Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database

Thillard, Eve-Marie; Gautier, Sophie; Babykina, Evgéniya; Carton, Louise; Amad, Ali; Bouzillé, Guillaume; Beuscart, Jean‐Baptiste; Ficheur, Grégoire; Chazard, Emmanuel

doi:10.3389/fphar.2020.00513

Cited by 19 publications

(20 citation statements)

References 56 publications

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“…1). The evidence available regarding the manic or hypomanic induced by TNF‐α antagonists is limited to four case reports 17,22–24 and a cohort study 25 . Information about the patients, such as demographics, previous treatment, treatment response, manic or hypomanic adverse effects, and follow‐up time, were extracted and summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Secondary Mania induced by TNF‐α inhibitors: A systematic review

Miola

Porto

Meda

et al. 2021

Psychiatry Clin Neurosci

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A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor-α (TNF-α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in patients with or without bipolar disorders remains controversial. Thus, we conducted a systematic review to study the anti-TNF-α medication-induced manic or hypomanic episodes. PubMed, Scopus, Medline, and Embase databases were screened for a comprehensive literature search from inception until November 2020, using The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Out of the initial 75 references, the screening resulted in the inclusion of four case reports (each describing one patient) and a cohort study (in which 40 patients out of 7600-0.53%experienced elated mood episodes after infliximab administration). Of these 44 patients, 97.7% experienced a manic episode and 2.3% hypomania. 93.2% of patients had no history of psychiatric disorder or psychotropic treatment. Only 6.8% had a history of psychiatric disorders with the affective spectrum (4.6% dysthymia and 2.3% bipolar disorder). The time of onset of manic or hypomanic symptoms varied across TNF-α inhibitors with an early onset for Infliximab and a later onset for Adalimumab and Etanercept. These findings suggest that medications targeting the TNF-α pathway may trigger a manic episode in patients with or without affective disorders. However, prospective studies are needed to evaluate the relative risk of such side effects and identify the population susceptible to secondary mania.

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Section: Resultsmentioning

confidence: 99%

Secondary Mania induced by TNF‐α inhibitors: A systematic review

Miola

Porto

Meda

et al. 2021

Psychiatry Clin Neurosci

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“…While infliximab has not been used for the adjunctive treatment of SZ or BD, a recent review examining the association between antibody immunotherapy for immune/inflammatory disorders and psychosis, found that 4 out of 8 antibody therapies suppressing TNF (including infliximab) correlated with a decreased risk of psychosis 71 . However, cases describing acute psychosis after the administration of TNF antibody therapy have also been reported 72,73 . Piroxicam has not been used as an adjunctive treatment for SZ or BD, but studies of non-selective COX inhibitor (aspirin) and selective COX-2 inhibitor (celecoxib) in SZ 74,75 have reported symptomatic improvement in SZ patients, with the greatest benefit during a first episode of psychosis 76 .…”

Section: Discussionmentioning

confidence: 99%

TNFα and MMP1 in brain microvascular endothelial cells regulate blood-brain barrier dysfunction in psychotic disorders

Lizano¹,

Pong²,

Santarriaga

et al. 2022

Preprint

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In schizophrenia and bipolar disorder, tight junction deficits in brain microvascular endothelial cells (BMECs) lead to blood brain barrier (BBB) dysfunction. Using an in vitro model of human BBB function, we show that BMECs derived from human induced pluripotent stem cells of schizophrenia patients show reduced BBB integrity and increased small molecule permeability when compared to healthy control BMECs. Stratification based on BBB function in schizophrenia and bipolar disorder patients identified a BBB-deficit subtype with reduced barrier function, increased permeability to larger molecules, and decreased claudin-5 (CLDN5) levels. BMECs from the BBB-deficit group show increased MMP1 activity, which correlated with reduced CLDN5 levels and worse BBB function, which were rescued by tumor necrosis factor α (TNFα and MMP1 inhibition. These results show intrinsic deficits in BMECs in psychotic disorders that result in BBB disruption and further identify TNFα and MMP1 as potential targets for ameliorating BBB deficits.

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“…Within days of the first infliximab infusion, he experienced symptoms of depression, which intensified over weeks and resulted in a serious suicide attempt. 7 In a cohort study analyzing data from the French national hospital higher risks were observed for certain pairs of adverse events and underlying pathologies: psychotic disorders in patient treated for ulcerative colitis, manic episodes in patients treated for severe psoriasis, and suicide attempts in patients treated for rheumatoid arthritis. 8 Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNF-α, and inhibits or prevents the effective binding of TNF-α with its receptors.…”

Section: Discussionmentioning

confidence: 99%

Suicidal thoughts in a patient after administration of infliximab

et al. 2021

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Infliximab (IFX) is a chimeric monoclonal antibody biologic drug that works against tumor necrosis factor alpha (TNF-α) and is used to treat autoimmune diseases. This is case of a 45year old female patient who had suicidal thoughts after receiving infusions with IFX. She did not report any family psychiatric history. She was diagnosed with ulcerative colitis. She had many relapses and she was treated with azathioprine and prednisolone. After many incidents of diarrhea, she started therapy with infliximab infusions. She had totally 13 infusions during a period of 13 months. The last year and in particular during the time of Infliximab intake, she reported suicidal ideation. Due to lack of improvement in her physical symptoms, she voluntarily discontinued medication and resorted to a nutritionist and a mental health counselor, where she followed cognitive and behavioral interventions. Treatment of autoimmune disorders with infliximab raise an awareness among medical and paramedical staff involved in the care of these patients about the psychiatric side effects of the drug.

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Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database

Abstract: The present retrospective, observational study confirmed that IFX treatment is associated with an elevated risk of psychiatric adverse events. Depending on the disease treated, physicians should be aware of these potential adverse events.

Cited by 19 publications

References 56 publications

Secondary Mania induced by TNF‐α inhibitors: A systematic review

Secondary Mania induced by TNF‐α inhibitors: A systematic review

TNFα and MMP1 in brain microvascular endothelial cells regulate blood-brain barrier dysfunction in psychotic disorders

Suicidal thoughts in a patient after administration of infliximab

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