Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews

Gartlehner, Gerald; Wagner, Gernot; Matyas, Nina; Titscher, Viktoria; Greimel, Judith; Lux, Linda J; Gaynes, Bradley N.; Viswanathan, Meera; Patel, Sheila V.; Lohr, Kathleen N

doi:10.1136/bmjopen-2016-014912

Cited by 141 publications

(117 citation statements)

References 51 publications

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“…More reliable than differences in subjective rating scales are objective outcomes such as premature treatment termination. Several meta-analyses did not detect a noticeable difference between antidepressant and placebo arms with respect to overall dropout rates in short-term RCT ( 51 – 53 ). Assuming that patients prematurely terminate a free treatment only if they perceived it as useless or even harmful ( 54 ), these findings indicate that the average patient experiences no clear benefits from antidepressants.…”

Section: Acute Therapymentioning

confidence: 99%

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants’ Efficacy and Harm

Hengartner

2017

Front. Psychiatry

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BackgroundIn current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants’ efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology.MethodsNarrative review based on a comprehensive search of the literature.ResultsIt is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased risk of suicide and that they have a higher rate of all-cause mortality than matched controls.ConclusionThe strong reliance on industry-funded research results in an uncritical approval of antidepressants. Due to several flaws such as publication and reporting bias, unblinding of outcome assessors, concealment and recoding of serious adverse events, the efficacy of antidepressants is systematically overestimated, and harm is systematically underestimated. Therefore, I conclude that antidepressants are largely ineffective and potentially harmful.

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Section: Acute Therapymentioning

confidence: 99%

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants’ Efficacy and Harm

Hengartner

2017

Front. Psychiatry

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“…The first-line treatment for depression may include either a selective serotonin reuptake inhibitor (SSRI) or a tricyclic antidepressant (TCA) [ 4 ]. Although several antidepressant formulations are available in the market for the therapeutic management of depression, the majority of them have a wide range of side effects [ 5 ]. Therefore, the use of herbal extracts in their crude from or a semi-purified form is gaining ground among clinicians as well as patients as an alternative therapy for depressive disorders [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Prospects of Naturally Occurring and Synthetic Indole Alkaloids for Depression and Anxiety Disorders

Munir

Shahid

Aslam

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Depression and anxiety are the most common disorders among all age groups. Several antidepressant drugs including benzodiazepine, antidepressant tricyclics, azapirone, noradrenaline reuptake inhibitors, serotonin selective reuptake inhibitors, serotonin, noradrenaline reuptake inhibitors, and monoamine oxidase inhibitors have been used to treat these psychiatric disorders. However, these antidepressants are generally synthetic agents and can cause a wide range of side effects. The potential efficacy of plant-derived alkaloids has been reviewed against various neurodegenerative diseases including Alzheimer’s disease, Huntington disease, Parkinson’s disease, schizophrenia, and epilepsy. However, data correlating the indole alkaloids and antidepressant activity are limited. Natural products, especially plants and the marine environment, are rich sources of potential new drugs. Plants possess a variety of indole alkaloids, and compounds that have an indole moiety are related to serotonin, which is a neurotransmitter that regulates brain function and cognition, which in turn alleviates anxiety, and ensures a good mood and happiness. The present review is a summary of the bioactive compounds from plants and marine sources that contain the indole moiety, which can serve as potent antidepressants. The prospects of naturally occurring as well as synthetic indole alkaloids for the amelioration of anxiety and depression-related disorders, structure-activity relationship, and their therapeutic prospects have been discussed.

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“…17,18 A systematic review published in 2017 revealed that in contrast to pharmacological treatment, most non-pharmacological interventions for treating patients with major depressive disorder are not evidence-based. 19 On the other hand, exercise therapy, bibliotherapy, CBT, short-term psychodynamic supportive psychotherapy, and interpersonal psychotherapy (IPT) are considered valid non-pharmacological treatments for adult patients with mild or moderate depression in Korea. 20 Anxiety disorders involve excessive fear and are irrational.…”

Section: Introductionmentioning

confidence: 99%

<p>Medication Profile and Treatment Cost Estimation Among Outpatients with Schizophrenia, Bipolar Disorder, Depression, and Anxiety Disorders in Indonesia</p>

Puspitasari¹,

Sinuraya²,

Rahayu³

et al. 2020

NDT

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The present retrospective study aimed to determine the medication profile and estimate the treatment costs from medical records of new outpatients with schizophrenia, bipolar disorder, depression, and anxiety disorders from a healthcare perspective at a national referral hospital in Indonesia from 2016 to 2018. Methods: Medical records (including medical and administrative data) of 357 new outpatients with schizophrenia, bipolar disorder, depression, or anxiety disorders were collected from the hospital information system. The records of new outpatients with schizophrenia, bipolar disorder, depression, or anxiety disorders aged >18 years and had only received drugs for treatment were included. The medication profile was descriptively assessed, and estimated costs were calculated based on direct costs from a healthcare perspective. Results: Overall, 173 medical records were further analyzed. The main drugs administered to the new outpatients were atypical and typical antipsychotics for schizophrenia, atypical antipsychotics and mood stabilizers for bipolar disorder, antidepressants and atypical antipsychotics for depression, and antidepressants and benzodiazepines for anxiety disorders. The average annual treatment costs per patient were IDR 3,307,931 (USD 236) for schizophrenia, IDR 17,978,865 (USD 1,284) for bipolar disorder, IDR 1,601,850 (USD 114) for depression, and IDR 1,190,563 (USD 85) for anxiety disorders. Conclusion: The most commonly prescribed drugs for schizophrenia were haloperidol and risperidone; for bipolar disorders, sodium divalproex and risperidone; for depression, fluoxetine and sertraline; and for anxiety disorders, sertraline and lorazepam. Considering the high prevalence and estimated treatment costs for mental disorders, special attention is required to prevent an increase in their prevalence in Indonesia.

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Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews

Cited by 141 publications

References 51 publications

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants’ Efficacy and Harm

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants’ Efficacy and Harm

The Therapeutic Prospects of Naturally Occurring and Synthetic Indole Alkaloids for Depression and Anxiety Disorders

<p>Medication Profile and Treatment Cost Estimation Among Outpatients with Schizophrenia, Bipolar Disorder, Depression, and Anxiety Disorders in Indonesia</p>

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