Leitliniengerechte Pharmakotherapie der bipolaren Störung: Lithium und andere Optionen

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Leitliniengerechte Pharmakotherapie der bipolaren Störung:

Lithium und andere Optionen

München, Trialogisches Symposium und Informationstag, 18.02.2017

PD Dr. med. habil. Emanuel Severus, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav

Carus, TU Dresden

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www.uniklinikum-dresden.de

Potentielle Interessenskonflikte

I Referent bei wissenschaftlichen Fortbildungsveranstaltungen während der letzten 5 Jahre: Lundbeck, Servier and Roche

I Mitglied von IGSLI

I Co-Chair der gemeinsamen „IGSLI ISBD Lithium Task Force“

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Evidenzbasierte Medizin

I Evidenzbasierte Medizin ist der gewissenhafte, ausdrückliche und vernünftige Gebrauch der gegenwärtig besten externen,

wissenschaftlichen Evidenz für Entscheidungen in der medizinischen Versorgung individueller Patienten.

I Die Praxis der Evidenzbasierten Medizin bedeutet die Integration individueller klinischer Expertise mit der bestverfügbaren

externen Evidenz aus systematischer Forschung.

Sackett et al., 1997

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www.uniklinikum-dresden.de 7

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WFSBP, 2013

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Tohen et al., 2009

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Tohen et al., 2009

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Grunze et al., 2013 WFSB, 2013

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Akutbehandlung Bipolare Manie

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Zugelassene orale Behandlungsoptionen in der Akutbehandlung der bipolaren Manie

I Aripiprazol I Asenapin I Lithium

I Olanzapin

I Quetiapin

I Risperidon

I Valproat

I Ziprasidon

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S3 – Leitlinie, 2014

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CANMAT, 2013

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Managing mania or hypomania in adults in secondary care

I If a person develops mania or hypomania and is not taking an antipsychotic or mood stabiliser, offer haloperidol, olanzapine, quetiapine, or risperidone, taking into account any advance

statements, the person’s preference, and clinical context (including physical comorbidity, previous response to treatment, and side

effects).

I If the person is already taking lithium, check plasma lithium levels to optimise treatment and consider adding haloperidol, olanzapine, quetiapine, or risperidone.

I If a person develops mania or hypomania and is taking an

antidepressant as monotherapy, consider stopping the antidepressant and offer an antipsychotic regardless of whether the antidepressant is stopped.

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NICE, 2014

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WFSBP, 2013

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Prophylaxe Bipolarer Erkrankungen

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Zugelassene Behandlungsoptionen in der Langzeittherapie Bipolarer Erkrankungen I Aripiprazol

I Carbamazepin I Lamotrigin

I Lithium

I Olanzapin

I Quetiapin

I Valproat

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CANMAT, 2013

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Managing bipolar disorder in adults in the longer term in secondary care

I When planning long term drug treatment to prevent relapse, take into account drugs that have been effective during episodes of mania or bipolar depression. Discuss with people whether they prefer to

continue this treatment or switch to lithium, and explain that lithium is the most effective long term treatment for bipolar disorder.

I Offer lithium as a first line long term drug treatment for bipolar disorder and:

I -If lithium is ineffective, consider adding valproate

I -If lithium is poorly tolerated or is not suitable (for example, because the person does not agree to routine blood monitoring), consider valproate or olanzapine instead or, if it has been effective during an episode of mania or bipolar depression, quetiapine.

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NICE, 2014

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Type of outcome measures

I Total number of participants with recurrence/relapse I Number of participants with hypomanic/manic episode I Number of participants with depressive episode

I Number of participants dropping out of treatment during the study period for reasons other than a mood episode

I Number of participants completing the study

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Criteria for considering studies for review

I Randomized controlled parallel-group studies I English or German

I Males and females aged 16+

I Diagnosis of bipolar disorders, in partial or full remission I Comparison of lithium with placebo or alternative treatment

(anticonvulsant or atypical antipsychotic) to prevent mood episodes with follow-up of at least 3 months

I Comparisons only included if at least two studies for each specific drugwere available

I Small studies (n<50 per treatment arm) were excluded if key data

regarding potentially outcome-relevant clinical variables (i.e. severity of the illness) between the intervention groups at baseline were missing

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Criteria for considering studies for review

I Discontinuation studies (in which patients who had been in remission on lithium for at least two consecutive months were selected, then randomly assigned to continued lithium treatment or

placebo/alternative treatment) were excluded

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Information sources and search

I Cochrane Controlled Clinical Trials Register (Central) was searched (CENTRAL includes relevant records retrieved from MEDLINE,

Embase, PsychINFO, Cochrane Review Groups registers

incorporating additional databases and handsearching activities) I Reference checking

I Hand searching

I Personal communication

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Prisma flowchart of the inclusion procedure

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WFSBP, 2013

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Lithium - Placebo

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Prevention of any type of episode

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Prevention of depressive and manic episode

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Discontinuation for reasons other than a mood episode

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Study completion

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Lithium - Anticonvulsants

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Prevention of any type of episode

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Prevention of depressive and manic episode

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Discontinuation for reasons other than a mood episode

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Study completion

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Summary, I

I Lithium decreases the probability of mood episodes compared to placebo for up to 2 years in patients with bipolar disorders.

I The treatment effect is present for prevention of both manic

relapse/recurrence and depressive relapse/recurrence, with the statistical significance of the latter finding dependent on the type of analysis performed.

I No single trial found lithium to be less effective than placebo regarding prevention of any type of mood episodes

I Lithium is inferior to placebo regarding drop-out to reasons other than a mood episode, but

I lithium is superior to placebo regarding study completion.

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Summary, II

I Lithium is superior to anticonvulsants regarding prevention of manic episodes, however there is no significant difference regarding overall mood episodes, depressive episodes, drop-out due to reasons other than a mood episode or study completion.

I When analyzing the data separately for lithium versus lamotrigine lithium was superior to lamotrigine in the prevention of (hypo)manic episodes, while lamotrigine did better than lithium in discontinuation for reasons other than a mood episode, with no significant difference between all other outcome parameter.

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Each node (circle) corresponds to a drug included in the analysis, with the size proportional to the number of

participants randomly assigned to that drug.

Each line represents direct comparisons between

drugs, with the width of the lines proportional to the number of trials

comparing each pair of treatments.

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Akutbehandlung Bipolare Depression

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Zugelassene Behandlungsoptionen in der Akutbehandlung der bipolaren Depression

I Lithium (Behandlung von bestimmten akuten Depressionen, z. B. bei Therapieresistenz oder Unverträglichkeit von Antidepressiva, bei V. a.

Umschlag in eine Manie, ggf. in Komb. mit Antidepressiva) I Quetiapin

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67 CANMAT, 2013

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Managing bipolar depression in adults in secondary care

I If a person develops moderate or severe bipolar depression and is already taking lithium, check the person’s plasma lithium level. If it is inadequate, increase the dose of lithium; if it is at maximum level, add either fluoxetine combined with olanzapine or quetiapine on its own, depending on the person’s preference and previous response to treatment.

I If the person prefers, consider adding olanzapine (without fluoxetine) or lamotrigine to lithium.

I If there is no response to the addition of fluoxetine combined with

olanzapine or quetiapine on its own, stop the additional treatment and consider adding lamotrigine to lithium.

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NICE, 2014

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Your responsibility

I The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available.

I When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs,

preferences and values of their patients or service users.

I The application of the recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the

circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

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NICE, 2014

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Vielen Dank für Ihre Aufmerksamkeit!

Adresse:

Universitätsklinikum Carl Gustav Carus an der TU Dresden AöR

Klinik für Psychiatrie und Psychotherapie Fetscherstraße 74

01307 Dresden

Kontakt:

PD Dr. med. habil. Emanuel Severus E-Mail: Emanuel.Severus@uniklinikum- dresden.de

http://psychiatrie.uniklinikum-dresden.de/