QCM de pharmacologie

Quel est l’antidépresseur qui fait le moins grossir, en moyenne ?

A) Quétiapine (Xeroquel)
B) Lithium
C) Paroxétine (Deroxat)
D) Abilify (Aripiprazole)
E) Lévothyroxine
F) Pramipexole
G) Phénelzine

Pour ceux qui n’ont pas encore répondu, je vous laisse réfléchir.

Évidemment, parmi les réponses, certains m’ont fait remarquer avec plus ou moins de finesse qu’il n’y avait dans cette liste qu’un seul “antidépresseur”. J’avais précisé qu’il n’y avait pas d’erreur dans la question, mais que voulez-vous.

Le lithium n’est pas un antidépresseur mais un régulateur de l’humeur... à bon entendeur.

Vous avez mélangé tous les médicaments !!

On voit vraiment que vous êtes de plus en plus décompensé, ça fait peur !

Alors déjà... rien que cette liste....la plupart ne sont pas des antidépresseurs. Vu que c’est signé d’un soi-disant ‘’psychiatre’‘...j’ai des doutes quant à son professionnalisme.

Ce ne sont que des exemples isolés, minoritaires, mais qui illustrent un principe fondamental : l’arrogance et l’ignorance vont souvent de pair.

La seconde chose notable, c’est l’importance de la sémantique. Il suffit que le laboratoire donne le nom “antidépresseur” à sa molécule, malgré une efficacité médiocre – pour ne pas dire à peine visible à l’oeil nu, en moyenne – pour que les cliniciens adoptent le nom. La pop culture fait le reste, et on se retrouve avec des “antidépresseurs” qui sont à peine plus efficaces qu’un placebo.

Juste pour être clair : les psychiatres sont les premiers responsables (et au début, les seuls). L’esprit critique a abandonné la profession.

En pratique, ce ne sont pas les laboratoires qui décident si une molécule est “antidépressive” ou non. Les autorités de santés donnent l’autorisation au laboratoire d’employer le terme “antidépresseur” lors de sa mise sur le marché, et ça s’arrête là. Ce sont les études observationnelles, puis randomisées quand c’est possible, qui justifient de ce terme. L’expérience des cliniciens se greffe ensuite dessus.

Les gens pensaient que la paroxétine et la phénelzine (un inhibiteur de la monoamine oxydase) étaient les seuls antidépresseurs de la liste. En réalité, la quétiapine, le lithium, les hormones thyroïdiennes et le pramipexole sont des antidépresseurs bien plus efficaces que la paroxétine, que ce soit chez les bipolaires ou les “unipolaires”. Que ce soit dans la prévention de la rechute, ou sur le long terme - pour certains, en tout cas.

Et dans cette liste, la levothyroxine ne fait en moyenne pas prendre de poids, et ne sédate pas. C’est une option thérapeutique qui n’est pas utilisée par ignorance, ou peur des autorités de santé. Parfois, des professionnels de santé peu scrupuleux vont même jusqu’à faire sauter la prescription, en disant qu’ils ne “connaissent pas”. Dans tous les cas, ça n’est pas acceptable. Je rappelle à toute fin utile qu’un livre entier traite du sujet.

Je vous ai mis plus bas les différentes études avec ces molécules, que ce soit en adjuvant (rajouté à un autre traitement déjà présent) ou en monothérapie ; dans la dépression bipolaire ou la dépression “unipolaire”. Il y a des études positives, des études négatives, du narratif; je vous laisse regarder.

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Mon livre est disponible sur Amazon, la Fnac et en librairie. Les deux liens sont affiliés.

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Lévothyroxine / hormones thyroïdiennes

Stamm et al. 2014 — Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study.
https://pubmed.ncbi.nlm.nih.gov/24345793/

Uhl et al. 2014 — Influence of levothyroxine in augmentation therapy for bipolar depression on central serotonergic function.
https://pubmed.ncbi.nlm.nih.gov/25002290/

Bauer et al. 2016 — Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.
https://pubmed.ncbi.nlm.nih.gov/25600111/

Walshaw et al. 2018 — Adjunctive Thyroid Hormone Treatment in Rapid Cycling Bipolar Disorder: A Double-Blind Placebo-Controlled Trial of Levothyroxine (L-T4) and Triiodothyronine (T3).
https://pubmed.ncbi.nlm.nih.gov/29869405/

Bauer & Whybrow 1990 — Rapid cycling bipolar affective disorder, II: treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study.
https://pubmed.ncbi.nlm.nih.gov/2184796/

Baumgartner et al. 1994 — Treatment of intractable non-rapid cycling bipolar affective disorder with high-dose thyroxine: an open clinical trial.
https://pubmed.ncbi.nlm.nih.gov/7916915/

Bauer et al. 1998 — Treatment of refractory depression with high-dose thyroxine.
https://pubmed.ncbi.nlm.nih.gov/9571653/

Pilhatsch et al. 2019 — Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms.
https://pubmed.ncbi.nlm.nih.gov/31583561/

George et al. 2022 — Efficacy and safety of supraphysiologic doses of levothyroxine for patients with bipolar depression in adults: A systematic review.
https://pubmed.ncbi.nlm.nih.gov/35574909/

Seshadri et al. 2022 — Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review.
https://pubmed.ncbi.nlm.nih.gov/36421864/

Lithium

Khan et al. 1987 — Lithium versus placebo in acute depression: a clinical trial.
https://pubmed.ncbi.nlm.nih.gov/3117877/

de Montigny et al. 1983 — Lithium Carbonate Addition in Tricyclic Antidepressant-Resistant Unipolar Depression: Correlations With the Neurobiologic Actions of Tricyclic Antidepressant Drugs and Lithium Ion on the Serotonin System.
https://pubmed.ncbi.nlm.nih.gov/6418109/

Heninger et al. 1983 — Lithium carbonate augmentation of antidepressant treatment. An effective prescription for treatment-refractory depression.
https://pubmed.ncbi.nlm.nih.gov/6418110/

Zusky et al. 1988 — Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study.
https://pubmed.ncbi.nlm.nih.gov/3131389/

Schöpf et al. 1989 — Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study.
https://pubmed.ncbi.nlm.nih.gov/2682692/

Joffe et al. 1993 — A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression.
https://pubmed.ncbi.nlm.nih.gov/8489327/

Stein & Bernadt 1993 — Lithium augmentation therapy in tricyclic-resistant depression. A controlled trial using lithium in low and normal doses.
https://pubmed.ncbi.nlm.nih.gov/8149115/

Katona et al. 1995 — Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine.
https://pubmed.ncbi.nlm.nih.gov/7894881/

Bauer et al. 2000 — Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression.
https://pubmed.ncbi.nlm.nih.gov/10964859/

Wilkinson et al. 2002 — Prophylactic therapy with lithium in elderly patients with unipolar major depression.
https://pubmed.ncbi.nlm.nih.gov/12112158/

Kantor et al. 1986 — The benefit of lithium carbonate adjunct in refractory depression--fact or fiction?
https://pubmed.ncbi.nlm.nih.gov/3089576/

Young et al. 2010 — A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I).
https://pubmed.ncbi.nlm.nih.gov/20122369/

Cleare et al. 2025 — Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment-resistant depression: a pragmatic, open-label, randomised controlled trial.
https://pubmed.ncbi.nlm.nih.gov/40113355/

Bauer & Döpfmer 1999 — Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies.
https://pubmed.ncbi.nlm.nih.gov/10505584/

Nelson et al. 2014 — A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression.
https://pubmed.ncbi.nlm.nih.gov/25069082/

Nierenberg et al. 2006 — A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report.
https://pubmed.ncbi.nlm.nih.gov/16946176/

Nuñez et al. 2022 — Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis.
https://pubmed.ncbi.nlm.nih.gov/34986373/

Quetiapine

Calabrese et al. 2005 — A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression.
https://pubmed.ncbi.nlm.nih.gov/15994719/

Thase et al. 2006 — Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study.
https://pubmed.ncbi.nlm.nih.gov/17110817/

Young et al. 2010 — A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I).
https://pubmed.ncbi.nlm.nih.gov/20122369/

McElroy et al. 2010 — A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II).
https://pubmed.ncbi.nlm.nih.gov/20122366/

Suppes et al. 2010 — Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression.
https://pubmed.ncbi.nlm.nih.gov/19903574/
Version corrigée/republiée : https://pubmed.ncbi.nlm.nih.gov/25538990/

Young et al. 2013 — Quetiapine monotherapy in bipolar II depression: combined data from four large, randomized studies.
https://pubmed.ncbi.nlm.nih.gov/25505677/

Young et al. 2014 — A randomised, placebo-controlled 52-week trial of continued quetiapine treatment in recently depressed patients with bipolar I and bipolar II disorder.
https://pubmed.ncbi.nlm.nih.gov/22404704/

Geddes et al. 2016 — Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy, and folic acid versus placebo, in bipolar depression (CEQUEL): a 2×2 factorial randomised trial.
https://pubmed.ncbi.nlm.nih.gov/26687300/

Cutler et al. 2009 — Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study.
https://pubmed.ncbi.nlm.nih.gov/19358790/

Weisler et al. 2009 — Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study.
https://pubmed.ncbi.nlm.nih.gov/19668121/

Liebowitz et al. 2010 — Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo-controlled trial.
https://pubmed.ncbi.nlm.nih.gov/20734365/

Bauer et al. 2009 — Extended-release quetiapine fumarate as adjunct to antidepressant therapy in patients with major depressive disorder: a randomized, placebo-controlled, double-blind study.
https://pubmed.ncbi.nlm.nih.gov/19358791/

El-Khalili et al. 2010 — Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study.
https://pubmed.ncbi.nlm.nih.gov/20175941/

Bauer et al. 2010 — A pooled analysis of two randomised, placebo-controlled studies of extended release quetiapine fumarate adjunctive therapy in patients with major depressive disorder.
https://pubmed.ncbi.nlm.nih.gov/20884063/

Bauer et al. 2013 — Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder.
https://pubmed.ncbi.nlm.nih.gov/23810357/

Katila et al. 2013 — Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder.
https://pubmed.ncbi.nlm.nih.gov/23567397/

Wang et al. 2014 — A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder.
https://pubmed.ncbi.nlm.nih.gov/24511235/

Bahji et al. 2020 — Comparative efficacy and tolerability of pharmacological treatments for the treatment of acute bipolar depression: a systematic review and network meta-analysis.
https://pubmed.ncbi.nlm.nih.gov/32339131/

Yildiz et al. 2023 — Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis.
https://pubmed.ncbi.nlm.nih.gov/37595997/

Zhou et al. 2015 — Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis.
https://pubmed.ncbi.nlm.nih.gov/25919841/

Pramipexole

Corrigan et al. 2000 — Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.
https://pubmed.ncbi.nlm.nih.gov/10812530/

Goldberg et al. 2004 — Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.
https://pubmed.ncbi.nlm.nih.gov/14992985/

Zarate et al. 2004 — Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
https://pubmed.ncbi.nlm.nih.gov/15219473/

Cusin et al. 2013 — A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder.
https://pubmed.ncbi.nlm.nih.gov/23945458/

Mishra et al. 2025 — Comparative efficacy of antidepressant augmentation with amantadine vs pramipexole in treatment-resistant unipolar depression: A randomised controlled trial.
https://pubmed.ncbi.nlm.nih.gov/40659070/

McAllister-Williams et al. 2025 — A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).
https://pubmed.ncbi.nlm.nih.gov/39829389/

Browning et al. 2025 — Pramipexole augmentation for the acute phase of treatment-resistant, unipolar depression: a placebo-controlled, double-blind, randomised trial in the UK.
https://pubmed.ncbi.nlm.nih.gov/40602411/

Ventorp et al. 2022 — Preliminary Evidence of Efficacy and Target Engagement of Pramipexole in Anhedonic Depression.
https://pubmed.ncbi.nlm.nih.gov/36225720/

Lindahl et al. 2023 — Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden.
https://pubmed.ncbi.nlm.nih.gov/38035737/

Ventorp et al. 2026 — Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial.
https://www.nature.com/articles/s41591-026-04465-9

Fawcett et al. 2016 — Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar Depression.
https://pubmed.ncbi.nlm.nih.gov/26844792/

Tundo et al. 2022 — Efficacy and safety of 24-week pramipexole augmentation in treatment-resistant depression.
https://pubmed.ncbi.nlm.nih.gov/34375683/

Tundo et al. 2023 — Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis.
https://pubmed.ncbi.nlm.nih.gov/37109571/

Berger et al. 2025 — Cost-effectiveness of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression: Economic evaluation of the PAX-BD study.
https://pubmed.ncbi.nlm.nih.gov/40683533/

Łaszewska et al. 2025 — Cost-effectiveness of pramipexole augmentation for acute-phase and maintenance therapy of treatment-resistant depression compared to placebo augmentation: economic evaluation of the PAX-D randomised controlled trial.
https://pubmed.ncbi.nlm.nih.gov/41333541/