[TREATMENT OF SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSRIS AND SNRIS) DURING PREGNANCY AND LACTATION].

INTRODUCTION: Women are more likely to develop depression during the perinatal period than at any other time in their lives. Studies from recent years raise significant concerns regarding the potential of a depressive disorder in the pregnant mother to cause adverse obstetric results for the mother and the newborn. As antidepressants can penetrate the placenta to different degrees, concern has been raised regarding their teratogenic potential. In recent years various inconsistent and ambiguous reports specifying mild risks to the fetus and newborn from exposure to serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy have been published. This paper provides a review of current medical knowledge regarding the pharmacological treatment with common antidepressants such as SSRIs and SNRIs in pregnant women. Based on this review we also present treatment and follow-up recommendations of the major published guidelines for the treatment of serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs) during pregnancy for the medical care providers.

[Antidepressant drugs-State of the art]. / Antidepressiva ­ State of the Art.

BACKGROUND: Due to their frequency, complications, and sequelae, depressive disorders are of great significance to patients, their environment, and society. They are considered the most frequent form of mental disturbances in old age. The use of antidepressant drugs (AD) represents a cornerstone of the treatment, which is always multidimensional. OBJECTIVE: The classification, mechanism of action, efficacy and tolerability of AD are described. Furthermore, the practical treatment procedure as well as special aspects, such as treatment resistance and special features in old age are presented. MATERIAL AND METHODS: Narrative review incorporating the most recent literature and the new edition of the national healthcare guidelines on unipolar depression. RESULTS: In the past 20 years, a large number of so-called 2nd generation ADs have been approved worldwide with comparable efficacy but more favorable side effect profiles than conventional (tricyclic) substances. Almost all ADs act by enhancing monoaminergic, mostly serotonergic, neurotransmission. Other common features include a latency in the onset of action, moderate response rates, and potential efficacy on all core symptoms of depression. Side effects can include cardiovascular, metabolic, or sexual dysfunction, but these may significantly differ between drug classes. This enables individualized treatment taking age, individual risk factors, comorbidities and comedications into account. CONCLUSION: With the correct interpretation of indications, knowledge of the risks, and consideration of the defined precautionary measures outlined here, treatment with AD is a safe and effective tool in the treatment of moderate and severe depression.

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study.

BACKGROUND: To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. METHOD: We conducted a case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. RESULTS: Compared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12-1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90-365 (OR: 1.07,95% CI: 0.87-1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12-3.31), venlafaxine (OR: 1.62, 95% CI: 1.13-2.31), mirtazapine (OR: 1.56, 95% CI: 1.00-2.43), paroxetine (OR: 1.44, 95% CI: 1.08-1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01-1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. CONCLUSIONS: The study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.

Pharmacologic Treatment of Depression.

The prevalence of depression and the use of antidepressant medications have risen steadily in the United States over the past three decades. Antidepressants are the most commonly prescribed medications for U.S. adults 20 to 59 years of age. Second-generation antidepressants (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin modulators, atypical antidepressants) are first-line therapy for depression. Psychotherapy, including cognitive behavior therapy and other types of individual and group therapy, is also a first-line treatment. The combination of medication and psychotherapy is preferred for severe depression. Treatment history, comorbidities, costs, and risk of adverse effects should be considered when choosing an antidepressant medication. Although many patients use antidepressants indefinitely, few studies have examined safety and effectiveness beyond two years. There is an increased risk of relapse or recurrence of depressive symptoms when an antidepressant is discontinued, compared with continued use. Gradually tapering the dosage while concurrently providing cognitive behavior therapy can decrease this risk. High-quality evidence on antidepressant use in pregnancy is lacking. Depression and use of antidepressants are both associated with preterm birth.

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.

BACKGROUND: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD). METHODS: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated. RESULTS: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%). LIMITATIONS: A short-term non-inferiority study without a placebo arm. CONCLUSIONS: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews.

OBJECTIVE: To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition. DESIGN: Overview of systematic reviews. DATA SOURCES: PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews comparing any antidepressant with placebo for any pain condition in adults. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework. RESULTS: 26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference -5.3, 95% confidence interval -7.3 to -3.3), postoperative pain (-7.3, -12.9 to -1.7), neuropathic pain (-6.8, -8.7 to -4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons). CONCLUSIONS: Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews-seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311073.

Servicio de indicación farmacéutica a pacientes tratados con medicamentos de estrecho margen terapéutico / Minor ailment service for patients treated with narrow therapeutic index drug

Se estudian los casos de dos pacientes que demandan nuestro servicio de indicación farmacéutica porque presentan sintomatología digestiva inespecífica. Ambos están siendo tratados con fármacos de estrecho margen terapéutico (carbonato de litio y digoxina, respectivamente). Durante la indicación, el análisis de la medicación revela la posibilidad de que la clínica que ambos manifiestan guarde relación con estos tratamientos en distinta medida: en el caso del carbonato de litio, por tratarse de una reacción adversa frecuente en tratamientos prolongados, y en el de la digoxina, porque la sintomatología va acompañada de bradicardia. En consecuencia, se proponen dos intervenciones, siendo una de ellas la derivación urgente al médico de atención primaria. El análisis de los tratamientos farmacológicos crónicos prescritos a los pacientes, especialmente aquellos de estrecho margen terapéutico, durante el proceso de indicación, es un punto clave para discriminar entre clínica debida exclusivamente a síntomas menores y otras situaciones que pueden incluso comprometer la vida. (AU)

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

PURPOSE: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. METHODS: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. RESULTS: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. CONCLUSION: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Selective Serotonin Reuptake Inhibitor (SSRI) Bleeding Risk: Considerations for the Consult-Liaison Psychiatrist.

PURPOSE OF REVIEW: To present a clinically oriented review of selective serotonin reuptake inhibitor (SSRI)-related bleeding issues commonly addressed by consult-liaison psychiatrists. RECENT FINDINGS: Concomitant medical, surgical, or hospital-based conditions exacerbate the risk of SSRI-related bleeding even though a review of the literature suggests it is only marginally elevated. Psychiatrists and other clinicians need to consider these conditions along with antidepressant benefits when answering the question: to start, hold, continue, or change the antidepressant? Where an evidence base is limited, mechanistic understanding may help consult-liaison psychiatrists navigate this terrain and collaborate with other medical specialties on responsible antidepressant management. Most often, the risk is cumulative; data are not directly applicable to complex clinical situations. This review incorporates a hematologic perspective and approach to bleeding risk assessment along with extant data on SSRI-induced bleeding risk ad specific medical conditions.

Risk of Poor Neonatal Adaptation Syndrome Among Infants Exposed to Second-Generation Atypical Antipsychotics Compared to Antidepressants: Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM).Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18-45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported.Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers.Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon.Trial Registration: ClinicalTrials.gov identifier: NCT01246765.

Antidepressant use during pregnancy and the risk for gestational diabetes: a systematic review and meta-analysis.

OBJECTIVE: Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy. METHODS: We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM. RESULTS: Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; p < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; p = .054; I2 = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors. CONCLUSIONS: The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.

[70-year history of studying the effectiveness of therapy of patients with depression with antidepressants - irreversible nonselective monoamine oxidase inhibitors]. / Semidesyatiletnyaya istoriya izucheniya effektivnosti terapii depressii neobratimymi neselektivnymi ingibitorami monoaminoksidazy.

The history of studying the effectiveness of therapy of patients with depression by irreversible non-selective monoamine oxidase inhibitors (MAOIs) is analyzed and systematized. Authors describe the stages of the appearance of the first data on the effectiveness of treatment by the first representatives (the 50s of the XX century), the targeted study of the effectiveness of the use of numerous «new¼ representatives and the emergence of disagreements in assessing the power of therapy (the end of the 50s-60s of the XX century), continuing to study the effectiveness of treatment by representatives who remained in clinical practice, and establishing its clinical predictors (80s-90s of the XX century), the appearance of the first data on the effectiveness of therapy for «atypical depression¼ (1959-1960) and further development of this issue (80s-90s of the XX century). The stage of formation and development of the idea of the effectiveness of treatment for resistant depression (late 70s-90s of the XX century) is characterized. Separately, the history of studying the effectiveness of application in the USSR and Russia (late 50s- 90s of the XX century) is outlined. The current state of the issue of assessing the effectiveness of therapy (the end of the 90s of the XX century - 2022) is shown.

Case Report: Performing a Medication Safety Review Assisted by Pharmacogenomics to Explain a Prescribing Cascade Resulting in a Patient Fall.

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.g., CYP2C19 or CYP2D6), drug-induced phenoconversion is common in patients on antidepressant combinations. This condition influences the interpretation of a patient's PGx results, overall risk of ineffective/adverse medication response due to multi-drug interactions, and the recommendations. This complex case describes a patient with MDD, generalized anxiety disorder, and chronic pain who experienced a fall due to excessive sedation following a prescribing cascade of fluoxetine, bupropion, and doxepin. These antidepressants delivered a significant additive sedative effect and interacted with the patient's hydrocodone, potentially contributing to uncontrolled pain, upward dose titration of hydrocodone, and a higher overall sedative burden. The PGx results and drug-induced phenoconversion described in this case report explain the patient's excessive sedation and possibly ineffective/toxic antidepressant and opioid treatment. This case report also illustrates how a more timely multi-drug interaction assessment (preferably in conjunction with preemptive PGx testing) may have informed a different prescribing pattern, reduced/avoided a prescribing cascade, and potentially prevented a drug-related fall.

When to stop medication in unipolar depression: A systematic review and a meta-analysis of randomized controlled trials.

BACKGROUND: Currently, there is no clear answer to the question of how long antidepressants should be continued or when they can be safely discontinued. METHODS: Pubmed/Medline was systematically searched from inception to Feb 20, 2021. Double-blind, randomized placebo-controlled trials (RCTs) with maintenance phase were selected to examine the relationship between relapse rate and treatment duration. Among 5351 screened records, 37 RCTs meeting inclusion criteria were selected. Odds ratios were calculated from relapse rates for each study and pooled in random-effect models. Possible predictors of effect sizes, i.e., open-label treatment duration, double-blind phase duration, age, medication type, history of recurrence, were analyzed by meta-regression. RESULTS: The random-effects model showed the superiority of active medication over placebo for relapse during the follow-up phase (OR = 0.37; 95 % CI, 0.32-0.42). The meta-regression did not show a relationship between treatment duration and the effect sizes. Other clinical variables were not related with effect sizes. Subgroup analysis revealed that, for atypical ADs the effect size increased as the treatment duration increased. Further analysis showed that the relapse rate in the placebo group decreased as function of time, which reduced the absolute benefit of continued treatment. CONCLUSION: The results may indicate that long term use of antidepressants may not be justified, and this strategy may expose the patients to more adverse effects.

Is psilocybin an effective antidepressant and what is its Mechanism of action?

Goodwin et al.1 report a single 25 mg dose of psilocybin has an antidepressant effect short-term in medication-resistant depression. Unanswered questions include drug blood level as a guide to dose, psychedelic effects relationship to antidepressant benefit, and potential suicide risk of psilocybin.

Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review.

OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.

Values and Preferences of Patients With Depressive Disorders Regarding Pharmacologic and Nonpharmacologic Treatments : A Rapid Review.

BACKGROUND: Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorder. PURPOSE: To assess patient values and preferences regarding pharmacologic and nonpharmacologic treatments of depressive disorder. DATA SOURCES: MEDLINE (Ovid) and PsycINFO (EBSCO) were searched for eligible studies published from 1 January 2014 to 30 November 2022. STUDY SELECTION: Pairs of reviewers independently screened 30% of search results. The remaining 70% of the abstracts were screened by single reviewers; excluded abstracts were checked by a second reviewer. Pairs of reviewers independently screened full texts. DATA EXTRACTION: One reviewer extracted data and assessed the certainty of evidence, and a second reviewer checked for completeness and accuracy. Two reviewers independently assessed risk of bias. DATA SYNTHESIS: The review included 11 studies: 4 randomized controlled trials, 5 cross-sectional studies, and 2 qualitative studies. In 1 randomized controlled trial, participants reported at the start of therapy that they expected supportive-expressive psychotherapy and antidepressants to yield similar improvements. A cross-sectional study reported that non-Hispanic White participants and men generally preferred antidepressants over talk therapy, whereas Hispanic and non-Hispanic Black participants and women generally did not have a preference. Another cross-sectional study reported that the most important nonserious adverse events for patients treated with antidepressants were insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction. For other comparisons and outcomes, no conclusions could be drawn because of the insufficient certainty of evidence. LIMITATIONS: The main limitation of this review is the low or insufficient certainty of evidence for most outcomes. No evidence was available on second-step depression treatment or differences in values and preferences based on gender, race/ethnicity, age, and depression severity. CONCLUSION: Low-certainty evidence suggests that there may be some differences in preferences for talk therapy or pharmacologic treatment of depressive disorders based on gender or race/ethnicity. In addition, low-certainty evidence suggests that insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction may be the most important nonserious adverse events for patients treated with antidepressants. Evidence is lacking or insufficient to draw any further conclusions about patients' weighing or valuation of the benefits and harms of depression treatments. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42020212442).

Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD. RECOMMENDATION 1A: ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence). RECOMMENDATION 1B: ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence). The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences. RECOMMENDATION 2: ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence) The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.