A Review Article: Antidepressants Drugs Action on Bipolar Disorder

Abstract

Bipolar disorder (BD) is a chronic psychiatric illness marked by alternating episodes of mania and depression. The management of depressive episodes in BD poses significant clinical challenges, particularly due to the potential for treatment-emergent mood switching and other complications. Antidepressant (AD) medications, including Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and Tricyclic Antidepressants (TCAs), are frequently employed to alleviate depressive symptoms. However, their efficacy and safety in the context of BD remain subjects of ongoing debate.This review critically evaluates the mechanisms of action, pharmacodynamic pathways, and pharmaceutical considerations related to the use of antidepressants in BD. Special attention is given to bioequivalence challenges and the role of personalized treatment strategies, offering comprehensive insights for clinicians and researchers. The goal is to support informed, evidence-based decision-making in the nuanced and often controversial application of antidepressants in bipolar disorder.

Introduction

Bipolar disorder (BD) is a chronic psychiatric illness characterized by alternating episodes of mania or hypomania and depression. It affects 40–50 million people worldwide, typically beginning between ages 20 and 40, with equal prevalence in men and women. BD is classified mainly into bipolar I (manic and depressive episodes) and bipolar II (hypomanic and depressive episodes). The disorder is often complicated by coexisting psychiatric conditions (like anxiety, ADHD, substance use) and physical health problems (such as obesity, diabetes, cardiovascular disease), leading to increased morbidity and mortality, especially from suicide.

Diagnosis is challenging due to symptom overlap with other disorders, including psychosis, and often delayed because depressive episodes may precede manic symptoms. Bipolar depression accounts for most of the illness’s burden. Treatment traditionally focuses on managing mania, but antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), are used cautiously to treat bipolar depression, usually alongside mood stabilizers to reduce the risk of triggering mania. The safety and effectiveness of antidepressants in bipolar disorder remain debated.

SSRIs are the most commonly prescribed antidepressants worldwide, effective for various conditions including depression, anxiety, OCD, PTSD, and more. They work by increasing serotonin levels in the brain and triggering molecular changes that enhance brain plasticity, although their full therapeutic effects often take weeks to develop.

Conclusion

Antidepressants may offer short-term benefit for bipolar depression—especially when combined with SGAs—yet their long-term effectiveness is limited by increased risk of affective switch. Treatment should be personalized, weighing patient subtype (e.g., BD I vs BD II), prior history of switching, and antidepressant class. The central clinical challenge is identifying which subsets of patients derive benefit versus harm from AD therapy. Future high-quality trials are needed to refine treatment algorithms and optimize risk stratification.

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Copyright

Copyright © 2025 Jibin Joy Zachariah, Arif Aasidulla Pathan, Smita Meshram, Sayyed Sajauddin G.. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.