First-line Treatment For Major Depressive Disorder Research Articles

SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings

Background: Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.
 Methods: A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.
 Results: 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.
 Conclusions: This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.

Impaired myelin ultrastructure is reversed by citalopram treatment in a mouse model for major depressive disorder

Major depressive disorder (MDD) is the most common and widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD. The relation between the inhibition of serotonin reuptake in the central nervous system and remission from MDD remains controversial, as reuptake inhibition occurs rapidly, but remission from MDD takes weeks to months. Myelination-related deficits and white matter abnormalities were shown to be involved in psychiatric disorders such as MDD. This may explain the delay in remission following SSRI administration. The raphe nuclei (RN), located in the brain stem, consist of clusters of serotonergic (5-HT) neurons that project to almost all regions of the brain. Thus, the RN are an intriguing area for research of the potential effect of SSRI on myelination, and their involvement in MDD. MicroRNAs (miRNAs) regulate many biological features that might be altered by antidepressants. Two cohorts of chronic unpredictable stress (CUS) mouse model for depression underwent behavioral tests for evaluating stress, anxiety, and depression levels. Following application of the CUS protocol and treatment with the SSRI, citalopram, 48 mice of the second cohort were tested via magnetic resonance imaging and diffusion tensor imaging for differences in brain white matter tracts. RN and superior colliculus were excised from both cohorts and measured for changes in miRNAs, mRNA, and protein levels of candidate genes. Using MRI-DTI scans we found lower fractional anisotropy and axial diffusivity in brains of stressed mice. Moreover, both miR-30b-5p and miR-101a-3p were found to be downregulated in the RN following CUS, and upregulated following CUS and citalopram treatment. The direct binding of these miRNAs to Qki, and the subsequent effects on mRNA and protein levels of myelin basic protein (Mbp), indicated involvement of these miRNAs in myelination ultrastructure processes in the RN, in response to CUS followed by SSRI treatment. We suggest that SSRIs are implicated in repairing myelin deficits resulting from chronic stress that leads to depression.

P367. Seasonal Depression Does Not Affect Depression Outcomes From Repetitive Transcranial Magnetic Stimulation

A seasonal pattern affects 10-20% of those with major depressive disorder (MDD) in temperate climates. While repetitive transcranial magnetic stimulation (rTMS) is a first-line treatment for MDD, whether a seasonal pattern to MDD affects rTMS outcomes for depression is unexplored.

Overview of a large transcranial magnetic stimulation patient outcomes database

Abstract While there is a clear evidence base from randomized clinical trials that demonstrate the efficacy of Transcranial Magnetic Stimulation (TMS) in the treatment of major depressive disorder (MDD), greater understanding of best practices in routine clinical practice is critically needed. This symposium will provide an in depth look at the first ten years of data collection of patient demographics, treatment parameters and outcomes from the NeuroStar® Advanced Therapy System Clinical Outcomes Registry. Methods: Registry data were collected at 103 practice sites. Of 7759 participants, 5010 patients were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the Patient Health Questionaire-9 (PHQ-9) before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3,814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. CGI-S ratings were obtained in smaller samples. Results: In the total ITT and Completer samples, response (58–83%) and remission (28–62%) rates were notably high across self-report and clinician-administered assessments. Female patients and those treated with a larger number of pulses per session had superior clinical outcomes. Conclusions: The extent of clinical benefit reported by patients and clinicians following TMS in routine practice compares favorably with alternative interventions for treatment-resistant depression. Strong efficacy and the low side effect and medical risk profile suggest that TMS be evaluated as a first-line treatment for MDD. The findings demonstrate the power of creating a large registry of clinical outcomes in MDD. Keywords: TMS, treatment outcomes, registry

Clinical outcomes in a large registry of patients with major depressive disorder treated with Transcranial Magnetic Stimulation

BackgroundRandomized clinical trials have demonstrated that Transcranial Magnetic Stimulation (TMS) is an effective treatment for episodes of major depressive disorder (MDD). However, characterization of outcomes in routine clinical practice is needed, as well as identification of patient- and treatment-related outcome predictors. This study documented patient-rated (PHQ-9) and clinician-rated (CGI-S) clinical outcomes in the NeuroStar® Advanced Therapy System Clinical Outcomes Registry. MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 patients were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3,814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. CGI-S ratings were obtained in smaller samples. ResultsIn the total ITT and Completer samples, response (58–83%) and remission (28–62%) rates were notably high across self-report and clinician-administered assessments. Female patients and those treated with a larger number of pulses per session had superior clinical outcomes. LimitationsSite participation in the registry was voluntary and treatment was open label. ConclusionsThe extent of clinical benefit reported by patients and clinicians following TMS in routine practice compares favorably with alternative interventions for treatment-resistant depression. Strong efficacy and the low side effect and medical risk profile suggest that TMS be evaluated as a first-line treatment for MDD. The findings derive from the largest registry of clinical outcomes in MDD for any treatment.

Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity.

Major depressive disorder (MDD) is the most prevalent mental illness contributing to global disease burden. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are the first-line treatment for MDD, but are only fully effective in 30% of patients and require weeks before improvement may be seen. About 30% of SSRI-resistant patients may respond to augmentation or switching to another antidepressant, often selected by trial and error. Hence a better understanding of the causes of SSRI resistance is needed to provide models for optimizing treatment. Since SSRIs enhance 5-HT, in this review we discuss new findings on the circuitry, development and function of the 5-HT system in modulating behavior, and on how 5-HT neuronal activity is regulated. We focus on the 5-HT1A autoreceptor, which controls 5-HT activity, and the 5-HT1A heteroreceptor that mediates 5-HT actions. A series of mice models now implicate increased levels of 5-HT1A autoreceptors in SSRI resistance, and the requirement of hippocampal 5-HT1A heteroreceptor for neurogenic and behavioral response to SSRIs. We also present clinical data that show promise for identifying biomarkers of 5-HT activity, 5-HT1A regulation and regional changes in brain activity in MDD patients that may provide biomarkers for tailored interventions to overcome or bypass resistance to SSRI treatment. We identify a series of potential strategies including inhibiting 5-HT auto-inhibition, stimulating 5-HT1A heteroreceptors, other monoamine systems, or cortical stimulation to overcome SSRI resistance.

Treatment recommendations for DSM-5-defined mixed features.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5-defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform future treatment guidelines.

C-QUALITY: Cost and Quality-of-Life Pharmacoeconomic Analysis of Antidepressants in Major Depressive Disorder in Italy

Major depressive disorder (MDD) is a common and disabling condition across the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used antidepressants. The objective of this study was to assess the cost-effectiveness [€ per quality-adjusted life year (QALY)] of all SSRIs and all SNRIs for the treatment of MDD in Italy. A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits agency model to reflect current clinical practice in the treatment of MDD in the largest Italian regions. This adaptation was possible thanks to the collaboration of an expert panel of Italian psychiatrists and health economists. The model evaluated patients with a first diagnosis of MDD and initiating an SSRI or an SNRI for the first time. The time horizon was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were considered for resource utilization and for treatment costs based on each regional health service perspective. Population-weighted regional data were used to define a national model. Scenario simulations, one-way sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model. The base case analysis showed that escitalopram was associated with a lower total cost (€ 1,562) and a larger health gain (QALYs) at 1 year (0.732) per patient and dominated the other treatment strategies since more QALYs were achieved at a lower total cost. Sensitivity analyses support the robustness of the model. The results indicate that escitalopram is the most cost-effective pharmacological treatment strategy for the Italian health service compared with other SSRIs and all SNRIs used in the first-line treatment of MDD.

Sexual Satisfaction and Quality of Life in Major Depressive Disorder Before and After Treatment With Citalopram in the STAR*D Study

Major depressive disorder (MDD) patients often experience impaired sexual satisfaction (ISS) and poor quality of life (QOL). Selective serotonin reuptake inhibitors (SSRIs), the first-line treatment for MDD, can cause sexual dysfunction, potentially worsening ISS and QOL. This study examined the impact of MDD and the SSRI citalopram on sexual satisfaction and QOL in level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (July 2001-September 2006). A retrospective analysis was conducted of the change in sexual satisfaction, as measured by item 9 of the Quality of Life Enjoyment and Satisfaction Questionnaire, the primary outcome measure, in 2,280 patients with DSM-IV-TR-defined MDD who were treated with citalopram for 12 weeks. The Quick Inventory of Depressive Symptomatology-Self Report was used to evaluate the impact of depression ratings on impaired sexual satisfaction and on QOL. Impaired sexual satisfaction was present in 64.3% of MDD patients at pretreatment, but that percentage declined to 47.1% at posttreatment with citalopram (P < .0001). Those who achieved remission had less ISS and better QOL. The prevalence of ISS in remitters was 21.2% versus 61.3% in nonremitters (P < 10(-8)). The mean ± standard deviation score for remitters increased from 2.32 ± 1.16 to 3.44 ± 1.23 (P < 10(-8); Cohen d = 0.81 [large effect size]), whereas in nonremitters it increased only from 1.99 ± 1.08 to 2.19 ± 1.19 (P < 10(-8); Cohen d = 0.16). The difference between remitters and nonremitters was highly significant (P < 10(-8)). Regression analyses at pretreatment and posttreatment demonstrated significant associations between depressive symptoms and ISS (P < .0001) and between ISS and lower QOL (P < .0001) as well as an association between citalopram and increased probability of ISS and a poorer QOL in patients who continue to have moderate-to-severe depression. A majority of MDD patients have impaired sexual satisfaction, a symptom associated with poor QOL. Despite the sexual side effects of the SSR citalopram, treating depression to full remission was associated with improvements in sexual satisfaction and QOL. ClinicalTrials.gov identifier: NCT00021528.

Preclinical discovery of duloxetine for the treatment of depression

Introduction: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD.Areas covered: The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine.Expert opinion: Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD.

Prescription Practices and Empirical Efficacy of Psychopharmacologic Treatments for Pediatric Major Depressive Disorder

Limited research on pharmacologic treatments for pediatric major depressive disorder (MDD) exists. Prescription practices data for MDD from 1,209 American Academy of Child and Adolescent Psychiatry members collected in 1998 are compared to the current empirical support for this treatment approach. Results indicated that psychiatrists have willingly used medication as a first-line treatment for MDD in children under age 7, despite a paucity of research support for this practice. Recent warnings regarding the use of selective serotonin reuptake inhibitors warrant the need to reexamine current prescription practices of psychiatric care providers for children diagnosed with MDD.

Biological Psychiatry Congress 2007

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Depressive symptoms and major depressive disorder (MDD) occur ≥ 3 times as common in coronary artery disease (CAD) patients as in the general community, which confers an adjusted relative risk of 2 to 4 for mortality. There are emerging data on how to manage depressed CAD patients with MDD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method:&lt;/strong&gt; The two previous clinical trials (SADHART and ENRICHD) confirm (i) failure of cognitive-behavior therapy to affect survival, (ii) improvement with placebo and usual care, (iii) clinical effect of sertraline, particularly in those with recurrent MDD, (iv) cardiac safety of sertraline. This presentation will highlight the findings of the recently concluded CREATE (Canadian cardiac evaluation of antidepressant and psychotherapy efficacy) study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; In a 2-by-2 factorial trial 284 patients with stable CAD were assigned to interpersonal psychotherapy (IPT) or clinical management (CM) and citalopram or placebo for 12 weeks. Citalopram reduced depressive symptoms more than placebo at 6 weeks (p=.01) and at 12 weeks (HAM-D-Hamilton Depression difference 3.3 points, p=.005). Citalopram was efficacious for 43% with recurrent depression compared to those experiencing MDD for the first time. However, there was no additional benefit of adding IPT to CM (HAM-D difference -2.3 points; p=.06), favoring CM over IPT in lowering depressive symptoms. IPT improved depression compared to CM for those subjects with high levels of functional performance. There were 12 cardiovascular and 23 other serious adverse events classified by independent committee and no electrocardiogram effects of the active drug were noted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Citalopram can be considered as a first line treatment of MDD in CAD patients. So far, besides CM, it has not been shown if any form of psychotherapy is indicated for such patients.&lt;/p&gt;

Cost-effectiveness analysis of escitalopram: a new SSRI in the first-line treatment of major depressive disorder in Austria

SUMMARYObjectives: To compare the cost-effectiveness of escitalopram, a new selective serotonin reuptake inhibitor (SSRI), with (generic) citalopram in the first-line treatment of major depressive disorder (MDD) in Austria.Methods: A two-path decision analytic model with a 6-month horizon was adapted to the Austrian setting using Austrian clinical guidelines. All patients (aged ≥ 18 years) started at the primary care path and were referred to specialist care in the secondary care path in case of insufficient response. Model inputs included drug-specific probabilities from head-to-head trial data, literature and expert opinion. The main outcome measure was success (i.e., remission defined as Montgomery–Åsberg Depression Rating Scale (MADRS) score ≤ 12) and costs of treatment (i.e., drug costs and medical care). The analysis was performed from the Austrian societal and Social Healthcare Insurance System (SHIS) perspectives. The Human Capital approach was used to estimate the societal costs of lost productivity.Results: Treatment with escitalopram yielded lower expected cost and greater effectiveness compared with citalopram. The expected success rate was higher for escitalopram (64.5%) compared to citalopram (59.1%). From the SHIS perspective, the total expected cost per successfully treated patient was lower (€115) for escitalopram (€608) compared with citalopram (€723). From the societal perspective, these expected costs were €3034 and €3269 respectively. Sensitivity analyses on unit costs and probabilities demonstrated the robustness of the results. From the societal perspective, escitalopram remained the dominant treatment option, even at a cost of €0 for (generic) citalopram.Conclusion: Escitalopram is a cost-effective alternative compared to (generic) citalopram in the first-line treatment of MDD in Austria.