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This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (ß =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.
Assuntos
Transtorno Depressivo Resistente a Tratamento , Ketamina , Adulto , Humanos , Depressão , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologia , Infusões Intravenosas , Ketamina/farmacologia , Ketamina/uso terapêutico , Indução de RemissãoRESUMO
OBJECTIVE: We conducted an open-label clinical trial ("Bio-K") using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission. Here, we report the clinical efficacy and side effect outcomes of Bio-K. METHODS: Across 4 US sites, 75 patients ages 18-65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period. Key exclusion criteria were psychotic symptoms, significant substance abuse, unstable medical conditions, and any use of cannabis. Pre-existing antidepressant medication was maintained. Primary outcome was remission as measured by Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcome of 50 % reduction in Beck Suicide Scale score. Safety monitoring and varying durations of infusions were also key parameters. RESULTS: Using remission as MADRS score <10, after 3 infusions 52 % achieved remission, with 67 % achieving response. Of those achieving response after a single infusion, 66 % (22 of 33) reached remission after 3 infusions, while 40 % (16 of 40) non-responders after the first infusion went on to achieve remission after 3 infusions. Only 20 % of non-responders after 2 infusions achieved remission. Most (81 %) participants had significant suicidal ideation at baseline; of these, two-thirds (67 %) experienced at least a 50 % reduction in suicidality. Side effects were minimal. Uniquely, we had three different types of infusion categories, with individuals receiving: (1) slow (100-min) infusions only or (2) regular (40-min) infusions only or (3) a mix of infusion durations. These three infusion groups showed comparable safety and efficacy. Exploration of clinical factors revealed no link between BMI, age, or gender to remission. CONCLUSIONS: The consistency of outcomes across 4 clinical sites and across multiple instruments, suggests high acute efficacy and safety of IV ketamine for serious depressive episodes. Duration of infusion did not alter outcomes. Meaningfully, 40 % of non-responders after a single infusion did reach remission subsequently, while only 20 % of non-responders after 2 infusions achieved remission, suggesting early response is suggestive for eventual remission. Our data on varying ketamine infusion duration adds novel insights into the clinical administration of this new treatment for refractory and severe patients. Our limitations included a lack of a control group, necessitating caution about conclusions of efficacy, balanced by the utility of reporting "real-world" outcomes across multiple clinical sites. We could also not separately analyze results for bipolar disorder due to small numbers. Together, the Bio-K clinical results are promising and provide significant sample sizes for forthcoming biological markers analyses.
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Transtorno Bipolar , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Ketamina/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Resultado do Tratamento , Infusões Intravenosas , Biomarcadores , DepressãoRESUMO
BACKGROUND: Intravenous (IV) ketamine is an effective therapy for treatment-resistant depression. A large data base is confirmatory and steadily expanding. Qualitative studies can inform best practices and suggest new research directions. As part of a clinical trial designed to identify biomarkers of ketamine response, a qualitative study was conducted to characterize experiences with: receiving infusions; recovering or not recovering from depression; and beliefs about why ketamine worked or did not work. METHODS: Adults with treatment-resistant depression received three IV ketamine infusions in a two-week period and were characterized as remitters or non-remitters via symptom reduction 24 h after the third infusion. Qualitative interviews of a subset of participants were audio recorded, transcribed verbatim, and coded using deductive and inductive methods. Themes were derived and compared across a broader construct of recovery status. RESULTS: Of the 21 participants, nine (43 %) were characterized as having experienced remission and 12 (57 %) non-remission. Of the 12 non-remitters, five were characterized as having experienced partial recovery based on their subjective experiences, reporting substantial benefit from ketamine infusions despite non-remission status based on scale measurements. Attributions for ketamine's effects included biological and experiential mechanisms. Among non-remitters there was risk of disappointment when adding another failed treatment. LIMITATIONS: A more diverse sample may have yielded different themes. Different patients had different amounts of time elapsed between ketamine infusions and qualitative interview. CONCLUSIONS: Qualitative methods may enhance researchers' characterization of IV ketamine's impact on treatment-resistant depression. While requiring confirmation, patients may benefit from a preparatory milieu that prepares them for multiple recovery pathways; decouples the psychedelic experience from clinical outcomes; and addresses potential risks of another failed treatment.
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Transtorno Depressivo Resistente a Tratamento , Alucinógenos , Ketamina , Adulto , Humanos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Alucinógenos/uso terapêutico , Infusões Intravenosas , Ketamina/uso terapêutico , Resultado do TratamentoRESUMO
Pharmacogenomic testing can be used to guide medication selection in patients with major depressive disorder (MDD). Currently, there is no consensus on which gene or genes to consider in medication management. Here, we assessed the clinical validity of the combinatorial pharmacogenomic algorithm to predict sertraline blood levels in a subset of patients enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial. Patients who reported taking sertraline within ≤2 weeks of the screening blood draw were included. All patients received combinatorial pharmacogenomic testing, which included a weighted assessment of individual phenotypes for multiple pharmacokinetic genes relevant for sertraline (CYP2C19, CYP2B6, and CYP3A4). Sertraline blood levels were compared between phenotypes based on: 1) the pharmacokinetic portion of the combinatorial pharmacogenomic algorithm, and 2) individual genes. When evaluated separately, individual genes (for CYP2C19 and CYP2B6) and the combinatorial algorithm were significant predictors of sertraline blood levels. However, in multivariate analyses that included individual genes and the combinatorial pharmacogenomic algorithm, only the combinatorial pharmacogenomic algorithm remained a significant predictor of sertraline blood levels. These findings support the clinical validity of the combinatorial pharmacogenomic algorithm, in that it is a superior predictor of sertraline blood levels compared to individual genes.
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Transtorno Depressivo Maior , Algoritmos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP2C19/genética , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Humanos , Sertralina/uso terapêutico , Resultado do TratamentoRESUMO
Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, p < .001) and 24 weeks (33.5% vs. 23.5%, p = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk.
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Transtorno Depressivo Maior , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Genômica , Humanos , Estudos Prospectivos , Aumento de PesoRESUMO
(Reprinted with permission from Am J Geriatr Psychiatry 2020; 28:933-945).
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The efficacy of subanesthetic intravenous ketamine for treatment resistant depression (TRD) has spurred a growth of clinics nationwide that provide this service. Ketamine is an FDA-approved drug as an anesthetic but remains unapproved for psychiatric indications, and this status raises a number of short- and long-term safety and efficacy concerns that need to be addressed when implementing and developing this type of clinic. Using a framework of systems, provider, and patient domains, we provide a review of the key challenges in providing ketamine infusions and suggest potential approaches. Under systems issues, we highlight broad stakeholder engagement involving cross-departmental and multidisciplinary considerations, business case development, and delineation of administrative standard operating procedures. In the provider domain, we highlight specific roles for different treatment team members as well as suggested training requirements. In the patient domain, we identify a variety of standard operating procedures involving initial patient assessment parameters, ketamine dosing and administration guidelines, and safety monitoring procedures. Together, this review provides key considerations for developing a ketamine clinic for depression, in an effort to meet the pressing demand for this novel treatment option while helping to ensure its safe implementation.
Assuntos
Transtorno Depressivo Resistente a Tratamento , Ketamina , Depressão , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , HumanosRESUMO
We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.
Assuntos
Transtorno Depressivo Maior/genética , Farmacogenética , Testes Farmacogenômicos/estatística & dados numéricos , Testes Farmacogenômicos/normas , Psicotrópicos/uso terapêutico , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
According to the World Health Organization, major depressive disorder is the world's leading cause of disability. If clinical remission is not attained and sustained, episodes tend to recur with greater severity and with lessening responsivity to conventional treatments. Reasonably well-established clues and guidelines are presented about the high risk and profound consequences of recurrence of major depressive disorder if successful antidepressant treatments are discontinued. The authors describe actions required to achieve a "lifetime wellness" focus for treatment. Current approaches would need to be transformed from attainment of clinical remission to attainment and maintenance of lifetime wellness, with the knowledge that some individuals may need continuous treatment. Risk factors would need to be assessed and used to formulate clinical treatment guidelines for risk of recurrence. Clinical trials would need to be greatly lengthened. Measurement-based care and precision medicine would be the foundation for informing clinical decisions. The authors provide guidance in determining how to discontinue antidepressants if that decision is made despite risks.
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OBJECTIVE: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD). DESIGN: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms. SETTING: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites. PARTICIPANTS: Adults age 65 years or older at baseline (nâ¯=â¯206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode. INTERVENTION: Combinatorial pharmacogenomic testing to inform medication selection (guided-care), compared with treatment as usual (TAU). OUTCOMES: Mean percent symptom improvement, response rate, and remission rateat week 8, measured using the 17-item Hamilton Depression Rating Scale; medication switching; and comorbidity moderator analysis. RESULTS: At week 8, symptom improvement was not significantly different for guided-care than for TAU (∆â¯=â¯8.1%, tâ¯=â¯1.64, dfâ¯=â¯187; pâ¯=â¯0.102); however, guided-care showed significantly improved response (∆â¯=â¯13.6%, tâ¯=â¯2.16, dfâ¯=â¯187; pâ¯=â¯0.032) and remission (∆â¯=â¯12.7%, tâ¯=â¯2.49, dfâ¯=â¯189; pâ¯=â¯0.014) relative to TAU. By week 8, more than twice as many patients in guided-care than in TAU were on medications predicted to have no gene-drug interactions (χ2â¯=â¯19.3, dfâ¯=â¯2; p <0.001). Outcomes in the guided-care arm showed consistent improvement through the end of the open-design 24-week trial, indicating durability of the effect. Differences in outcomes between arms were not significantly impacted by comorbidities. CONCLUSIONS: Combinatorial pharmacogenomic test-informed medication selection improved outcomes over TAU among older adults with depression.
Assuntos
Antidepressivos , Transtorno Depressivo Maior , Testes Farmacogenômicos/métodos , Idoso , Antidepressivos/administração & dosagem , Antidepressivos/classificação , Antidepressivos/farmacocinética , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Substituição de Medicamentos , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Escalas de Graduação Psiquiátrica , Falha de TratamentoRESUMO
Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) trial who were taking citalopram/escitalopram at screening and had available blood level data were included (N=191). In multivariate analysis of the individual genes and combinatorial pharmacogenomic test separately (adjusted for age, smoking status), the F statistic for the combinatorial pharmacogenomic test was 1.7 to 2.9-times higher than the individual genes, showing that it explained more variance in citalopram/escitalopram blood levels. In multivariate analysis of the individual genes and combinatorial pharmacogenomic test together, only the combinatorial pharmacogenomic test remained significant. Overall, this demonstrates that the combinatorial pharmacogenomic test was a superior predictor of citalopram/escitalopram blood levels compared to individual genes.
Assuntos
Antidepressivos/sangue , Antidepressivos/farmacocinética , Citalopram/sangue , Citalopram/farmacocinética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/sangue , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Adulto , Algoritmos , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Testes Farmacogenômicos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: Mood disorders are among the most burdensome public health concerns. The National Network of Depression Centers (NNDC) is a nonprofit consortium of 26 leading clinical and academic member centers in the United States providing care for patients with mood disorders, including depression and bipolar disorder. The NNDC has established a measurement-based care program called the Mood Outcomes Program whereby participating sites follow a standard protocol to electronically collect patient-reported outcome assessments on depression, anxiety, and suicidal ideation in routine clinical care. This article describes the approaches taken to develop and implement the program. METHODS: Since 2015, eight pilot sites have implemented the program and followed more than 10,000 patients. This pilot study presents descriptive statistics based on the first 24-month period of data collection. RESULTS: In this sample, 58.6% of patients with bipolar disorder (N=849) and 57.5% of patients with unipolar depression (N=3,998) remained symptomatic at follow-up. Lifetime rates of planned or actual suicide attempts were high, ranging from 27.6% for patients with unipolar mood disorders to 33.5% for patients with bipolar disorder. Men, unmarried individuals, and those with comorbid anxiety had a poorer longitudinal course. This initial snapshot of clinical burden is consistent with public health data indicating that mood disorders are severely debilitating. CONCLUSIONS: This study demonstrates the potential of the Mood Outcomes Program to create a nationwide "learning health system" for mood disorders. This goal will be further realized as the program expands in reach and scope across additional NNDC sites.
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Transtorno Bipolar , Depressão , Transtorno Bipolar/terapia , Depressão/epidemiologia , Depressão/terapia , Humanos , Masculino , Transtornos do Humor/epidemiologia , Transtornos do Humor/terapia , Projetos Piloto , Ideação SuicidaRESUMO
BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS: At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS: The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.
Assuntos
Transtorno Depressivo Maior/diagnóstico , Farmacogenética , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Duplo-Cego , Humanos , Resultado do TratamentoRESUMO
OBJECTIVE: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. METHODS: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depreâssion Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. RESULTS: Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission). CONCLUSIONS: By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02109939â.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Farmacogenética , Adulto , Transtorno Depressivo Maior/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Resultado do TratamentoRESUMO
Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (Nâ¯=â¯1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use as directed' or 'use with caution' test categories) or incongruent ('use with increased caution and with more frequent monitoring' test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17â¯≤â¯7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, pâ¯=â¯0.107); however, improvements in response (26.0% versus 19.9%, pâ¯=â¯0.013) and remission (15.3% versus 10.1%, pâ¯=â¯0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, pâ¯=â¯0.002), response (28.5% versus 16.7%, pâ¯=â¯0.036), and remission (21.5% versus 8.5%, pâ¯=â¯0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Testes Farmacogenômicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Estudos de Coortes , Sistema Enzimático do Citocromo P-450/genética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 5-HT2A de Serotonina/genética , Indução de Remissão , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto JovemRESUMO
OBJECTIVE: The Peer-to-Peer Depression Awareness Program (P2P) is a school-based program that aims to decrease mental illness and promote well-being among students by empowering high school students as both learners and educators. Specific goals include improving the school climate around mental health, directing students to resources, and encouraging help-seeking behavior. METHODS: In the 2015-2016 academic year, 121 students across 10 high schools organized into teams and were trained to develop and implement peer-to-peer depression awareness campaigns. Outcomes were assessed via pre- and posttest questionnaires. RESULTS: A total of 878 students completed questionnaires. Outcomes demonstrated improved knowledge and attitudes toward depression, increased confidence in identifying and referring peers with depression, improved help-seeking intentions, and reduced stigma. CONCLUSIONS: The P2P program increased depression literacy through the use of youth-designed and youth-implemented depression awareness and outreach activities, which may ultimately result in earlier detection of depression and in fewer depression sequelae.