942 research outputs found
The present and future of precision medicine in psychiatry: Focus on clinical psychopharmacology of antidepressants
No full textPrecision medicine is a concept which is recently gaining momentum in all branches of medicine. In particular in psychiatry it is greatly needed given the huge societal costs of psychiatric disorders and given the long time needed to observe benefit from treatments and the response variability. The future will be based on biological determinants, however until such an interesting but still futuristic aim will be reached, at present we may only rely on clinical features to guide our individualized prescription which is currently still frequently based on personal opinion and subjective previous experiences. The aim of this review is to offer an overview of the main aspects to take into consideration when prescribing an antidepressant treatment to reach the best precision medicine using clinical information. More than 40 compounds are available for treating depression and a similar amount of compounds for other psychiatric disorders. The process of matching the profile of the patient with all different profiles of available compounds is therefore quite complex. Our everyday prescribing procedure should take into consideration a number of factors such as the knowledge of the profile of available compounds versus the symptomatology profile of the subject, previous efficacy, medical comorbidities, tolerability profile, individual preferences, and family history. While we are waiting more complex algorithms including biological or genetic measures, it is possible to optimize our current prescription practice by using all available information in order to obtain as much as possible an evidence based precision medicine prescription
Brexpiprazole: a step forward for precision medicine in resistant depression
No full textIntroduction: Resistant depression is still a common and burdensome issue and there is an urgent need for new and effective adjunctive treatments. Areas covered: In this paper, the author discusses the background, trial design, results and implications of a recent study (NCT02196506, Sirius study) which confirmed the possible benefit of brexpiprazole as adjunctive treatment in depressed subjects with inadequate benefit from first line treatments. As secondary aims, the study confirmed the effects in subjects with minimal benefit from standard treatments and in subjects with anxious distress. Despite some reported side effects such as akathisia, restlessness, and increased weight, the treatment was well tolerated. Expert opinion: The unique pharmacodynamic profile of brexpiprazole, in terms of reduced dopamine intrinsic stimulation and a range of other more anxiolytic receptor effects, suggests that brexpiprazole should be preferred in specific subpopulations, particularly where a more sedative profile is needed. Indeed, this study suggests another step in the direction of precision medicine
Genetyka i farmakogenetyka zaburzeÅ nastroju = Genetics and pharmacogenetics of mood disorders
No full textGenetic research in Psychiatry is viewed by clinicians with both hope and curiosity sometimes mixed with disillusionment. Indeed, in the last 30 years many results have not been confirmed and clinical applications are still missing. However, recent findings suggest that we are at the beginning of a new era. A set of variants within neuroplasticity and inflammation genes have been identified as a valid basis for both bipolar disorder and major depression. Similarly, a set of genes has been identified as a liability factor for response and tolerability to antidepressants and the first clinical applications are already in the market. However, some caution should be applied until definite findings are available
Authors' reply to "Recommendations for conducting mindfulness based cognitive therapy trials".
No full textTo the Editors:
We appreciated very much the commentary by Siddaway and Wood (2013) on our review and meta-analysis “Mindfulness based cognitive therapy for psychiatric disorders: A systematic review and meta-analysis” (Chiesa and Serretti, 2011) and we are grateful for having the possibility to further explore the issues they raised. As the authors of the commentary noted, the main findings of our meta-analysis were that mindfulness-based cognitive therapy (MBCT) as an adjunct to treatment as usual (TAU) could be significantly superior to TAU only and the combination of MBCT and gradual discontinuation of antidepressant therapy could be as efficacious as the continuation of maintenance antidepressant therapy for the prevention of depressive relapses in recovered depressed patients with three or more prior depressive episodes (Chiesa and Serretti, 2011). In addition, we also found that MBCT+TAU could be significantly superior to TAU only for the reduction of residual depressive symptoms in currently depressed patients (Chiesa and Serretti, 2011).
However, the authors of the commentary also noted that our critique of the methodology employed in MBCT trials to date did not go far enough and they cautioned against the assumption that “third wave” cognitive therapies, such as MBCT, are unequivocally superior to first or second wave therapies. The present response is aimed at further exploring our conclusions in relationship to the issues raised by the authors of the commentary.
First of all, we would like to underscore that in the discussion of our work we did not suggest that “third wave” cognitive therapies, such as MBCT, are unequivocally superior to first or second wave therapies. Rather, we underscored that, taking into account the inadequate sophistication of the control groups, further better designed studies should be aimed at distinguishing between the specific and the non-specific effects of MBCT. Results in this direction can usually be achieved through different study designs. A first possibility is to employ a control group that is specifically structured to include the majority of non-specific “ingredients” of the active treatment under investigation, including, among others, benefits' expectation, teacher's care, group support, contact time with the therapist and amount of home practice, while excluding the claimed active ingredient (or ingredients) of the treatment under investigation, such as mindfulness meditation practice (Chiesa, 2011). If MBCT is found to be superior to such control condition, it can reasonably be suggested that MBCT could provide patients with significantly higher benefits than those expected only in relationship to the non-specific elements of MBCT.
It is worth mentioning that, since the publication of our review and meta-analysis, some preliminary results in this direction have been published. As an example, the preliminary results of an ongoing trial from our group suggested that MBCT could be more efficacious than a psycho-educational group designed ad hoc to match as much as possible the non-specific elements of MBCT for the reduction of depressive symptoms in depressed patients with residual depressive symptoms (Chiesa et al., 2012).
A second possibility to rule out that the effects of a new treatment, such as MBCT, are only due to non-specific elements is to compare such treatment with an existing treatment that already proved efficacy for the specific condition under investigation (for better details see Chiesa (2011)). Although limited by the small sample size and the lack of an a priori power calculation, the results of a recent randomized controlled trial provided preliminary evidence to suggest that MBCT could be as efficacious as group cognitive behavioural therapy (CBT) to reduce depressive symptoms in currently depressed patients (Manicavasgar et al., 2011). In addition, in a further randomized controlled trial, Segal et al. (2010) found that MBCT+gradual discontinuation of antidepressant therapy could be as efficacious as the continuation of maintenance antidepressant therapy and that both treatments could be more efficacious than placebo for the prevention of depressive relapses in recovered patients with major depression.
In sum, the results of some recent randomized controlled trials aimed at exploring the efficacy of MBCT for the prevention of major depression relapses and for the reduction of acute and residual depressive symptoms provided preliminary support for the notion that MBCT could be associated with specific effects in addition to the non-specific effects that are shared by all psychological and pharmacological treatments. However, the results of these studies do not (or do not yet) provide support to the notion that MBCT is superior to other first or second wave cognitive treatments and do not unequivocally provide information about the distinctive features of MBCT. To the best of our knowledge, no trial has yet been published that specifically provided support to the notion that MBCT is superior to established treatments for the treatment of psychological disorders such as major depression.
In addition, as the authors of the commentary aptly noted, we agree that, as the investigation of MBCT moves forwards, it will be increasingly important to compare MBCT with different active control conditions that are aimed at testing each specific ingredient of the MBCT program, including, among others, the underlying interactive cognitive system (ICS) theoretical model, the particular contribution of changing the content of cognitions versus changing the function and process of cognitions and the contribution of low arousal affective states.
In line with these issues, an important question raised by the authors of the commentary to our review and meta-analysis is whether the ICS information-processing theory that underpins MBCT and purports to specifically explain recurrent episodes of depression (Teasdale et al., 1995) can be adapted to treat a range of acute problems. We also agree with the authors that, because several recent trials investigated the efficacy of MBCT as a treatment for a range of acute problems and sometimes tweaked the MBCT protocol, they could be re-interpreted as dismantling studies that provide important evidence regarding shared and unique therapeutic factors.
Similarly, we agree with the authors of the commentary that further challenging issues, including the reasons behind the notion that MBCT could help prevent relapses in patients with three or more previous depressive episodes but not in those with only two previous depressive episodes and the need for investigating the neural mechanisms of MBCT, require further investigation so as to better understand the mechanisms underlying MBCT as well as its strengths and limitations as a means to treat a different set of clinical conditions.
In conclusion, we underscore that available studies provide preliminary support to the efficacy of MBCT for the prevention of depression relapses and the reduction of depressive symptoms in patients suffering from major depression. However, future trials investigating the original and the many adapted versions of MBCT should employ stronger methodological paradigms aimed at (1) distinguishing between the specific and the non-specific effects of MBCT, (2) investigating the distinctive features of MBCT in comparison with several related interventions such as Mindfulness based Stress Reduction, CBT or relaxation training, (3) understanding to which extent the ICS model that underpins MBCT can be adapted to treat a range of different acute problems, (4) investigating the psychological and neurobiological mechanisms of action of MBCT and (5) providing evidence as to which adaptations are needed so as to best tailor future MBCT programs and studies to the unique needs, learning styles and temperamental profiles of individuals suffering from different clinical conditions in different phases of their disorder
Role of 108 schizophrenia-associated loci in modulating psychopathological dimensions in schizophrenia and bipolar disorder
No full textThe Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) identified 108 loci associated with schizophrenia, but their role in modulating specific psychopathological dimensions of the disease is unknown. This study investigated which symptom dimensions may be affected by these loci in schizophrenia, and bipolar disorder. Positive, negative and depressive symptoms, suicidal ideation, cognition, violent behaviors, quality of life, and early onset were investigated in schizophrenia and bipolar disorder using the clinical antipsychotic trials of intervention effectiveness (CATIE) and systematic treatment enhancement program for bipolar disorder (STEP-BD) studies. Individual loci were investigated, then genes within 50 Kbp from polymorphisms with p < 0.10 were included in an enrichment analysis (Cytoscape GeneMania plugin) and used to estimate polygenic risk scores (PRS). Covariates were center, age, gender, ancestry-informative population, principal components, and for cognition, also years of education were considered. Eighty-nine polymorphisms were available, 479 and 810 white subjects were included from CATIE and STEP-BD, respectively. rs75059851 (IGSF9B gene) was associated with negative symptoms in CATIE (p = 0.00048). Genes within 50 Kbp from variants contributing to negative symptoms and suicide were enriched with GO terms involved in acetylcholine neurotransmission, cognition showed enrichment with GO terms involved in vitamin B6 and fucose metabolism while early onset with GO terms related to extracellular matrix structure. PRS showed nominal associations with violent behaviors and depressive symptoms. This study provided preliminary evidence that a schizophrenia-associated variant (rs75059851) may modulate negative symptoms. Multi-locus models may provide interesting insights about the biological mechanisms that mediate psychopathological dimensions
22q11.2 rearrangements: clinical and research implications of population-based risk of neuropsychiatric and developmental disorders
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Antidepressant emergent mood switch in major depressive disorder: onset, clinical correlates and impact on suicidality
No full textAntidepressant (AD)- emergent mood switch (AEMS) is a common complication of bipolar depression. This study aimed to investigate the prevalence and clinical correlates of subthreshold AEMS (i.e. not fulfilling DSM criteria for hypomanic episodes) in major depressive disorder (MDD) and, prognostically, its impact on AD treatment outcome and suicidality. The study involved 425 outpatients with MDD followed during the acute phase (12 weeks) and continuation (weeks 13-28) AD treatment. AEMS was assessed through the Altman Self-Rating Mania scale (ASRM ≥ 6). Several clinical features differentiated individuals with or without subthreshold AEMS (n = 204 vs. 221): negative self-perception [odds ratio (OR) 1.017-1.565]; panic disorder (OR 1.000-1.091); subthreshold hypomanic episodes (OR 1.466-13.352); childhood emotional abuse (OR 1.053-2.447); lifetime suicidal behaviour (OR 1.027-1.236); AD-related remission (χ2 = 22.903 P < 0.0001) and suicide ideation (χ2 = 16.701 P < 0.0001). In AEMS earlier onset showed a strong correlation with bipolar spectrum disorder (overall score: P = 0.0053; mixed depression: P = 0.0154; subthreshold hypomania: P = 0.0150) whereas late-onset was associated with more severe suicidal behaviour (P < 0.001). In conclusion, our results demonstrate that subthreshold mood switches occur frequently in unipolar depression during acute AD treatment as well as in continuation phase. Time of switch onset seems to have the greatest diagnostic and prognostic value
Is long-acting injectable aripiprazole useful for the treatment of acute exacerbation of schizophrenia?
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Persistence of suicidal ideation within acute phase treatment of major depressive disorder: analysis of clinical predictors
No full textSuicidal ideation (SI) is common in major depressive disorder (MDD), and it is a risk factor for suicidal behaviour. Antidepressants are effective in reducing SI, but in some subjects, SI may persist for weeks. This study aimed to disentangle the contribution of baseline clinical characteristics in SI nonremission at week 6. Research involved 198 outpatients with MDD and SI collected within the Combining Medications to Enhance Depression Outcomes trial and treated with different antidepressant combinations. Although SI decreased from baseline to week 6 (P < 0.0001), 78 patients (39%) failed to achieve SI remission. Insomnia [OR, 0.72; 95% confidence interval (CI), 0.52-0.99], reduced need for sleep (OR, 0.75; 95% CI, 0.58-0.99), self-confidence (OR, 0.52; 95% CI, 0.32-0.82), cheerfulness (OR, 0.57; 95% CI, 0.33-0.98), and comorbid panic disorder (OR, 0.93; 95% CI, 0.87-0.99) at baseline were associated with lack of SI remission after controlling for baseline depression and SI scores. The combination of baseline SI and insomnia was moderately effective in predicting the lack of SI remission, with a specificity of 80% (95% CI, 72-87%) and an NPV of 68% (95% CI, 63-72%). In individuals with MDD and SI, the presence of insomnia and bipolar features should prompt a search for more effective treatment solutions in order to favour SI remission and prevent suicidal behaviour
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