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Interactions Between Antipsychotic and Antihypertensive Drugs
Abstract
To provide a comprehensive review of the pharmacokinetic and pharmacodynamic interactions between antipsychotics and antihypertensive and to provide recommendations for the selection of antihypertensive in patients receiving antipsychotic therapy.
A MEDLINE search of the English-language literature was used to identify pertinent human and animal studies, reviews, and case reports.
All available sources were reviewed.
Background information was obtained from comprehensive reviews. Individual case reports were assimilated, and pertinent data were extracted.
Because hypertension is common in patients with psychiatric illness and antihypertensive agents are used for a multiplicity of indications, significant numbers of patients receive concurrent therapy with antihypertensives and antipsychotics. Many antipsychotics may block the antihypertensive efficacy of guanethidine and related drugs. The interaction between clonidine and antipsychotics is defined less clearly. Limited data suggest possible additive hypotensive effects when chlorpromazine and methyldopa are given in combination. Increased plasma concentrations of thioridazine with a resultant increase in adverse effects have been reported when propranolol or pindolol are added to the regimen. A similar increase in chlorpromazine concentrations has been reported when propranolol was added. Although there are no reports documenting an interaction between a calcium-channel antagonist and an antipsychotic, the possible inhibition of oxidative metabolism of antipsychotics, additive calcium-blocking activity, and additive pharmacodynamic effects are theorized. Hypotension and postural syncope were reported in a patient given therapeutic dosages of chlorpromazine and captopril, and in 2 patients when clozapine was added to enalapril therapy.
No antipsychotic-antihypertensive combination is absolutely contraindicated, but no combination should be considered to be completely without risk. Antihypertensives with no centrally acting activity, such as diuretics, may be the least likely to result in adverse reactions. The combination of the beta-antagonists propranolol or pindolol with thioridazine or chlorpromazine should be avoided if possible. Scrupulous patient monitoring for attenuated or enhanced activity of either agent is essential whenever antipsychotics and antihypertensives are given concurrently.
... For example, the concentration-to-dose ratio of risperidone was significantly higher in patients co-treated with metoprolol compared to the risperidone-only control group [72]. Propranolol increased the plasma concentration of chlorpromazine [73]. Also, thioridazine levels were increased by pindolol and propranolol. ...
... Also, thioridazine levels were increased by pindolol and propranolol. Therefore, these combinations should not be used [70,73]. In a recent report, CYP2D6 inhibition by metoprolol was considered to be the culprit of adverse reactions associated with aripiprazole, clozapine, and sertindole [68]. ...
Introduction:
Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug-drug interactions.
Areas covered:
This review summarizes the knowledge regarding the known or potential drug-drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this we performed a literature search in PubMed and Scopus databases, up to July 31, 2021.
Expert opinion:
The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug-drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians to selecting safer drug combinations as summarized here.
... [62] A review of drug-drug interactions in 1995 already underlined the importance of risk assessment of concurrently prescribed antipsychotic and antihypertensive agents. [63] This suggestion extends to almost all hypertension patients with BPD, since most of these are under psychotropic medication. [9,10,64] In our study, we found no publications on harmful drug-drug or drug-disease interactions within or between psychotropic and antihypertensive agents in patients with hypertension and BPD. ...
... Harmful drug-drug and drug-disease interactions occur especially within but also between the groups of psychotropic and antihypertensive agents. [63] As an example of a drug-drug interaction between 2 psychotropic agents, the antipsychotic agent Quetiapine might increase the central-nervous toxicity and induce QT-prolongation effect of an antidepressant agent Citalopram. [71] The antipsychotic Clozapine induces weight gain for 4% to 31% of the patients predisposing patients with hypertension, representing a drug-disease interaction. ...
Background:
Caregivers encounter serious and substantial challenges in managing hypertension in patients with subclinical or clinical borderline personality disorder (BPD). These challenges include therapeutic conflicts resulting from harmful drug-drug, and drug-disease interactions. Current guidelines provide no recommendations for concurrent psychotropic and antihypertensive treatment of hypertensive BPD patients who are at even greater cardiovascular risk.
Methods:
We conducted a systematic literature review to assess the extent of available evidence on prevalence rates, cardiovascular risk factors, therapeutic conflicts, and evidence-based treatment recommendations for patients with co-occurring hypertension and BPD. Search terms were combined for hypertension and BPD in PubMed, MEDLINE, EMBASE, Cochrane, and PsycINFO databases.
Results:
We included 11 articles for full-text evaluation and found a very high prevalence of hypertension and substantial cardiovascular risk in studies on co-occurring BPD and hypertension. However, we identified neither studies on harmful drug-drug and drug-disease interactions nor studies with treatment recommendations for co-occurring hypertension and BPD.
Conclusions:
Increased prevalence of hypertension in BPD patients, and therapeutic conflicts of psychotropic agents strongly suggest careful evaluation of treatment strategies in this patient group. However, no studies or guidelines recommend specific therapies or strategies to resolve therapeutic conflicts in patients with hypertension and BPD. This evidence gap needs attention in this population at high risk for cardiovascular disease.
... The effect of induction is simply to increase the amount of P450 present and speed up the oxidation and clearance of a drug, leading to decreased plasma drug concentrations [19,20] . However, the induction, in natural environment can lead to unexpected drug-drug interactions which may lead to the formation of drug residues and thus threaten the safety of fishery products. ...
Cytochrome P450 3A and its role in metabolism of erythromycin by hepatic microsomes of Indian major carps, Labeo rohita (Ham.), Catla catla (Ham.) and Cirrhinus mrigala (Ham.) Abstract Indian major carps, Labeo rohita, Catla catla and Cirrhinus mrigala were challenged intraperitoneally with a dose of erythromycin (50 mg kg-1 body weight) for 24 hrs, 48 hrs, 72 hrs and 96 hrs and hepatic microsomes were isolated. Cytochrome P450 3A (CYP3A) specific erythromycin N-demethylation activity (ERND) in the hepatic microsome was assayed. All three species showed positive reactions for CYP3A. In addition, CYP1A catalyzed ethoxyresorufin-O-deethylase activity (EROD) and CYP2E catalyzed aniline-p-hydroxylation activity (APH) were also studied. It was concluded that the activity of CYP3A was induced in all the fishes while CYP1A and CYP2E activities were not significantly altered.
... A similar interaction was reported in patients taking carbamazepine along with ciprofloxacin, able to inhibit CYP3A4 isoenzyme, also responsible for carbamazepine metabolism (Shahzadi et al., 2011). Again, Fasipe and colleagues reported a severe pharmacodynamic interaction between α-methyldopa and haloperidol, reducing the clinical efficacy of haloperidol (Fasipe et al., 2018) by acting as a pharmacodynamic antagonist in the chemoreceptor trigger zone (CTZ) site and the mesocorticolimbic system D 2 receptors, respectively (Markowitz et al., 1995). The same study (Fasipe et al., 2018) reported that phenobarbital when associated with cyclosporin can trigger a severe pharmacokinetic interaction, as phenobarbital, a strong CYP3A and GlycoproteinP (P-gp) inducer, decreases blood concentration of cyclosporin. ...
Chronic kidney disease (CKD) is a long-term condition characterized by a gradual loss of kidney functions, usually accompanied by other comorbidities including cardiovascular diseases (hypertension, heart failure and stroke) and diabetes mellitus. Therefore, multiple pharmacological prescriptions are very common in these patients. Epidemiological and clinical observations have shown that polypharmacy may increase the probability of adverse drug reactions (ADRs), possibly through a higher risk of drug-drug interactions (DDIs). Renal impairment may further worsen this scenario by affecting the physiological and biochemical pathways underlying pharmacokinetics and ultimately modifying the pharmacodynamic responses. It has been estimated that the prevalence of DDIs in CKD patients ranged between 56.9% and 89.1%, accounting for a significant increase in healthcare costs, length and frequency of hospitalization, with a detrimental impact on health and quality of life of these patients. Despite these recognized high-risk conditions, scientific literature released on this topic is still limited. Basing on the most commonly prescribed therapies in patients with CKD, the present short review summarizes the current state of knowledge of the putative DDIs occurring in CKD patients undergoing polytherapy. The most relevant underlying mechanisms and their clinical significance are also debated.
... The effect of induction is simply to increase the amount of P450 present and speed up the oxidation and clearance of a drug, leading to decreased plasma drug concentrations [19,20] . However, the induction, in natural environment can lead to unexpected drug-drug interactions which may lead to the formation of drug residues and thus threaten the safety of fishery products. ...
A comprehensive handbook covering current, controversial, and debated topics in psychiatric practice, aligned to the EPA Scientific Sections. All chapters been written by international experts active within their respective fields and they follow a structured template, covering updates relevant to clinical practice and research, current challenges, and future perspectives. This essential book features a wide range of topics in psychiatric research from child and adolescent psychiatry, epidemiology and social psychiatry to forensic psychiatry and neurodevelopmental disorders. It provides a unique global overview on different themes, from the recent dissemination in ordinary clinical practice of the ICD-11 to the innovations in addiction and consultation-liaison psychiatry. In addition, the book offers a multidisciplinary perspective on emerging hot topics including emergency psychiatry, ADHD in adulthood, and innovation in telemental health. An invaluable source of evidence-based information for trainees in psychiatry, psychiatrists, and mental health professionals.
Purpose of review
Bipolar disorder is a psychiatric disorder that commonly affects women of reproductive age. Many women with bipolar disorder require treatment during pregnancy and the post-partum period to optimize their health. The following review examines recent evidence regarding the risks and benefits of using commonly prescribed medications for bipolar disorder in pregnancy and lactation.
Recent findings
Current research has not found significant and consistent risks with use of atypical antipsychotics compared to other psychotropic agents, and some previously established teratogens, such as lithium, appear to carry lower risk of malformation than initially reported. Studies that examine the impact of polytherapy, however, are needed.
Summary
A patient-centered approach with minimal effective dosing of necessary medications is likely to produce the best outcome for optimization and simplification of the medical regimen for mother and child.
Neuroleptika (NL) sind die Mittel der Wahl in der Behandlung schizophrener Psychosen; auch psychotische Syndrome bei affektiven Erkrankungen oder in der Folge anderer Krankheiten können mit NL in der Regel gut beeinflußt werden. Fast fünf Jahrzehnte pharmakologischer Erfahrung mit den klassischen NL und drei Jahrzehnte mit dem atypischen NL Clozapin haben Behandlungsregeln etabliert, die für den überwiegenden Teil der Therapien sichere und dem Patienten nutzbringende Wege aufzeigen. Die erheblichen Nebenwirkungsraten der klassischen NL, das Problem der Nonresponder und die unbefriedigende Beeinflußbarkeit der Negativsymptome chronifizierter Schizophrenien haben erhebliche Anstrengungen stimuliert, wirksamere, vor allem nebenwirkungsärmere Pharmaka zu entwickeln, die weitgehend das Rezeptorbindungsprofil des Clozapins zu imitieren oder zu modifizieren versuchen. Clozapin und die neueren Atypika haben unsere Vorstellungen über die pathophysiologischen Mechanismen der Schizophrenie von der reinen Dopaminhypothese weg zu einer Störung im Regelkreis glutamaterger, serotonerger, adrenerger und cholinerger zusammen mit dopaminergen Mechanismen erweitert.
Eines der Hauptprobleme bei der Optimierung neuroleptischer Therapie ? dies betrifft auch die Phenothiazine (Chlorpromazin, Fluphenazin, Levomepromazin, Promazin, Promethazin, Perazin, Perphenazin und Thioridazin) ? stellt die erhebliche interindividuelle Variabilit?t pharmakokinetischer und pharmakodynamischer Faktoren dar. Die pharmakokinetische Variabilit?t bedingt eine hohe Streuung der interindividuellen Neuroleptika-Serumspiegel bei gleicher Dosierung (Dosis-Konzentrations-Beziehung). Um die medikament?se Therapie und den therapeutischen Effekt m?glichst optimal zu gestalten, sollte der therapeutische Serumkonzentrationsbereich oberhalb des unwirksamen und unterhalb des toxischen Bereichs liegen. Im Zusammenhang von Dosis und Wirkungsintensit?t spielen pharmakokinetische Einflu?faktoren (z. B. Absorption und Verteilung) eine wichtige Rolle.
Hyperthyroidism is the principal endocrine indication for propranolol treatment. High levels of thyroid hormones result in a hyperdynamic cardiovascular state including increased stroke volume, augmented myocardial contractility and growth of the left ventricle. Thyroid hormones have a direct effect on the cardiovascular system. They increase cardiac output and lower systemic vascular resistance; also amplify intrinsic activity of sinoatrial node. Such actions lead to increased heart rate with a higher chance of supraventricular tachyarrhythmia, and the most common of them is atrial fibrillation. Thyroid hormones have positive chronotropic and dromotropic activity. Hyperthyroidism creates higher sensitivity to sympathetic stimulation which is conducted through greater number of ß-adrenergic receptors. Myocytes contain an enzyme called type 2 deiodinase which increases local conversion T4 to T3. As a non-selective inhibitor of ß-adrenergic receptors, propranolol is ideal for treating hyperthyroidism. By blocking ß 1 receptors affects the sinoatrial and AV nodes propranolol lowers heart frequency, weakens myocardial contractions and leads to lower oxygen demand. By influencing ß 2 receptors peripheral vasoconstriction rises. Thyroid hormone impact on ß 2 receptors changes the activity of the peripheral 5'-monodeiodinase which converts T4 on the periphery in the active forms of T3. By using propranolol the tremor is reduced. Since the drug is lipophilic it crosses the bloodbrain barrier influencing central nervous system. With propranolol in hyperthyroidism there is less emotional lability and mental tension. The amount of the drug is 10-40 mg divided into 3-4 doses a day, and maximal dosage is 160 mg
The central hypotensive action of clonidine, infused into the vertebral artery of chloralose-anaesthetized cats was antagonized by several phenothiazine-neuroleptics (chlorpromazine, promazine, promethazine, thiethylperazine, thioridazine), by chlorprothixene and to a limited extent by haloperidol administered via the same route. Pimozide and some benzodiazepines (chlordiazepoxide, diazepam and flurazepam) hardly influenced the central hypotensive response to clonidine. The antagonism between clonidine and the psychotropic drugs is probably associated with central alpha-adrenoceptors, clonidine being the agonist and the neuroleptic agents the antagonists at these receptors. Virtually the same type of antagonism was observed in conscious, spontaneously hypertensive rats where both clonidine and the neuroleptic drugs were injected intravenously. The phenothiazines and also piperoxane effectively diminished the centrally induced hypotensive response to clonidine, whereas the initial pressor effect to clonidine was not reduced.
Two cases are reported here. In each the patient had been receiving methyldopa at a constant dosage for over one year, denied adverse mental effects during that time, was observed to have a dementia syndrome within one week after haloperidol was added to the methyldopa, and showed complete clearing of mental symptoms within 72 hours after haloperidol was discontinued.
A group of 156 psychiatric patients from an urban community psychiatric unit for chronic psychiatric patients was routinely medically screened and reported on. Re-evaluation of the medical diseases found in those patients was carried out three years later. Those who were still being treated--73 patients (47%)--were interviewed, as were their psychiatrist and, where necessary, their general practitioner (GP). The implementation of medical recommendations given following the physical screening by the specialist in internal medicine was also assessed. Re-evaluation of the diagnoses confirmed that 36% of this population had one or more physical diseases, rather than the 53% found earlier. The results show that the majority of physical complaints and diseases as well as functional illnesses were as persistent as the psychiatric diagnoses in this patient group. The patients' GP seems to be the person best suited as the primary physician responsible for the patient's physical health.
THE use of a group of drugs collectively referred to as "calcium antagonists," "slow channel antagonists," or "calcium-channel blockers" is likely to increase in the coming years. Currently, calcium antagonists are used primarily in the treatment of cardiovascular disease, and only three of these drugs —nifedipine, verapamil, and diltiazem — are available in the United States. However, numerous others that are already available to European clinicians are likely to be used in this country in the near future. One of the most striking aspects of the calcium-antagonist drugs is their chemical heterogeneity (Fig. 1). Many of these drugs were developed . . .
Calcium channel blockers have an established role in the treatment of various cardiovascular disorders and potential applications in psychiatry. Preliminary reports based on limited numbers of patients indicate that they are promising for mania, of uncertain utility for depression or schizophrenia, and deserving of further investigation for a number of other psychiatric disorders. The authors conclude their review with guidelines for clinical use and precautions to preclude possible undesirable drug interactions.
The relationships between various psychosocial factors and blood pressure were examined in a probability sample of the adult population of the state of Michigan in 1980-1983. Excluding individuals diagnosed by a physician as having high blood pressure and controlling for the major risk factors for hypertension, a number of psychosocial factors significantly predicted blood pressure. Among both men and women, those who generally did not express their emotions (including anger) and who harbored grudges and aggressive impulses had higher diastolic blood pressure. Among men only, those with low self-confidence and less perceived control over their lives had higher systolic and diastolic blood pressures. Those who reported poorer mental health had higher diastolic blood pressure. Among women only, those who rated their relationships with family and best friend more poorly had higher systolic blood pressure. Possible explanations are discussed for the gender-specific relationships between blood pressure and certain psychosocial factors.
The interaction of neuroleptics, tricyclic antidepressants, monoamine oxidase inhibitors, lithium and anxiolytic sedatives with other drugs and food is reviewed with special emphasis on drug interactions commonly encountered in psychiatric practice. Clinical relevance and mechanism of action of such interactions are discussed. An update of the interaction of lithium with prostaglandin inhibitors is presented.