Focused Feedback on General Guideline Instruction in Reducing Antipsychotic Polypharmacy in Inpatients.

PURPOSE/BACKGROUND: Antipsychotic polypharmacy (APP) is the concurrent use of more than one antipsychotic by a patient. Multiple antipsychotics are often prescribed, although all relevant guidelines discourage this practice. These recommendations are based on a lack of evidence for effectiveness and an increased risk of serious adverse events with APP. Studies on the effects of educational interventions targeted at physicians have demonstrated inconclusive results. Moreover, it is unclear how individualized these interventions need to be. In this study, we aimed to assess the effect of a general intervention and the additional impact of an individualized, prescriber-focused intervention on guidelines adherence, that is, the prescription of APP. METHODS/PROCEDURES: We conducted a 36-month 2-step serial intervention study with 4 stages of 9 months each (baseline, general intervention, addition of an individualized intervention, and follow-up) including all 20 inpatient units of one regional mental health organization. The primary outcome was the proportion of patients with regular prescriptions for APP ≥30 consecutive days across all patients with a prescription of at least one antipsychotic. The secondary outcome was the proportion of patient days on APP over the total number of patient days on at least one antipsychotic. FINDINGS/RESULTS: The general intervention was ineffective on both outcome measures. Addition of an individualized intervention decreased the proportion of patients with prescriptions for episodes of persistent APP significantly by 49.6%. The proportion of patient days on APP significantly decreased by 35.4%. IMPLICATIONS/CONCLUSIONS: In contrast to a general intervention, the addition of an individualized intervention was effective in improving adherence to guidelines with respect to APP prescription in inpatients.

Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness.

OBJECTIVE: The purpose of this study was to review the scientific evidence for neurobiological rationale, efficacy, tolerability and cost effectiveness of antipsychotic polypharmacy (APP). DATA SOURCES: A systematic literature search of Medline, Embase, Ovid and the Cochrane Database of Systematic Reviews until April 2012 was carried out. RESULTS: Theories behind APP have only modest pre-clinical and clinical evidence. We found limited statistical evidence supporting modest efficacy of APP in patients with psychotic symptoms refractory to clozapine. APP is associated with increased mortality, metabolic syndrome, decreased cognitive functioning, high dose prescription and non-adherence. It brings up extra costs, lacking evidence for cost-effectiveness. CONCLUSIONS: Pre-clinical studies underpinning neurobiological hypotheses in APP are lacking. Evidence supporting efficacy of APP is limited with modest beneficial clinical relevance. APP is associated with several serious adverse effects and increased health costs. In the absence of more convincing pre-clinical support and clinical evidence we advise adherence to existing guidelines and limiting combinations of antipsychotics (in consideration with other pharmacotherapeutic, somatic and psychotherapeutic options) to patients with clozapine-refractory psychosis in well-evaluated individual trials that might need 10 weeks or more.