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Journal of Neurological Surgery. Part... Dec 2023Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We...
Stereotactic Radiosurgery Outcomes in Medically and Surgically Failed or Nonsurgical Candidates with Medically Failed Prolactinomas: A Systematic Review and Meta-Analysis.
Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We sought to summarize the efficacy of stereotactic radiosurgery (SRS) in the medically and surgically failed prolactinomas as well as in nonsurgical candidates with medically failed prolactinomas by systematic review and meta-analysis. A literature search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. A total of 11 articles (total = 709) met inclusion criteria. Thirty-three percent of patients were able to achieve endocrine remission at a mean follow-up of 54.2 ± 42.2 months with no association between stopping DA and endocrine remission. Sixty-two percent of patients were able to achieve endocrine control with DA therapy and 34% of patients were able to decrease the dose of DA dose when compared with pre-SRS DA dose at the end of the follow-up period. However, 54% of patients required DA at the end of the follow-up to control hyperprolactinemia. Ninety percent of patients were able to achieve radiologic control at the end of the follow-up in comparison to pre-SRS imagings. Furthermore, 26% of patients newly developed hypopituitarism (one or more pituitary hormones) post-SRS throughout the follow-up period. This systematic review and meta-analysis demonstrates SRS as an effective adjunct therapy in medically failed nonsurgical candidates or surgically and medically recalcitrant prolactinomas with a 33% chance of achieving endocrine remission, 62% of patients achieved hormonal control with DA and GKRS (gamma knife radio-surgery), with a 34% chance of decreasing DA dose and 90% chance of achieving radiologic control.
PubMed: 37854534
DOI: 10.1055/a-1934-9028 -
Journal of the Academy of... 2024Othello syndrome (OS) is a condition characterized by a delusion of jealousy that one's spouse is having extramarital affairs. As in the eponymous Shakespearean tragedy,... (Review)
Review
BACKGROUND
Othello syndrome (OS) is a condition characterized by a delusion of jealousy that one's spouse is having extramarital affairs. As in the eponymous Shakespearean tragedy, there is an unfortunate risk of violence. For patients with these symptoms, consultation-liaison psychiatrists may be asked to assist with evaluating the differential diagnosis, assessing safety, and developing treatment options.
OBJECTIVE
This study's objective was to solidify current knowledge of the clinical presentations and management of OS through a systematic review of the literature and description of 2 new cases.
METHODS
We conducted a literature search from the start of relevant databases through August 2023 to identify English language case reports of adults (≥18 years) with OS that described clinical evaluations, biological treatments, and outcomes. We extracted demographics, proposed etiologies, treatment choices and responses, duration of delusions, comorbid psychiatric symptoms, neuro-radiographic findings, and presence of physical violence. We reported clinical findings for 2 new cases.
RESULTS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we screened 705 abstracts and conducted full-text reviews of 118 articles to identify 73 cases published from 1983 to 2023 meeting inclusion criteria. The mean age was 58.2 years with male predominance (M:F = 1.88). Etiologies included primary psychiatric disorders (16, 22%), other medical conditions (38, 52%), and medications or other substances (19, 26%). Delusional disorder, cerebrovascular accident, and dopaminergic agonists were the most common etiologies, respectively, in these groups. Antipsychotics were the most common treatment (57, 78%). Symptom remission was reported in 51 (70%) cases. The average duration of OS was 39.5 months. Of 32 cases reporting brain imaging insults, 12 of 20 (60%) showed right-sided lesions, and 8 of 20 (40%) showed left-sided lesions, with 9 of 32 (28%) located in the frontal lobes. The most commonly co-existing psychiatric symptom was depression (14, 19%). Violence was reported in 25 cases (34%). Our 2 new cases were consistent with these findings.
CONCLUSIONS
OS may be a manifestation of several neuropsychiatric conditions, primarily delusional disorder, cerebrovascular accident, Alzheimer's dementia, and the use of dopaminergic agonists. One-third of cases include violent behaviors. It appears to respond to antipsychotic medications, but treatment is delayed more than 3 years on average. Available data have not localized OS to a specific brain region.
Topics: Adult; Humans; Male; Middle Aged; Female; Schizophrenia, Paranoid; Delusions; Dopamine Agonists; Antipsychotic Agents; Stroke
PubMed: 37832650
DOI: 10.1016/j.jaclp.2023.09.006 -
Movement Disorders Clinical Practice Sep 2023Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD). (Review)
Review
BACKGROUND
Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD).
METHODS
A systematic review of all published articles in English on CSAI for PD till January 30, 2022 was conducted.
RESULTS
A total of 82 articles met the search criteria. Publications included retrospective or prospective open-label observational studies, with a limited number of randomized control trials (RCT). Publications were highly heterogeneous and focused on different aspects of CSAI and included clinical audits, effects on cognition/behavior, axial symptoms, nocturnal issues, adverse events/reasons for discontinuation and comparison with other continuous dopaminergic therapies. CSAI was used in patients who presented severe motor fluctuations not resolved by oral therapy, poor candidates for deep brain stimulation (DBS) due to cognitive/behavioral issues or in those with DBS weaning effect. Recent studies have also shown that CSAI was useful for nocturnal usage in advanced PD, in addition to daytime utilization. Adverse effects were common and include skin lesions, sedation and nausea. Pump management difficulties and patient decisions were common reasons for therapy dropout, predominantly during the initial stages of the CSAI.
CONCLUSION
There is consistent agreement on the benefits of CSAI in reducing OFF periods and improving ON periods without troublesome dyskinesia and specific motor and non-motor symptoms. Although there is a paucity of RCTs, current data from almost 30 years of use suggests CSAI to be beneficial in advanced cases of PD.
Topics: Apomorphine; Parkinson Disease; Humans; Infusions, Subcutaneous; Antiparkinson Agents; Dopamine Agonists; Deep Brain Stimulation
PubMed: 37772305
DOI: 10.1002/mdc3.13810 -
Medicine Sep 2023Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.
BACKGROUND
Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.
METHODS
We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.
RESULTS
56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.
CONCLUSION
Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.
Topics: Adult; Humans; Depressive Disorder, Major; Antipsychotic Agents; Network Meta-Analysis; Quetiapine Fumarate; Aripiprazole; Olanzapine; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37746943
DOI: 10.1097/MD.0000000000034670 -
Cureus Jul 2023Diabetes mellitus (DM), one of the oldest diseases known to mankind has always been difficult to treat even with the availability of a variety of medications. In such a... (Review)
Review
Diabetes mellitus (DM), one of the oldest diseases known to mankind has always been difficult to treat even with the availability of a variety of medications. In such a scenario, the Food and Drug Administration (FDA) has approved a novel therapeutic, bromocriptine, with a different mechanism of action than the traditional medications since 2009 but has not been used as either first-line therapy or add-on therapy. In this systematic review, we searched databases like PubMed, Medline, PubMed Central, Cochrane Library, Clinicaltrials.gov, and Wiley Online Library. The selected articles were screened using inclusion and exclusion criteria and quality appraised; finally, 11 studies including eight clinical trials and three narrative reviews were included. It was found that an increase in dopamine and serotonin levels were hypothesized to convert the insulin-resistant (IR) state to an insulin-sensitive (IS) state. Hence in DM, as there is an IR state, the administration of dopamine was hypothesized to increase insulin sensitivity. In our study based on included studies, it was found that bromocriptine was superior as an add-on therapy to metformin compared to metformin alone, also it was found beneficial in people failing treatment with any one oral hypoglycemic agent. On the contrary, bromocriptine was found inferior to teneligliptin in treating DM. Still, more studies are required to make an accurate and reliable assessment of the efficacy of bromocriptine in treating DM.
PubMed: 37588318
DOI: 10.7759/cureus.41931 -
The Psychiatric Quarterly Dec 2023Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for... (Review)
Review
Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for treating BPD. This study aimed to investigate the efficacy and safety of aripiprazole in patients with BPD. On July 2, 2021, the protocol (CRD42021256647) was registered in PROSPERO. PubMed, Scopus, Web of Science, Ovid-Medline, Embase, PsycINFO, and Cochrane (CENTRAL) were searched without regard for language or publication date. We also searched trial registries on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomized clinical trials with adult patients diagnosed with BPD met the inclusion criteria. The Cochrane risk of bias for randomized trials (RoB-2) method was used to assess the quality of the included studies. We included two previously published randomized clinical trials. There were 76 patients with BPD, with 38, 12, and 26 assigned to the aripiprazole, olanzapine, and placebo groups, respectively. Most patients (88.16%) were females, with ages ranging from 22.1 to 28.14 yr. Aripiprazole has been proven to reduce anxiety, depression, anger, hostility, clinical severity, and obsessive-compulsive behavior, insecurity, melancholy, anxiety, aggressiveness/hostility, phobic anxiety, paranoid thinking, psychoticism, and somatization. The adverse effects were headache, insomnia, restlessness, tremor, and akathisia. The risk of bias was considerable in both trials, which is somewhat problematic considering that prejudice can lead to incorrect outcomes and conclusions. Aripiprazole has demonstrated encouraging outcomes in the treatment of patients with BPD. More randomized controlled studies are needed.
Topics: Adult; Female; Humans; Male; Aripiprazole; Borderline Personality Disorder; Antipsychotic Agents; Olanzapine; Anxiety Disorders
PubMed: 37566261
DOI: 10.1007/s11126-023-10045-8 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
Pituitary Oct 2023Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the... (Review)
Review
PURPOSE
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.
METHODS
A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.
RESULTS
196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.
CONCLUSION
Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.
Topics: Female; Adult; Male; Humans; Prolactinoma; Pituitary Neoplasms; Hyperprolactinemia; Prolactin; Amenorrhea; Dopamine Agonists; Hypopituitarism; Vision Disorders; Adrenocorticotropic Hormone
PubMed: 37544978
DOI: 10.1007/s11102-023-01337-0 -
Psychological Medicine Dec 2023Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common.
METHODS
We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events.
RESULTS
We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of -6.45 [95% confidence interval (CI) -8.13 to -4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects ( = 0.003) and also weight gain ( < 0.00001), sedation ( < 0.00001) and increased appetite ( = 0.001) in the antipsychotic group.
CONCLUSIONS
There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.
Topics: Child; Humans; Antipsychotic Agents; Aripiprazole; Risperidone; Psychotic Disorders; Autism Spectrum Disorder; Randomized Controlled Trials as Topic
PubMed: 37539448
DOI: 10.1017/S003329172300212X -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y