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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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Abstract
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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[Use of Verapamil and Dilthiasem in treating patients at high cardiovascular risk (review of literature)].
Baryshnikova, GA, Chorbinskayva, SA, Stepanova, II, Blochina, OE, Zverkov, IV, Maslovskyi, LV, Korchazhkina, NB, Maslennikova, OM
Meditsina truda i promyshlennaia ekologiia. 2016;(2):15-8
Abstract
The article deals with usage of nondihydropiridine calcium antagonists--verapamil and dilthiasem--in treating patients with arterial hypertension, cardiomyopathy and arrhythmia, for secondary prevention of IHD. Data also concern cardio-, angio--and nephroprotective activity of the medications, their ability to prevent left ventricle hypertrophy, possible usage in patients after myocardial infarction. The authors also discuss problems of tolerance and safety of calcium antagonists with prolonged action vs. those with short-term action.
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Intralipid Emulsion Rescue Therapy: Emerging Therapeutic Indications in Medical Practice.
Muller, SH, Diaz, JH, Kaye, AD
The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society. 2016;(3):101-3
Abstract
Intralipid emulsion therapy is well-established for the treatment of local-anesthetic systemic toxicities. In recent years, its role has expanded as an important therapeutic agent in the reversal of other types of drug overdoses, including certain types of antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. A literature review identified thirty-one case reports including forty-nine separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The present clinical case study describes an elderly unresponsive woman refractory to conventional treatments after ingesting a potentially lethal amount of 5.6 grams of diltiazem in a suicide attempt. After treatment with Intralipid over a twenty-four hour period, the patient's hemodynamic and metabolic derangements were corrected and stabilized completely. Intralipid emulsion rescue therapy provides another potential strategy for the reversal of many drug toxicities, most likely by providing a lipid layer safety net for drug overdose by passive diffusion. Clinicians are urged to embrace an expanded role of Intralipid emulsion rescue therapy, not only for local anesthetic drug toxicities, but also for other lipophilic drug overdoses.
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Treatment of calcium channel blocker intoxication with insulin infusion: case report and literature review.
Marques, M, Gomes, E, de Oliveira, J
Resuscitation. 2003;(2):211-3
Abstract
We present a case report of successful treatment of shock induced by the calcium channel blocker (CCB) diltiazem. A 75-year-old woman took a combination of tablets, including diltiazem. Soon after arrival, she developed haemodynamic shock which persisted despite treatment with fluids, dopamine, dobutamine, norepinephrine (noradrenaline), calcium gluconate and glucagon. Haemodynamic stability was not achieved until an insulin infusion and glucose administration was started. We review the literature and the updated guidelines for the treatment of CCB intoxication, with particular emphasis on situations where insulin and glucose infusions can be live saving.
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Poisoning with calcium channel blockers--a case report and review of the literature.
Amorim, S, Dias, P, Rocha, G, Gama, G, de Campos, M, Pires, S
Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. 2001;(12):1249-57
Abstract
The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. We present a clinical case of bradycardia and shock of unknown cause, which came to be revealed a poisoning by 3240 mg of slow-release diltiazem, managed with temporary transvenous pacing and dopamine in high concentration. We make a review of the cardiovascular manifestations of the three classic calcium channel blockers: verapamil, diltiazem and nifedipine; namely, hypotension, rhythm and conduction disturbances. We point out the late appearance of the beginning of manifestations with the use of slow releasing formulations. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. The bradyarrhythmias are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. If the intoxication causes depression of cardiac contractility, the use of calcium or/and glucagon is indicated. If there is refractoriness with these measures, catecholamines should be employed. There are alternative and adjuvant drugs such as amrinone, insulin-glucose, 4-aminopyridine and calcium entry promoters. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest.
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Anomalies in the dosing of diltiazem.
Pool, PE
Clinical cardiology. 2000;(1):18-23
Abstract
From early research, investigators understood that the dose of diltiazem required for the treatment of hypertension (commonly 360 mg/day) was greater than that required for the treatment of angina (commonly 240 mg/day). Nonetheless, studies of recent prescribing practices show that the 240 and 180 mg capsule strengths constitute more than 70% of the diltiazem prescriptions for hypertension. Physicians became accustomed to the lower antianginal doses of diltiazem for 7 years before a hypertension indication was approved. Subsequently, these dosing levels were reinforced by the production of once-a-day formulations with highest capsule strengths of 240 mg and 300 mg. These strengths were dictated by the sheer bulk of the formulations, which limited how much diltiazem could be inserted into the #00 capsule, the largest capsule that can be comfortably administered. An examination of the combined data from the six randomized, blinded, and placebo-controlled trials submitted to the FDA for the original new drug applications of the three formulations of diltiazem available in the United States shows a clear linear dose-response relationship between diltiazem dose and blood pressure lowering through the 480-540 mg/day range. It also demonstrates that the 90-120 mg/day range is the "no-effect dose." These conclusions are supported by a MEDLINE review of all other studies of multilevel dosing of higher dose levels of diltiazem. The data support the conclusion that diltiazem is generally underdosed, but when properly dosed may be the single most potent antihypertensive overall.