Thomas Charpeaud

Clinicians' Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

Abstract Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists’ attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians’ attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.

Investigational drugs in recent clinical trials for treatment-resistant depression.

ABSTRACT Introduction: The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.

What is the evidence for the use of second-generation antipsychotic long-acting injectables as maintenance treatment in bipolar disorder?

Abstract Background: In recent years, the use of second-generation antipsychotics long-acting injectable in the maintenance treatment of bipolar disorder has sparked interest in improving adherence and reducing the risk of relapse. Aims: This report aims to review the available evidence concerning the use of second-generation antipsychotics depot in bipolar disorder and specify the typology of patients that could be eligible for this formulation. Methods: A systematic review of the literature was conducted using Pubmed and EMBASE. Results: Data available for the clinician assessing the interests of second-generation antipsychotics depot in long-term treatment of bipolar disorder are limited to risperidone. It seems particularly relevant for bipolar patients with poor adherence or early in the course of illness and can be used as monotherapy with manic polarity. It should always be considered for use in combination with at least one other mood stabilizer in patients with depressive polarity. As for other medications, the benefit/risk ratio for a long-acting should be evaluated individually. Conclusions: If using a depot formulation could be considered for all patients in order to approach a perfect compliance, patients with certain clinical profiles could be an argument for prioritizing the use of long-acting injectable as maintenance treatment. Additional studies are needed with other second-generation antipsychotics depot in bipolar patients to generalize their use in the maintenance treatment of bipolar disorder but the future golden standard of studies with long-acting formulations remains to be defined.

Rural-urban variation in incidence of psychosis in France: a prospective epidemiologic study in two contrasted catchment areas

BackgroundThe aim of our study is to provide data on the incidence of psychotic disorders in France and compare the incidence rates in populations with different levels of urbanization.MethodsWe prospectively included the incident cases of psychotic disorders from two catchment areas with contrasted levels of urbanization. In the more rural area, we also calculated incidence rates in three different groups of population defined by the size of towns in which they live (small, medium and large towns).ResultsThe annual incidence of psychosis was greater in the urban area (36.02/100000 person-year at risk) than in the rural area (17.2/100000 person-year at risk).Non-affective psychoses were the majority of cases and their incidence was greater in males and younger subjects. The affective psychoses were slightly more frequent in women and showed less variation with age. In the rural centre, greater levels of urbanicity were associated with an increase in the incidence of all psychoses (affective and non-affective).ConclusionsOur study confirms previous observations of increased incidence rates for non-affective psychoses in the more urbanized areas and suggests that a similar pattern might be present for affective psychoses.

Asenapine in bipolar I disorder: evidence and place in patient management

Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Post hoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment. Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.

Dépression résistante : les stratégies de changement et d’association de médicaments antidépresseurs

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

Dépression résistante : les stratégies de potentialisation

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

Switching and combining strategies of antidepressant medications

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.