Case report: Dopamine Dysregulation Syndrome, mania, and compulsive buying in a patient with Parkinson's disease.

Neuropsychiatric symptoms and syndromes are among the most common non-motor symptoms of Parkinson's Disease but they are frequently unrecognized and untreated. Dopamine Dysregulation Syndrome is an uncommon complication of the treatment of Parkinson's disease, characterized by an addictive use of dopamine far more than the dosage required for treatment of objective motor impairment, leading to severe dyskinesia, euphoria, aggressivity, or psychosis. We present a paradigmatic case of Dopamine Dysregulation Syndrome, Mania, and Compulsive Buying in a 55-year-old male with Parkinson's Disease. We also reviewed the risk factors and the therapeutic management of Dopamine Dysregulation Syndrome in Parkinson's Disease.

Managing antipsychotic-related sexual dysfunction in patients with schizophrenia.

INTRODUCTION: Schizophrenia is a psychotic disorder and one of the most severe and impactful mental illnesses. Sexual dysfunction is highly prevalent in patients with schizophrenia but remains underdiagnosed and undertreated. Sexual dysfunction is frequently attributed to antipsychotics which may reduce medication adherence, but negative symptoms can also reduce sexual drive. AREAS COVERED: This review provides an overview of the current knowledge about sexual dysfunction in patients with schizophrenia. The authors first review the literature concerning the mechanisms of sexual dysfunction and explore the impact of antipsychotics on sexual function. Finally, they present the available non-pharmacological and pharmacological treatment strategies for sexual dysfunction in patients with schizophrenia. EXPERT OPINION: Sexual dysfunction in patients with schizophrenia is still underrated by clinicians despite having a negative impact on the quality of life and therapeutic adherence. Antipsychotic treatment is still perceived as a major cause of sexual impairment. Psychiatrists must be aware of this condition and actively question the patients. A comprehensive approach, addressing pharmacological and non-pharmacological aspects, is fundamental for managing sexual dysfunction in schizophrenia. Pharmacological strategies include (1) Serum-level adjustment of the antipsychotic dose, if possible (2) switching to a well-tolerable antipsychotic (aripiprazole, brexpiprazole) and (3) adding a coadjuvant drug (phosphodiesterase-5 inhibitors).

High frequency of Depressive Disorders and Suicidal Phenomena in Late-Stage Parkinson´s Disease - A Cross-Sectional Study.

BACKGROUND: Depressive disorders (DD) are widely recognized as one of the most frequent neuropsychiatric disorders in Parkinson´s disease. Patients with late-stage Parkinson´s disease (LSPD) continue to be a neglected population, and little is known about DD frequency in LSPD. OBJECTIVES: To determine the frequency of DD in LSPD patients through a clinical diagnostic interview (CDI) and according to diagnostic DSM- 5 criteria. Secondary objectives were to determine the predictive ability of depressive scales to detect DD, to identify potential predictors of DD in LSPD and, to evaluate suicidal phenomena in LSPD. METHODS: A cross-sectional study including LSPD patients (≥7 years from symptom onset and Hoehn and Yahr scale score >3 or a Schwab and England scale score <50% in the ON condition) was conducted. Patients were subjected to psychiatric, neurological, and neuropsychological evaluations. Six depression scales were applied. RESULTS: 92 LSPD patients were included. 59.78% of LSPD patients had a current diagnosis of DD according to CDI, 38.04% patients had a diagnosis of major depressive disorder, and 21.72% non-major depressive disorder. Suicidal ideation was present in 36.96% of patients. All applied scales were able to detect depressive disorders. CONCLUSIONS: More than half of LSPD patients met DD diagnostic criteria and over one-third were diagnosed with major depressive disorder. Overall, the LSPD population seem to have a unique clinical phenotype regarding the frequency and features of DD, whose early identification and treatment could improve the quality of life of patients and caregivers.

Frequency of Depressive Disorders in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Depressive disorders are recognized as a common neuropsychiatric disorder of Parkinson's disease (PD). Reported frequencies vary widely among studies and depend on the diagnostic criteria, the methods of ascertainment used, and the population sampled. OBJECTIVE: We aimed to evaluate the frequency of depressive disorders in PD and to investigate the relationship with PD clinical variables. METHODS: A systematic review and meta-analysis of observational studies (community-based, prospective and retrospective cohort, case-control, and cross-sectional studies) reporting the frequency of depressive disorders in PD patients. RESULTS: Electronic database search wielded 3,536 articles; an additional 91 were identified through citation chaining. 163 full-text articles were assessed for eligibility. Of these, 49 met the inclusion criteria for our analysis. The pooled frequency of depressive disorders was 30.7% (95% confidence interval [CI] 25.6 to 36.2; I2 = 95%; 49 studies; combined n = 10,039). The pooled frequency of major depressive disorder was 14.0% (95% CI 10.5 to 18.5; I2 = 88%; 23 studies; combined n = 5,218). Subgroup/meta-regression analyses were conducted to investigate the relationship between frequency and study inclusion criteria, methodology used for diagnosis, and study design. We found a statistically significant correlation between study design and depressive disorders frequency (ranging from 8% in the community-based study to 44% in the retrospective studies) and a statistically significant positive correlation between mean baseline PD duration and major depressive disorder frequency. CONCLUSION: The current meta-analysis found a global frequency of depressive disorders of 30.7% and major depressive disorder of 14.0%. Study design influenced the frequency of depressive disorders in PD. Mean baseline PD duration and major depressive disorder frequency were positively correlated.

Profile of cognitive impairment in late-stage Parkinson's disease.

INTRODUCTION: The profile of cognitive impairment associated with the late stages of Parkinson's disease (LSPD) is rarely reported. Its characterization is necessary to better understand the cognitive changes that occur as the disease progresses and to better contribute to its management. METHODS: In this cross-sectional study, we characterized the cognitive profile of LSPD patients using the comprehensive assessment methodology proposed by the International Parkinson and Movement Disorders Society Task Force. The association of clinical and demographic variables with dementia diagnosis was also investigated using binary logistic regression analysis. RESULTS: Eighty-four LSPD patients were included (age 75.4 ± 6.9; disease duration 16.9 ± 7.5). Fifty-four (64.3%) were classified as demented and presented a global impairment cognitive profile. In the nondemented group (N = 30), 25 (83.3%) LSPD patients met the diagnostic criteria for mild cognitive impairment, mostly with multiple domain impairment (96.0%) and a heterogeneous profile. Memory was the most frequent and severely impaired cognitive domain in both groups. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities were significantly associated with dementia diagnosis (p < .05). CONCLUSIONS: Cognitive impairment in multiple domains was common in LSPD patients. The most frequent and prominent deficits were in the memory domain, with a strong interference from attention impairment. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities proved to be important determinants for dementia diagnosis.

Frequency and Characteristics of Psychosis in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Psychotic symptoms are highly frequent in Parkinson's disease (PD) patients and are associated with poor prognosis. They include hallucinations, delusions, and minor psychotic phenomena, including sense of presence, passage hallucinations, and illusions. OBJECTIVE: To evaluate the frequency of psychosis in PD patients. METHODS: A systematic review and meta-analysis of clinical trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies reporting the frequency of psychosis, hallucinations, and delusions in PD. RESULTS: Electronic database search wielded 3536 articles, an additional 91 were identified through citation chaining. Of these, 163 were fully inspected, 57 removed, and 106 included as relevant for neuropsychiatric events frequency, with 32 meeting our inclusion criteria (psychosis and/or specific psychotic phenomena). The pooled frequency of psychosis was 20.7% (95% CI 14.5 to 28.6; I2 = 94%, 15 studies; combined n = 2919). None of the pre-defined meta-regressions or subgroup analyses were statistically significant or helped explain the statistical heterogeneity. The pooled frequency of any form of hallucination was 21.6% (95% CI 14.7 to 30.6; I2 = 95%; 18 studies; combined n = 3161). Duration of PD at baseline and mean baseline Hoehn & Yahr stage helped explain the statistical heterogeneity in the meta-analysis of hallucinations. CONCLUSION: Based on the available evidence, around a fifth of PD patients experience psychosis or hallucinations. The risk of developing hallucinations is likely moderated by the disease duration, Hoehn & Yahr stage, and the cognitive status.

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

OBJECTIVES: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. METHODS: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. RESULTS: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. CONCLUSION: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

Clinical Diagnostic Criteria Have a High Impact on the Frequency of Dementia in Late-Stage Parkinson's Disease.

Background: Cognitive impairment is a potential late feature of Parkinson's disease (PD). However, studies in patients with late-stage PD are lacking due to the particular characteristics of this population. Objectives: To evaluate the frequency of dementia in late-stage PD patients and to assess the impact of using different diagnostic criteria. Methods: We conducted a cross-sectional study to estimate the frequency of dementia in late-stage PD patients using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria as the primary outcome. We also applied other diagnostic criteria [MDS (Level I), DSM-IV, and DSM-5 criteria] to determine their applicability and impact on dementia frequency. Results: 93 participants with a mean age of 75.8 years (SD 6.8) and 16.5 years (SD 7.5) of disease duration were included. 64.3% were classified as demented using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria. We observed a high discrepancy on the frequency of dementia depending on the criteria applied [6.2% with MDS (Level I), 58.8% with DSM-IV, and 72.0% with DSM-5 criteria]. Conclusions: We found a frequency of dementia below what was observed in similar populations. The particular characteristics of our sample may have contributed as protective factors for late-stage dementia. Dementia frequency varied depending on the criteria used mainly due to the presence of major depression.

High frequency of psychosis in late-stage Parkinsons disease.

BACKGROUND: Psychosis is a frequent non-motor symptom in Parkinson's disease (PD). Estimates of the frequency of Parkinsons disease psychosis (PDP) vary widely. Knowledge about the frequency and phenomenology of psychosis in late-stage (LS) PD patients is limited.This study aimed to determine the frequency of psychosis in LSPD patients through clinical diagnostic interview (CDI) (gold standard), according to NINDS/NIMH diagnostic criteria for PDP. The secondary objectives were to characterize the phenomenology, to test selected instruments and assess their adequacy in comparison to CDI, and to assess the psychiatric comorbidities. METHODS: A cross-sectional study including LSPD patients (patients with ≥ 7 years from symptoms onset and Hoehn and Yahr scale score > 3 or a Schwab and England scale score < 50% in the ON condition) was conducted. Patients were subjected to psychiatric, neurological, and neuropsychological evaluations. Each patient was interviewed by a psychiatrist who performed a CDI. RESULTS: 92 LSPD patients were included. 55.4% experienced psychotic symptoms according to NINDS/NIMH diagnostic criteria for PDP. Hallucinations were present in 94.1% and delusions in 29.4% of the psychotic patients. Visual hallucinations were the most common (88.23%) psychotic symptom. 72.5% of LSPD patients with psychotic symptoms had at least one comorbid psychiatric diagnosis. Lower frequency of psychosis was found when the assessment was performed only through selected instruments rather than CDI. CONCLUSIONS: A high frequency (55.4%) of psychotic symptoms and comorbid psychiatric (72.5%) diagnosis were found in LSPD patients. The use of CDI, in addition to structured scales may increase the sensitivity of detecting psychotic symptoms.

Psychosis in Huntington´s Disease. a rare and Under-Investigated Psychiatric Manifestation / Psychosis in Huntington's Disease: uma manifestação psiquiátrica rara e pouco investigada

Introduction: Psychotic symptoms are among the least prevalent and under-investigated psychiatric manifestations (PM) of Huntington's disease (HD). Case report: We herein report a case of a 31-year-old male patient who presented PM with a predominance of negative symptoms, without any significant abnormal movement. HD was diagnosed based on positive DNA analysis and family history. HD imposes longitudinal follow-up through a multidisciplinary approach in order to improve the quality of life and prognosis. Conclusion: This case report highlights the importance of comprehending the PM in the initial presentation of HD so that the diagnosis is not delayed until the onset of motor symptoms.

Introdução: Os sintomas psicóticos estão entre as manifestações psiquiátricas (MP) menos prevalentes e pouco investigadas da doença de Huntington (DH). Relado de caso: Relatamos o caso de um paciente do sexo masculino, 31 anos, que apresentou MP com predomínio de sintomas negativos, sem qualquer movimento anormal significativo. A DH foi diagnosticada com base em uma análise de DNA positiva e na história familiar. A DH impõe um acompanhamento longitudinal por meio de uma abordagem multidisciplinar, a fim de melhorar a qualidade de vida e o prognóstico. Conclusão: Este relato de caso destaca a importância da compreensão das MPs na apresentação inicial da DH, para que o diagnóstico não seja atrasado até ao aparecimento dos sintomas motores

Risk of Developing Parkinson Disease in Bipolar Disorder: A Systematic Review and Meta-analysis.

Importance: Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD. Objective: To assess the association of BD with a later diagnosis of idiopathic PD. Data Sources: An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. Study Selection: Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. Data Extraction and Synthesis: Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2. Main Outcome and Measures: Odds ratios of PD. Results: Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect. Conclusions and Relevance: This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.

Facilitating the Delivery of Cognitive Remediation in First-Episode Psychosis: Pilot Study of a Home-Delivered Web-Based Intervention.

We explored the adherence to a home-delivered, computer-based, cognitive remediation protocol in a first-episode psychosis outpatient cohort. Seventeen patients underwent a cognitive training protocol for 6 months using an online platform accessible from their home under the supervision of a qualified neuropsychologist. Neuropsychological, psychopathological, and functional data were collected at baseline and postintervention, whereas qualitative appraisal of the intervention was assessed monthly. Overall, participants' evaluation of the program was positive. This was reflected in a good adherence rate with 12 (70%) of 17 patients completing 80% of the prescribed sessions. Exploratory analysis revealed significant improvements in sustained attention (p = 0.020) and verbal memory (p = 0.018). A decrease in negative symptoms and an improvement on the Clinical Global Impression were also found (p = 0.009). We believe these are encouraging results to further explore the adopted delivery approach, which could facilitate access to cognitive training earlier and to a larger group of patients.

Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: Results of a levodopa challenge test.

BACKGROUND: Non-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated. OBJECTIVE: To assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients. METHODS: 20 LSPD patients, defined as Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge. RESULTS: Systolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients. CONCLUSIONS: This exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients.

Pimavanserin for the treatment of Parkinson's disease psychosis.

INTRODUCTION: Parkinson´s disease (PD) is a synucleinopathy that affects millions of people worldwide and leads to progressive disability. Psychosis is highly prevalent in PD patients and is associated with poor prognosis. Until April 2016, there were no licensed drugs available in the United States of America (USA) for the treatment of PD psychosis (PDP). Pimavanserin is the first Food and Drug Administration approved medicine for the treatment of hallucinations and delusions associated with PDP. AREAS COVERED: A MEDLINE literature search, publicly available information provided by ACADIA Pharmaceuticals, and expert opinion were used for this review. A review of PDP, its current treatment and limitations is followed by the rationale for development of pimavanserin. The mechanism of action, preclinical data, pharmacokinetics, pharmacodynamics, and clinical data supporting the efficacy and safety of pimavanserin in PDP are reviewed. We also describe the potential benefits of pimavanserin in other contexts such as schizophrenia and sleep disorders. EXPERT OPINION: Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP. The development of pimavanserin as an antipsychotic represents a major breakthrough in the pharmacotherapy of psychotic symptoms associated with PD.

Pharmacological treatment and staging in bipolar disorder: evidence from clinical practice

Objectives: Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD. Methods: One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV. Results: Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed. Conclusions: This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness. .

Pharmacological treatment and staging in bipolar disorder: evidence from clinical practice.

OBJECTIVES: Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD. METHODS: One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV. RESULTS: Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed. CONCLUSIONS: This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness.

Biomarkers and staging of bipolar disorder: a systematic review.

INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. METHODS: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. RESULTS: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. CONCLUSIONS: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression.