A Systematic Review of a Polyvagal Perspective on Embodied Contemplative Practices as Promoters of Cardiorespiratory Coupling and Traumatic Stress Recovery for PTSD and OCD: Research Methodologies and State of the Art.

Baseline respiratory sinus arrhythmia (RSA) has been proposed as a transdiagnostic biomarker of stress vulnerability across psychopathologies, and a reliable association between PTSD, OCD and lower resting RSA was found. Contemplative practices have been linked to the activation of the vagus as well as to an increased RSA that, according to the polyvagal theory, reflects the activation of the ventral vagal complex (VVC) and may promote PTSD and OCD recovery. PubMed and Scopus databases were selected to conduct a search following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines, and A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) was used to appraise the methodological quality for this systematic review. Six articles met the inclusion criteria (one cross-sectional study, one study with pre-post measurements, two cohort studies and two RCT studies). Mindfulness-related interventions promoted parasympathetic activity, an increased vagal tone and improvements in PTSD and OCD symptoms. According to the polyvagal theory, mindfulness-related and compassion-related meditations would be conceptualized as neural exercises expanding the capacity of the ventral vagal complex to regulate the present state and to promote resilience. Clinical and methodological issues are discussed.

Efficacy of antidepressants in juvenile depression: meta-analysis.

BACKGROUND: The safety of antidepressants in children and adolescents is being questioned and the efficacy of these drugs in juvenile depression remains uncertain. AIMS: To assess antidepressant efficacy in juvenile depression. METHOD: Systematic review and meta-analysis of randomised controlled trials (RCTs) comparing responses to antidepressants, overall and by type, v. placebo in young people with depression. RESULTS: Thirty drug-placebo contrasts in RCTs lasting 8 weeks (median) involved 3069 participants (512 person-years) of average age 13.5 years. Meta-analysis yielded a modest pooled drug/placebo response rate ratio (RR=1.22, 95% CI 1.15-1.31), with little separation between antidepressant types. Findings were similar for response rate differences and corresponding number needed to treat (NNT): overall NNT=9; tricyclic antidepressants NNT=14 > serotonin reuptake inhibitors NNT=9 > other antidepressants NNT=8. Numbers needed to treat decreased with increasing age: children (NNT=21) > mixed ages (NNT=10) > adolescents (NNT=8). CONCLUSIONS: Antidepressants of all types showed limited efficacy in juvenile depression, but fluoxetine might be more effective, especially in adolescents. Studies in children and in severely depressed, hospitalised or suicidal juvenile patients are needed, and effective, safe and readily accessible treatments for juvenile depression are urgently required.

Mania in the Swedish Twin Registry: criterion validity and prevalence.

BACKGROUND: In population surveys, the assessment of mania is commonly done by trained lay interviewers using structured diagnostic instruments: the validity of this approach has been questioned. We examined the criterion validity and prevalence of lifetime mania in a survey of Swedish twins conducted with interview methodology usually applied in psychiatric epidemiology. METHODS: 41 838 individuals in the Swedish Twin Registry were evaluated via a telephone interview that included the eight DSM-IV mania items, and these data were merged with inpatient hospitalization discharge diagnoses from two comprehensive national registries (the criterion). An algorithm with eight cut-points was used to diagnose lifetime mania, and compared by a receiver operator characteristic curve to the criterion. The algorithm requiring at least four positive items resembling a DSM-IV diagnosis. RESULTS: History of hospitalization for a psychiatric condition that included a manic episode was present for 0.7% of all living twins, and predicted non-response to the survey (OR = 0.5; 95% CI = 0.4-0.6). The incidence rate for first hospitalization was 2.1/10 000 year(-1). For > or =1 symptom (first cut-point), the prevalence, sensitivity and specificity were 3.6%, 39.0% and 96.6%; for > or = 4 symptoms (DSM-IV-like cut-point) 2.6%, 36.5% and 97.6%; and for eight symptoms 0.3%, 18.0% and 99.8%. Positive predictive values were, respectively, 5.5%, 7.0% and 29.8%. CONCLUSIONS: The performance of the telephone screening for mania by lay interviewers in terms of positive predictive power was not satisfactory; despite a high specificity, the false positive rate was high. The low population prevalence of mania, non-response bias, criterion choice and inherent limitations of the interviewing method are among the explanations. Assessment of a lifetime manic episode based on lay interviewer screening may yield misleading data.

Pramipexole in treatment-resistant depression: an extended follow-up.

We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score= <2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression.

Antidepressants in bipolar disorder: the case for caution.

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re-examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood-cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long-term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15-20% of bipolar depressed patients).

Evidence-based pharmacotherapy of bipolar disorder.

This Commentary summarizes findings from three other papers in this issue with recommendations for evidence-based treatment with lithium, anticonvulsants, antipsychotics, and antidepressants in bipolar disorder. We will also provide a summary of levels of evidence and examine two important methodological issues in assessing drug-induced mania: reliance on significance testing for assessment of side-effects, and limitations of randomized controlled trials (RCTs) for assessing frequency of side-effects. If a study is not specifically powered and designed to assess a side-effect, then no significance testing should be conducted, and side-effects should simply be reported as effect estimates and confidence intervals. Further, RCTs only establish a categorical response to a research question, i.e. whether or not something happens. The frequency of an event (treatment response, side-effects) is often more accurately assessed with observational studies.