Antidepressants are commonly prescribed for mood disorders. Epidemiological studies suggest antidepressant use may be associated with cataracts and glaucoma. We aim to investigate the association between antidepressants and cataracts and glaucoma.

Data was collected from the United States Food and Drug Administration Adverse Event Reporting System. Reporting odds ratio (ROR) and Bayesian information components (IC025) were calculated for antidepressants (ie, selective serotonin reuptake inhibitors [SSRIs], selective norepinephrine reuptake inhibitors [SNRIs], serotonin-norepinephrine-dopamine reuptake inhibitors, serotonin modulators and stimulators, serotonin antagonists and reuptake inhibitors [SARIs], norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, tricyclic antidepressants [TCAs], tetracyclic antidepressants [TeCAs], and monoamine oxidase inhibitors [MAOIs]). The reference agent was acetaminophen.

TeCAs and MAOIs were significantly associated with a decreased risk of cataracts (ROR = 0.11-0.65 and 0.16-0.69, respectively). TCAs, brexanolone, esketamine, and opipramol reported an increased cataract risk (ROR = 1.31-12.81). For glaucoma, SSRIs, SNRIs, SARIs, TCAs, MAOIs, and other investigated antidepressants reported significant RORs ranging from 1.034 to 21.17. There was a nonsignificant association of angle closure glaucoma (ACG) and open angle glaucoma (OAG) with the investigated antidepressants.

For adverse event cases, multiple suspected product names are listed, and as cases are not routinely verified, there may be a possibility of duplicate reports and causality cannot be established.

Most of the investigated antidepressants were associated with a lower risk of cataract reporting. TCAs, brexanolone, esketamine, and opipramol were associated with greater odds of cataract. For most antidepressants, there was an insignificant increase in reports of ACG and OAG.

Depressive disorders are a major public health issue in Western societies, particularly among adolescents, young adults and women. The COVID-19 pandemic has exacerbated mental health challenges, increasing depression and anxiety symptoms, especially in younger people. This study focuses on the hard-hit Emilia-Romagna Region (ERR) in Italy, examining changes in antidepressant (AD) drug use post-COVID-19 to understand the pandemic’s effect on mental health.

A population-based interrupted time series design and a segmented regression analysis was carried out on ERR pharmaceutical data (FED, direct dispensation pharmaceuticals, AFT, territorial pharmaceutical assistance) out to estimate changes in AD use during the three pandemic years (2020, 2021 and 2022) compared to 2017–2019.Analyses were stratified by age, gender, citizenship, population density of the area of residence.

A notable increase in AD consumption compared to what was expected was observed among younger age groups, and especially in females. In the 12–19 age group, a gradual increase was recorded from January 2021 until it reached +48% in 2022 (+58% among women, +30% among men). An even more remarkable growth in AD usage among non-Italian residents in the same age group was recorded compared to expected. A relevant increase, although smaller, was detected among individuals in the 20–34 age group, with a peak of +9% in 2022. These differences persisted up until the end of the observation period.

The study suggests that the COVID-19 pandemic may have had a lasting negative impact on the mental health of younger individuals. The observed increase in AD use may foreshadow a potential long-term need for enhanced mental healthcare and services directed at this subpopulation.

Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient.

Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment.

Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment.

We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.

Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes.

Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions.

Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13.

The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.

How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown.

We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models.

Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment (p < 0.001). By week 8, the response for benzodiazepines and SSRIs (p = 0.103) and SNRIs (p = 0.911) did not differ nor did SSRIs and SNRIs differ (p = 0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference − 12.42, CrI: −25.05 to −0.78, p = 0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4 weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders.

Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

Major depression is associated with changes in plasma L-carnitine and acetyl-L-carnitine. But its association with acylcarnitines remains unclear. The aim of this study was to assess metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls (HCs).

Metabolomic profiles of 38 plasma short-, medium-, and long-chain acylcarnitines were performed by liquid chromatography-mass spectrometry in 893 HCs from the VARIETE cohort and 460 depressed patients from the METADAP cohort before and after 6 months of antidepressant treatment.

As compared to HCs, depressed patients had lower levels of medium- and long-chain acylcarnitines. After 6 months of treatment, increased levels of medium- and long-chain acyl-carnitines were observed that no longer differed from those of controls. Accordingly, several medium- and long-chain acylcarnitines were negatively correlated with depression severity.

These medium- and long-chain acylcarnitine dysregulations argue for mitochondrial dysfunction through fatty acid β-oxidation impairment during major depression.

Treatment-resistant depression (TRD) is an important clinical challenge and may present differently between age groups.

A total of 893 depressed patients recruited within the framework of the European research consortium “Group for the Studies of Resistant Depression” were assessed by generalized linear models regarding age effects (both as numerical and factorial predictors) on treatment outcome, number of lifetime depressive episodes, hospitalization time, and duration of the current episode. Effects of age as numerical predictor on the severity of common depressive symptoms, measured with Montgomery–Åsberg Depression Rating Scale (MADRS) for two-time points, were assessed by linear mixed models, respectively, for patients showing TRD and treatment response. A corrected p threshold of 0.001 was applied.

Overall symptom load reflected by MADRS (p < 0.0001) and lifetime hospitalization time (p < 0.0001) increased with age in TRD patients but not treatment responders. In TRD, higher age was predicting symptom severity of inner tension, reduced appetite, concentrations difficulties, and lassitude (all p ≤ 0.001). Regarding clinical significance, older TRD patients were more likely to report severe symptoms (item score > 4) for these items both before and after treatment (all p ≤ 0.001).

In this naturalistic sample of severely ill depressed patients, antidepressant treatment protocols were equally effective in addressing TRD in old age. However, specific symptoms such as sadness, appetite, and concentration showed an age-dependent presentation, impacting residual symptoms in severely affected TRD patients and calling for a precision approach by a better integration of age profiles in treatment recommendations.

Major depressive disorder (MDD) is a complex disorder with a significant public health burden. Depression remission is often associated with weight gain, a major risk factor for metabolic syndrome (MetS). The primary objective of our study was to assess prospectively the impact of response to antidepressant treatment on developing MetS in a sample of MDD patients with a current major depressive episode (MDE) and who are newly initiating their treatment.

In the 6-month prospective METADAP cohort, non-overweight patients, body mass index <25 kg/m2, with MDD and a current MDE were assessed for treatment response after 3 months of treatment, and incidence of MetS after 3 and 6 months of treatment. Outcome variables were MetS, number of MetS criteria, and each MetS criterion (high waist circumference, high blood pressure, high triglyceridemia, low high-density lipoprotein-cholesterolemia, and high fasting plasma glucose).

In total, 98/169 patients (58%) responded to treatment after 3 months. A total of 2.7% (1/38) developed MetS out of which 12.7% (10/79) (p value < 0.001) had responded to treatment after 3 months. The fixed-effect regression models showed that those who responded to treatment after 3 months of follow-up had an 8.6 times higher odds of developing MetS (odds ratio = 8.58, 95% confidence interval 3.89–18.93, p value < 0.001).

Compared to non-responders, non-overweight patients who responded to treatment after 3 months of antidepressant treatment had a significantly higher risk of developing MetS during the 6 months of treatment. Psychiatrists and nurses should closely monitor the metabolic profile of their patients, especially those who respond to treatment.

Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.

Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.

In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.

Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.

ClinicalTrials.gov NCT02332291

Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD.

Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD.

Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up.

Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.

Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia.

We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted.

A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)].

The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

White matter abnormalities have been identified in major depressive disorder (MDD). Although several diffusion tensor imaging studies found decreased fractional anisotropy (FA) in MDD, the effect of antidepressants (AD) treatment on white matter integrity has been insufficiently studied.

We sought to examine the effect of AD treatment of MDD on white matter, using DTI, in responders compared to nonresponders.

We included 25 individuals with MDD (HAMD >/=20) without inflammatory, unstable medical/neurological conditions or prolonged duration (> 1 year),or AD or anti-inflammatory treatment >/=1 week preceding first evaluation. Evaluation before treatment and at 16 weeks included depression rating scales, a cognitive battery, inflammatory markers and MRI. Desvenlafaxine was initiated at 50mg with a possible increase to 100mg at 8 weeks.

Changes included: increased volume in responders in the right Inferior Fronto-Occipital fasciculus (p=0.0315) and Superior Longitudinal Fasciculus part 3 (p=0.0050); in remitters in the right Inferior Fronto-Occipital fasciculus (p=0.0359) and Superior Longitudinal Fasciculus part 2 (p<0.05) and 3 (p=0.0481); decreased volume in responders in the left Superior Longitudinal Fasciculus part 1 (p=0.0147) and left Corona Radiata(p<0.05); and in remitters in the left Superior Longitudinal Fasciculus part 1 (p=0.0109) and the Corpus Callosum part 5 (p<0.05); decreased FA in the right Cortico Spinal Tract in remitters (p=0.0175) and responders (p=0.0272), and an increase in FA in the left Uncinate Fasciculus in nonremitters (p=0.0493). These results lose significance following Bonferroni correction.

Overall, AD treatment of MDD was not associated with significant changes in FA, whole brain, or specific tract volume in this study.

This research was funded by Pfizer Canada.

At present, there is no universally approach to treating patients at clinical high-risk for psychosis (CHR) without comorbid mental disorders. However, if there are revealed depressive symptoms, proper treatment becomes necessary.

Establish pharmacological classes and doses of drugs that have proved effective in treating depressive patients at CHR.

A comparative study of pharmacological classes and doses of drugs was carried out, showing the effectiveness in treatment of 219 depressive patients at CHR and 52 depressive patients without CHR. The treatment effectiveness was carried out on the reduction of depression symptoms on the HDRS scale, and the CHR symptoms on the SOPS scale.

A significant reduction of depression symptoms was achieved in the group of depressive patients with and without CHR on the HDRS scale (67.9% and 76.6% respectively). The reductions of the CHR symptoms were 46.1% and 53.3% respectively. There were differences between the severity of depression symptoms and CHR symptoms before and after the treatment. Both groups used antidepressants followed by the prescription of antipsychotics to increase the effectiveness of the therapy. No difference was found in the doses of antidepressants for the fluoxetine equivalent (46.0 vs 42.6 mg per day, p 0.05) and some differences were found for the average effective doses of antipsychotics for the chlorpromazine equivalent (385.4 vs 230.8 mg per day, p 0.05).

The same pharmacological classes are used for the treatment of young depressive patients with and without CHR, but the former have significantly higher doses of antipsychotics.

No significant relationships.

Antidepressant withdrawal manic states are rare and controversial phenomena. The underlying pathophysiology and the clinical implications have not been thoroughly discussed in the literature.

We aimed to review reports of antidepressant discontinuation manic states and to discuss the different hypothetical pathophysiological changes underlying this phenomenon. We also argued in favor of its inclusion in the bipolar spectrum.

We searched Pubmed using the key words: ‘antidepressant withdrawal’ or ‘antidepressant discontinuation’ plus ‘mania’ or ‘hypomania’ from January 2008 until January 2018.

Twenty-nine cases of antidepressant discontinuation manic states were identified. Hypotheses involve the implication of Catecholamines, Acetylcholine and Serotonin in the pathophysiology of this paradoxical phenomenon. The search for red flags for bipolar disorder in these case reports revealed psychiatric histories in favor of a bipolar spectrum disorder in 12 individuals while five were already known to have bipolar disorder.

Antidepressant discontinuation mania should be considered on the bipolar spectrum.

No significant relationships.

The efficacy and of current antidepressants is insufficient. Esketamine, a new antidepressant administered by nasal route, is available since 2019 in the management of resistant characterized depressive episodes.

To evaluate the response profile of patients to Esketamine in our institution specialized in mental health.

We included all patients treated with Esketamine in our institution from November 2019 to September 2021.We collected efficacy and tolerability data using the computerized and paper patient record, prescribing support software, and nursing staff.

Since 2019, we treated 11 patients with Esketamine in combination with an antidepressant as indicated in the MA. Two patients from the 11 were found resistant, three discontinued due to adverse events, four relapsed after an initial clinical response, and two were still ongoing at the end of the study.

Despite an initial and rapid response, our study does not highlight any long-term efficacy of Esketamine in resistant depressive disorder. This highlight the fact that its use in the acute phase of depression or earlier in the management strategy could be a good alternative because of its rapid onset of action. Esketamine was initiated as a last line therapy, which may represent a bias in the evaluation of the molecule, as the later the depression is treated, the lower the response rate. The place of Esketamine in the therapeutic strategy is not yet well determined due to a lack of hindsight, and the question of pharmacological tolerance and dependence on the molecule arises.

No significant relationships.

No significant relationships.

Depression during pregnancy leads to deterioration of the mothers’ and the fetus’ health.

To explore women’s perception and attitude towards using antidepressants during pregnancy and identify the factors that influence decision making regarding antidepressants use.

A cross-sectional survey of 991 subjects using convenient sampling. All study subjects (PNU affiliates; staff and students) were invited to fill out an electronic questionnaire, KAAUH staff and PNU female associates who were less than 18 years old were excluded. Answers were reported using 5- point Likert scale. The responses were summed up to give a total score for each respondent. The cutoff point is 75%. Respondents who scored above or equal 75% of the total score was considered as positive perception or favorable attitude.

The majority of women had negative perception and favorable attitude towards using antidepressants during pregnancy reaching 64%. While, women with positive perception and favorable attitude represented about 20% of the study subjects. The main factors influencing decision making were, education specialty (health, none-health) and subject history of diagnosis with any psychological disorder. Social stigma, religious believes and fear of addiction were reported by surveyors to be the reason influencing their perception and attitude about antidepressants use (P value <0.005).

This study reveals that although Saudi women reflect a negative perception towards using antidepressants during pregnancy, yet they have a favorable attitude once depression during pregnancy becomes an issue.

No significant relationships.

Bipolar disorder is a frequent and particularly severe psychiatric pathology that causes significant morbidity and mortality. The rapid cycling forms are more severe in terms of their expression, evolutionary course, therapeutic responses and associated comorbidities.

The aim of this study is to conduct a descriptive assessment of therapeutic characteristics in patients with rapid cycling bipolar disorder.

Our work involved a population of 97 patients followed for bipolar disorder diagnosed according to DSM5 criteria, including 37 patients meeting the specification “with rapid cycles”. The patients were divided into two groups: - Group of patients with bipolar disorder with rapid cycles (TBCR) - Group of patients with bipolar disorder without rapid cycling (TBNCR). We compared the therapeutic features among these two groups.

The dominant polarity was depressive in patients with rapid cycles. They required more mood stabilizers. A greater proportion of them had received treatment with serotonin reuptake inhibitor antidepressants. They were more likely to use hypnotics such as antihistamines and zolpidem.

Rapid cycling TB is a relatively common clinical modality that should be investigated and identified.The use of antidepressants is associated with this course of the disease. Their utilization in the treatment of bipolar depression must be thoughtful and well studied

No significant relationships.

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.

Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome.

Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2–17.1%) of them (n = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P (n = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56–0.90) in the fixed-effects model (z = −2.79; p = 0.005), and 0.78 (0.58–1.05) in the random-effects model (z = −1.77; p = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's Q = 18.45; df = 15; p = 0.239; I2 = 18.7%).

Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.