Condition Watch: Mental Health

Simvastatin Does Not Enhance Escitalopram Response in Comorbid Depression, Obesity

Results from the SIMCODE study (NCT04301271) published in JAMA Psychiatry demonstrate that adding simvastatin (Zocor; Merck) to escitalopram (Lexapro; Forest Laboratories) did not elicit additional antidepressive effects in patients with comorbid major depressive disorder and obesity despite improving cardiovascular risk, affirming that statins should not be relied upon to help manage depression.^1-3

The study authors randomly assigned 160 patients (placebo: n = 79; simvastatin: n = 81) to either simvastatin at 40 mg per day or placebo as an add-on to escitalopram. Patients received 10 mg of escitalopram for the first 2 weeks, then 20 mg until the study concluded. The primary outcome measure was the change in their Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12.¹

In both patient groups, MADRS scores from baseline to week 12 decreased substantially (simvastatin: –13.97 points [95% CI,–15.88 to –12.06]; placebo: –13.50 points [95% CI, –15.41 to –11.58]). Patients in the intent-to-treat sample demonstrated no significant treatment effects of add-on simvastatin compared with add-on placebo in MADRS scores, with preplanned sensitivity analyses confirming the result, according to the investigators.¹

Despite the lack of effect on mental health end points, treatment with simvastatin had robust positive impacts on metabolic health. Simvastatin helped reduce low-density lipoprotein and total cholesterol levels compared with placebo, suggesting strong adherence to the regimen among participants and the beneficial role statins can still play in this comorbid population.¹—Luke Halpern, Assistant Editor

REFERENCES

1. Otte C, Chae WR, Dogan DY, et al. Simvastatin as add-on treatment to escitalopram in patients with major depression and obesity: a randomized clinical trial. JAMA Psychiatry. 2025;82(8):759-767. doi:10.1001/jamapsychiatry.2025.0801

2. Charité – Universitätsmedizin Berlin. Cholesterol-lowering drugs have no antidepressive effect. News release. EurekAlert! June 4, 2025. Accessed July 16, 2025. https://www.eurekalert.org/news-releases/1086367

3. Simvastatin add-on treatment to standard antidepressant therapy in patients with comorbid obesity and major depression (SIMCODE). ClinicalTrials.gov. Updated December 9, 2024. Accessed July 16, 2025. https://clinicaltrials.gov/study/NCT04301271

Community Pharmacist Collaboration Expands Access to Long-Acting Injectable Antipsychotics

As part of a concerted effort to combat nonadherence to antipsychotic medications—a leading cause of symptom relapse and hospitalization among individuals with serious mental illness—a multidisciplinary team within Yale New Haven Hospital in Connecticut developed and implemented a collaborative practice agreement (CPA) to empower community pharmacists to administer long-acting injectable antipsychotics (LAIAs). The team identified 2 integrated community pharmacies within its health system as ideal pilot sites due to their accessibility and the readiness of pharmacy staff to engage in the project. Site visits were conducted to evaluate workflow logistics and ensure the availability of private spaces for injection administration. The project resulted in a fully operational CPA, allowing community pharmacists to administer 5 LAIAs commonly used within the health system’s formulary. Authorization is based on a valid prescription issued by a clinician signed onto the CPA with the participating pharmacist. Three pharmacists across the 2 community pharmacy locations completed the training and are actively participating in the program. As the mental health needs of patients continue to rise and the demand for innovative care models grows, this project offers a replicable framework for health systems nationwide. It exemplifies the evolving role of pharmacists as frontline providers capable of delivering high-impact interventions in partnership with the broader care team.—Aislinn Antrim, Managing Editor

REFERENCE

Orellana ZT, Monestime S, Morrow G, Renauer M. Development of a long-acting injectable antipsychotic (LAIA) collaborative practice agreement within an integrated community pharmacy at an academic medical center. Presented at: American Society of Health-System Pharmacists (ASHP) 2025 Pharmacy Futures; June 7-11, 2025; Charlotte, NC.

Depression May Increase Risk of Dementia

Study findings published in eClinicalMedicine demonstrate that depression may increase the risk of developing dementia. The authors wrote that a life course approach to the treatment and prevention of depression may help reduce the burden of dementia. However, such efforts will require scaling up access to effective mental health care for populations that are vulnerable.The investigators conducted an umbrella review and meta-analysis to assess incident dementia in participants with a noncurrent history of depression. Additionally, systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included. Pooled HRs indicated depression that was present later in life (HR, 1.95; 95% CI, 1.68-2.26; I2 = 77.5%) and midlife (HR, 1.56; 95%CI, 1.12-2.18; I2 = 97.5%) significantly increased the risk of all-cause dementia. Among 7763 records identified, 9 were included in the umbrella review, and 18 studies were included in the meta-analysis. In the umbrella review, only 1 review was judged to be of moderate quality, whereas the others were either low (n = 3) or critically low (n = 5). For the meta-analyses, 18 studies reporting depression onset in later life (7595 incident dementia cases amid a cumulative 901,762 participants) and 7 studies on depression assessed during midlife (n ≥ 2,501,269 participants, n ≥ 276,929 incident dementia cases) were included. The authors determined that the studies in the meta-analyses were all of good quality, with no strong evidence of publication bias.The authors said their findings contribute to the evidence supporting depression as a potentially modifiable risk factor for dementia, while also highlighting a complex temporal gradient within this association. Additionally, they suggest that additional research be conducted to clarify whether a stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes.—Gillian McGovern, Associate Editor

REFERENCE

Brain J, Alshahrani M, Kafadar AH, et al. Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis. eClinicalMedicine. 2025:103266. doi:10.1016/j.eclinm.2025.103266