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The psychopharmacology algorithm project at the Harvard South Shore Program: An algorithm for adults with obsessive-compulsive disorder.
Beaulieu, AM, Tabasky, E, Osser, DN
Psychiatry research. 2019;:112583
Abstract
A previous algorithm for the pharmacological treatment of obsessive-compulsive disorder was published in 2012. Developments over the past 7 years suggest an update is needed. The authors conducted searches in PubMed, focusing on new studies and reviews since 2012 that would support or change previous recommendations. We identified exceptions to the main algorithm, including pregnant women and women of child-bearing potential, the elderly, and patients with common medical and psychiatric co-morbidities. Selective serotonin reuptake inhibitors (SSRIs) are still first-line. An adequate trial requires a period at typical antidepressant doses and dose adjustments guided by a plasma level to evaluate for poor adherence or ultra-rapid metabolism. If the response is inadequate, consider a trial of another SSRI this time possibly taken to a very high dose. Clomipramine could be an alternative. If the response to the second trial remains inadequate, the next recommendation is to augment with aripiprazole or risperidone. Alternatively, augmentation with novel agents could be selected, including glutamatergic (memantine, riluzole, topiramate, n-acetylcysteine, lamotrigine), serotonergic (ondansetron), and anti-inflammatory (minocycline, celecoxib) agents. A third option could be transcranial magnetic stimulation. Lastly, after several of these trials, deep brain stimulation and cingulotomy have evidence for a role in the most treatment-refractory patients.
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Neuroleptic malignant syndrome in pregnancy: case report and literature review.
Escobar-Vidarte, MF, Loaiza-Osorio, S, Messa, AA, Macías, GE
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(14):2438-2441
Abstract
BACKGROUND Neuroleptic malignant syndrome (NMS) is a serious complication associated with the use of drugs that affect dopaminergic system neurotransmission. The occurrence of NMS during pregnancy or gestation is considered a life-threatening obstetric emergency. CASE We are reporting the first case in Latin America of NMS in one pregnant women with acute psychotic episode. One day after starting with antipsychotic therapy, she developed a fever higher than 39.0 °C with tachycardia, tachypnea, generalized muscle rigidity and somnolence, with creatine kinase (CPK) levels evidencing a result of 2800 U/L. She was treated successfully with levetiracetam, biperiden and quetiapine. DISCUSSION A search in PubMed, Embase and Ovid from 1988 to 2016 resulted in seven cases reported in either pregnant or puerperal women. In general, NMS resolves within 3-14 days; most NMS cases reported during pregnancy have involved the use of haloperidol (5 case reports) which is concordant with this report. The obstetric results were good in cases reported, only two women showed signs, among them: hyperemesis gravidarum and preterm delivery. Most of the pregnant women who had NMS presented other associated comorbidities, being mostly of infectious origin. In other investigations, it has been affirmed that NMS can become lethal in adults; however, in our search for pregnant women with this disease, no associated mortality was found. CONCLUSIONS NMS is seen infrequently during pregnancy. The clinical diagnosis requires high suspicion by the examiner. It is important that obstetricians timely recognize the condition.
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Nutrients in Alzheimer's Disease: The Interaction of Diet, Drugs and Disease.
Liyanage, SI, Vilekar, P, Weaver, DF
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2019;(1):23-34
Abstract
In recent decades, clinical trials in Alzheimer's disease (AD) have failed at an unprecedented rate. The etiology of AD has since come under renewed scrutiny, both to elucidate the underlying pathologies and to identify novel therapeutic strategies. Here, diet has emerged as a potential causative/protective agent. A variety of nutrients, including lipids, minerals, vitamins, antioxidants and sugars as well as broader dietary patterns and microbiotal interactions have demonstrated associations with AD. Although clinical trials have yet to definitively implicate any singular dietary element as therapeutic or causative, it is apparent that dietary preferences, likely in complex synergies, may influence the risk, onset and course of AD. This review catalogs the impact of major dietary elements on AD. It further examines an unexplored reciprocal association where AD may modulate diet, as well as how potential therapeutics may complicate these interactions. In doing so, we observe diet may have profound effects on the outcome of a clinical trial, either as a confounder of a drug/disease interaction or as a generally disruptive covariate. We therefore conclude that future clinical trials in AD should endeavor to control for diet, either in study design or subsequent analyses.
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Association between Serum Lipids and Antipsychotic Response in Schizophrenia.
Kim, DD, Barr, AM, Fredrikson, DH, Honer, WG, Procyshyn, RM
Current neuropharmacology. 2019;(9):852-860
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Abstract
Metabolic abnormalities are serious health problems in individuals with schizophrenia. Paradoxically, studies have noted an association where individuals who gained body weight or who have increased their serum lipids demonstrated a better antipsychotic response. As serum lipids serve as more specific physiological markers than body weight, the objective of this study was to review studies that examined the association between changes in serum lipids and changes in symptoms during antipsychotic treatment in individuals with schizophrenia. A Medline® literature search was performed. Fourteen studies were included and analyzed. Evidence suggests that increases in serum lipids may be associated with decreases in symptoms during antipsychotic treatment. This inverse association may be independent of confounding variables, such as weight gain, and may be most evident during treatment with clozapine. Also, according to recent randomized controlled trials, lipid-lowering agents do not appear to worsen symptoms although this needs to be further investigated in clozapine-treated patients. Future studies should investigate the association in question in a larger population and identify underlying mechanisms.
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Facets of shared decision-making on drug treatment for adults with an eating disorder.
Himmerich, H, Bentley, J, Lichtblau, N, Brennan, C, Au, K
International review of psychiatry (Abingdon, England). 2019;(4):332-346
Abstract
Shared decision-making (SDM) means that clinicians and the patient make decisions about the treatment together. Regarding drug treatment in eating disorders (EDs), such decisions may include psychopharmacological treatment for the ED itself, medications for potential co-morbid psychiatric disorders, pharmacological strategies to alleviate the health consequences of an ED, or 'pro re nata' (PRN) medication which is given in acute care when required. Decisions regarding drug treatment in EDs should be specific in terms of the active pharmacological substance, its dose, its route of administration, and the duration of treatment. Decisions should be made with regard to the specific health risks of patients with EDs and the entire treatment approach, and should take alternative measures, additional therapies, and specific combinations of therapies into account. The differences in the expectations of patients, carers, and clinicians towards drug treatment, the lack of specific suggestions in clinical practice guidelines, and the lack of approved psychopharmacological treatment options make SDM necessary, but also a challenge. However, SDM may be limited due to the patient's impaired insight or limited capacity due to the ED. Thus, the legal framework must be taken into consideration.
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Beyond evidence-based treatment of bipolar disorder: Rational pragmatic approaches to management.
Post, RM, Yatham, LN, Vieta, E, Berk, M, Nierenberg, AA
Bipolar disorders. 2019;(7):650-659
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Abstract
The evidence for efficacy of many currently available treatments for bipolar disorder is based on studies of nonrefractory patients with bipolar disorder. Therefore, not surprisingly, most treatment recommendations and guidelines for the treatment of bipolar disorder and its many comorbidities depend heavily on data from placebo controlled randomized clinical trials (RCTs), but these RCTs provide little direction for the clinician as to what next steps might be optimal in non- or partial-responders and in those with ongoing medical and psychiatric comorbidities. Given this and the paucity of RCTs at later treatment junctures, we thought it appropriate to begin a discussion of the quality of the data that some experts in the field might consider using in choosing and sequencing drugs and their combination. We acknowledge that many other clinical investigators may prefer very different sequences, but thought the suggestions offered here might be useful to some clinicians in the field, might start discussions of other options in the literature, and, at the same time, provide a preliminary outline for a new round of much-needed clinical trials to better inform clinical practice. Given the very wide range of the quality of the data and clinical principles on which the current suggestions are based, only minimal references are included and a comprehensive review of the literature supporting each option would be outside the scope of this manuscript.
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Vitamin E for antipsychotic-induced tardive dyskinesia.
Soares-Weiser, K, Maayan, N, Bergman, H
The Cochrane database of systematic reviews. 2018;(1):CD000209
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BACKGROUND Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD. OBJECTIVES The primary objective was to determine the clinical effects of vitamin E in people with schizophrenia or other chronic mental illness who had developed antipsychotic-induced TD.The secondary objectives were:1. to examine whether the effect of vitamin E was maintained as duration of follow-up increased;2. to test the hypothesis that the use of vitamin E is most effective for those with early onset TD (less than five years) SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA We included reports if they were controlled trials dealing with people with antipsychotic-induced TD and schizophrenia who remained on their antipsychotic medication and had been randomly allocated to either vitamin E or to a placebo, no intervention, or any other intervention. DATA COLLECTION AND ANALYSIS We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. MAIN RESULTS The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence). However, people allocated to placebo may show more deterioration of their symptoms compared with those given vitamin E (5 RCTs, N = 85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21, 95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects (1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or acceptability of treatment (measured by participants leaving the study early) (medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes designated important to patients. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. AUTHORS' CONCLUSIONS Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.
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Alzheimer disease: Non-pharmacological and pharmacological management of cognition and neuropsychiatric symptoms.
Loi, SM, Eratne, D, Kelso, W, Velakoulis, D, Looi, JC
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists. 2018;(4):358-365
Abstract
OBJECTIVES This clinical update review focuses on the management of cognition and the neuropsychiatric features of Alzheimer's disease (AD) and highlights current issues regarding pharmacological and non-pharmacological treatment, putative therapeutics and recent relevant research findings in this area. CONCLUSIONS AD is a neurodegenerative progressive condition characterised by cognitive impairment and functional decline. Most people with AD will demonstrate neuropsychiatric features, better known as behavioural and psychological symptoms of dementia (BPSD). Early recognition and treatment of BPSD are essential, as these cause considerable distress and carer burden. While there are many disease-modifying therapies for the cognitive symptoms still in the research stage, only symptomatic treatments are currently available for these and the BPSD.
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Calcium channel blockers for antipsychotic-induced tardive dyskinesia.
Essali, A, Soares-Weiser, K, Bergman, H, Adams, CE
The Cochrane database of systematic reviews. 2018;(3):CD000206
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BACKGROUND Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. OBJECTIVES To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. DATA COLLECTION AND ANALYSIS We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. MAIN RESULTS Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. AUTHORS' CONCLUSIONS Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.
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Mood stabilizers in pregnancy and child developmental outcomes: A systematic review.
Haskey, C, Galbally, M
The Australian and New Zealand journal of psychiatry. 2017;(11):1087-1097
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BACKGROUND Research suggests that maintaining treatment during pregnancy for women with bipolar affective disorder reduces the risk of relapse. However, one of the key questions for women and clinicians during pregnancy is whether there are implications of exposure to mood stabilizers for longer term child development. Despite these concerns, there are few recent systematic reviews comparing the impact on child developmental outcomes for individual mood-stabilizing agents to inform clinical decisions. OBJECTIVES To examine the strengths and limitations of the existing data on child developmental outcomes following prenatal exposure to mood stabilizers and to explore whether there are any differences between agents for detrimental effects on child development. METHOD Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a rigorous systematic search was carried out of four electronic databases from their respective years of inception to September 2016 to identify studies which examined the effects of mood stabilizers including sodium valproate, carbamazepine, lamotrigine, lithium and second-generation antipsychotics on child developmental outcomes. RESULTS We identified 15 studies for critical review. Of these, 10 examined antiepileptic drugs, 2 studied lithium and 3 studied second-generation antipsychotics. The most consistent finding was a dose-response relationship for valproate with higher doses associated with poorer global cognitive abilities compared to other antiepileptic drugs. The limited data available for lithium found no adverse neurodevelopmental outcomes. The limited second-generation antipsychotic studies included a report of a transient early neurodevelopmental delay which resolved by 12 months of age. CONCLUSION This review found higher neurodevelopmental risk with valproate. While the existing data on lithium and second-generation antipsychotics are reassuring, these data are both limited and lower quality, indicating that further research is required. The information from this review is relevant for patients and clinicians to influence choice of mood-stabilizing agent in childbearing women. This must be balanced against the known risks associated with untreated bipolar affective disorder.