ABSTRACT
Some data suggest that antipsychotics may adversely affect brain structure. We examined the relationship among olanzapine exposure, relapse, and changes in brain structure in patients with major depressive disorder with psychotic features. We analyzed data from the Study of the Pharmacotherapy of Psychotic Depression II trial (STOP-PD II), a randomized, placebo-controlled trial in patients with psychotic depression who attained remission on sertraline and olanzapine and were randomized to continue sertraline plus olanzapine or placebo for 36 weeks. Olanzapine steady state concentration (SSC) were calculated based on sparsely-sampled levels. Rates of relapse and changes in brain structure were assessed as outcomes. There were significant associations between dosage and relapse rates (N = 118; HR = 0.94, 95% CI [0.897, 0.977], p = 0.002) or changes in left cortical thickness (N = 44; B = -2.0 × 10-3, 95% CI [-3.1 × 10-3, -9.6 × 10-4], p < 0.001) and between SSC and changes in left cortical thickness (N = 44; B = -8.7 × 10-4, 95% CI [-1.4 × 10-3, -3.6 × 10-4], p = 0.001). Similar results were found for the right cortex. These associations were no longer significant when the analysis was restricted to participants treated with olanzapine. Our findings suggest that, within its therapeutic range, the effect of olanzapine on relapse or cortical thickness does not depend on its dosage or SSC. Further research is needed on the effect of olanzapine and other antipsychotics on mood symptoms and brain structure.
ABSTRACT
BACKGROUND: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory. METHOD: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics. RESULTS: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model. CONCLUSIONS: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.
Subject(s)
Depressive Disorder, Major , Psychotic Disorders , Humans , Olanzapine/therapeutic use , Depression , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Psychotic Disorders/drug therapy , Sertraline/therapeutic useABSTRACT
PURPOSES/BACKGROUND: The goals of this preliminary study were to survey psychiatrists and to examine the impact of advertisements on their prescription of psychotropic medications. The study specifically looked at psychiatrists in Massachusetts and Michigan, as the authors were able to readily contact the members of their respective state psychiatric societies. METHODS/PROCEDURES: We used the survey software, Quatrics, to create an online survey that was sent via email link to the members of the Massachusetts Psychiatric Society (1400 estimated members), and the Michigan Psychiatric Society (700 estimated members). Details were obtained about how challenging it was for the psychiatrist to convince the patient that a medication was not indicated. Information regarding how the psychiatrist first heard about new medications and where they go to learn more about these medications was included in the survey. FINDINGS/RESULTS: We received 162 partial or full responses to our survey, representing a response rate of 8%. Those who were less than 10 years out of training were less likely to find it "easy" to change the minds of these patients, when compared with those more than 10 years out of training (Fisher exact test, P = 0.0396). The most frequent medication named as a response to "which medications do patients request" was Rexulti (brexpiprazole), followed by Vraylar (cariprazine), Caplyta (lumateperone), and aripiprazole. IMPLICATIONS/CONCLUSIONS: This survey points to the prevalence of psychiatrists getting requests for these advertised medications and illustrates that those with fewer years out of training may have a more difficult time redirecting patients from medications that are not indicated for their illness.
Subject(s)
Direct-to-Consumer Advertising , Humans , Michigan , Advertising , MassachusettsABSTRACT
BACKGROUND: Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD. METHODS: We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD. FINDINGS: PBD is a complex disorder, with 50%-75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary. CONCLUSION: PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.
Subject(s)
Antipsychotic Agents , Bipolar Disorder , Humans , Bipolar Disorder/drug therapy , Antipsychotic Agents/therapeutic use , Electroconvulsive Therapy , Antimanic Agents/therapeutic use , Antidepressive Agents/therapeutic use , Drug Therapy, Combination , Psychotic Disorders/drug therapyABSTRACT
The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain.
Subject(s)
Antipsychotic Agents , Depressive Disorder, Major , Humans , Antipsychotic Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Olanzapine/therapeutic use , Sertraline/therapeutic use , Benzodiazepines , Drug Therapy, Combination , Magnetic Resonance ImagingABSTRACT
INTRODUCTION: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. METHODS: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. RESULTS: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse. CONCLUSION: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.
Subject(s)
Antipsychotic Agents , Sertraline , Male , Humans , Female , Olanzapine/therapeutic use , Sertraline/therapeutic use , Depression , Antipsychotic Agents/therapeutic use , Benzodiazepines/therapeutic use , Drug Therapy, Combination , Treatment Outcome , Genomics , Double-Blind MethodABSTRACT
BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , GABA Modulators/therapeutic use , Pregnanes/therapeutic use , Pyrazoles/therapeutic use , Receptors, GABA-A/metabolism , Administration, Oral , Adult , Allosteric Regulation , Antidepressive Agents/adverse effects , Depressive Disorder, Major/classification , Dizziness/chemically induced , Double-Blind Method , Female , GABA Modulators/adverse effects , Humans , Least-Squares Analysis , Male , Middle Aged , Nausea/chemically induced , Pregnanes/adverse effects , Psychiatric Status Rating Scales , Pyrazoles/adverse effectsABSTRACT
BACKGROUND: In the 1980s, the response rate of major depressive disorder with psychotic features (MDD-Psy) to placebo pills was reported to be close to 0%. To our knowledge, this placebo response rate has not been systematically reassessed. We undertook a systematic review of randomized controlled trials (RCTs) that have used a placebo or sham control group for MDD-Psy. METHODS: We searched MEDLINE and identified 9 relevant publications reporting on 10 studies comparing a placebo or sham interventions versus an active intervention. We extracted reported rates of response or of dropout for all causes associated with placebo versus active intervention(s) and aggregated response and dropout rates across trials. RESULTS: Two sham-controlled electroconvulsive therapy (ECT) trials did not provide response rates. In the 3 pharmacotherapy studies published in the 1980s, 0 of 12 participants (0%) responded to placebo versus 13 of 38 (34.2%) responding to the active interventions. In contrast, 5 RCTs published in the 2000s, 114 of 339 participants (33.6%) randomized to placebo responded versus 149 of 373 participants (39.9%) randomized to active interventions; dropout rates were 71/236 (30.1%) for placebo versus 84/282 (29.8%) for the active interventions. CONCLUSIONS: As expected, response rates to placebo pills in RCTs for MDD-Psy increased markedly from the 1980s to the 2000s. Methodological issues in the design and conduct of more recent RCTs may have contributed to the high placebo response. However, one needs to consider this placebo response rate when interpreting the result of recent trials of MDD-Psy, which typically have not included a "pure" placebo condition.
Subject(s)
Depressive Disorder, Major , Humans , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Placebo Effect , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: Identify the health profiles of older nursing home residents with and without at-admission self-reported suicidal ideation (SI) and examine the association between the identified profiles and self-reported SI at 90 days. METHODS: Using the Minimum Data Set 3.0 and the ninth Patient Health Questionnaire-9 (PHQ-9) item, we identified 15,277 older residents with and 562,184 without self-reported SI at nursing home admission. Latent class analysis, using frailty, cognitive impairment, palliative care index, pain, and remaining PHQ-9 items as indicators, identified health profiles by at-admission SI and the BCH method estimated their association with SI at 90 days. RESULTS: Profiles identified for residents without at-admission SI were: (1) frail and depressedNoSI (prevalence: 33.9%); (2) frail and severe cognitive impairmentNoSI (38.1%); (3) pre-frailNoSI (28.0%). Residents in the frail and depressedNoSI group had greater odds [adjusted OR: 2.80; 95% Confidence Interval: 2.60-3.00] while those in the frail and severe cognitive impairmentNoSI group had lower odds [aOR: 0.79; 95% CI: 0.71-0.86] of 90-day SI than those in the pre-frailNoSI group. Profiles identified for residents with at-admission SI were: (1) frail and all depressive symptomsSI (22.8%); (2) frail and some depressive symptomsSI (32.2%); (3) frail and severe cognitive impairmentSI (22.9%); (4) pre-frailSI (22.0%). Compared to those in the pre-frailSI group, residents in the frail and all depressive symptomsSI group had greater odds of continuing reporting SI at 90 days [aOR: 1.22; 95% CI:1.09-1.35]. CONCLUSIONS: Findings indicated unique health profiles of nursing home residents at higher risk of new onset of or continued SI.
Subject(s)
Cognitive Dysfunction , Frailty , Humans , Aged , Suicidal Ideation , Latent Class Analysis , Nursing Homes , Cognitive Dysfunction/epidemiology , Frail ElderlyABSTRACT
BACKGROUND: Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression. METHODS: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse. RESULTS: Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups. CONCLUSIONS: PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.
ABSTRACT
PURPOSE/BACKGROUND: Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years. METHODS/PROCEDURES: We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT. FINDINGS/RESULTS: A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare. IMPLICATIONS/CONCLUSIONS: The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT.
Subject(s)
Depression/prevention & control , Electroconvulsive Therapy/methods , Psychotic Disorders/therapy , Adult , Aged , Aged, 80 and over , Antidepressive Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Depression/therapy , Drug Therapy, Combination , Female , Humans , Lithium Compounds/administration & dosage , Male , Middle Aged , Psychotic Disorders/psychology , Recurrence , Retrospective Studies , Secondary Prevention/methodsABSTRACT
OBJECTIVE: To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine. METHODS: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures. RESULTS: Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18-59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures. CONCLUSION: Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not.
Subject(s)
Antipsychotic Agents , Sertraline , Adolescent , Adult , Aged , Aged, 80 and over , Antipsychotic Agents/adverse effects , Benzodiazepines/adverse effects , Depression , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Olanzapine/adverse effects , Sertraline/adverse effects , Treatment Outcome , Young AdultABSTRACT
OBJECTIVES: To longitudinally examine the latent statuses of depressive symptoms and their association with cognitive impairment in older U.S. nursing home (NH) residents. METHOD: Using Minimum Data Set 3.0, newly-admitted, long-stay, older NH residents with depression in 2014 were identified (n = 88,532). Depressive symptoms (Patient Health Questionnaire-9) and cognitive impairment (Brief Interview of Mental Status) were measured at admission and 90 days. Latent transition analysis was used to examine the prevalence of and the transition between latent statuses of depressive symptoms from admission to 90 days, and the association of cognitive impairment with the statuses at admission. RESULTS: Four latent statuses of depressive symptoms were identified: 'Multiple Symptoms' (prevalence at admission: 17.3%; 90 days: 13.6%), 'Depressed mood' (20.0%; 19.5%), 'Fatigue' (27.4%; 25.7%), and 'Minimal Symptoms' (35.3%; 41.2%). Most residents remained in the same status from admission to 90 days. Compared to residents who were cognitively intact, those with moderate impairment were more likely to be in 'Multiple Symptoms' and 'Fatigue' statuses; those with severe impairment had lower odds of belonging to 'Multiple Symptoms', 'Depressed Mood', and 'Fatigue' statuses. CONCLUSION: By addressing the longitudinal changes in the heterogeneous depressive symptoms and the role of cognitive impairment, findings have implications for depression management in older NH residents.
Subject(s)
Cognitive Dysfunction , Depression , Aged , Cognitive Dysfunction/epidemiology , Depression/epidemiology , Hospitalization , Humans , Nursing Homes , Prevalence , United States/epidemiologyABSTRACT
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.
Subject(s)
Antidepressive Agents , Depressive Disorder, Major , Pharmacogenomic Testing/methods , Aged , Antidepressive Agents/administration & dosage , Antidepressive Agents/classification , Antidepressive Agents/pharmacokinetics , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Drug Substitution , Female , Humans , Male , Outcome Assessment, Health Care , Patient Selection , Psychiatric Status Rating Scales , Treatment FailureABSTRACT
OBJECTIVES: To identify subgroups of nursing home (NH) residents in the USA experiencing homogenous depression symptoms and evaluate if subgroups vary by cognitive impairment. METHODS: We identified 104 465 newly admitted, long-stay residents with depression diagnosis at NH admission in 2014 using the Minimum Data Set 3.0. The Patient Health Questionnaire-9 was used to measure depression symptoms and the Brief Interview of Mental Status for cognitive impairment (intact; moderately impaired; severely impaired). Latent class analysis (LCA) with logistic regression was used to: (a) construct the depression subgroups and (b) estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the associations between the subgroups and cognitive impairment level, adjusting for demographic and clinical characteristics. RESULTS: The best-fitted LCA model suggested four subgroups of depression: minimal symptoms (latent class prevalence: 42.4%), fatigue (32.0%), depressed mood (14.5%), and multiple symptoms (11.2%). Odds of subgroup membership varied by cognitive impairment. Compared to residents with intact cognition, those with moderate or severe cognitive impairment were less likely to belong to the fatigue subgroup [aOR(95% CI): moderate: 0.75 (0.71-0.80); severe: 0.26 (0.23-0.29)] and more likely to belong to the depressed mood subgroup [aOR (95% CI): moderate: 4.54 (3.55-5.81); severe: 6.41 (4.86-8.44)]. Residents with moderate cognitive impairment had increased odds [aOR (95% CI): 1.19 (1.12-1.27)] while those with severe impairment had reduced odds of being in the multiple symptoms subgroup [aOR (95% CI): 0.63 (0.58-0.68)]. CONCLUSIONS: Findings provide a basis for improving depression management with consideration of both subgroups of depression symptoms and levels of cognitive function.
Subject(s)
Cognitive Dysfunction , Depression , Aged , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Depression/epidemiology , Humans , Latent Class Analysis , Nursing Homes , United States/epidemiologyABSTRACT
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.
Subject(s)
Depressive Disorder, Major/diagnosis , Pharmacogenetics , Psychiatric Status Rating Scales , Randomized Controlled Trials as Topic , Double-Blind Method , Humans , Treatment OutcomeABSTRACT
Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.