Feb 12, 2025

Public workspaceA Systematic Review on Adverse Effects of Antidepressants for Pharmacological Treatment of Depression Over a Decade

DOI
dx.doi.org/10.17504/protocols.io.dm6gp9q21vzp/v1
  • 1Melmaruvathur Adhiparasakthi institue of medical sciences and research
Razia Abdul Rasheed
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DOI: dx.doi.org/10.17504/protocols.io.dm6gp9q21vzp/v1
Protocol Citation: Razia Abdul Rasheed, Dr.Sridevi, krishna kishore, Dr.Vijayalakshmi s, Dr.T.A.R Raja, Dr.Senthil G, Dr.Renuga Devi P, Dr.Ramanarayana Reddy, SANJAI RATHINAM P 2025. A Systematic Review on Adverse Effects of Antidepressants for Pharmacological Treatment of Depression Over a Decade. protocols.io https://dx.doi.org/10.17504/protocols.io.dm6gp9q21vzp/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: February 05, 2025
Last Modified: February 12, 2025
Protocol Integer ID: 119585
Abstract
Depression is a severe heterogeneous disease that affects a person's mood, physical health and behavior. Depression was ranked the fourth leading cause of disability and premature death. Depression treatment modalities involve pharmacotherapy, psychotherapy or both. However, some studies have reported that, dropout rates on antidepressants are 50% in first 2-4 months .Adverse drug reactions are an important factor in non-adherence to antidepressant treatment. Therefore, prevention of side effects should be the vital part of treatment. Objectives: To assess the Adverse Effects of Antidepressants for Pharmacological Treatment of Depression Over a Decade. Materials and method: Databases:PUBMED/MEDLINE   and COCHRANE. Search strategies  :    Antidepressants, SSRIs, SNRIs, Side effects, TCAs, ADRs with year limit 2011-2020. Data extraction: Authors will review the electronic abstracts and selected full-text articles for inclusion. The following information will be extracted from each included study: Mean age, sample size, study population, study design, category and name of antidepressants used, dosage, dosing regimen, side effects of each agent. Data extraction will be performed according to PRISMA guidelines.
INTRODUCTION
INTRODUCTION
Depression is a severe heterogeneous disease that affects a person's mood, physical health and behavior. Depression was ranked the fourth leading cause of disability and premature death.1 Globally, An estimated 3.8% of the population suffers from depression, including 5% of adults (4% of men, 6% of women) and 5.7% over the age of 60.1  A report by WHO in 2015 found that 4.5% of the Indian population, suffer from depressive disorders. 2-4
Major depressive disorder is characterized by a depressed mood or loss of pleasure/interest for at least 2 weeks. It is also accompanied by at least three (for a total of at least five) of the following symptoms present most days: weight loss or change in appetite, insomnia or hypersomnia, psychomotor retardation or agitation, fatigue or loss of energy, excessive/inappropriate guilt or feelings of worthlessness, indecisiveness or diminished ability to concentrate or think, and recurrent thoughts of death or suicidal ideation or suicide plan or attempt.5-7
Depression treatment modalities involve pharmacotherapy, psychotherapy or both. Without treatment, 10 to 15% of people suffering from severe depressive disorder commit suicide.8 The American Psychiatric Association (APA) in 2012 and the American College of Physicians (ACP) in 2016, published guidelines for major depressive disorder (MDD), where antidepressants were recommended as the first treatment option. 9, 10   it also guided that, drug selection should be based on side effect profile, patient preference, dosing schedule, cost, and drug interactions. Overall, the guidelines suggested that selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), bupropion, or mirtazapine are the optimal initial treatment for the majority of patients.11
Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are recognized pharmacological classes for treating depression, but due to safety concerns and drug properties, these classes are not considered first-line therapy. 12
Although antidepressants have excellent therapeutic effects, they all have potential side effects. TCAs are more sedative (eg drowsiness), (anti)cholinergic (eg dry mouth) and cause cardiovascular side effects (eg heart palpitations). In contrast, SSRIs have been shown to have more activating (such as insomnia) and gastrointestinal (such as nausea) adverse events. 13, 14
Taking antidepressant medication for at least 6 to 9 months will prevent relapse after the remission of a depressive episode.15 However, some studies have reported that, dropout rates on antidepressants are 50% in first 2-4 months .16Adverse drug reactions are an important factor in non-adherence to antidepressant treatment.17 Therefore, prevention of side effects should be the vital part of treatment.
AIM AND OBJECTIVE
AIM AND OBJECTIVE
To assess the Adverse Effects of Antidepressants for Pharmacological Treatment of Depression Over a Decade.
Materials and method:
Databases              :   PUBMED/MEDLINE   and COCHRANE.
Search strategies  :    Antidepressants, SSRIs, SNRIs, Side effects, TCAs, ADRs with year limit 2011-2020.
Selection criteria   :   
Inclusion criteria  :   
  1. RCTs that diagnosed major depressive disorder (MDD) based on; Diagnostic and Statistical Manual of Mental Disorders (DSM-5), International classification of diseases   (ICD-10), Montgomery-Asberg depression rating scale (MADRS), Hamilton depression rating scale (HDRS).
  2. RCTs with primary or secondary outcome documenting adverse effects
  3. RCTs that documented antidepressants adverse effect with Generic Assessment of Side Effects Scale antidepressants (GASE-AD), Toronto Side Effects Scale 
Exclusion criteria:
 
  1. Duplicated studies
  2. Language other than English
  3. Phytochemical based RCT
Data extraction:
Data extraction:
Authors will review the electronic abstracts and selected full-text articles for inclusion. The following information will be extracted from each included study: Mean age, sample size, study population, study design, category and name of antidepressants used, dosage, dosing regimen, side effects of each agent. Data extraction will be performed according to PRISMA guidelines.
Data collection procedure:
Data collection procedure:
  1. Antidepressant side effects will be assessed according to the Generalized Side Effects Assessment Scale GASE-AD (Antidepressant Specific Side Effects) - 36 points and the Toronto Side Effects Scale (TSES) - 32 points. These scales are used directly by treating physicians to identify adverse events. 
  2. Central nervous system (CNS) side effects - Nervousness, Agitation, Tremor, Myoclonus, Fatigue, Dizziness, Postural hypotension, Somnolence, Increased sleep, Decreased sleep Sweating, Flushing, Edema, Headache and Blurred vision 
  3. Gastrointestinal (GI) side effects - Abdominal pain, Dyspepsia, Nausea, Diarrhea, Constipation, Decrease appetite, Increase appetite, Dry mouth, Weight gain and Weight loss. Sexual functioning (SF) side effect – Anorgasmia, Increased libido, Decreased libido, premature ejaculation, Delayed ejaculation and Erectile dysfunction.
Analysis plan:
Analysis plan:
 Data will be entered and analyzed using SPSS version 23.0 software.
Descriptive statistics will be used to analyze the data.
Implications of the study
Implications of the study
The study highlights the need for careful consideration of adverse effects when prescribing antidepressants for depression. By systematically reviewing side effects over the past decade, it emphasizes improving patient adherence through personalized treatment plans, monitoring, and minimizing adverse reactions, ultimately optimizing pharmacological management of depression
References:
References:
  1.      Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx).  https://vizhub.healthdata.org/gbd-results/ (Accessed 4 March 2023).
  2.      Woody CA, Ferrari AJ, Siskind DJ, Whiteford HA, Harris MG. A systematic review and meta-regression of the prevalence and incidence of perinatal depression. J Affect Disord. 2017;219:86–92.
  3.      Evans-Lacko S, Aguilar-Gaxiola S, Al-Hamzawi A, et al. Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys. Psychol Med. 2018;48(9):1560-1571.
  4.      "Highlights of Changes from DSM-IV-TR to DSM-5". American Psychiatric Association. May 17, 2013. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Fifth edition. 2013.
  5.      Burley CV, Burns K, Lam BCP, Brodaty H. Nonpharmacological approaches reduce symptoms of depression in dementia: A systematic review and meta-analysis. Ageing Res Rev. 2022 Aug;79:101669. 
  6.      Fried EI, Epskamp S, Nesse RM, Tuerlinckx F, Borsboom D. What are 'good' depression symptoms? Comparing the centrality of DSM and non-DSM symptoms of depression in a network analysis. J Affect Disord. 2016 Jan 1;189:314-20. 
  7.      Kim HS, Moore MT. Symptoms of depression and the discrepancy between implicit and explicit self-esteem. J Behav Ther Exp Psychiatry. 2019 Jun;63:1-5. 
  8.      Brådvik L. Suicide Risk and Mental Disorders. Int J Environ Res Public Health. 2018 Sep 17;15(9):2028. 
  9.      American Psychological Association. (2019). Clinical practice guideline for the treatment of depression across three age cohorts. Retrieved from https://www.apa.org/depression-guideline
  10.   Qaseem A, Barry MJ, Kansagara D; Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients with Major Depressive Disorder: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2016 Mar 1; 164(5):350-9. 
  11.   Sabella D. Antidepressant Medications. Am J Nurs. 2018 Sep;118(9):52-59. 
  12.   Cuijpers, P. (2013). Effective therapies or effective mechanisms in treatment guidelines for depression? Depression and Anxiety, 30, 1055–1057. 
  13.   Cuijpers, P. (2015). Psychotherapies for adult depression: Recent developments. Current Opinion Psychiatry, 28, 1–6. 
  14.   Cohen, Z. D., & DeRubeis, R. J. (2018). Treatment selection in depression. Annual Review of Clinical Psychology, 14, 209–236. 
  15.   Cleare A, Pariante CM, Young AH et al (2015) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol 29:459– 525. 
  16.   Serna MC, Cruz I, Real J et al (2010) Duration and adherence of antidepressant treatment (2003 to 2007) based on prescription database. Eur Psychiatry 25:206–213. 
  17.   ECRI Institute. (2015). Management of major depressive disorder: Evidence synthesis report—clinical practice guildeline. Falls Church, VA: The Lewin Group
  18.   Brent DA. Antidepressants and Suicidality. Psychiatr Clin North Am. 2016 Sep;39(3):503-12. 
  19.   Rao Y, Yang R, Zhao J, Cao Q. Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Aug 1;51(4):480-490. English. 
  20.   Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, Li X, Cuijpers P, Coghill D, Xiang Y, Hetrick SE, Leucht S, Qin M, Barth J, Ravindran AV, Yang L, Curry J, Fan L, Silva SG, Cipriani A, Xie P. Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2020 Jul;7(7):581-601. 
  21.   Shinohara K, Efthimiou O, Ostinelli EG, Tomlinson A, Geddes JR, Nierenberg AA, Ruhe HG, Furukawa TA, Cipriani A. Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis. BMJ Open. 2019 May 19;9(5):e027574. 
source of funding
source of funding
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