Sustained Improvement of Negative Self-Schema After a Single Ketamine Infusion: An Open-Label Study

Conventional antidepressants have several important limitations, including a lack of direct effects on negative self-schema, which is at the core of Beck’s cognitive theory of depression. Based on previous studies showing a positive effect of ketamine on negative cognition, we compared reductions in negative self-schema between responders and non-responders to a single infusion of ketamine. In an open-label study, 26 participants with treatment-resistant depression received 0.5 mg/kg ketamine via infusion. Depression symptoms were assessed at baseline, 24 h, and 7 days after treatment with Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI-II). Nine of the 26 participants fulfilled response criteria after 24 h. Of these, eight still fulfilled response criteria after 7 days. Response was defined as a reduction in MADRS total score of 50% or more. Responders improved significantly more than non-responders both 24 h and 7 days after ketamine treatment on the following BDI-II items: item 1 (“Sadness”), item 7 (“Self-Dislike”), and item 8 (“Self- Criticalness”). These results suggest an important therapeutic effect of ketamine on negative self-schema, which is a fundamental cognitive aspect of depression. This effect is unique and might be associated with ketamine’s profound effects on neuroplasticity. Small sample size and lack of a placebo control group are the major limitations of this study

Risk factors of postpartum depression and depressive symptoms: umbrella review of current evidence from systematic reviews and meta-analyses of observational studies

BackgroundEvidence on risk factors for postpartum depression (PPD) are fragmented and inconsistent.AimsTo assess the strength and credibility of evidence on risk factors of PPD, ranking them based on the umbrella review methodology.MethodDatabases were searched until 1 December 2020, for systematic reviews and meta-analyses of observational studies. Two reviewers assessed quality, credibility of associations according to umbrella review criteria (URC) and evidence certainty according to Grading of Recommendations-Assessment-Development-Evaluations criteria.ResultsIncluding 185 observational studies (n = 3 272 093) from 11 systematic reviews, the association between premenstrual syndrome and PPD was the strongest (highly suggestive: odds ratio 2.20, 95%CI 1.81–2.68), followed by violent experiences (highly suggestive: odds ratio (OR) = 2.07, 95%CI 1.70–2.50) and unintended pregnancy (highly suggestive: OR=1.53, 95%CI 1.35–1.75). Following URC, the association was suggestive for Caesarean section (OR = 1.29, 95%CI 1.17–1.43), gestational diabetes (OR = 1.60, 95%CI 1.25–2.06) and 5-HTTPRL polymorphism (OR = 0.70, 95%CI 0.57–0.86); and weak for preterm delivery (OR = 2.12, 95%CI 1.43–3.14), anaemia during pregnancy (OR = 1.47, 95%CI 1.17–1.84), vitamin D deficiency (OR = 3.67, 95%CI 1.72–7.85) and postpartum anaemia (OR = 1.75, 95%CI 1.18–2.60). No significant associations were found for medically assisted conception and intra-labour epidural analgesia. No association was rated as ‘convincing evidence’. According to GRADE, the certainty of the evidence was low for Caesarean section, preterm delivery, 5-HTTLPR polymorphism and anaemia during pregnancy, and ‘very low’ for remaining factors.ConclusionsThe most robust risk factors of PDD were premenstrual syndrome, violent experiences and unintended pregnancy. These results should be integrated in clinical algorithms to assess the risk of PPD

Risk factors of postpartum depression and depressive symptoms: umbrella review of current evidence from systematic reviews and meta-analyses of observational studies

Background: Evidence on risk factors for postpartum depression (PPD) are fragmented and inconsistent. Aims: To assess the strength and credibility of evidence on risk factors of PPD, ranking them based on the umbrella review methodology. Method: Databases were searched until 1 December 2020, for systematic reviews and meta-analyses of observational studies. Two reviewers assessed quality, credibility of associations according to umbrella review criteria (URC) and evidence certainty according to Grading of Recommendations-Assessment-Development-Evaluations criteria. Results: Including 185 observational studies (n = 3 272 093) from 11 systematic reviews, the association between premenstrual syndrome and PPD was the strongest (highly suggestive: odds ratio 2.20, 95%CI 1.81-2.68), followed by violent experiences (highly suggestive: odds ratio (OR) = 2.07, 95%CI 1.70-2.50) and unintended pregnancy (highly suggestive: OR=1.53, 95%CI 1.35-1.75). Following URC, the association was suggestive for Caesarean section (OR = 1.29, 95%CI 1.17-1.43), gestational diabetes (OR = 1.60, 95%CI 1.25-2.06) and 5-HTTPRL polymorphism (OR = 0.70, 95%CI 0.57-0.86); and weak for preterm delivery (OR = 2.12, 95%CI 1.43-3.14), anaemia during pregnancy (OR = 1.47, 95%CI 1.17-1.84), vitamin D deficiency (OR = 3.67, 95%CI 1.72-7.85) and postpartum anaemia (OR = 1.75, 95%CI 1.18-2.60). No significant associations were found for medically assisted conception and intra-labour epidural analgesia. No association was rated as 'convincing evidence'. According to GRADE, the certainty of the evidence was low for Caesarean section, preterm delivery, 5-HTTLPR polymorphism and anaemia during pregnancy, and 'very low' for remaining factors. Conclusions: The most robust risk factors of PDD were premenstrual syndrome, violent experiences and unintended pregnancy. These results should be integrated in clinical algorithms to assess the risk of PPD

Postpartum hemorrhage and postpartum depression: A systematic review and meta-analysis of observational studies.

OBJECTIVE To assess the postpartum depression (PPD) risk in women with postpartum hemorrhage (PPH) and moderators. METHODS We identified observational studies of PPD rates in women with versus without PPH in Embase/Medline/PsychInfo/Cinhail in 09/2022. Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcome was the odds ratio (OR, 95% confidence intervals [95%CI]) of PPD in women with versus without PPH. Meta-regression analyses included the effects of age, body mass index, marital status, education, history of depression/anxiety, preeclampsia, antenatal anemia and C-section; subgroup analyses were based on PPH and PPD assessment methods, samples with versus without history of depression/anxiety, from low-/middle- versus high-income countries. We performed sensitivity analyses after excluding poor-quality studies, cross-sectional studies and sequentially each study. RESULTS One, five and three studies were rated as good-, fair- and poor-quality respectively. In nine studies (k = 10 cohorts, n = 934,432), women with PPH were at increased PPD risk compared to women without PPH (OR = 1.28, 95% CI = 1.13 to 1.44, p < 0.001), with substantial heterogeneity (I2  = 98.9%). Higher PPH-related PPD ORs were estimated in samples with versus without history of depression/anxiety or antidepressant exposure (OR = 1.37, 95%CI = 1.18 to 1.60, k = 6, n = 55,212, versus 1.06, 95%CI = 1.04 to 1.09, k = 3, n = 879,220, p < 0.001) and in cohorts from low-/middle- versus high-income countries (OR = 1.49, 95%CI = 1.37 to 1.61, k = 4, n = 9197, versus 1.13, 95%CI = 1.04 to 1.23, k = 6, n = 925,235, p < 0.001). After excluding low-quality studies the PPD OR dropped (1.14, 95%CI = 1.02 to 1.29, k = 6, n = 929,671, p = 0.02). CONCLUSIONS Women with PPH had increased PPD risk amplified by history of depression/anxiety, whereas more data from low-/middle-income countries are required

Use of Long-Acting Injectable Antipsychotics in Inpatients with Schizophrenia Spectrum Disorder in an Academic Psychiatric Hospital in Switzerland

Long-acting injectable antipsychotics (LAIs) offer many benefits to patients with schizophrenia spectrum disorder (SSD). They are used with very different frequencies due to questions of eligibility or patients and prescribers’ attitudes towards LAI use. We assessed the prescribing rates of LAIs in a large academic psychiatric hospital with a public service mandate in Switzerland and compared them with other countries and health care systems. To our knowledge, this study is the first to investigate inpatient LAI use in Europe. Medical records of all patients diagnosed with SSD discharged from the Clinic of Adult Psychiatry of the University Hospital of Psychiatry Zurich over a 12 month period from January to December 2019 were evaluated regarding the prescribed antipsychotics at the time of discharge. The rates of use of LAIs among all patients and among patients receiving LAI-eligible antipsychotic substances were assessed retrospectively. We assessed records of 885 patients with SSD. Among all cases, 13.9% received an LAI. Among patients who received antipsychotic medication that was eligible for LAI use (n = 434), 28.1% received an agent as an LAI. LAI use included paliperidone palmitate (69.9%), aripiprazole monohydrate (14.6%), risperidone (4.9%) and first-generation LAIs (9.8%). Compared to international frequencies of LAI administration, the prescription rate of LAIs in SSD patients was low. Further studies will evaluate patient- and prescriber-related reasons for this low rate

A recent suicide attempt and the heartbeat: Electrophysiological findings from a trans-diagnostic cohort of patients and healthy controls

Suicidal behavior is influenced by a multitude of factors, making prediction and prevention of suicide attempts (SA) a challenge. A useful tool to uncover underlying pathophysiology or propose new therapy approaches are biomarkers, especially within the context of point-of-care tests. Heart rate variability (HRV) is a well-established biomarker of mental health, and measures the activity of the sympathetic and parasympathetic nervous system (PNS). Previous studies reported a correlation between lower PNS activity and suicidality. However, most studies involved participants from a healthy population, patients without history of suicide attempts, or patients with a single diagnosis. 52 in-patients with a recent suicide attempt (<6 months), and 43 controls without history of SA or psychiatric diagnoses confirmed study participation. The included patients age ranged between 18 and 65 years, 65% had psychiatric comorbidities. Patients with dementia, cognitive impairments, acute psychosis, chronic non suicidal self-harming behavior, or current electroconvulsive therapy were excluded. A 15-min resting state electrocardiography was recorded with two bipolar electrodes attached to the right and left insides of the wrists. The multiple regression analyses showed lower parasympathetic, and higher sympathetic activity in patients compared to controls. Partial correlation found a positive trend result between self-reported suicidality and the very low frequency band. ROC curve analysis revealed an acceptable to excellent clinical accuracy of HRV parameters. Therefore, HRV parameters could be reliable discriminative biomarkers between in-patients with a recent SA and healthy controls. One limitation is the lack of a control group consisting of in-patients without life-time suicidal ideation or attempts

Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database

Introduction: Evidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions. Objective: To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions. Methods: This is a case/non-case pharmacovigilance study, based on the VigiBase®, the WHO global database of individual case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis of reports of antidepressant-related withdrawal syndrome (calculating reporting odds ratio [ROR] and Bayesian information component [IC]). We compared antidepressants to all other drugs, to buprenorphine (positive control), and to each other within each class of antidepressants (selective serotonin reuptake inhibitors [SSRIs], tricyclics and other antidepressants). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. Serious versus non-serious reactions were compared. Results: There were 31,688 reports of antidepressant-related withdrawal syndrome were found. A disproportionate reporting was detected for 23 antidepressants. The estimated ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95% CI 14.08-14.45), 17.01 for other antidepressants (95% CI 16.73-17.29), 13.65 for SSRIs (95% CI 13.41-13.90) and 2.8 for tricyclics (95% CI 2.59-3.02). Based on clinical priority ranking, the strongest disproportionate reporting was found for paroxetine, duloxetine, venlafaxine and desvenlafaxine, being comparable to buprenorphine. Withdrawal syndrome was reported as severe more often in males, adolescents, persons in polypharmacy, and with a longer antidepressant treatment duration (p < 0.05). Conclusions: Antidepressants are associated with an increased reporting of withdrawal syndrome compared with other drug classes. When prescribing and discontinuing antidepressants, clinicians should be aware of the potentially different proclivity of withdrawal syndrome across individual antidepressants, and the liability to experience more severe withdrawal symptoms in relation to specific patient characteristics

An international guideline with six personalised titration schedules for preventing myocarditis and pneumonia associated with clozapine

White blood cell (WBC) monitoring has reduced clozapine-treated patient deaths associated with agranulocytosis to a rarity. However, clozapine protocols and package inserts worldwide provide no instructions for preventing myocarditis or pneumonia during clozapine titrations. Prescribers worldwide are largely unaware of that. Meanwhile, as they worry about agranulocytosis, their clozapine-treated patients are at risk of dying from pneumonia or myocarditis. Consequently, an international guideline with 104 authors from 50 countries/regions was recently published to provide personalised clozapine titration schedules for adult inpatients. This forum article reviews pneumonia and myocarditis occurring during clozapine titration, as well as the three most innovative aspects of this new guideline: (1) personalised titration, (2) C reactive protein (CRP) measures, and (3) dose predictions based on blood levels. Clozapine metabolism is influenced by 3 levels of complexity: (1) ancestry groups, (2) sex-smoking subgroups, and (3) presence/absence of poor metabolizer status. These 3 groups of variables should determine the maintenance dose and speed of clozapine titration; they are summarised in a table in the full-text. The international clozapine titration guideline recommends measuring CRP levels simultaneously with WBC, at baseline and weekly at least for the first 4 weeks of titration, the highest risk period for clozapine-induced myocarditis