Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), but initial outcomes can be modest.

To compare SSRI dose optimisation with four alternative second-line strategies in MDD patients unresponsive to an SSRI.

Of 257 participants, 51 were randomised to SSRI dose optimisation (SSRI-Opt), 46 to lithium augmentation (SSRI+Li), 48 to nortriptyline combination (SSRI+NTP), 55 to switch to venlafaxine (VEN) and 57 to problem-solving therapy (SSRI+PST). Primary outcomes were week-6 response/remission rates, assessed by blinded evaluators using the 17-item Hamilton Depression Rating Scale (HDRS-17). Changes in HDRS-17 scores, global improvement and safety outcomes were also explored. EudraCT No. 2007-002130-11.

Alternative second-line strategies led to higher response (28.2% v. 14.3%, odds ratio = 2.36 [95% CI 1.0–5.6], p = 0.05) and remission (16.9% v. 12.2%, odds ratio = 1.46, [95% CI 0.57–3.71], p = 0.27) rates, with greater HDRS-17 score reductions (−2.6 [95% CI −4.9 to −0.4], p = 0.021]) than SSRI-Opt. Significant/marginally significant effects were only observed in both response rates and HDRS-17 decreases for VEN (odds ratio = 2.53 [95% CI 0.94–6.80], p = 0.067; HDRS-17 difference: −2.7 [95% CI −5.5 to 0.0], p = 0.054) and for SSRI+PST (odds ratio = 2.46 [95% CI 0.92 to 6.62], p = 0.074; HDRS-17 difference: −3.1 [95% CI −5.8 to −0.3], p = 0.032). The SSRI+PST group reported the fewest adverse effects, while SSRI+NTP experienced the most (28.1% v. 75%; p < 0.01), largely mild.

Patients with MDD and insufficient response to SSRIs would benefit from any other second-line strategy aside from dose optimisation. With limited statistical power, switching to venlafaxine and adding psychotherapy yielded the most consistent results in the DEPRE'5 study.

The prevalence of mental health disorders has significantly increased in recent years, posing substantial challenges to healthcare systems worldwide, particularly primary care (PC) settings. This study examines trends in mental health diagnoses in PC settings in Catalonia from 2010 to 2019 and identifies associated sociodemographic, clinical characteristics, psychopharmacological treatments, and resource utilization patterns.

Data from 947,698 individuals without prior severe mental illness, derived from the Data Analytics Program for Health Research and Innovation (PADRIS), were analyzed for this study. Sociodemographic data, diagnoses, and resource utilization were extracted from electronic health records. Descriptive statistics, chi-square tests, Mann–Whitney tests, and a multivariate binary logistic regression were employed to analyze the data.

Over the study period, 172,112 individuals (18.2%) received at least one mental health diagnosis in PC, with unspecified anxiety disorder (40.5%), insomnia (15.7%) and unspecified depressive disorder (10.2%) being the most prevalent. The prevalence of these diagnoses increased steadily until 2015 and stabilized thereafter. Significant associations were found between mental health diagnoses, female sex, lower socioeconomic status, higher BMI, and smoking status in a multivariate binary logistic regression.

This study highlights a growing burden of stress-related mental health diagnoses in PC in Catalonia, driven by demographic and socioeconomic factors. These findings may be indicative of broader trends across Europe and globally. Addressing this rising prevalence requires innovative approaches and collaborative strategies that extend beyond traditional healthcare resources. Engaging stakeholders is essential for implementing effective, sustainable solutions that promote mental health in Catalonia and potentially inform similar initiatives worldwide.

The pathological basis of tardive dyskinesia is unknown. Although its clinical features implicate the basal ganglia, imaging studies have not found clear evidence that it is associated with volume changes in these or other brain structures.

To determine, using voxel-based structural imaging, whether there are regions of grey matter volume change in people with schizophrenia who also have tardive dyskinesia compared with those without tardive dyskinesia.

A total of 81 people with chronic schizophrenia, 32 with tardive dyskinesia and 49 without, were examined using magnetic resonance imaging (MRI) and whole-brain, optimised voxel-based morphometry. A comparison group of 61 healthy controls was also examined.

Compared with those without tardive dyskinesia, patients with tardive dyskinesia showed a pattern of volume reductions in predominantly subcortical regions, including the basal ganglia and the thalamus. Within the basal ganglia, volume reductions were seen in the caudate nucleus, to a lesser extent in the putamen, and only marginally in the globus pallidus. The patients with tardive dyskinesia, but not those without, showed significant volume reductions in the basal ganglia compared with the healthy controls but both groups had smaller volumes than controls in other affected areas.

The pathological process or processes that underlie the development of tardive dyskinesia are not just neurochemical in nature, but affect brain structure.