Monoclonal Antibody a Promising Treatment for Depression

PDF - Export to EndNote - PubMed Central XML format - PubMed Central XML format - PubMed Central XML format
PMID: 30800237 (PubMed) - PMCID: PMC6359698 - View online: PubReader
Volume 11, Issue 1, January-March , Page 1 to 2
Wednesday, September 26, 2018 :Received , Saturday, December 15, 2018 :Accepted

  • Corresponding author Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
    - Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran


Major depressive disorder (MDD) is one of the prominent causes of disability in the world, affecting 15-20% of people over the period of a lifetime. Patients commonly experience continuous remaining symptoms, functional impairment, and diminished health 1.
Treatment of MDD is still far from optimal and drug resistance in MDD is still considered a serious clinical challenge. Only about one-third of patients completely respond to their first antidepressant medication, first with an approximate lag time of 2 months. This notable lag time for onset of therapeutic efficacy is associated with significant morbidity and suicidal risk. As a result, there is a widely accepted need for fast acting antidepressants. Another downside of the currently available treatments is their side effects which are documented in large proportion of patients 1,2.
Patients who do not respond to their first-line medication are generally treated by either switching to another treatment or with augmentation therapy to achieve favorable response. Combination therapy from start of treatment has been suggested recently to gain quicker and better response and remission rates, however, not all studies have supported this opinion. Most MDD pathophysiology etiological theories used to focus on brain modulatory monoamine systems (dopamine, serotonin and norepinephrine) 3,4. A more recent line of evidence points to glutamate, the brain’s principal excitatory neurotransmitter, as playing a role in MDD’s pathophysiology. Additionally, glutamate dysregulation is known to cause impairments in structural plasticity and cellular resilience, which seems to be implicated in mood disorders as well. It is therefore reasonable to hypothesize that medications which reduce glutamatergic tone may be able to play a role in treatment of depression 5.
Depression is demonstrated to be accompanied with parallel increases in the immuno-inflammatory biomarkers including significantly higher levels of pro-inflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) in depressed patients compared to normal individuals. The dynamic interaction between pro-inflammatory cytokines, prostaglandin (PG)-E2 synthesis and depression has led to suggestions that anti-inflammatory agents could be useful for treatment of depression 6,7. Celecoxib, a nonsteroidal anti-inflammatory drug that acts via the selective inhibition of cyclooxygenase (COX)-2, has shown promising outcomes in several psychiatric diorders, including autistic disorder, schizophrenia, and depression. Antidepressive effects of celecoxib is suggested to be largely attributed to its inhibitory effect on the levels of pro-inflammatory cytokines. In line with this idea, baseline levels of serum IL-6 is demonstrated to be significantly correlated with the Hamilton Depression Rating Scale (HDRS) score. In the same article, adjunctive therapy with celecoxib, as an antidepressant, resulted in significant decreases in both serum IL-6 levels and HDRS scores. Although most of the previous research has focused on the antidepressant effects of celecoxib as an add-on treatment, few reports have investigated the safety and efficacy of celecoxib as a monotherapy 8-10.
In clinical trials, two new classes of anti-inflammatory drugs-anti-cytokine monoclonal antibodies and cytokine inhibitors have been shown to reduce inflammation in a range of autoimmune diseases, and these drugs have already started to be administered to patients who do not respond to standard treatments 11,12.




References :
  1. Ma L, Xu Y, Wang G, Li R. What do we know about sex differences in depression: A review of animal models and potential mechanisms. Prog Neuropsychopharmacol Biol Psychiatry 2019;89:48-56.   [PubMed]
  2. Johnson D, Dupuis G, Piche J, Clayborne Z, Colman I. Adult mental health outcomes of adolescent depression: A systematic review. Depress Anxiety 2018;35(8):700-716.   [PubMed]
  3. Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S. Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial. Neuropsychopharmacology 2012;37(9):2093-2100.   [PubMed]
  4. Modabbernia A, Sohrabi H, Nasehi AA, Raisi F, Saroukhani S, Jamshidi A, et al. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl) 2012;223(4):381-388.   [PubMed]
  5. Khajavi D, Farokhnia M, Modabbernia A, Ashrafi M, Abbasi SH, Tabrizi M, et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2012;73(11):1428-1433.   [PubMed]
  6. Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord 2012;141(2-3):308-314.   [PubMed]
  7. Jafari S, Ashrafizadeh SG, Zeinoddini A, Rasoulinejad M, Entezari P, Seddighi S, et al. Celecoxib for the treatment of mild-to-moderate depression due to acute brucellosis: a double-blind, placebo-controlled, randomized trial. J Clin Pharm Ther 2015;40(4):441-446.   [PubMed]
  8. Mohammadinejad P, Arya P, Esfandbod M, Kaviani A, Najafi M, Kashani L, et al. Celecoxib versus diclofenac in mild to moderate depression management among breast cancer patients: A double-blind, placebo-controlled, randomized trial. Ann Pharmacother 2015;49(9):953-961.   [PubMed]
  9. Arabzadeh S, Ameli N, Zeinoddini A, Rezaei F, Farokhnia M, Mohammadinejad P, et al. Celecoxib adjunctive therapy for acute bipolar mania: a randomized, double-blind, placebo-controlled trial. Bipolar Disord 2015;17(6):606-614.   [PubMed]
  10. Alamdarsaravi M, Ghajar A, Noorbala AA, Arbabi M, Emami A, Shahei F, et al. Efficacy and safety of celecoxib monotherapy for mild to moderate depression in patients with colorectal cancer: A randomized double-blind, placebo controlled trial. Psychiatry Res 2017;255:59-65.   [PubMed]
  11. Sun Y, Wang D, Salvadore G, Hsu B, Curran M, Casper C, et al. The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman's disease. Brain Behav Immun 2017;66:156-164.   [PubMed]
  12. Zhou AJ, Lee Y, Salvadore G, Hsu B, Fonseka TM, Kennedy SH, et al. Sirukumab: A potential treatment for mood disorders? Adv Ther 2017;34(1):78-90.   [PubMed]