Intravenous haloperidol: A systematic review of side effects and recommendations for clinical use.

INTRODUCTION: Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in patients with delirium in the hospital setting. Over the years, concerns have emerged regarding side effects of IVH, particularly its potential to cause QT prolongation, torsades de pointes (TdP), extrapyramidal symptoms and catatonia. METHODS: We conducted a systematic review of literature of published literature related to side effects of IVH in PubMed in accordance with PRISMA guidelines. RESULTS: 77 of 196 identified manuscripts met inclusion criteria, including 34 clinical trials and 34 case reports or series. DISCUSSION: Extrapyramidal symptoms, catatonia and neuroleptic malignant syndrome appears to be relatively rare with IVH. In most prospective studies, IVH did not cause greater QT prolongation than placebo, and rates of TdP with IVH appear to be low. There is not clear evidence to suggest that IVH carries greater risk for QT prolongation or TdP than other antipsychotics. CONCLUSIONS: Based on the available literature, we provide modified evidence-based monitoring recommendations for clinicians prescribing IVH in hospital settings. Specifically, we recommend electrocardiogram monitoring only when using doses >5 mg of IVH and telemetry only for high-risk patients receiving cumulative doses of at least 100 mg or with accurately corrected QTc >500 ms.

Consultation-Liaison Psychiatry vs Psychosomatic Medicine: What's in a name?

BACKGROUND: In November of 2017, The Academy of the Psychosomatic Medicine voted to change its name to the Academy of Consultation-Liaison Psychiatry. It followed a similar change in which the American Board of Medical Specialties voted to change the name of the field to Consultation-Liaison Psychiatry. OBJECTIVE: The authors, all instrumental in bringing about this change, discuss the history and rationale for this name change.

Relationship of genetic variation in the serotonin transporter gene (SLC6A4) and congenital and acquired cardiovascular diseases.

Recent reports have suggested an association between variation in the serotonin transporter and primary pulmonary hypertension and myocardial infarction. We set out to determine whether these associations were present in a population of patients who underwent SLC6A4 genotyping and to explore whether genetic variation in the serotonin transporter might be also associated with other cardiovascular functional and structural abnormalities. Included were 3473 patients who were genotyped for the SLC6A4 5HTTLPR polymorphism and a subset for rs25531 (n=816) and STin2 (n=819). An association was observed between 5HTTLPR and primary pulmonary hypertension (p=0.0130), anomalies of the cerebrovascular system (p<0.0001), and other anomalies of great veins (p=0.0359). The combined 5HTTLPR and rs25531 genotype was associated with tachycardia (p=0.0123). There was an association of the STin2 genotype with abnormal electrocardiogram (ECG) (p=0.0366) and abnormal cardiac study (0.0311). Overall, these results represent a step toward the understanding of the impact of SLC6A4 variation on cardiovascular pathology.

Essential articles on collaborative care models for the treatment of psychiatric disorders in medical settings: a publication by the academy of psychosomatic medicine research and evidence-based practice committee.

BACKGROUND: Collaborative care interventions for psychiatric disorders combine several components integrated into the medical setting: (1) systematic psychiatric assessment, (2) use of a nonphysician care manager to perform longitudinal symptom monitoring, treatment interventions, and care coordination, and (3) specialist-provided stepped-care recommendations. Collaborative care interventions have now been evaluated in a wide spectrum of care settings and offer great promise as a way of increasing quality of patient care, improving health of populations, and reducing health care costs. METHODS: A systematic search of PubMed/MEDLINE databases was performed for publications between January 1970 and May 2013 to identify articles describing collaborative care and related interventions. Identified articles were then evaluated independently by multiple reviewers for quality and importance; additional articles were identified by searching reference lists and through recommendations of senior content-matter experts. The articles considered to be both of high quality and most important were then placed into categories and annotated reviews performed. RESULTS: Over 600 articles were identified of which 67 were selected for annotated review. The results reported in these articles indicate that collaborative care interventions for psychiatric disorders have been consistently successful in improving key outcomes in both research and clinical intervention studies; cost analyses also suggest that this model is cost effective. CONCLUSIONS: Collaborative care models for psychiatric disorders are likely to serve an increasingly large role in health care given their effect on patient and population outcomes and their focus on integration of care.

"Diminished" association between the serotonin transporter linked polymorphism (5HTTLPR) and body mass index in a large psychiatric sample.

BACKGROUND: The role of the promoter polymorphism (5HTTLPR) of the serotonin transporter gene (SLC6A4) in psychiatric illnesses has been studied extensively. Serotonergic function also regulates many central nervous system, including appetite and feeding behaviors. The 5HTTLPR short allele was found to be associated with increased body mass index and obesity risk among the general population. No data is available to support generalizability of such association among psychiatric population. METHODS: We examined the relationship between BMI and the 5HTTLPR genotype in a large sample of 1831 psychiatric patients at Mayo Clinic, Rochester, Minnesota, using a retrospective chart review. RESULTS: Average BMI among groups with the short/short (28.29 ± 7.27 kg/m(2)), the short/long (28.07 ± 6.45 kg/m(2)) and the long/long (28.15 ± 7.51 kg/m(2)) genotypes of 5HTTLPR were not statistically different. This negative association persisted even with the sub-analysis of the Caucasians. However, we observed an increased rate of obesity among our psychiatric patient sample compared to the general population of Minnesota (36.6% versus 27.6%, p=0.0001 for males, 30.3% versus 24.4%, p=0.0001 for females). Also, sub-analysis showed female inpatients to have a significantly higher average BMI than outpatients (28.64 ± 8.08 kg/m(2) versus 27.13 ± 6.92 kg/m(2), p=0.026). This confirmed a significant association between mental health disorder and BMI. LIMITATIONS: Retrospective study design with limited control for potential confounders. CONCLUSIONS: In this large sample of psychiatric patients we found no significant association between 5HTTLPR genotype and BMI, which is different from the case with general population reported in the literature.

Patient body mass index does not predict six-month clinical outcome of depression managed under collaborative care.

Obesity and depression are often comorbid conditions. There appears to be a bidirectional relationship between these. Obesity at baseline has been shown to increase the risk of onset of depression and depression at baseline increased the odds for developing obesity. Less is understood about the impact of obesity on depression treatment outcomes. The authors' hypothesis was that obesity (body mass index [BMI] ≥ 30 kg/m²) and morbid obesity (BMI ≥ 40 kg/m²) would each have negative effects on depression remission rates after 6 months of enrollment into collaborative care management for depression. In a retrospective analysis of 1111 depressed patients with a PHQ-9 (Patient Health Questionnaire) score of 10 or greater, multivariate analysis for the odds ratio of achieving remission at 6 months demonstrated that the patient's BMI at baseline was not an independent risk factor for depression outcome at 6 months. Collaborative care management for depression has been shown to be effective for improving depression outcomes, yet minimal prior research has focused on other clinical comorbidities that might affect outcomes. Although obesity was common in the study population, it was reassuring, based on this study that 6-month depression treatment outcomes do not appear to be significantly affected by the patient's baseline BMI.

State dependent gene-environment interaction: serotonin transporter gene-child abuse interaction associated with suicide attempt history among depressed psychiatric inpatients.

BACKGROUND: The serotonin transporter gene polymorphism (5HTTLPR) and child abuse history have been associated with an increased suicide risk for general population, but such association is not clear among psychiatric depressed inpatients. METHODS: A chart review identified 422 depressed inpatients genotyped for 5HTTLPR. Child abuse and suicide attempt history were recorded. The relationship between 5HTTLPR, child abuse, and suicide attempts were analyzed. RESULTS: There was a significant relationship between 5HTTLPR and history of suicide attempt (the long/long versus the short carriers, 47.9% versus 31.8%, p=0.0015). There was also a significant main effect from child abuse history (abused versus not abused, 45.1% versus 28.6%, p=0.0001). The likelihood ratio test showed a significant result for the l/l genotype group with child abuse history (odds ratio 4.11, χ2 = 23.5, p<0.0001). No significant result was obtained from other groups. LIMITATIONS: This is a retrospective study based on chart review. Replication with more standardized research setting for measurements of child abuse history and suicide attempt history is needed. The rs25531 variant among a long allele (long-A and long-G) of 5HTTLPR was not genotyped. CONCLUSIONS: In addition to the direct effect from 5HTTLPR and child abuse history, an interaction between the 5HTTLPR gene and child abuse history influenced psychiatric profiles of depressed inpatients. Contrary to the widely recognized "reactivity" associated with the short allele, our patients with the l/l genotype and child abuse history showed significantly severer psychiatric pathology than short carriers with child abuse history.

Testing a diathesis-stress model: potential genetic risk factors for development of distress in context of acute leukemia diagnosis and transplant.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes, specifically in the context of stressful life events. We hypothesized that this single-nucleotide polymorphism will predict the development of psychological distress among patients diagnosed with acute leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also explored the relationship of other genetic factors to psychological distress, including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype. METHOD: In a retrospective cohort design, 107 adult acute leukemia survivors preparing for HSCT at a major medical center completed a pre-HSCT psychological evaluation and volunteered to donate blood to the HSCT Cell and Serum Research Repository for future research studies. RESULTS: There was evidence of a potential association between BDNF (Val66Met) and psychological distress. More specifically, rs6265 was related to both personal mental health history (P = 0.09, 0.06 adjusted) and diagnosis of depression/adjustment disorder at time of pre-transplant evaluation (P = 0.11, 0.09 adjusted). Other genetic factors were unrelated to distress. CONCLUSION: The BDNF Val66Met polymorphism may contribute to development of depressive symptomatology in patients undergoing stressful life events, such as diagnosis of acute leukemia and preparation for HSCT. The SNPs in BDNF might be applicable in identifying patients at risk for developing psychological distress and depression in the context of coping with stressful medical conditions. Polymorphism in other genes (FKBP5, CRHR1, and 5HTT) did not show any significant relationships. Replication studies are needed with larger samples of people undergoing similar significant life stressors.

Factors associated with depression treatment-response in an outpatient psychosomatic medicine practice: an exploratory retrospective study.

BACKGROUND AND OBJECTIVE: The author explored depression management outcomes in an outpatient psychosomatic medicine (PM) practice to identify factors associated with treatment response. METHODS: Medical records of 251 patients seen in the Mayo Clinic Rochester outpatient PM clinic who had patient health questionnaire-9 (PHQ-9) scores at the time of initial consultation and after consultation were reviewed. Comparisons of differences in pre- and post-consultation PHQ-9 scores were evaluated to identify patients with treatment response (score decreased > 50%). RESULTS: A total of 112 (44.6%) patients had initial PHQ-9 scores ≥ 5. Univariate comparisons revealed higher likelihood of response (25.9%) with lower average number of past antidepressant and antipsychotic trials, and reported good friend and family social support. After controlling for average number of medication trials, reported good friend support remained predictive of response (OR 3.4225, χ2 4.6743, P = 0.31); there was a trend for reported good family support to remain predictive (OR 2.7956; χ2 2.5933, P= 0.097). CONCLUSION: Though exploratory and underpowered to adequately assess all potential contributors, retrospective examination of factors associated with depression treatment-response in this outpatient PM practice emphasizes the relevance of perception of social support as markers of prognosis and outcome.

Investigation of serotonin transporter gene (SLC6A4) by child abuse history interaction with body mass index and diabetes mellitus of White female depressed psychiatric inpatients.

BACKGROUND: The serotonin transporter gene promoter polymorphism (5HTTLPR) and child abuse have been associated with an increased risk for depression. We previously reported the long/long (l/l) genotype of 5HTTLPR being associated with higher heart rate among patients with a history of child abuse compared with those without a history of child abuse, whereas the short allele carriers did not have heart rate differences dependent on child abuse history. This time, we extended our investigation to other outcomes with body mass index (BMI), and diabetes mellitus (DM) diagnosis. METHODS: A retrospective chart review identified 185 White female depressed inpatients who were genotyped for 5HTTLPR. Child abuse history, BMI, and DM diagnosis were recorded. The relationship between 5HTTLPR, child abuse, and BMI, as well as a prevalence of DM were analyzed. RESULTS: Among the l/l genotype group, patients with a history of child abuse had a higher prevalence of DM (14.3 vs. 0%, P=0.06), and higher BMI (32.3 vs. 27.3 kg/m, P=0.03) compared with those without. Patients with the short allele (s/s or s/l) had fewer differences on the basis of abuse history. CONCLUSION: A potential interaction between 5HTTLPR and child abuse influenced metabolic profiles of White female depressed inpatients. In contrast with the widely recognized 'reactivity' associated with the short allele of 5HTTLPR, our White female depressed psychiatric inpatients with the l/l genotype showed relatively greater clinical pathology in metabolic profiles if they have a history of child abuse than inpatients with at least one short allele who had a history of child abuse.

Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients.

BACKGROUND: Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a history of child abuse have been shown to be associated with an increased risk for posttraumatic stress disorder (PTSD). It has also been demonstrated that the same polymorphisms of FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. However, there are only limited numbers of studies replicating the polymorphisms as vulnerability factors for the development of mental illnesses, such as PTSD and depression after stressful life event, especially with a specific incidence, such as kidney transplant surgery. METHODS: A retrospective analysis was conducted using the electronic medical records of 131 adult kidney transplant recipients. Depression severity after kidney transplantation was measured by PHQ-9, and stored blood was genotyped for variants in the Serotonin Transporter (SLC6A4), Brain-Derived Neurotrophic Factor, Catecholamine-O-Methyltransferase, Corticotropin-Releasing Hormone Receptor, and FKBP5 genes. Spearman correlations were used to test for association between genetic variants and depression severity. RESULTS: The rare alleles at three out of four SNPs in FKBP5 (rs1360780, rs9296158, and rs9470080) were associated with increased PHQ-9 scores (P<.05), whereas the last FKBP5 SNP (rs3800373) showed a trend of association (P<.10). All four FKBP5 SNPs are in strong linkage disequilibrium. Although in a subgroup of Caucasian non-Hispanic subjects the association was not statistically significant, the direction of association was consistent with that observed in the entire sample as well as in previous studies. Polymorphisms in genes other than FKBP5 were not associated with PHQ-9 scores. CONCLUSIONS: Polymorphisms in FKBP5 may be associated with higher depression scores in kidney transplant recipients.

Variability of judgments of capacity: experience of capacity evaluators in a study of research consent capacity.

BACKGROUND: Assessment of decision-making capacity is a common and important function of psychiatric consultants. However, the sources of variability in evaluators' judgments have not been well characterized. OBJECTIVE: To examine the degree and potential sources of variability in the categorical capacity judgments of experienced psychiatrists. METHOD: The setting was a study comparing the decision-making capacities of 188 persons with Alzheimer's disease to appoint a research proxy and to consent to two hypothetical randomized controlled trials for dementia (a new drug RCT and a neurosurgical RCT). We compared five experienced consultation psychiatrists' capacity judgments for 555 videotaped capacity interviews. Both quantitative and qualitative data were used. RESULTS: Pair wise kappa statistics ranged from slight agreement (0.17) to substantial agreement (0.64) with group kappa statistics ranging from fair to moderate agreement (0.40 to 0.45) for the psychiatrists' judgments regarding the three capacities. The sources of variability included varying "strictness" among judges, moderate test-retest reliability within judges, the relative novelty of assessing decision-making capacity for research participation decisions, as well as the limitations of the methods used to obtain capacity judgments in the study. DISCUSSION: There is considerable variability in capacity judgments of experienced consultation psychiatrists regarding the capacities to appoint a research proxy and to consent to research. The potential sources of variability identified in this study may provide starting points for more effective training in capacity assessment.

Reprint of: Psychosomatic medicine and consultation-liaison psychiatry: scope of practice, processes, and competencies for psychiatrists working in the field of CL psychiatry or psychosomatics. A consensus statement of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) and the Academy of Psychosomatic Medicine (APM).

OBJECTIVE: In 2008, the Board of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) and the Academy of Psychosomatic Medicine (APM) Council commissioned the creation of a task force to study consensus-based summaries of core roles, scope of clinical practice, and basic competencies for psychiatrists working in the field of Psychosomatic Medicine (PM) and/or Consultation-Liaison Psychiatry (CLP). METHOD: The task force used existing statements of competencies and feedback from EACLPP and APM symposia and workshops to develop a draft document. After review by the EACLPP and APM committees, and the EACLPP Board and APM Council, a period of comment from the field preceded a final draft resubmitted for consideration of the EACLPP Board and APM Council in February 2010. RESULTS: The two organizations completed approval of final publication of the consensus statement on June 11, 2010. This consensus statement is a summary of clinical competencies, scope of clinical effort, and roles considered by the sponsoring organizations to be fundamental to the practice of this subspecialty or special area of expertise, anywhere, of PM or CLP. CONCLUSION: This consensus statement delineates a set of basic competencies and roles of a PM/CLP psychiatrist to serve as an internationally recognized base that may be used by national societies and institutions to formulate their own competencies, scope of practice, and roles or help with guideline formulation.

Pharmacogenomic testing in a tertiary care outpatient psychosomatic medicine practice.

BACKGROUND: Pharmacogenomic testing (PGT) has applicability in psychosomatic medicine (PM) practice where medical comorbidity and polypharmacy present particularly difficult challenges of drug-drug and drug-disease interactions. No guidelines currently exist for cost-effective use of PGT in PM practice. OBJECTIVE: The authors tested the hypothesis that naturalistically observed PGT ordering patterns and clinical data on test utility derived from a PM practice where PGT is readily available may inform the development of clinical guidelines for cost-effective use of PGT. METHOD: Two sets of data were collected from an outpatient PM practice staffed by seven PM-certified psychiatrists. Psychiatrists were surveyed regarding their indications for ordering PGT. Medical records of patients seen in the PM practice during 2008 were reviewed. Patients who had PGT were compared with two sets of case controls who were not tested, one matched by demographics, the other by ordering psychiatrist. Psychiatrists' ordering indications were compared with clinical data derived from the case-control analyses. RESULTS: Psychiatrists listed treatment-resistance as the most common reason for PGT, ahead of intolerance to previous medications. Tested patients differed from controls on measures of both clinical severity and treatment-resistance, including higher self-reported anxiety and depression levels, greater likelihood of family history of mood or anxiety disorders, and larger numbers of prior antidepressant, mood stabilizer, and antipsychotic medication trials. CONCLUSION: Ordering guidelines that emphasize markers of clinical severity and early indicators of treatment-resistance may provide a useful rationale for PGT in outpatient PM practice. Prospective investigations of this proposition are warranted.

Serotonin transporter gene promotor polymorphism (5-HTTLPR) associations with number of psychotropic medication trials in a tertiary care outpatient psychiatric consultation practice.

OBJECTIVE: The authors tested the hypothesis that the short allele of 5-HTTLPR is associated with number of psychotropic medication trials as a measure of treatment-resistance or intolerance in psychosomatic medicine (PM) outpatients. METHODS: Review of Mayo Clinic PM outpatient 2008 records identified 44 (20.6%) who had 5-HTTLPR genotype tests. A univariate analysis screened for factors that could account for number of medication trials. Logistic regression then determined degree of association between 5-HTTLPR genotype category and number of pharmacological trials. RESULTS: Univariate analysis revealed significant differences across the ordinal genotype spectrum long/long, short/long, short/short in mean number of overall psychotropic medication trials (8.9, 14.8, 18.0, P = 0.002), mean number of antidepressant trials (4.3, 7.2, 8.1, P = 0.018), mean number of mood stabilizer trials (0.8, 1.9, 2.3, P = 0.008), percent living alone (7%, 25%, 50%, P = 0.020), reported family history of depression (93%, 65%, 40%, P = 0.006), and reported family history of chemical dependency treatment (50%, 35%, 10%, P = 0.050). There were trends for differences in consultation reason for unexplained symptoms (14%, 25%, 50%, P = 0.063), and diagnoses of somatoform disorder (7%, 30%, 40%, P = 0.060), and generalized anxiety disorder (43%, 65%, 80%, P = 0.064). After controlling for other differences, presence of the short allele remained associated with number of psychotropic medication trials (OR 4.779, 95% CI 2.263-6.771, P = 0.004), and number of antidepressant trials (OR 1.591, 95% CI 1.072-2.762, P = 0.019). CONCLUSION: 5-HTTLPR testing may identify PM outpatients at higher relative risk for pharmacotherapy treatment non-response or intolerance who may benefit from alternative or augmentative medication recommendations or non-pharmacological interventions.

Psychosomatic medicine and consultation-liaison psychiatry: scope of practice, processes, and competencies for psychiatrists working in the field of CL psychiatry or psychosomatics. [corrected] A consensus statement of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) and [corrected] the Academy of Psychosomatic Medicine (APM). [corrected]

OBJECTIVE: In 2008, the Board of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) [corrected] and the Academy of Psychosomatic Medicine (APM) Council commissioned the creation of a task force to study consensus-based summaries of core roles, scope of clinical practice, and basic competencies for psychiatrists working in the field of Psychosomatic Medicine (PM) and/or Consultation-Liaison Psychiatry (CLP). METHOD: The task force used existing statements of competencies and feedback from EACLPP and APM symposia and workshops to develop a draft document. After review by the EACLPP and APM committees, and the EACLPP Board and APM Council, a period of comment from the field preceded a final draft resubmitted for consideration of the EACLPP Board and APM Council in February 2010. RESULTS: The two organizations completed approval of final publication of the consensus statement on June 11, 2010. This consensus statement is a summary of clinical competencies, scope of clinical effort, and roles considered by the sponsoring organizations to be fundamental to the practice of this subspecialty or special area of expertise, anywhere, of PM or CLP. CONCLUSION: This consensus statement delineates a set of basic competencies and roles of a PM/CLP psychiatrist to serve as an internationally recognized base that may be used by national societies and institutions to formulate their own competencies, scope of practice, and roles or help with guideline formulation.

Psychiatric manifestations of voltage-gated potassium-channel complex autoimmunity.

The authors describe the neuropsychiatric spectrum of voltage-gated potassium-channel complex (VGKC) autoimmunity among 67 seropositive patients; 2 had initially been assigned a primary psychiatric diagnosis. Diverse manifestations were recorded, often affective-predominant. Symptoms for 24 patients with florid presentations included confusion, 92%; memory impairment, 75%; personality change, 58%; depression, 33%; and anxiety, 29%. Of 15 who received immunotherapy, 67% improved. Forty-three patients with milder presentations or low positive VGKC complex Ab values are also described. Neuropsychiatric presentations were significantly associated with higher autoantibody values. Improvements were most evident in patients treated early, which emphasizes the need for early diagnosis and immunotherapy initiation.