Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data.

Cariprazine is one of the newest dopamine-serotonin partial agonists, also known as 'atypical' second generation antipsychotics. Originally approved for acute and maintenance treatment of schizophrenia as well as for acute mania and mixed mania/depression, cariprazine has now been approved for bipolar I depression. Additionally, analyses of bipolar I depressed subjects show that both those with and those without concurrent manic features were improved following treatment with cariprazine.

Pharmacologic Treatment of Mixed States.

Despite the relatively high prevalence of mixed symptoms and features among patients with mood disorders, the current literature supporting the specific efficacy of second-generation antipsychotics and mood stabilizers for the treatment of mixed symptoms is limited. Several studies have demonstrated that acute affective episodes with mixed symptoms or features tend to respond unsatisfactory to treatments that are usually more effective for the management of other affective phases. There is clearly a need for clinical trials in order to determine the more adequate pharmacologic option for the treatment of individuals suffering from affective episodes with mixed features.

Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.

Patients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions.

Drug information update. Unconventional treatment strategies for schizophrenia: polypharmacy and heroic dosing.

The majority of patients respond to antipsychotic monotherapy at standard doses, but a subset of patients will require more heroic measures that include antipsychotic polypharmacy and high-dose monotherapy. Indeed, research has shown that roughly 30% of patients with psychosis are prescribed multiple antipsychotic medications. We discuss the potential benefits and challenges of these approaches and provide a rationale for why and when they should be utilised.

Guidelines for the recognition and management of mixed depression.

A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM-5 codified a new nosological entity, the "mixed features specifier," referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.

Modulating the serotonin system in the treatment of major depressive disorder.

Discuss the theory of modulation of receptor activity or the blockade of the reuptake of multiple neurotransmitter systems for the future treatment of MDD. Major depressive disorder (MDD) is a serious and often crippling psychiatric illness with a high risk of relapse and treatment resistance. In this article, we discuss the role of the serotonergic system in MDD including our current understanding of how various serotonin (5HT) receptors modulate monoamine neurotransmission and behavior.

California State Hospital Violence Assessment and Treatment (Cal-VAT) guidelines.

Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice.

California State Hospital Violence Assessment and Treatment (Cal-VAT) guideline.

Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice.

Treating the violent patient with psychosis or impulsivity utilizing antipsychotic polypharmacy and high-dose monotherapy.

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive.

Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed.

Twisting the night away: a review of the neurobiology, genetics, diagnosis, and treatment of shift work disorder.

Although not all individuals who work outside of standard daytime hours develop physical and psychiatric issues, there is a substantial portion of shift workers who develop shift work disorder. Shift work disorder is due to a misalignment between an individual's endogenous circadian rhythms and environmental stimuli, and can have potentially serious consequences to an individual's health and quality of life. This article reviews the neurobiological and genetic underpinnings of shift work disorder, and describes how desynchronization of the molecular clock may lead to both physical and psychiatric illnesses.

“Meta-guidelines” for the management of patients with schizophrenia.

Guidelines for treating various conditions can be helpful in setting practice standards, but the presence of several sets of guidelines from different countries, experts, and settings, written at different times, can also create confusion. Here we provide a "guideline of guidelines" for the treatment of schizophrenia, or "meta-guidelines, which not only reconcile the various existing standards but also update them to include the use of several newer agents, most of which were marketed following the publication of existing standards.

Serotonergic drugs for depression and beyond.

The current generation of antidepressant drugs acts predominantly by targeting the serotonin transporter (SERT). The original trend to do this selectively (e.g.

Optimizing outcomes in schizophrenia: long-acting depots and long-term treatment.

Antipsychotics are the mainstay of treatment for patients with schizophrenia. However, these medications only work if they are taken and perhaps work best if they are taken for longer periods of time than seen in typical research trials. Here we explore the idea of "time as drug" by reviewing the data showing the potential benefits of long-term antipsychotic use.

Relevance of transgenic mouse models to human Alzheimer disease.

During the past 2 decades, the elucidation of susceptibility and causative genes for Alzheimer disease as well as proteins involved in the pathogenic process has greatly facilitated the development of genetically altered mouse models. These models have played a major role in defining critical disease-related mechanisms and in evaluating novel therapeutic approaches, with many treatments currently in clinical trial owing their origins to studies initially performed in mice. This review discusses the utility of transgenic mice as a research tool and their contributions to our understanding of Alzheimer disease.

Neural stem cells improve memory in an inducible mouse model of neuronal loss.

Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain.