Hoarding Symptoms in Late Life Depression are Associated With Greater Executive Dysfunction and Disability and Poorer Response to Depression Treatment.

OBJECTIVES: Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD. DESIGN: Cross-sectional. SETTING: Outpatient psychiatry program. PARTICIPANTS: Eighty-three community-dwelling adults ages 65-90 with LLD. INTERVENTION: Problem-solving therapy. MEASUREMENTS: Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson's chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity. RESULTS: 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X2(1)=4.0, p = 0.045; Stroop-Interference, X2(1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t[70] = -2.1, ß = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, ß = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, ß = -0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X2[1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t[72] = 2.97, ß = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X2(1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t(67) = -2.15, ß = -15.6, p = 0.035. CONCLUSIONS: We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group.

Feasibility and acceptability of an integrated mind-body intervention for depression: whole-body hyperthermia (WBH) and cognitive behavioral therapy (CBT).

OBJECTIVE: To examine the feasibility of an integrated mind-body MDD treatment combining cognitive behavioral therapy (CBT) and whole-body hyperthermia (WBH). METHODS: In this single-arm trial, 16 adults with MDD initially received 8 weekly CBT sessions and 8 weekly WBH sessions. Outcomes included WBH sessions completed (primary), self-report depression assessments completed (secondary), and pre-post intervention changes in depression symptoms (secondary). We also explored changes in mood and cognitive processes and assessed changes in mood as predictors of overall treatment response. RESULTS: Thirteen participants (81.3%) completed ≥ 4 WBH sessions (primary outcome); midway through the trial, we reduced from 8 weekly to 4 bi-weekly WBH sessions to increase feasibility. The n = 12 participants who attended the final assessment visit completed 100% of administered self-report depression assessments; all enrolled participants (n = 16) completed 89% of these assessments. Among the n = 12 who attended the final assessment visit, the average pre-post-intervention BDI-II reduction was 15.8 points (95% CI: -22.0, -9.70), p = 0.0001, with 11 no longer meeting MDD criteria (secondary outcomes). Pre-post intervention improvements in negative automatic thinking, but not cognitive flexibility, achieved statistical significance. Improved mood from pre-post the initial WBH session predicted pre-post treatment BDI-II change (36.2%; rho = 0.60, p = 0.038); mood changes pre-post the first CBT session did not. LIMITATIONS: Small sample size and single-arm design limit generalizability. CONCLUSION: An integrated mind-body intervention comprising weekly CBT sessions and bi-weekly WBH sessions was feasible. Results warrant future larger controlled clinical trials.Clinivaltrials.gov Registration: NCT05708976.

Cognitive outcomes are differentially associated with depression severity trajectories during psychotherapy treatment for late life major depressive disorder.

OBJECTIVES: Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD. METHODS: 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance. RESULTS: Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed. CONCLUSIONS: The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD.

Improvements in Functional Disability After Psychotherapy for Depression Are Associated With Reduced Suicide Ideation Among Older Adults.

OBJECTIVE: To evaluate the association between changes in functional disability and suicide ideation among older adults following psychotherapy for depression. METHODS: Sixty-five participants (65-91 years old, 72% White, and 66% female) with depression completed 12 sessions of problem solving therapy (PST) and completed measures of disability (WHO Disability Assessment Schedule 2.0) and suicide ideation (Geriatric Suicide Ideation Scale [GSIS]) at baseline and post-treatment. RESULTS: Hierarchical linear regressions found that reductions in functional disability were associated with overall reductions in suicide ideation on the GSIS (F[4,60] = 4.06, p < 0.01), particularly with the Loss of Worth GSIS subscale (F[4,60] = 7.86, p < 0.001, ΔR2 = 0.140). CONCLUSIONS: Results suggest decreased functional disability following depression treatment is associated with decreased suicide ideation, especially thoughts regarding loss of worth. These results highlight the potential for treatments that reduce functional disability (e.g., PST) to reduce risk of suicide among older adults.

The relationship of frailty and disability with suicidal ideation in late life depression.

OBJECTIVES: Frailty and disability are commonly found in Late Life Depression (LLD) and have been associated with increased depression severity, health comorbidities and mortality. Additionally, physical frailty has been associated with suicide in later life, independent of presence of a mood disorder. The objective of our study was to assess the associations of physical frailty and functional disability with suicidal ideation, controlling for depression severity and demographic factors, in an older depressed sample. METHODS: This study used data from community-dwelling older adults with major depression. Eligible participants were ≥ 65 years old, completed measures of depression symptom severity (Hamilton Depression Rating Scale-24 item; HDRS-24), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and physical frailty/functional capacity measures. RESULTS: Participants were 88 older adults with a mean age of 71.5 (SD = 6.0) and 66% of the sample was female. Poorer performance on frailty measures of gait speed (B = .239, p = .003) and muscle weakness (B = -.218, p = .01) were significantly associated with higher levels of suicidal ideation, independent of depression severity and demographic factors. Functional disability was also significantly related to suicide ideation, specifically impairment in financial capacity (B = -.290, p = .008), social interaction (B = .408, p < .001), and communication skills (B = .373, p = .001). CONCLUSION: Our findings show that, in LLD, frailty and functional disability are significantly associated with higher levels of suicide ideation, independent of depression symptom severity.

Screening for Executive Dysfunction in Late-Life Depression: Utility of Trail Making Test and Self-Report Measures.

OBJECTIVE: Prior work suggests executive dysfunction (ED) on the Stroop Color and Word Test (SCWT) and the Mattis Dementia Rating Scale-2 Initiation/Perseveration subscale (DRS IP) predicts poor antidepressant response in late-life depression. This study examined if either patient perception of ED or the Trail Making Test Part B (TMT-B) could identify patients with impairment on the SCWT or DRS IP. METHODS: Patients were 65 or older and had a diagnosis of major depression without dementia. Cognition was assessed with the TMT-B, the SCWT, and the DRS IP. A self-reported Perceived Deficits Questionnaire (PDQ) subscale assessed patients' perceptions of ED. RESULTS: In 247 participants (mean age 71.3 years), the PDQ subscale was not associated with test performance. The sensitivity of the TMT-B in identifying impairment on the SCWT or DRS IP was low (35% and 23%, respectively). CONCLUSION: Neither the TMT-B nor self-reports are useful screening tools for ED on the SCWT or DRS IP.

A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression.

BACKGROUND: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. METHODS: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. RESULTS: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. CONCLUSIONS: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

A systematic review and meta-analysis of psychotherapy for late-life depression.

OBJECTIVES: To determine the efficacy of psychotherapy in late-life depression and to determine the effect of the type of control group on the magnitude of psychotherapy effects. DESIGN: A systematic review and meta-analysis of randomized controlled psychotherapy trials for late-life depression. SETTING: Outpatient clinics or in subjects' home. PARTICIPANTS: Subjects aged 55 years or older with acute-phase depressive disorder. MEASUREMENTS: Change in depressive symptoms was measured with validated scales. Standardized mean differences (SMD) were calculated for each therapy-control contrast, as meta-analytic summaries for contrasts using a similar control, and for all contrasts combined. RESULTS: The search identified 27 trials with 37 therapy-control contrasts and 2,245 subjects. Trials utilized five types of control groups (waitlist, treatment-as-usual, attention, supportive therapy, placebo). In the combined contrasts, psychotherapy was effective (SMD: 0.73; 95% confidence interval [CI]: 0.51, 0.95; z=6.42, p<0.00001). The SMD varied widely (from 0.05 to 1.36) and significantly (χ2=35.67, df=4, p<0.00001) between subgroups by type of control. In five trials that compared psychotherapy with supportive therapy, the SMD was 0.39 (95% CI: 0.16, 0.61; z=3.37, p<0.0007; I2=0%). The SMD was 0.11 within the waitlist controls and 1.10 within the supportive therapy subgroup. CONCLUSIONS: Psychotherapy is effective for late-life depression, but the magnitude of the effect varies widely with the type of control group. Supportive therapy appears to best control for the nonspecific elements of psychotherapy and is associated with considerable change itself, but few trials have utilized it as a control.

Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

OBJECTIVE: To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. DESIGN: Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. SETTING: United States, France, Mexico, Puerto Rico. PARTICIPANTS: Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. INTERVENTION: Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. MEASUREMENTS: Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. RESULTS: Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). CONCLUSIONS: Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain.

Association of age at depression onset with cognitive functioning in individuals with late-life depression and executive dysfunction.

OBJECTIVE: To compare patterns of cognitive performance in older adults with late-onset depression (LOD; ≥65 years of age) with that of older adults with early-onset depression (EOD; <65 years). METHODS: Participants were 171 adults aged 60 years or older with major depression and executive dysfunction who were participating in a randomized psychotherapy trial. Participants included 72 LOD and 99 EOD individuals. Cognitive performance on measures of verbal learning, memory, and executive functioning were evaluated. Demographic and clinical characteristics, severity of cerebrovascular risk factors, and disability ratings were also compared between groups. RESULTS: The LOD group was older and had fewer previous episodes of depression and lower severity of depression compared with EOD participants. The LOD group demonstrated poorer performance on measures of verbal learning (F(1,161) = 4.28, p = 0.04) and memory (F(1,160) = 4.65, p = 0.03) than the EOD group. Linear regression analysis demonstrated that LOD and fewer years of education were significant predictors of poorer verbal learning (F(7,114) = 6.25, p <0.001) and memory (F(7,113)=7.24, p <0.001). Performance on measures of executive functioning, severity of vascular risk factors, and disability ratings did not differ between the two groups. CONCLUSION: In older adults with depression and executive dysfunction, LOD was associated with poorer performance on measures of verbal learning and memory. Aging-related brain changes associated with LOD may play a more important role, leading to dysfunction in these cognitive domains than a history of recurrent depressive episodes in older adults with a dysexecutive syndrome.

Cognitive outcomes after psychotherapeutic interventions for major depression in older adults with executive dysfunction.

OBJECTIVE: The purpose of this study was to determine the impact of psychotherapy on cognitive functioning in older adults with late-life depression (LLD) and executive dysfunction. METHODS: Two hundred twenty-one adults aged 60 years and older participated in a randomized clinical trial comparing the efficacy of Problem Solving Therapy (PST) and Supportive Therapy (ST) for LLD. Cognitive performance on seven tests of executive functioning, verbal learning, and memory was evaluated at baseline, after 12 weeks of treatment, and at 24 weeks after the completion of treatment. RESULTS: Performance on a measure of executive functioning with a significant information processing speed component (Stroop Color and Word Test) improved after treatment, F (1, 312) = 8.50, p = 0.002, and improved performance was associated with a reduction in depressive symptoms but not treatment type. Performance on other measures of executive functioning, verbal learning, and memory did not change significantly after 12 weeks of psychotherapy treatment. CONCLUSION: Our results suggest that improvements in cognitive functioning after psychotherapy treatment for depression in older adults with executive dysfunction are likely focal and not distributed across all cognitive domains. Although previous analyses reported that PST was superior to ST in the treatment of depression, this analysis indicated no difference between the two treatments with regard to improvements in cognitive functioning.

Clinical relevance of fatigue as a residual symptom in major depressive disorder.

Residual symptoms of major depressive disorder (MDD) following treatment are increasingly recognized as having a negative impact on the patient because of their association with lack of remission, poorer psychosocial functioning, and a more chronic course of depression. Although the effects of specific residual symptoms have not been as systematically studied, several symptoms, including fatigue, sleep disturbance, anxiety, and concentration difficulties, commonly occur as part of the residual state in MDD. In particular, the relatively high prevalence of residual fatigue suggests that this symptom is not being adequately addressed by standard antidepressant therapies. A review of the clinical relevance of residual fatigue was undertaken, using the published literature with respect to its assessment, neurobiology, and treatment implications. The findings of this review suggest that fatigue is highly prevalent as a residual symptom; its response to treatment is relatively poor or delayed; and the presence of residual fatigue is highly predictive of inability to achieve remission with treatment as well as impaired psychosocial functioning. Recognition of the significant consequences of residual fatigue should reinforce the need for further therapeutic interventions to help reduce the impact of this symptom of MDD.

Efficacy and safety of selegiline transdermal system (STS) for the atypical subtype of major depressive disorder: pooled analysis of 5 short-term, placebo-controlled trials.

OBJECTIVE: The objective of the present study is to investigate the efficacy and safety of the selegiline transdermal system (STS) in major depressive disorder (MDD) with atypical features. METHODS: This was a post-hoc analysis of 5 short-term trials. The atypical subtype was defined as the presence of at least 1 item with a score of 2 or greater from items 22-26 on the 28-item Hamilton Depression Rating Scale (HAMD-28), and a maximum score of 1 point for items 6 (insomnia late), 12 (somatic symptoms, gastrointestinal), and 16 (loss of weight) to exclude vegetative features of melancholic depression. The mean changes of HAMD-28 total score from baseline to the endpoint (response rate defined as ≥50% reduction in HAMD-28 scores and remission rate defined as ≤10 HAMD-28 total score at the treatment endpoint) were compared between atypical and nonatypical groups. RESULTS: In this analysis, 352 subjects (STS = 168 vs placebo = 184) met the definition of atypical subtype at baseline. STS (n = 641) significantly decreased HAMD-28 total score compared with placebo (n = 648) from beginning to end of treatment (-10.7 ± 9.3 vs -9.4 ± 9.3; p = 0.014). STS showed comparable efficacy in patients with the atypical subtype compared with the nonatypical subtype for placebo-subtracted mean change in HAMD-28 total score (-2.11 ± 1.01 vs. -1.0 ± 0.60; p = 0.34), odds ratio (OR) for response (1.41 vs 1.23, p = 0.62), and OR for remission (1.77 vs 1.18, p = 0.22). CONCLUSION: STS appears to be comparably efficacious and tolerable in atypical and nonatypical subtypes of MDD. Adequately powered, controlled, clinical trials are necessary to confirm our findings.

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy.

INTRODUCTION: Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT). METHODS: This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery-Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10. RESULTS: Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo). CONCLUSION: These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

Patterns of reduced cortical thickness in late-life depression and relationship to psychotherapeutic response.

OBJECTIVE: Cortical atrophy has been associated with late-life depression (LLD) and recent findings suggest that reduced right hemisphere cortical thickness is associated with familial risk for major depressive disorder, but cortical thickness abnormalities in LLD have not been explored. Furthermore, cortical atrophy has been posited as a contributor to poor antidepressant treatment response in LLD, but the impact of cortical thickness on psychotherapy response is unknown. This study was conducted to evaluate patterns of cortical thickness in LLD and in relation to psychotherapy treatment outcomes. METHODS: Participants included 22 individuals with LLD and 12 age-matched comparison subjects. LLD participants completed 12 weeks of psychotherapy and treatment response was defined as a 50% reduction in depressive symptoms. All participants underwent magnetic resonance imaging of the brain, and cortical mapping of gray matter tissue thickness was calculated. RESULTS: LLD individuals demonstrated thinner cortex than controls prominently in the right frontal, parietal, and temporal brain regions. Eleven participants (50%) exhibited positive psychotherapy response after 12 weeks of treatment. Psychotherapy nonresponders demonstrated thinner cortex in bilateral posterior cingulate and parahippocampal cortices, left paracentral, precuneus, cuneus, and insular cortices, and the right medial orbitofrontal and lateral occipital cortices relative to treatment responders. CONCLUSIONS: Our findings suggest more distributed right hemisphere cortical abnormalities in LLD than have been previously reported. In addition, our findings suggest that reduced bilateral cortical thickness may be an important phenotypic marker of individuals at higher risk for poor response to psychotherapy.

Medical costs and hospitalizations among patients with depression treated with adjunctive atypical antipsychotic therapy: an analysis of health insurance claims data.

BACKGROUND: Depression is frequently debilitating. The American Psychiatric Association recommends adjunctive atypical antipsychotics as a treatment option when response to antidepressants is inadequate. OBJECTIVE: To compare medical costs and hospitalizations among patients with depression treated with adjunctive aripiprazole, olanzapine, or quetiapine. METHODS: This retrospective analysis used medical and pharmacy claims data and enrollment information from a large US health plan. Patients were adult members of a commercial health plan who were diagnosed with depression (ie, ICD-9-CM 296.2x, 296.3x, or 311) and who received an antidepressant with adjunctive atypical antipsychotic therapy (aripiprazole, olanzapine, or quetiapine) between January 1, 2004, and January 31, 2010. Patients were continuously enrolled for 6-month pre- and 12-month postaugmentation periods. Those with schizophrenia or bipolar disorder were excluded. Postaugmentation outcomes were total and mental health-related medical costs and hospitalizations. Costs and hospitalizations were modeled with generalized linear models (ie, gamma distribution, log link) and logistic regression, respectively. Regressions controlled for dose, demographics, and general and medical health-related health status. RESULTS: A total of 10,292 patients were identified across atypical antipsychotic cohorts: 3849 used aripiprazole, 1033 used olanzapine, and 5410 used quetiapine. Mean (SD) age was 44.1 (11.6) years and 70.3% were female. Compared with patients in the aripiprazole cohort, those in the olanzapine cohort had higher total medical costs (cost ratio [CR] 1.22, 95% CI 1.07-1.39) and higher mental health-related medical costs (CR 1.33, 95% CI 1.11-1.59), as well as higher odds of any (total) hospitalization (OR 1.58, 95% CI 1.30-1.92) and any mental health-related hospitalization (OR 1.81, 95% CI 1.38-2.38). Similarly, the quetiapine cohort had higher total medical costs (CR 1.27, 95% CI 1.16-1.39) and higher mental health-related medical costs (CR 1.23, 95% CI 1.09-1.39), as well as higher odds of any (total) hospitalization (OR 1.65, 95% CI 1.44-1.90) and any mental health-related hospitalizations (OR 1.78, 95% CI 1.45-2.18), compared with the aripiprazole cohort. CONCLUSIONS: Compared with adjunctive olanzapine or quetiapine, adjunctive aripiprazole was associated with lower mean total and mental health-related medical costs and with lower odds of total and mental health-related hospitalizations in patients with depression.