Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials

Solmi, Marco; Veronese, Nicola; Zaninotto, Leonardo; Loos, Marc; Gao, Keming; Schaffer, Ayal; Reis, Catherine; Normann, Claus; Anghelescu, Ion; Correll, Christoph U.

doi:10.1017/s1092852916000523

Cited by 58 publications

(37 citation statements)

References 76 publications

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“… 28) However, researchers indicated the methodological flaws in double blind trials reporting negative results, 29) and the superiority of LMT over placebo was reported in a meta-analysis as a monotherapy and augmentation strategy. 30) Moreover, recent evidence-based guidelines recommend the use of LMT in patients with bipolar depression. 24 , 31 , 32) …”

Section: Discussionmentioning

confidence: 99%

Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018): Fourth Revision

Woo

Bahk

Lee

et al. 2018

Clin Psychopharmacol Neurosci

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ObjectiveThe Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP.MethodsA 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts.ResultsThe preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression.ConclusionThe recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.

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Section: Discussionmentioning

confidence: 99%

Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018): Fourth Revision

Woo

Bahk

Lee

et al. 2018

Clin Psychopharmacol Neurosci

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“…For divalproex monotherapy, 4 small trials suggest possible value in acute bipolar depression (Table 4), but it remains FDA-unapproved for depression or long-term treatment in BD. Evidence that lamotrigine is effective in acute bipolar depression rests on pooling inconsistent data, including from individually failed trials vs. placebo (Table 4) (Solmi et al 2016). Lamotrigine is FDA-approved only for long-term prophylaxis in BD, with partial effectiveness against recurrences of depression but little efficacy against acute or recurrent mania (Frye et al 2011;Baldessarini 2013).…”

Section: Mood-stabilizersmentioning

confidence: 99%

Bipolar depression: a major unsolved challenge

Baldessarini

Vázquez

Tondo

2020

Int J Bipolar Disord

167

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Depression in bipolar disorder (BD) patients presents major clinical challenges. As the predominant psychopathology even in treated BD, depression is associated not only with excess morbidity, but also mortality from co-occurring general-medical disorders and high suicide risk. In BD, risks for medical disorders including diabetes or metabolic syndrome, and cardiovascular disorders, and associated mortality rates are several-times above those for the general population or with other psychiatric disorders. The SMR for suicide with BD reaches 20-times above general-population rates, and exceeds rates with other major psychiatric disorders. In BD, suicide is strongly associated with mixed (agitated-dysphoric) and depressive phases, time depressed, and hospitalization. Lithium may reduce suicide risk in BD; clozapine and ketamine require further testing. Treatment of bipolar depression is far less well investigated than unipolar depression, particularly for long-term prophylaxis. Short-term efficacy of antidepressants for bipolar depression remains controversial and they risk clinical worsening, especially in mixed states and with rapid-cycling. Evidence of efficacy of lithium and anticonvulsants for bipolar depression is very limited; lamotrigine has long-term benefit, but valproate and carbamazepine are inadequately tested and carry high teratogenic risks. Evidence is emerging of short-term efficacy of several modern antipsychotics (including cariprazine, lurasidone, olanzapine-fluoxetine, and quetiapine) for bipolar depression, including with mixed features, though they risk adverse metabolic and neurological effects.

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“…A comprehensive meta-analysis of efficacy and safety outcomes in short-term trials of lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression showed that lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium (Solmi et al 2016). …”

Section: Lithium Augmentation In Acute Treatment Of Depressionmentioning

confidence: 99%

Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression

Abou‐Saleh

Müller‐Oerlinghausen

Coppen³

2017

Int J Bipolar Disord

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BackgroundDepressive disorders are a leading cause of the global burden of disease and are associated with high recurrent often continuing morbidity and high excess mortality by suicide and cardiovascular disease. Whilst there are established, effective and cost-effective treatments for depression, their long-term management is often neglected: there is continuing controversy over the case of need for long-term treatment including lifelong treatment and safety issues.Objective and methodsIn this narrative review, we critically examine the evidence for the effectiveness and safety of lithium salts in the long-term management of unipolar depression. We refer to existing recent international guidelines as well as the scientific literature selectively and against the background of our longstanding experience with patients suffering from unipolar depression who are often under treated or inappropriately treated.Results and discussionAccording to many studies mostly dating back to the 1970/1980s, lithium is efficacious in the prophylaxis of unipolar depression particularly depression with melancholia and delusional depression and showing a clearly episodic course. Also the efficacy of lithium maintenance treatment following recovery by ECT has been clearly shown. Moreover, convincing evidence exists that lithium has added value and benefit for its unique anti-suicidal effects as well as reducing mortality by other causes. The anti-suicidal effect has been convincingly demonstrated in bipolar as well as in unipolar patients. Nevertheless its use in the management of patients with unipolar depression has not been properly recognized by a majority of textbooks and guidelines. Whilst it has been well considered as an effective treatment for depression that has not responded to antidepressants as an adjunct treatment, also called augmentation, it has been much less recommended for the prevention of recurrent episodes of unipolar depression. One of the reasons for this neglect is the blurring of the diagnosis “unipolar depression” by modern diagnostic tools. Lithium will hardly work in a patient with “unipolar depression spectrum disease”.ConclusionsWe conclude that lithium is an effective prophylactic treatment for carefully selected patients with unipolar depression and is safe when prescribed in recommended doses/plasma lithium levels and with regular, careful monitoring. We propose that lithium prophylaxis can be indicated in patients with unipolar depression and that the occurrence of 2 episodes of depression within 5 years is a practical criterion for starting lithium prophylaxis particularly in severe depression with psychotic features and high suicidal risk. Furthermore, an indication might be considered especially in unipolar patients in whom a bipolar background is suspected. In some cases, lithium prophylaxis may be recommended after a single episode of depression that is severe with high suicidal risk and continued life-long.

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Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials

Abstract: Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.

Cited by 58 publications

References 76 publications

Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018): Fourth Revision

Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018): Fourth Revision

Bipolar depression: a major unsolved challenge

Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression

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