Holistic Psychopharmacology of Fumaria indica(Fumitory)

Fumaria indica is a medicinal plant of the fumitory family wildly growing throughout India. Classical texts of Ayurveda, i.e. the oldest traditionally known health care and medical system originating in Indian subcontinent, mentions diverse medicinal uses of the plant. During more recent decades broad spectrums of therapeutically interesting pharmacological properties of its extracts and secondary metabolites have also been reported. Recent observations made during efforts to define its pharmacological activity profile according to the Ayurvedic concepts of mind body medicine have revealed exceptionally broad spectrums of psychopharmacological activity profiles of diverse types of hydro alcoholic extracts of the plant. These effects of the extracts become apparent after their repeated daily doses only. Taken together with prior preclinical knowledge on the plant, these observations strongly suggest that Fumaria indica could be an easily available source for discovering and developing phyto-pharmaceuticals or drugs potentially useful for treatments of mental health problems commonly associated with numerous physical disorders and chronic diseases. Since several psychoactive and other phytochemical of Fumaria indica are also encountered in other plants commonly used in Chinese and other traditionally known medical systems, observations made and the holistic strategy used for defining its psychopharmacological activity profile could be of interest of others involved in efforts necessary for proper understanding of therapeutic potentials of many plants containing Fumaria alkaloids and other bioactive phytochemicals present in Fumaria indica.

Lactate:a prospective target for therapeutic intervention in psychiatric disease

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Keep in mind sex differences when prescribing psychotropic drugs

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.

First 150 years of catatonia:Looking back at its complicated history and forward to the road ahead

Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years ago.Although Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical conditions.In his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease entity.Because of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th century.However,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early 2000s.The past two decades have witnessed a resurgence of interest in catatonia.The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical conditions.The introduction of an independent diagnostic category termed“Catatonia Not Otherwise Specified”significantly stimulated research in this field.The authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.

Tourette syndrome associated with attention deficit hyperactivity disorder: The impact of tics and psychopharmacological treatment options

Tourette syndrome(TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperactivity disorder(ADHD). Fifty percent of children diagnosed with ADHD have comorbid tic disorder. ADHD related symptoms have been reported in 35% to 90% of children with TS. Since ADHD is the most prevalent comorbid condition with TS and those with concomitant TS and ADHD present with considerable psychosocial and behavioral impairments, it is essential for clinicians to be familiar with these diagnoses and their management. This paper highlights the association between treating ADHD with stimulants and the development of tic disorders. The two cases discussed underscore the fact that children with TS may present with ADHD symptomatology prior to the appearance of any TS related symptoms. Appropriate management of TS in a patient diagnosed with ADHD can lead to quality of life improvements and a reduction in psychosocial impairments.

Obsessive-compulsive disorder:Evidence-based treatments and future directions for research

Over the past three decades, obsessive-compulsive disorder(OCD) has moved from an almost untreatable,life-long psychiatric disorder to a highly manageable one. This is a very welcome change to the 1%-3% of children and adults with this disorder as, thanks to advances in both pharmacological and psychological therapies, prognosis for those afflicted with OCD is quite good in the long term, even though most have comorbid disorders that are also problematic. We still have far to go, however, until OCD can be described as either easily treatable or the effective treatments are widely known about among clinicians. This review focuses on the current state of the art in treatment for OCD and where we still are coming up short in our work as a scientific community. For example, while the impact of medications is quite strong for adults in reducing OCD symptoms, current drugs are only somewhat effective for children. In addition, there are unacceptably high relapse rates across both populations when treated with pharmacological alone. Even in the cognitive-behavioral treatments, which show higher effect sizes and lower relapse rates than drug therapies, drop-out rates are at a quarter of those who begin treatment. This means a sizable portion of the OCD population who do obtain effective treatments(which appears to be only a portion of the overall population) are not effectively treated.Suggestions for future avenues of research are also presented. These are primarily focused on(1) increased dissemination of effective therapies;(2) augmentation of treatments for those with residual symptoms, both for psychotherapy and pharmacotherapy; and(3) the impact of comorbid disorders on treatment outcome.

Phantom bite syndrome:Revelation from clinically focused review

Phantom bite syndrome(PBS),also called occlusal dysesthesia,is characterized by persistent non-verifiable occlusal discrepancies.Such erroneous and unshakable belief of a“wrong bite”might impel patients to visit multiple dental clinics to meet their requirements to their satisfaction.Subsequently,it takes a toll on their quality of life causing,career disruption,financial loss and suicidal thoughts.In general,patients with PBS are quite rare but distinguishable if ever encountered.Since Marbach reported the first two cases in 1976,there have been dozens of published cases regarding this phenomenon,but only a few original studies were conducted.Despite the lack of official classification and guidelines,many authors agreed on the existence of a PBS“consistent pattern”that clinicians should be made aware.Nevertheless,the treatment approach has been solely based on incomplete knowledge of etiology,in which none of the proposed theories are fully explained in all the available cases.In this review,we have discussed the critical role of enhancing dental professionals’awareness of this phenomenon and suggested a comprehensive approach for PBS,provided by a multidisciplinary team of dentists,psychiatrists and exclusive psychotherapists.

Newer antipsychotics: Brexpiprazole, cariprazine, and lumateperone: A pledge or another unkept promise?

Antipsychotic agents are used for various indications in the treatment of psychiatric disorders.Despite their proven roles in multiple conditions,the treatment-emergent side effects of antipsychotic medications,such as metabolic side effects,are often the limiting factor for their long-term and short-term uses.Moreover,antipsychotic medications are often criticized for being less effective in treating different disabling symptoms such as negative symptoms of schizophrenia.As a result,the search for safer and more efficacious antipsychotic agents is ongoing.Newer antipsychotic agents are gaining attention related to emerging efficacy and tolerability data in treating neuropsychiatric conditions.In this review,we attempt to appraise the scientific data on psychopharmacology,safety profile,and efficacy of the newer additions to the list of second-generation antipsychotics,namely brexpiprazole,cariprazine,and lumateperone.We conducted a selective review utilizing PubMed,clinicaltrials.gov,and Cochrane databases to gather appropriate publications,keeping broad inclusion criteria.There were no restrictions on the age of the study population or the year of publication.We also cross-referenced articles and references to capture all existing studies.Our review of the current literature indicates that all three antipsychotic agents appear to be promising based on their short-term studies,while long-term studies remain limited.There is also a need for a head to head comparison between the newer antipsychotics with the other antipsychotic agents to ascertain if the newer agents are any better than the others.

Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry

Traditional therapeutic methods in psychiatry,such as psychopharmacology and psychotherapy help many people suffering from mental disorders,but in the long-term prove to be effective in a relatively small proportion of those affected.Therapeutically,resistant forms of mental disorders such as schizophrenia,major depressive disorder,and bipolar disorder lead to persistent distress and dysfunction in personal,social,and professional aspects.In an effort to address these problems,the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results.For instance,neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity,integration,and segregation of neural networks,focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy(ECT),transcranial magnetic stimulation(TMS),transcranial direct current stimulation(tDCS)and deep brain stimulation(DBS).These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders.The current review is focused on the translational approach in the management of schizophrenia and mood disorders,as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT,TMS,tDCS and DBS.

Role of serendipity in the discovery of classical antidepressant drugs:Applying operational criteria and patterns of discovery

The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combination of accidents and sagacity.We have implemented an operational definition of serendipity based on finding something unexpected or unintended,regardless of the systematic process that led to the accidental observation,and we have established four different patterns of serendipitous attributability.In this paper,we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs,tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic,“atypical”or“second generation”antidepressants.The discovery of the antidepressant properties of imipramine and iproniazid,the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors,respectively,fits the mixed type II pattern;initial serendipitous discoveries(imipramine was an antipsychotic and iproniazid was an antituberculosis agent)led secondarily to non-serendipitous discoveries.But the other components of these two families of drugs were developed specifically as antidepressants,modifying the chemical structure of the series leaders,thereby allowing all of them to be included in the type IV pattern,characterized by the complete absence of serendipity.Among the heterocyclic drugs,mianserin(originally developed as an antihistamine)also falls into the type II pattern.

Subgrouping time-dependent prescribing patterns of first-onset major depressive episodes by psychotropics dissection

BACKGROUND Subgrouping patients with major depressive disorder is a promising solution for the issue of heterogeneity.However,the link between available subtypes and distinct pathological mechanisms is weak and yields disappointing results in clinical application.AIM To develop a novel approach for classification of patients with time-dependent prescription patterns at first onset in real-world settings.METHODS Drug-naive patients experiencing their first major depressive episode(n=105)participated in this study.Psychotropic agents prescribed in the first 24 mo following disease onset were recorded monthly and categorized as antidepressants,augmentation agents,and hypnosedatives.Monthly cumulative doses of agents in each category were converted into relevant equivalents.Four parameters were used to summarize the time-dependent prescription patterns for each psychotropic load:Stability,amount,frequency,and the time trend of monthly prescriptions.A K-means cluster analysis was used to derive subgroups of participants based on these input parameters of psychotropic agents across 24 mo.Clinical validity of the resulting data-driven clusters was compared using relevant severity indicators.RESULTS Four distinct clusters were derived from K-means analysis,which matches experts’consent:"Short-term antidepressants use","long-term antidepressants use","long-term antidepressants and sedatives use",and"long-term antidepressants,sedatives,and augmentation use".At the first 2 years of disease course,the four clusters differed on the number of antidepressants used at adequate dosage and duration,frequency of outpatient service use,and number of psychiatric admissions.After the first 2 years following disease onset,depression severity was differed in the four subgroups.CONCLUSION Our findings suggested a new approach to optimize the subgrouping of patients with major depressive disorder,which may assist future etiological and treatment response studies.

An open-label trial of divalproex sodium extended release for pediatric bipolar spectrum disorder in children age 6 - 12 years

Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.

Telepsychiatry:The Evaluation and Treatment of Seniors in Rural Retirement Communities

Few studies examine the benefits from geriatric telepsychiatry in rural retirement communities.Objectives:1.To demonstrate that using telepsychiatry(a)standard approaches to psychiatric evaluation would yield diagnoses in Diagnostic and Statistical Manual of Mental Disorders(DSM-V);(b)psychotherapies and pharmacotherapy could be effectively administered.2.To examine the relationships among cognition,mood,agitation and functions at baseline and the response to treatment over time.Design:Prospective longitudinal study.Measures:Geriatric Depression scale(GDS),Mini Mental State Exam(MMSE),Barthel Index(BI),Pittsburgh Agitation Scale(PAS).Setting:Video Teleconferencing.Interventions:Psychotherapy,psychopharmacology.Participants:428 Seniors over 55,met criteria for at least one DSM-V diagnosis.Results:Treatments were administered for a full range of psychiatric diagnoses and age-related medical conditions.The most frequently prescribed pharmacological agents were:antidepressants(78%)antipsychotics(64%),memory enhancers(38%).Participants(66%)received psychotherapy:individual(31%),couple(7%),family(13%).Variation in the MMSE scores were observed:55%remained stable,11%declined,18%improved.GDS Scores improved from baseline to 26 weeks(p=0.02,d=0.99:95%CI 0.39-1.56).PAS scores declined from baseline to 52 weeks(McNemar’s S=11.27,p=0.0008,d=1.17:95%CI 0.63-1.68).Function(BI)at week 26 was not statistically significantly different from baseline(t(26)=1.66,p=0.11,d=0.65:95%CI-0.16-1.42).Participants maintained independence(64.5%)at 52 weeks(McNemar’s S=6.23,p=0.013,d=0.79:95%CI 0.19-1.36)Conclusion:This study demonstrates the feasibility and benefit of providing a full complement of services via telepsychiatry to seniors and provides a rationale for more comprehensive reimbursement plans.