Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD).

Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data.

At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: −2.73 [−3.63, −1.82], p < 0.0001) and amotivation scores (mean, 95% CI: −0.78 [−1.04, −0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time.

This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs.

The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes.

There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms.

The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies.

This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).

We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.

Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.

Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

SSRI’s are consistently associated with violent events in the adult population. However, the causality between SSRI use and violent behaviour was never found. Several recent studies draw the attention to this hypothesis while they were inspired by several mass murderers in the United States.

A literature research on studies exploring the association between SSRI use and violent behaviour.

The authors performed a literature search (1966–2020) using PubMed and Embase to review studies where a possible link between SSRI’s and violent behaviour in adults was assessed.

94 studies were identified, of which 6 studies were included. There is no association between the use of SSRI’s and violent behaviour in the general population. However, an increased hazard of violent behaviour was observed in young man and those with a history of violent crime.

Overall, SSRI treatment is safe in the general population. Certain subgroups can, however, be vulnerable to aggressive flare-ups, especially during on-treatment period and the first 12 weeks after drug discontinuation. Therefore, careful monitoring throughout these critical periods is strongly recommended.

No significant relationships.

Serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants thanks to the overall safety and tolerability spectrum. However, they can cause different side effects that not all of them are well identified.

We intend to clarify the clinical presentation of mydriasis caused by Escitalopram.

Reporting the case of a patient suffering a major depressive disorder, that presented a mydriasis after adjusting her antidepressant medication. Then, we conducted a literature review using “PubMed” database and keywords “Mydriasis”, “escitalopram”, “SSRI”,” side effects”.

A 29-year-old female with no past clinical history, presented in May 2021 a severe depression requiring an antidepressant treatment. Under 10 mg per day of escitalopram there was a partial remission of the symptoms, leading to increase the dose by another 10 mg. One month after taking 20 mg/day, she consults before the appointment suffering from a blurry vision and photophobia. Ophthalmologic examination showed a bilateral reactive half-mydriasis, eye pressure was 14 mmHg and fundus examination was normal. Iatrogenic origin of mydriasis was suspected. A gradual interruption of the medication lead to disappearance of the latter. A pharmacological investigation concluded to the suspension of escitalopram and to be vigilant if antidepressant medication would be needed.

Mydriasis is an uncommon side effect caused by SSRI that needs to be kept in mind by clinicians. Therapeutic patient education can help to detect abnormal side effects and treat them if needed.

No significant relationships.

Anxiety disorders are the most prevalent mental disorder in children and young people. Developing effective therapy for these children is critical to reduce mental disorders across the lifespan. The study aimed to evaluate the efficacy of combining cognitive behavioural therapy (CBT) and sertraline (SERT) in the treatment of anxiety in youth, using a double-blind randomised control trial design.

Ninety-nine youth (ages 7–15 years) with an anxiety disorder were randomly allocated to either individual (CBT) and SERT or individual CBT and pill placebo and assessed again immediately and 6 months after treatment.

There were no significant differences between conditions in remission of primary anxiety disorder or all anxiety disorders. Furthermore, there were no significant differences in rates of change in diagnostic severity, parent-reported anxiety symptoms, child-reported anxiety symptoms or life interference due to anxiety.

The efficacy of CBT for children and adolescents with anxiety disorders is not significantly enhanced by combination with a short-term course of anti-depressants over and above the combined effects of pill placebo.

The UNIQUE study assessed the effect of Quetiapine fumarate augmentation on the overall depression status of patients with major depressive disorder and who did not respond to any acute treatment with selective serotonin reuptake inhibitors (SSRIs) or selective noradrenalin reuptake inhibitors (SNRIs) and naïve to any atypical antipsychotics.

Between March 2006 and November 2007, 39 male and female patients, aged 18-65, were enrolled into this four-week, open label, non-comparative, multicentric, phase II prospective study. Treatment with Quetiapine fumarate began at enrolment, with a titration to a target dose of 300mg. The following scales were completed during all five visits: Montgomery-Asberg Depression Rating Scale (MADRS); Clinical Global Impression (CGI); Brief Psychiatric Rating Scale (BPRS); Sheehan Disability Scale (SDS).

All questionnaire mean scales were significantly reduced (Friedman P< 0.0001) at the end of the study from baseline: MADRS 16.9 (12.8-21.0); CGI 1.94 (1.52-2.37); BPRS 10.3 (6.7-13.6); SDS 8.5 (5.6-11.5). Response, defined as a reduction in MADRS total score >50% was observed in 45.9% of the 37 patients completing at least 2 weeks of the study and 37.8% were considered in remission e.g. MADRS total score ≤ 12 at visit 5.

Quetiapine fumarate augmentation improved the overall depression status of patients resistant to SSRI or SNRI treatment.