Geographical disparities in prescription practices of lithium and clozapine: a community‐based study

Verdoux, Hélène; Pambrun, Élodie; Cortaredona, Sébastien; Coldefy, Magali; Neindre, Charlène Le; Tournier, Marie; Verger, Pierre

doi:10.1111/acps.12554

Cited by 18 publications

(11 citation statements)

References 45 publications

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“…Nevertheless, adjunctive lithium was less frequently prescribed in our survey (4.11% of all participants) than for instance augmentation with antipsychotics (25.67% of all participants). Probably, the use of lithium in the clinical practice is limited by the need of continuous plasma level measurements to ensure the achievement of the therapeutic window and due to the anticipation of adverse effects . On the other hand, the increased risk for metabolic adverse effects and sedation should be critically taken into account when considering SGA augmentation strategies.…”

Section: Discussionmentioning

confidence: 99%

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder

Dold

Bartova

Mendlewicz³

et al. 2018

Acta Psychiatr Scand

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ObjectiveThis multicenter, multinational, cross‐sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD).MethodSociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses.Results60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in‐patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive‐compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses.ConclusionOur findings suggest a clear association between augmentation/combination strategies and treatment‐resistant/difficult‐to‐treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities.

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Section: Discussionmentioning

confidence: 99%

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder

Dold

Bartova

Mendlewicz³

et al. 2018

Acta Psychiatr Scand

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“…Clozapine ADRs of interest showed a peak in 2008, but an overall increase was observed between 2010 and 2018. One could argue that this upward trend may have been associated with a range of factors, including the increasing rates of worldwide availability of clozapine due to an overwhelming evidence of its effectiveness [2,[49][50][51] and/or a major awareness of the relevant and significant impact of pharmacovigilance processes and issues, resulting in a rise of spontaneous reporting practices related to safety monitoring of medicinal products in general [52].…”

Section: Discussionmentioning

confidence: 99%

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

et al. 2020

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Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal- and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose- and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern.

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“…In a study in France, only 1.2% of the users of antipsychotics was using clozapine. However, 6.6% of the total population was using antipsychotics, so the clozapine prescription rate among patients with NAPD may be much higher ( 13 ). Although different study designs may contribute to these differences, a large international database study ( 25 ) also showed that prescription rates in the Netherlands are higher than in most other countries.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of clozapine prescription rates show large international differences ( 13 – 15 ). In the Netherlands, the proportion of patients with Non-Affective Psychotic Disorder (NAPD) using this drug is unknown.…”

Section: Introductionmentioning

confidence: 99%

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

et al. 2018

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Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients).Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH).Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8–34.7% (mean: 23.0%), type 2: 0–8.2% (mean: 3.5%), type 3: 1.7–15.6% (mean: 6.9%), type 4: 1.8–16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0–90.9% (mean: 68.8%). These figures were lower in early intervention teams.Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher.Registration number: NTR5135 http://www.trialregister.nl/trialreg/index.asp

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Geographical disparities in prescription practices of lithium and clozapine: a community‐based study

Abstract: A sufficient density of GPs and an effective communication and collaboration between mental healthcare services and primary care seems to favor greater access to psychotropic drugs with demonstrated efficacy but often viewed as 'risky' to prescribe.

Cited by 18 publications

References 45 publications

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

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