The effectiveness of restarted lithium treatment after discontinuation: reviewing the evidence for discontinuation‐induced refractoriness

Vries, Christine de; Bergen, Annet van; Regeer, Eline J.; Benthem, Elsje M.; Kupka, Ralph; Boks, Marco P.

doi:10.1111/bdi.12105

Cited by 23 publications

(14 citation statements)

References 27 publications

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“…However, the assumption for the existence of lithium-discontinuation-related refractoriness is not supported by studies reporting that even when samples enriched for lithium refractoriness were used, no inferiority of lithium to the other agent was documented (Bowden et al, 1994). Also a recent meta-analysis of all published cases concluded that there is not sufficient data to support such a concept (de Vries et al, 2013). …”

Section: Efficacy Datamentioning

confidence: 99%

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Fountoulakis

Yatham

Grunze

et al. 2016

IJNPPY

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Background:The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.Material and Methods:The PRISMA method was used in the literature search with the combination of the words ‘bipolar,’ ‘manic,’ ‘mania,’ ‘manic depression,’ and ‘manic depressive’ with ‘randomized,’ and ‘algorithms’ with ‘mania,’ ‘manic,’ ‘bipolar,’ ‘manic-depressive,’ or ‘manic depression.’ Relevant web pages and review articles were also reviewed.Results:The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.Conclusions:A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

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Section: Efficacy Datamentioning

confidence: 99%

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Fountoulakis

Yatham

Grunze

et al. 2016

IJNPPY

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“…Konklusiv auch zu diesen neuen "real world" Studienergebnissen empfiehlt die NICE-Leitlinie (National Institute for Health and Care Excellence) Patienten nach Abschluss einer Akutbehandlung mit einer anderen Substanz als Lithium darüber aufzuklären, dass Lithium die effektivste Phasenprophylaxe darstellt und zu besprechen, ob die Fortsetzung der bisherigen Behandlung oder der Wechsel zu Lithium gewünscht wird [5]. Darüber hinaus scheint Lithium entgegen früherer Befürchtungen weder im Langzeitverlauf (prospektive Nachuntersuchung bis zu 20 Jahre, im Mittel 10 Jahre) [19] noch nach Wiederaufnahme einer Lithiumbehandlung an Effektivität einzubüßen [20].…”

Section: Phasenprophylaxeunclassified

Update – Lithium in der Phasenprophylaxe Bipolarer Störungen

Petzold

Bauer

Severus

2018

Fortschr Neurol Psychiatr

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ZusammenfassungLithium ist der Goldstandard in der Phasenprophylaxe Bipolarer Störungen und das einzige Medikament für das es eine überzeugende suizidpräventive Wirkung bei affektiven Erkrankungen gibt. Unter Berücksichtigung eines regelmäßigen Monitorings ist Lithium eine zumeist gut verträgliche und sichere Phasenprophylaxe, die nach sorgfältiger Risiko-Nutzen-Abwägung auch eine off-label Therapieoption in Schwangerschaft und Stillzeit darstellt. Darüber hinaus gibt es Hinweise, dass Lithium neuroprotektiv wirken mag und möglicherweise das Risiko für eine Alzheimer-Demenz und Schlaganfälle senken kann. Perspektivisch könnten Biomarker zur Verfügung stehen, mit denen man das Ansprechen auf Lithium voraussagen kann und damit personalisiertere Therapien entwickeln könnte.

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“…Neither, conclusive evidence exists about the actual occurrence of loss of lithium prophylaxis and/or enduring response over the time [ 9 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Does the “Silver Bullet” Lose its Shine Over the Time? Assessment of Loss of Lithium Response in a Preliminary Sample of Bipolar Disorder Outpatients

Fornaro

Stubbs

Berardis³

et al. 2016

CPEMH

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Background:Though often perceived as a “silver bullet” treatment for bipolar disorder (BD), lithium has seldom reported to lose its efficacy over the time.Objective:The aim of the present study was to assess cases of refractoriness toward restarted lithium in BD patients who failed to preserve maintenance.Method:Treatment trajectories associated with re-instituted lithium following loss of achieved lithium-based maintenance in BD were retrospectively reviewed for 37 BD-I patients (median age 52 years; F:M=17:20 or 46% of the total) over an 8.1-month period on average.Results:In our sample only 4 cases (roughly 11% of the total, of whom F:M=2:2) developed refractoriness towards lithium after its discontinuation. Thirty-three controls (F:M=15:18) maintained lithium response at the time of re-institution. No statistically significant difference between cases and controls was observed with respect to a number of demographic and clinical features but for time spent before first trial ever with lithium in life (8.5 vs. 3 years; U=24.5, Z=-2.048, p=.041) and length of lithium discontinuation until new therapeutic attempt (5.5 vs. 2 years; U=8, Z=-2.927, p=.003) between cases vs. controls respectively. Tapering off of lithium was significantly faster among cases vs. controls (1 vs. 7 days; U=22, Z=-2.187), though both subgroups had worrisome high rates of poor adherence overall.Conclusion:Although intrinsic limitations of the present preliminary assessment hamper the validity and generalizability of overall results, stating the clinical relevance of the topic further prospective research is warranted. The eventual occurrence of lithium refractoriness may indeed be associated with peculiar course trajectories and therapeutic outcomes ultimately urging the prescribing clinicians to put efforts in preserving maintenance of BD in the absence of any conclusive research insight on the matter.

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The effectiveness of restarted lithium treatment after discontinuation: reviewing the evidence for discontinuation‐induced refractoriness

Abstract: Although studies are scarce, review and meta-analysis of the available literature does not provide convincing evidence that lithium is less effective when treatment is discontinued and restarted, compared to uninterrupted treatment.

Cited by 23 publications

References 27 publications

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Update – Lithium in der Phasenprophylaxe Bipolarer Störungen

Does the “Silver Bullet” Lose its Shine Over the Time? Assessment of Loss of Lithium Response in a Preliminary Sample of Bipolar Disorder Outpatients

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