The Efficacy of Antidepressants: A Review of Medical Evidence and Psychological Perspectives

By Raqi Saeed, 22 July 2023


Depression is a widespread and debilitating mental health condition that affects millions of people globally. In recent years, antidepressant medications have become a common treatment option for managing depression. However, the effectiveness of these medications has been a subject of debate. This article aims to critically review the medical evidence and psychological perspectives on the limitations of antidepressants in treating depression.

1 Medical Evidence

Numerous clinical trials and meta-analyses have investigated the efficacy of antidepressant medications. While some studies show positive outcomes, several others indicate limited effectiveness, especially in mild to moderate cases of depression. For instance:

1a. Turner et al. [1]. analysed 30 Phase II/III double-blind placebo-controlled trials involving 13,747 patients, focusing on newer antidepressants. They compared the transparent reporting of positive and negative trial outcomes and the effect size inflation for these drugs in comparison to older antidepressants.

Positive findings include all positive trials among the newer antidepressants having transparent publication, indicating accurate reporting of results in alignment with regulatory assessments. The effect size inflation for newer antidepressants was lower compared to older ones, suggesting progress in reducing reporting bias.

Negative findings include only 47% of negative trials among newer antidepressants having transparent publication, raising concerns about non-reporting of negative results and potential publication bias. The study’s limited scope, with a small number of trials and drugs from a single class, also limits generalisability.

1b. Kirsch et al. [2] performed a meta-analysis on published and unpublished clinical trials and revealed that the effect of antidepressants was not significantly different from placebo in mild and moderate depression but was only significant in severe depression.

1c. Fournier et al. [3] analysed data from six clinical trials and reported that the effect size of antidepressants compared to placebo was relatively small, with limited clinical significance.

2 Tolerance and Withdrawal Effects

One concern associated with long-term antidepressant use is the development of tolerance and withdrawal effects. Patients on antidepressants may experience reduced efficacy over time, requiring higher doses or switching to alternative medications. Abrupt discontinuation of antidepressants can lead to withdrawal symptoms, including anxiety, dizziness, and sleep disturbances [4], [5].

3 Placebo Effect

The placebo effect plays a significant role in antidepressant efficacy studies. Patients receiving placebos often experience improvements in depressive symptoms due to the power of suggestion and expectation [6]. This can lead to an overestimation of antidepressant effectiveness in clinical trials, especially when the difference between the drug and placebo responses is small.

4 Biopsychosocial Factors

Depression is a complex disorder influenced by a variety of biopsychosocial factors, such as genetics, brain chemistry, personality traits, life events, and social support. Antidepressants primarily target biological factors by altering neurotransmitter levels, but they may not adequately address the psychological and social aspects of depression.

5 Psychological Perspectives

5a) Cognitive-Behavioural Therapy (CBT): CBT is a well-established psychotherapeutic approach for treating depression. Studies have shown CBT can be as effective as antidepressant medications, especially in preventing relapse [7], [8]. CBT helps patients identify and modify negative thought patterns, leading to lasting improvements in mood and coping skills.

5b) Mindfulness-Based Interventions: Mindfulness-based interventions, such as Mindfulness-Based Cognitive Therapy (MBCT), have also demonstrated promising results in reducing depressive symptoms and preventing relapse [9], [10]. These interventions focus on increasing present-moment awareness and acceptance, reducing rumination, and enhancing emotional regulation.


While antidepressants can be beneficial for some individuals with severe depression, the medical evidence and psychological perspectives suggest limitations in their overall efficacy, especially in mild to moderate cases. Combining pharmacological approaches with evidence-based psychotherapies like CBT and mindfulness-based interventions may offer a more comprehensive and effective treatment approach for depression.


[1] Turner, E. H., Cipriani, A., Furukawa, T. A., Salanti, G., & de Vries, Y. A. (2022). Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials. PLoS Medicine, 19(1), e1003886.

[2] Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008). Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine, 5(2), e45.

[3] Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010). Antidepressant drug effects and depression severity: a patient-level meta-analysis: A patient-level meta-analysis. JAMA: The Journal of the American Medical Association, 303(1), 47–53.

[4] Haddad, P. M. (2001). Antidepressant discontinuation syndromes: Clinical relevance, prevention and management. Drug Safety: An International Journal of Medical Toxicology and Drug Experience, 24(3), 183–197.

[5] Fava, G. A., Gatti, A., Belaise, C., Guidi, J., & Offidani, E. (2015). Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: A systematic review. Psychotherapy and Psychosomatics, 84(2), 72–81.

[6] Kirsch, I. (2019). The Emperor’s New Drugs: Exploding the Antidepressant Myth. Bodley Head.

[7] Hollon, S. D. (2005). Prevention of Relapse Following Cognitive Therapy vs. Medications in Moderate to Severe Depression. Archives of General Psychiatry, 62(4), 417–422.

[8] Derubeis, R. J. (2005). Cognitive Therapy vs. Medications for Depression: Treatment Outcomes and Neural Mechanisms. Nature Reviews Neuroscience, 6(11), 835–847.

[9] Segal, Z. V. (2010). Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse. Guilford Press.

[10] Piet, J. (2012). The Effectiveness of Mindfulness-Based Cognitive Therapy on Recurrence Prevention in Patients with Major Depressive Disorder: A Systematic Review and Meta-analysis. Journal of Affective Disorders, 141(1), 1–10.