The prevalence of depression is gradually increasing worldwide with an increasing utilization of antidepressants. Nevertheless, despite their lower costs, generic-brand antidepressants were reported to be less prescribed. We aimed to examine the costs of reference- versus generic-brand antidepressant prescriptions in primary care practice.

This cross-sectional study included electronic prescriptions for adult patients that contained antidepressants (World Health Organization’s Anatomical Therapeutic Chemical (ATC) code: N06A), which were generated by a systematically selected sample of primary care doctors (n = 1431) in Istanbul in 2016. We examined the drug groups preferred, the reference- versus generic-brand status, and pharmacotherapy costs.

The majority of the prescriptions were prescribed for women (71.8%), and the average age of the patients was 53.6 ± 16.2 years. In prescriptions with a depression-related indication (n = 40 497), the mean number and cost of drugs were 1.5 ± 1.0 and 22.7 ± 26.4 United States Dollar ($) per prescription, respectively. In these prescriptions, the mean number and cost of antidepressants per encounter were 1.1 ± 0.2 and $17.0 ± 13.2, respectively. Reference-brand antidepressants were preferred in 58.2% of depression-related prescriptions, where the mean cost per prescription was $18.3 ± 12.4. The mean cost per prescription of the generics, which constituted 41.8% of the antidepressants in prescriptions, was $15.1 ± 11.4. We found that if the generic version with the lowest cost was prescribed instead of the reference-brand, the mean cost per prescription would be $12.9 ± 11.2.

Our study highlighted the substantial pharmacoeconomic impact of generic-brand antidepressant prescribing, whose preference over reference-brands could reduce the cost of antidepressant medication treatment by 17.5% in primary care, which could be approximately doubled if the cheapest generic antidepressant had been prescribed.

This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised.

The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients’ severity of depressed symptoms records were screened for MADRS-S scores.

No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model.

Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801.

We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 – 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 – 0.957), p = 0.032) to be associated with hypoNa.

Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation.

We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings.

The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25–0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups.

The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

It remains unclear how SSRIs and other antidepressants are associated with the risk of repeated suicide attempts. We aimed to analyse the association between redeemed antidepressant prescriptions and the risk of repeated suicide attempts, hypothesising that antidepressant treatment is associated with increased risk of repeated suicide attempts.

The study was based on Danish register data and a validated cohort of 1842 suicide attempts. We used three Cox regression models (crude, adjusted and propensity score matched) to analyse the data; these models included both static and dynamic time-dependent factors.

1842 individuals attempted suicide in the study period, with a total of 210 repeated attempts. Individuals redeeming antidepressant prescriptions were more likely to repeat a suicide attempt. All crude models showed all antidepressants to be significant risk factors (HR around 1.39), whereas all adjusted models showed all antidepressants to be insignificant risk factors.

We found no significant increased risk of repeated suicide attempts in individuals redeeming a prescription for any antidepressant (or only SSRIs) when considering the individuals' baseline risk of repetition. This study is based on validated suicide attempts, register data, and strong epidemiology designs, but it still has some limitations, and the results should be replicated and confirmed in other studies.

We studied the relation between individual and neighborhood socioeconomic characteristics and the probability of:

• – new long-duration antidepressant treatment;

• – early antidepressant discontinuation.

We followed two cohorts of inhabitants of Marseille (aged 18–64 years) covered by the National Health Insurance Fund (NHIF) for 2.5 years. In the first cohort (316,412 individuals in 2008), we studied new long-duration antidepressant treatments (≥ 4 antidepressants prescription claims within 6 months after the index claim, and none in the 6 months before). The second cohort was restricted to the 14,518 individuals with a new episode of antidepressant treatment prescribed by a private GP in 2008–2009 to study early treatment discontinuation: < 4 antidepressant prescription claims in the 6 months following the index claim. We developed a deprivation index at the neighborhood level (census block) and used multivariate multilevel logistic models adjusted for consultations with GPs and psychiatrists. In the second cohort, analyses were further adjusted on GPs characteristics.

First cohort: the probability of new long-duration antidepressant treatments was negatively associated with both individual low income and neighborhood deprivation. Second cohort: low income, and prescribers’ clientele composition (high proportion of disadvantaged patients) were independently associated with an increased risk of early discontinuation. A significant interaction was found between low income and gender.

Our results add further evidence supporting the existence of inequalities in antidepressant treatment at both the individual, GP and neighborhood levels, and that these inequalities occur principally during the processes of care. Inequalities in antidepressant continuation are more pronounced among women. Further research is warranted to improve our understanding of their mechanisms.

The Temperament and Character Inventory (TCI) is commonly used in adult populations. Our aim was to explore: (1) if there are specific differences in temperament dimensions related to depression in comparison with general population, (2) if the treatment response during the acute phase of major depressive disorder (MDD) is predictable by TCI temperament dimensions.

Temperament profiles in 98 MDD patients were compared with a Finnish community sample. The patients were treated with serotonin selective reuptake inhibitors (SSRIs) for 6weeks and their temperament profiles were assessed at baseline and endpoint. The harm avoidance (HA) and depression scores at baseline and endpoint were modelled with path analysis. For path modelling, we tested the relationships between different temperament dimensions and depression symptoms and other clinical variables with Mancova model.

The HA scores were significantly higher in patients both at baseline and endpoint compared to the Northern Finland 1966 Birth Cohort (NFBC). The patients, and especially males, had slightly higher reward dependency (RD) scores. HA at endpoint explained moderately the Montgomery Åsberg Depression Rating Scale (MADRS) endpoint score. HA endpoint score was strongly explained by HA baseline score.

HA is associated with risk of and treatment response to depression.

The evidence informing the management of cardiovascular risk in patients with psychiatric disorders is weak.

This cohort study used data from all patients, aged ≥ 30, registered in 140 primary care practices (n = 524,952) in London to estimate the risk of developing diabetes, hypertension, hyperlipidemia, tobacco consumption, obesity, and physical inactivity, between 2005 and 2015, for patients with a previous diagnosis of schizophrenia, depression, anxiety, bipolar or personality disorder. The role of antidepressants, antipsychotics and social deprivation in these associations was also investigated. The age at detection of cardiovascular risk factor was compared between patients with and without psychiatric disorders. Variables, for exposures and outcomes, defined from general practitioners records, were analysed using multivariate regression.

Patients with psychiatric disorders had an increased risk for cardiovascular risk factors, especially diabetes, with hazard ratios: 2.42 (2.20–2.67) to 1.31 (1.25–1.37), hyperlipidemia, with hazard ratios: 1.78 (1.60–1.97) to 1.25 (1.23–1.28), and obesity. Antidepressants, antipsychotics and social deprivation did not change these associations, except for smoking and physical inactivity. Antidepressants were associated with higher risk of diabetes, hypertension and hyperlipidemia. Antipsychotics were associated with a higher risk of diabetes. Antidepressants and antipsychotics were associated with lower risk of other risk factors. Patients with psychiatric conditions have later detection of cardiovascular risk factors. The interpretation of these results should acknowledge the lower rates of detection of risk factors in mentally ill patients.

Cardiovascular risk factors require special clinical attention among patients with psychiatric disorders. Further research could study the effect of antidepressants and antipsychotics on cardiovascular risk factors.

Symptoms of depression and anxiety are common in neuroendocrine tumor (NET), yet controversy exists over whether serotonin-mediated antidepressants (SAs) are safe in this population. We sought to address this knowledge gap.

Following PRISMA guidelines, we conducted a systematic review to identify NET patients who were prescribed SA.

We identified 15 articles, reporting on 161 unique patients, 72 with carcinoid syndrome (CS) and 89 without. There was substantial agreement between reviewers at the full-text stage (κ = 0.69). Three of the articles, all with low risk of bias, accounted for most of the cases (149/161; 93%). Among the 72 NET patients with CS prior to antidepressant usage, CS was exacerbated in 6 cases (8%), only 3 (4%) of whom chose to discontinue the antidepressant. The remaining 89 patients had no prior CS symptoms, and none developed CS following antidepressant usage. Overall, no instances of carcinoid crisis or death were reported.

We found no evidence for serious adverse outcomes related to SA usage in NET patients. Previous authors have recommended avoiding antidepressants in NET, but our findings do not support those recommendations. Oncologists should nonetheless monitor for symptom exacerbation when prescribing SA to patients with NET.

Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.

Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.

Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.

Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.

Emerging genetic, ex-vivo, and clinical trial evidence indicates that calcium channel blockers (CCB) can improve mood and cognitive function. The objective of this study was to examine the effect of selective serotonin reuptake inhibitor (SSRI) therapy augmented with CCB on depression and cognitive decline in an elderly population with hypertension.

Prospective study of 296 persons treated with SSRI and antihypertensive drugs. Baseline and two year clinic assessments were used to categorize participants as users of SSRI + CCB (n = 53) or users of SSRI + other antihypertensives (n = 243). Clinic visits were performed up to four times in a ten-year period to assess depression and cognitive function.

The sample mean age was 75.2 ± 5.47 years and 78% of participants were female. At two year follow-up there was a significant group by time interaction showing lower Center for Epidemiological Studies-Depression (CESD) scores in the SSRI + CCB group, F(1,291) = 4.13, p = 0.043, η2p = 0.014. Over ten-years follow-up, SSRI + CCB use was associated with improved general cognitive function (Mini-Mental State Examination: β = 0.97; 95% CI 0.14 to 1.81, p = 0.023) and immediate visual memory (Boston Visual Retention Test: β = 0.69; 95% CI 0.06 to 1.32, p = 0.033).

The findings provide general population evidence that SSRI augmentation with CCB may improve depression and cognitive function.

The aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice.

Male Swiss mice (n=6–8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1–30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes.

According to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle.

Data suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

Although prescription rates of antidepressants for children and adolescents have increased, concerns have been raised regarding effects on neurodevelopment and long-term outcome. Using a genetic animal model of depression, this study investigated the long-term effects of pre-pubertal administration of fluoxetine (FLX) on depressive-like behaviour in early adulthood, as well as on central monoaminergic response to an acute stressor. We postulated that pre-pubertal FLX will have lasting effects on animal behaviour and monoaminergic stress responses in early adulthood.

Flinders sensitive line (FSL) rats received 10 mg/kg/day FLX subcutaneously from postnatal day 21 (PnD21) to PnD34 (pre-pubertal). Thereafter, following normal housing, rats were either subjected to locomotor testing and the forced swim test (FST) on PnD60 (early adulthood), or underwent surgery for microdialysis, followed on PnD60 by exposure to acute swim stress and measurement of stressor-induced changes in plasma corticosterone and pre-frontal cortical monoamine concentrations.

Pre-pubertal FLX did not induce a late emergent effect on immobility in FSL rats on PnD60, whereas locomotor activity was significantly decreased. Acute swim stress on PnD60 significantly increased plasma corticosterone levels, and increased pre-frontal cortical norepinephrine (NE) and 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations. Pre-pubertal FLX significantly blunted the pre-frontal cortical NE and 5-HIAA response following swim stress on PnD60. Baseline dopamine levels were significantly enhanced by pre-pubertal FLX, but no further changes were induced by swim stress.

Pre-pubertal FLX did not have lasting antidepressant-like behavioural effects in genetically susceptible, stress-sensitive FSL rats. However, such treatment reduced locomotor activity, abrogated noradrenergic and serotonergic stressor responses and elevated dopaminergic baseline levels in adulthood.

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.

In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.

We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.

TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.

Antidepressants are used to treat depression and behavioral symptoms in Alzheimer's disease (AD), although their effectiveness has been questioned and evidence about the risks is accumulating. The objective of this study was to compare antidepressant use among persons with and without AD in Finland.

The Social Insurance Institution of Finland (SII) identified all persons with a verified diagnosis of AD in Finland on December 31, 2005. For each person with AD a comparison person matched for age, sex and region of residence was also identified. Data on reimbursed drug purchases in 2005 were extracted from the Finnish National Prescription Register (FNPR). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for antidepressant use.

The study sample comprised of 28,089 matched pairs of persons with and without AD (mean age 80.0 SD 6.8, 32.2% men).The prevalence of antidepressant use was higher among persons with AD than without AD (29.4% vs. 10.7%, OR = 3.54; 95% CI: 3.38, 3.70). Among the persons with AD, the prevalence of antidepressant use increased with time since AD diagnosis but not with age. Overall, 90.4% of antidepressant users with AD were co-dispensed anti-dementia drugs.

The antidepressant use was three times more prevalent among persons with AD compared to those without. Though the antidepressant selection was largely consistent with clinical practice guidelines, the high prevalence of use warrants further investigation given the uncertain effectiveness and adverse events related to these drugs.