Search

ABSTRACTIntroductionNon-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses.Areas CoveredThis narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation.Expert opinionThe available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

ABSTRACTIntroductionMajor depressive disorder remains a major challenge due to its biopsychosocial burden with increased morbidity and mortality. Despite successful treatment options for the acute episode, recurrence rates are high, on average four times in a life span.Areas coveredBoth pharmacological as non-pharmacological evidence-based therapeutic options to prevent and treat recurrent depression are discussed.Expert opinionAlthough some risk factors for recurrence are well known, better evidence is needed. Antidepressant medication should be continued after acute treatment at its full therapeutic dose for longer periods, at least 1 year. There are no clear differences between classes of antidepressant medication when treatment is focused on preventing relapse. Bupropion is the only antidepressant with a proven efficacy to prevent recurrence in seasonal affective disorder. Recent findings conclude maintenance subanesthetic ketamine and esketamine treatment can be effective in sustaining antidepressant effect following remission. Furthermore, the pharmacological approach must be integrated with lifestyle interventions, especially aerobic exercise. Finally, combining pharma- and psychotherapy seems to improve outcome. Network and complexity sciences will help to decrease the high recurrence rates of MDD by developing more integrative and personalized approaches.

Ruptured anterior communicating artery aneurysms are commonly associated with deficits in memory and executive functions. However, little studies are available on the effect of surgical clipping (SC) and endovascular coiling (EC) on cognitive functioning. This study evaluates cognitive functioning in 35 patients with subarachnoid hemorrhage after ruptured anterior communicating artery aneurysm (ACoA) compared to 20 healthy controls (HC) and assesses the effect of SC (n= 19) compared to EC (n= 16) on cognitive performances. All participants were investigated with an extensive neuropsychological test battery assessing attention, memory and visuospatial and executive functions. The strength of this study is an in-depth investigation of several cognitive domains together and several memory functions together within the auditory–verbal and visuospatial memory domain for unrelated and related information. The ACoA group was significantly more deficient in attention, auditory–verbal and visuospatial memory and executive functions compared to HCs. No significant differences were found between both groups concerning visuospatial functions. Within the patient group, the SC group, as compared to the EC group, showed a significantly worse performance for auditory–verbal and visuospatial memory. No significant differences could be detected between both groups with regard to attention and visuospatial and executive functions. In conclusion, this study provides evidence for the advantage of EC in ACoA patients over SC in terms of cognitive outcome.

•Are cognitive deficits more pronounced in older adults with psychotic depression, compared to older adults with nonpsychotic depression?•Older patients with psychotic depression show more cognitive deficits on all cognitive domains, except for verbal fluency, compared to patients with nonpsychotic depression.•Researchers should be aware of the adverse influences not only of depression severity and advancing age but also of psychotic features in older patients.

ABSTRACTIntroduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.

ABSTRACTIntroduction: Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient nonadherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently US Food and Drug Administration-approved treatment option for maintenance therapy that could be of great value.Areas covered: This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder.Expert opinion: AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder. However, further research is still needed to determine the position of AOM LAI relative to other available treatment options.

ABSTRACTIntroduction: A seasonal affective disorder (SAD) is a subtype of unipolar and bipolar major depressive disorders. It is characterized by its annual recurrence of depressive episodes at a particular season, mostly seen in winter and is responsible for 10–20% of the prevalence of major depressive disorders. Some pathophysiological hypotheses, such as the phase delay and the monoamine depletion hypotheses, have been postulated but the exact cause has not been fully unraveled yet. Studies on treatment for SAD in the last decade are lacking. To tackle this chronic disease, attention needs to be drawn to the gaps in this research field.Areas covered: In this systematic review, the authors give a broad overview of the pharmacological therapy available for SAD. Also, nutritional substances fitting well with the postulated hypotheses are reviewed for the treatment and prevention of SAD. There is a specific focus on the quality of the currently performed studies.Expert opinion: Light therapy and fluoxetine are the only proven and effective acute treatment options for SAD, while bupropion is the only registered drug for prevention of SAD. This area of research is in dire need of valid large-scale and sufficiently reproducible randomized control trials.

ABSTRACTIntroduction: Bipolar I disorder (BD I) is complex with a chronic course that significantly impacts a sufferer’s quality of life. As of right now, there are many available treatments that aim to rapidly treat manic or depressive episodes and stabilize mood. The purpose of this report is to provide an up-to-date comprehensive review of the available evidence-based trials of pharmacotherapy for the treatment of BD I.Areas covered: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of current pharmacotherapy in adults with BD I from phase III to clinical practice. Monotherapy and combination therapy for acute and long-term treatment were reviewed for this purpose.Expert opinion: There are many treatments available for BD mania; however, the depressive and stabilization phases of the illness remain a clinical challenge. Unfortunately, randomized controlled trials do not represent ‘real world’ patients, as their strict inclusion and exclusion criteria do not allow for different features sometimes present in patients to be considered. Research efforts must also focus on treating cognitive deficits, which adds to lower functional outcome. The authors believe that there is dire need for new, more targeted treatments in BD I, with a critical view of the side effects.

In this study, we evaluated persistent cognitive deficits in whiplash injury (WI) patients and compared these to cognitive functioning in mild traumatic brain injury (MTBI) patients and healthy controls (HC). Sixty-one patients suffering from a WI were compared with 57 patients suffering from a MTBI and with 30 HC. They were examined with an extensive neuropsychological test battery assessing attention, memory, and visuospatial and executive functions. In both patient groups, participants showed persistent cognitive symptoms (more than 6 months post-injury). The two patient groups did not differ significantly with regard to measurements of attention, memory, and visuospatial and executive functions. The WI group, as compared to the HC group, was found to be significantly more deficient in speed of performance during sustained and divided attention, focused attention, alternating attention, the storage of new auditory-verbal unrelated information into memory, the long-term delayed recall of stored auditory-verbal related information from memory, abstract reasoning and accuracy of performance during planning and problem solving. No differences could be found between both groups concerning speed of information processing, visuospatial abilities and verbal fluency.

Supplemental Digital Content is Available in the Text.

The pharmacological treatment of bipolar depression has low response rates. Twenty percent to 30% of patients have an insufficient response to medication. The guidelines suggest that electroconvulsive therapy (ECT) is the next step. The aim of this case study is to evaluate the effect of ECT on the perfusion of the brain in bipolar depression, while monitoring effects on mood and cognition. We present a case study of 56-year-old female patient who suffered from a psychotic depression and cognitive impairment. Before ECT, she took several antidepressants and atypical antipsychotics, but there was no improvement in her symptoms. By using single-photon emission computed tomography, we obtained the status of the regional cerebral blood flow and found a decreased perfusion in the anterior part of the left temporal lobe, the posterior part of the right temporal lobe, and in the left gyrus frontalis inferior. This is consistent with previous findings. Electroconvulsive therapy resulted in a resolution of the patient's depression and an improvement in her neurocognitive performance. Markedly, this was only in visual learning and working memory, domains in which the patient was already relatively stronger pre-ECT treatment. A new single-photon emission computed tomography, 4 weeks after the last ECT course, showed normalization of the regional cerebral blood flow.

Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain.

Quetiapine, an atypical antipsychotic drug, is recommended for the treatment of schizophrenia and mood disorders. In addition, given its sedative effects, a low dose of the agent is also widely used in the treatment of anxiety disorders, personality disorders, substance abuse, and sleep disturbances. In this case study, quetiapine was the first effective drug in reducing chronic insomnia in a male patient with a long treatment history. Because its effect declined over time, in the course of two years, a gradual dose increase led to a posology 50 times higher than the off-label dosage used to obtain sedation, i.e. 25–100 mg quetiapine administered once daily. This case raises awareness of the ease with which dose escalation of quetiapine occurs. The risk of side effects and, possibly, dependence and abuse underlines the importance of regular and careful patient monitoring. Given the unexpected effectiveness of the agent and the absence of side effects in the described case, we argue that in treatment-resistant insomnia, a high dose of quetiapine may be justifiable in selected cases but also urge that further research on the long-term effects and potential adverse events of quetiapine for this indication is of the utmost importance.

Introduction:Seasonal affective disorder (SAD) is a psychiatric illness with recurring depressive episodes during particular seasons, mostly winter. Bupropionis effective in the preventive treatment of SAD and is probably also effective in the acute treatment of SAD.Areas covered:This review covers the pharmacokinetics and pharmacodynamics of bupropion. The authors also evaluate bupropion's clinical efficacy as well as its safety and tolerability.Expert opinion:Bupropion is available in an immediate release formulation, as well as a sustained release formulation and an extended release (XR) formulation. The XR formulation is recommended for SAD due to its ease of use and is the only formulation currently used as a therapy. Due to the predictable nature of SAD, the use of bupropion XR is considered a relevant treatment option. Bupropion's efficacy is shown in three trials that started in autumn at a time when SAD symptoms were not yet present although treatment effects were relatively small compared with a placebo. Bupropion was also shown to have efficacy in an open-label study. That being said, in order to reach definitive conclusions about its efficacy with acute treatment of SAD, more placebo-controlled trials are needed.

Over the last years, genome‐wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the “common disease, rare variant” hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome‐wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5containing duplication. A second index patient presented with an NRXN1containing deletion and two adjacent duplications containing MYT1Land SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non‐symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc.

The aim of this review is to provide information for interpreting outcome results from monitoring of antipsychotics in biological samples. A brief overview of the working mechanisms, pharmacological effects, drug interactions, and analytical methods of classical and atypical antipsychotics is given. Nineteen antipsychotics were selected based on their importance in the worldwide market as follows: amisulpride, aripiprazole, asenapine, bromperidol, clozapine, flupenthixol, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, perphenazine, pimozide, pipamperone, quetiapine, risperidone, sertindole, sulpiride, and zuclopenthixol. A straightforward relationship between administered dose, plasma or serum concentration, clinical outcome, or adverse effects is often lacking. Nowadays, focus lies on therapeutic drug monitoring and individualized therapy to find adequate treatment, to explain treatment failure or nonresponse, and to check patient compliance. However, extensive research in this field is still mandatory.

From a number of genome‐wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom‐tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (1–2%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders. © 2012 Wiley Periodicals, Inc.

Introduction:Bipolar disorder is a psychiatric illness with recurring episodes of mania and depression. Armodafinil, the R-enantiomer of modafinil, approved for treating excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder, is possibly effective as an adjunctive treatment for bipolar depression.Areas covered:This review covers the pharmacokinetics of armodafinil, with an emphasis on its use in bipolar depression. Its clinical efficacy in the treatment of bipolar depression is evaluated, along with current data regarding its safety and tolerability.Expert opinion:One placebo-controlled trial is available, in which armodafinil was efficacious as an adjunctive treatment in bipolar depression. Armodafinil shows a linear pharmacokinetic profile over a broad dose range of 50 – 400 mg (maximal plasma concentration and area under concentration–time curve). Compared with modafinil, an equivalent dose of armodafinil attains higher blood concentrations 4 – 6 h post-dose. The possibility of drug interactions is generally low, although interactions have been shown with some drugs used in bipolar disorder, through mild CYP3A4-induction and CYP2C19-inhibition. Armodafinil is well tolerated and presents a possible new treatment option for bipolar depression. However, further investigation is still needed in order to confirm its efficacy and to clarify its role in the treatment of bipolar depression.

The GWAS‐based association of CACNA1Cwith bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1Cbelongs to the family of CACNgenes encoding voltage‐dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACNgenes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACNgenes in a patient‐control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7 kb in CACNA2D4in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17–26 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular. © 2012 Wiley Periodicals, Inc.

Chronic fatigue syndrome (CFS) is characterized by severe and prolonged fatigue, along with a set of nonspecific symptoms and signs, such as sore throat, muscle pain, headaches, and difficulties with concentration or memory.

Major depressive disorder (MDD) is characterized by disturbances of mood and affect, but also by a distinct pattern of psychomotor and cognitive deficits such as motor retardation and impaired executive functioning. An important aspect of executive functioning is performance monitoring, i.e., a continuous checking whether intended action goals have been reached and whether correction of the applied strategy is necessary. A well-known marker for action monitoring is the error negativity (Ne) or error-related negativity (ERN), an event-related potential (ERP) component generated in the anterior cingulate cortex (ACC) following erroneous responses. To date, Ne/ERN amplitudes have been investigated in moderately depressed patients only. The present study is the first to investigate action monitoring in severely depressed patients (mean Hamilton score=28.4). In addition, the patients' psychomotor performance was assessed to see whether there is a relationship between action monitoring and psychomotor retardation.

Background: Autopsy and neuroimaging research in stably abstinent alcoholics illuminated structural and functional abnormalities in brain areas that organize and coordinate motor functioning. Researchers that used behavioural tasks to measure motor functioning found that abstinent alcoholics perform worse than healthy controls. These researchers however did not analyze timed responses into their cognitive and motor components. They thus were unable to decide which aspects of information processing are impaired. We here used a Fitts’ task to examine differences in cognitive and motor components between abstinent alcoholics and healthy controls.

Impaired psychomotor function has been shown to be associated with clinical and functional outcome in schizophrenia. However, few studies have investigated the short-term effects of antipsychotics on the cognitive and psychomotor functions of this patient group. Because many confounding factors tend to influence the test results in patient research, this study investigates the drugs' effects in healthy volunteers.

Background: Impairments in decision making are a consistent finding in substance use disorder (SUD) populations. However, decision‐making deficits are not specific for SUDs and are also reported in the context of other psychiatric disorders such as antisocial and borderline personality disorders (PDs). Given the frequent comorbidity between SUD and cluster B PD, it might be questioned whether the decision‐making impairments typically reported in SUD populations reflect the addictive disorder, the cluster B PD, or a combination of the 2.

Background:In a previous study, using computerized analysis of fine motor behaviour, seriously underweight anorexia nervosa patients in the early phase of treatment were found to have shorter reaction times, but not movement times, in experimental drawing and copying tasks. These differences persisted with weight restoration. Sampling and Methods:Using computerized analysis of writing and drawing behaviour during the performance of a Digit Symbol Substitution Test, 15 anorexia nervosa patients were compared with 15 normal controls, matched for age, sex and educational level. Patients were retested after weight restoration, as were controls after a similar interval. Results:Patients turned out to be superior in the cognitive, but not in the motor aspects of the Digit Symbol Substitution Test. These differences persisted after weight restoration. A practice effect, due to repeated testing, was found in both groups, which turned out to be cognitive in nature. Conclusions:The findings show that this new technique can add to the interpretation of classic neuropsychological tests. The results are compatible with previous findings of intact or even superior functioning in anorexia nervosa patients on neuropsychological tasks requiring considerable cognitive effort.

The present review covers various intriguing aspects of psychomotor disturbances in schizophrenia and depression that are, to a large extent, poorly understood as yet. These include clinical manifestations, prevalence, diagnostic significance, assessment, underlying cognitive and motor processes, and changes that occur during treatment of the psychotic or depressive disorder.