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Major depressive disorder (MDD) is among the most prevalent psychiatric conditions and a leading cause of disability worldwide. MDD presents a diverse range of symptoms that significantly impact personal, societal, and economic dimensions. Despite the availability of numerous antidepressant treatments (ADTs) targeting different molecular mechanisms, a substantial proportion of patients experience inadequate response, presenting a considerable challenge in MDD management. As a result, adjunctive strategies, particularly involving atypical antipsychotics, are often employed to enhance treatment efficacy. Cariprazine, a D2/D3 partial agonist, is distinguished from other atypical antipsychotics by its selective action on the D3 receptor and its modulation of 5-HT1A, 5-HT2A, and alpha 1B receptors. This distinctive pharmacological profile warrants investigation into its potential effectiveness and tolerability across various symptom domains of MDD, including pleasure, interest, and motivation; mood and suicidality; sleep and appetite; fatigue; psychomotor activity and anxiety; and cognitive function. Preliminary evidence from animal studies and clinical trials suggests that cariprazine may improve motivation, anhedonia, and cognitive function symptoms. Cariprazine shows promise in alleviating mood-related symptoms, though its impact on anxiety and its effects on agitation and psychomotor retardation remains uncertain. Cariprazine may be particularly beneficial for patients with MDD exhibiting anhedonia, cognitive deficits, and possibly fatigue and hypersomnia. Evaluating cariprazine’s efficacy across these symptom domains could reveal patterns that support more personalized treatment approaches for depression. Further research is essential to elucidate the role of cariprazine as an adjunctive therapy for adults with major depressive disorder who have an inadequate response to antidepressant monotherapy.

The introduction of a new psychopharmaceutical medication instead of the previous one always poses a certain challenge. In the case of antipsychotics (AP), these problems are considerably more complicated and are mainly caused by the question of dose equivalents, but also by the pharmacokinetic properties of the drug. In the case of partial dopamine D2 agonists, an additional issue is the possibility of deterioration when switching from the previous D2 antagonists to these drugs. Cross-titration is therefore generally recommended. Finally, due to the capsule form, it is not possible to increase the dose of cariprazine by less than 1.5 mg during titration. In this paper, we have presented our proposal to replace the most commonly used second-generation APs with the third-generation AP cariprazine. We have taken into account the dose equivalents, the pharmacological forms of the drugs and their pharmacokinetic and pharmacodynamic properties.

Background: Antidepressant use is on the rise, while the problem of depression on a population wide level is not being tackled. One of the hypothesis why this may be happening is the effect of adverse effects and withdrawal symptoms of antidepressants, as well as pathologization of normal sadness. Methods: In this study we did partial watchful waiting using (1) psychosocial advice; (2) depathologization; and (3) shared decision making. The study comprised of 83 consecutive non-suicidal out-patients with depressive symptoms. Results: The first among the three main findings of our study was that watchful waiting, when coupled with psychosocial advice, depathologization and shared decision making, was effective in 64.5 % of patients who ended up with no pharmaco- or psychotherapy after the three-month follow-up period. Severity of depression did not correlate with the efficacy of watchful waiting. Expectations from pharmacotherapy were the dominant factor influencing whether a patient will enter or finish the study without pharmacotherapy. Limitations: This was not a randomized control trial and the goal was to see if this approach is feasible. A randomized controlled trial comparing watchful waiting approach with pharmacotherapy could not factor in all parameters involved (i.e. self-fulfilling prophecy through pathologization, withdrawal and risk of chronicity). Conclusions: Our study showed that watchful waiting might be effective, particularly when coupled with depathologization, psychosocial advice and shared decision making, suggesting that this approach should be tested as the first-line of treatment in non-suicidal patients with depressive symptoms.

Abstract The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Autism spectrum disorders (ASD) are a group of disorders characterized by impairment in social communication and repetitive and stereotyped behaviors. ASD etiology is very complex, including the effect of both genetic and environmental factors. So far, no specific treatment for the core symptoms of ASD has been developed, although attempts have been made for the treatment of repetitive behavior. The pharmacological treatment is aimed at treating non-specific symptoms such as irritability and aggression. Recent studies pointed out to the possible role of altered dopamine signaling in mesocorticolimbic and nigrostriatal circuits in ASD. In addition, several research pointed out to the association of dopamine receptors polymorphism and ASD, specifically repetitive and stereotyped behavior. In this paper, we will provide a review of the studies regarding dopamine signaling in ASD, existing data on the effects of D2/D3 partial agonists in ASD, possible implications regarding their individual receptor profiles, and future perspectives of their possible use in ASD treatment.

Major depressive disorder (MDD) is among the most prevalent psychiatric conditions and a leading cause of disability worldwide. MDD presents a diverse range of symptoms that significantly impact personal, societal, and economic dimensions. Despite the availability of numerous antidepressant treatments (ADTs) targeting different molecular mechanisms, a substantial proportion of patients experience inadequate response, presenting a considerable challenge in MDD management. As a result, adjunctive strategies, particularly involving atypical antipsychotics, are often employed to enhance treatment efficacy. Cariprazine, a D2/D3 partial agonist, is distinguished from other atypical antipsychotics by its selective action on the D3 receptor and its modulation of 5-HT1A, 5-HT2A, and alpha 1B receptors. This distinctive pharmacological profile warrants investigation into its potential effectiveness and tolerability across various symptom domains of MDD, including pleasure, interest, and motivation; mood and suicidality; sleep and appetite; fatigue; psychomotor activity and anxiety; and cognitive function. Preliminary evidence from animal studies and clinical trials suggests that cariprazine may improve motivation, anhedonia, and cognitive function symptoms. Cariprazine shows promise in alleviating mood-related symptoms, though its impact on anxiety and its effects on agitation and psychomotor retardation remains uncertain. Cariprazine may be particularly beneficial for patients with MDD exhibiting anhedonia, cognitive deficits, and possibly fatigue and hypersomnia. Evaluating cariprazine’s efficacy across these symptom domains could reveal patterns that support more personalized treatment approaches for depression. Further research is essential to elucidate the role of cariprazine as an adjunctive therapy for adults with major depressive disorder who have an inadequate response to antidepressant monotherapy. [ABSTRACT FROM AUTHOR]