Journal articles: 'Psychotropic drugs – pharmacokinetics'

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Fernandes Santos, C., and R. Gomes. "Specificities of the Use of Psychotropic Drugs in Bariatric Surgery." European Psychiatry 65, S1 (June 2022): S478—S479. http://dx.doi.org/10.1192/j.eurpsy.2022.1216.

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Introduction Bariatric surgery is considered an effective treatment against obesity. Psychiatric illness is relatively common in patients who have undergone bariatric surgery. Over one-third of these patients are prescribed psychotropic drugs, particularly antidepressants. Unlike medications for diabetes, hypertension or hyperlipidemia, which are generally reduced and at times discontinued, postsurgery psychotropic use is only slightly reduced. The surgical intervention and the subsequent weight loss can affect several pharmacokinetic parameters, leading to a possible need of dosing adjustment. Objectives To review the influence of bariatric surgery on the use and pharmacokinetics of psychotropic drugs. Methods Non-systematic review of literature through search on PubMed/MEDLINE for publications from 2011 to 2021, following the terms psychotropic and bariatric surgery. Textbooks were consulted. Results It is difficult to predict how psychotropics will be affected by bariatric surgery because of interindividual differences and limited data. Malabsorptive surgical procedures have a relatively greater potential to alter drug exposure. Medication disintegration, dissolution, absorption, metabolism and excretion have been found to be altered in postbariatric patients. Antidepressants are the best studied psychotropics in the bariatric population and their absorption is reduced. The risk of gastric bleeds with bariatric surgery will probably be increased by serotoninergic antidepressants. Antipsychotics and mood stabilisers are not well studied in these patients. Depot antipsychotics avoid the risk of reduced absorption after surgery. Lithium use requires particular close monitoring. Conclusions Close treatment monitoring and the ongoing monitoring of symptoms are needed after bariatric surgery. Many patients may not require significant changes to drug treatment after surgery. Disclosure No significant relationships.

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BOURIN, M., and A. COUETOUX DU TERTRE. "PHARMACOKINETICS OF PSYCHOTROPIC DRUGS IN CHILDREN." Clinical Neuropharmacology 15 (1992): 224A—225A. http://dx.doi.org/10.1097/00002826-199201001-00117.

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Sit, D. K., J. M. Perel, J. Helsel, and K. L. Wisner. "Pharmacokinetics of psychotropic drugs in pregnancy." Neurotoxicology and Teratology 29, no. 3 (May 2007): 411. http://dx.doi.org/10.1016/j.ntt.2007.03.051.

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Burns, Alistair, and Robert Baldwin. "Prescribing psychotropic drugs for the elderly." Advances in Psychiatric Treatment 1, no. 1 (September 1994): 23–31. http://dx.doi.org/10.1192/apt.1.1.23.

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The pharmacological treatment of the elderly differs from that of younger patients, mainly because of altered pharmacokinetics and the higher proportion of patients with organic disorders. We deal here with dementia, delirium, affective disorder, late-life schizophrenia, sleep disturbance, and rapid tranquillisation.

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Marazziti, Donatella, Stefano Baroni, Michela Picchetti, Armando Piccinni, Marina Carlini, Elena Vatteroni, Valentina Falaschi, Amedeo Lombardi, and Liliana Dell'Osso. "Pharmacokinetics and pharmacodinamics of psychotropic drugs: effect of sex." CNS Spectrums 18, no. 3 (February 4, 2013): 118–27. http://dx.doi.org/10.1017/s1092852912001010.

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Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990–2012.Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described.Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

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Baumann, P. "JS01-01 - Pharmacokinetics of psychotropic drugs - keys for treatments’ improvements." European Psychiatry 26, S2 (March 2011): 1995. http://dx.doi.org/10.1016/s0924-9338(11)73698-7.

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Non-response, adverse effects and pharmacokinetic interactions with clinical consequences are frequent manifestations observed in psychiatric patients treated with psychotropic drugs. These risks are increased in patients belonging to the category of “special populations”: elderly patients, children and adolescents, patients with a genetic particularity of metabolism or suffering from somatic or psychic comorbidities. Increasingly, the use of generics has been shown to represent a source of unexpected treatment outcomes. Therapeutic drug monitoring (TDM) is not only recommended in these situations, but especially also in patients who are suspected to be non-compliant. In addition, the increasing knowledge of the metabolism of psychotropic drugs allows the use of phenotyping and/or genotyping techniques (e.g. cytochrome P-450, P-glycoprotein) in patients and to adapt their medication considering their pharmacogenetic status. Pharmacokinetic (TDM) and pharmacogenetic tests are therefore useful to solve problems in psychopharmacotherapy and thus improve efficacy and safety of the drugs. An earlier developed Consensus guideline on TDM (Baumann et al., 2004) has recently been updated (Hiemke et al., 2011).

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Pichini, Simona, Esther Papaseit, Xavier Joya, Oriol Vall, Magí Farré, Oscar Garcia-Algar, and Rafael de laTorre. "Pharmacokinetics and Therapeutic Drug Monitoring of Psychotropic Drugs in Pediatrics." Therapeutic Drug Monitoring 31, no. 3 (June 2009): 283–318. http://dx.doi.org/10.1097/ftd.0b013e31819f3328.

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Iannaccone, Teresa, Carmine Sellitto, Valentina Manzo, Francesca Colucci, Valentina Giudice, Berenice Stefanelli, Antonio Iuliano, Giulio Corrivetti, and Amelia Filippelli. "Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters." Pharmaceuticals 14, no. 3 (March 1, 2021): 204. http://dx.doi.org/10.3390/ph14030204.

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Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

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Moschny, Nicole, Gudrun Hefner, Renate Grohmann, Gabriel Eckermann, Hannah B. Maier, Johanna Seifert, Johannes Heck, et al. "Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs—Influence of Smoking Behavior and Inflammation on Pharmacokinetics." Pharmaceuticals 14, no. 6 (May 27, 2021): 514. http://dx.doi.org/10.3390/ph14060514.

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Both inflammation and smoking can influence a drug’s pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients’ drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior—both clinically relevant in psychiatry—that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment.

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Telles-Correia, Diogo, António Barbosa, Helena Cortez-Pinto, Carlos Campos, Nuno B. F. Rocha, and Sérgio Machado. "Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity." World Journal of Gastrointestinal Pharmacology and Therapeutics 8, no. 1 (2017): 26. http://dx.doi.org/10.4292/wjgpt.v8.i1.26.

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Athanasiu, Lavinia, Lisa-Lena H. Smorr, Martin Tesli, Jan I. Røssberg, Ida E. Sønderby, Olav Spigset, Srdjan Djurovic, and Ole A. Andreassen. "Genome-wide association study identifies common variants associated with pharmacokinetics of psychotropic drugs." Journal of Psychopharmacology 29, no. 8 (May 5, 2015): 884–91. http://dx.doi.org/10.1177/0269881115584469.

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DeVane, C. Lindsay, and David W. Boulton. "Great Expectations in Stereochemistry: Focus on Antidepressants." CNS Spectrums 7, S1 (April 2002): 28–33. http://dx.doi.org/10.1017/s1092852900028571.

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ABSTRACTChirality has become an increasingly important consideration in the development of psychoactive drugs because enantiomers often show major differences in their pharmacokinetic and pharmacologic properties. This review illustrates the implications of stereochemistry in clinical psychopharmacology using the antidepressant class of drugs as a focus. In many cases, a better understanding of stereochemistry can improve therapeutic outcomes. For example, with citalopram, the racemic formulation is effective for depression as well as panic and obsessive-compulsive disorders. However, the S-enantiomer, escitalopram, is at least twice as potent as racemic citalopram as an inhibitor of serotonin reuptake, implying that it can be used at lower doses, while offering an improved therapeutic index as well as an improved safety profile and reduced drug interaction liability. Clinical trial data support these advantages. Continuing research on the stereochemical properties of psychoactive drugs should simplify the characterization of dose-response relationships, and clarify the effects of disease states, genetic polymorphisms, pregnancy, age, and gender on stereoselective pharmacokinetics and pharmacodynamics. Better understanding of the fate of chiral psychotropic agents and the factors that influence their stereoselective disposition and actions will provide a rational basis for their expanded use in various patient populations.

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Jorge, B., C. Pedro, J. Carvalho, S. Carneiro, and M. Mangas. "428 - Reflections on geriatric psychopharmacology in Portugal." International Psychogeriatrics 33, S1 (October 2021): 48–49. http://dx.doi.org/10.1017/s1041610221001873.

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Background:The most common psychiatric illnesses include depressive and anxiety disorders. However, the gap between therapeutic indication and pharmacological consumption is evident, with anxiolytics and antidepressants being some of the most prescribed drugs for the general population and, in particular, for the elderly. However, several of these psychotropic drugs are part of the list of potentially inappropriate medications for the elderly. Thus, the question arises: is the appropriate care being given to older patients, in this domain?Research objective:This work aims to reflect on the current structure of the mental health care network for elderly patients, focusing on consumption patterns among thevarious categories of psychotropic drugs and their physiological impact, taking into account the particularities of the target population.Method:A non-systematic review of the literature is presented. Bibliographic selection was carried out through keyword research in MEDLINE, Google Scholar and also by cross-referencing between articles.Results:In Portugal it was possible to infer that the consumption of anxiolytics and antidepressants increased ans was in line with the European trend. On the other hand, there has been a downward trend in the consumption of sedatives and hypnotics, opposite to the general trend in Europe. Due to changes related to pharmacokinetics and pharmacodynamics, older patients are more susceptible to the development of adverse reactions, the prevalence of potentially inappropriate medications is high in the context of mental health care. Switching drugs such as benzodiazepines, certain antipsychotics, tricyclic antidepressants and first-generation antihistamines significantly reduced the risk of adverse reactions.Discussion:Mental health care policies must be aligned with the conscious use of psychotropic drugs in the elderly population, at risk of the main objective, their well- being and care, being compromised.

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Darnaud, Léa, Clément Delage, Youssef Daali, Anne-Priscille Trouvin, Serge Perrot, Nihel Khoudour, Nadia Merise, et al. "Phenotyping Indices of CYP450 and P-Glycoprotein in Human Volunteers and in Patients Treated with Painkillers or Psychotropic Drugs." Pharmaceutics 15, no. 3 (March 18, 2023): 979. http://dx.doi.org/10.3390/pharmaceutics15030979.

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Drug-metabolizing enzymes and drug transporters are key determinants of drug pharmacokinetics and response. The cocktail-based cytochrome P450 (CYP) and drug transporter phenotyping approach consists in the administration of multiple CYP or transporter-specific probe drugs to determine their activities simultaneously. Several drug cocktails have been developed over the past two decades in order to assess CYP450 activity in human subjects. However, phenotyping indices were mostly established for healthy volunteers. In this study, we first performed a literature review of 27 clinical pharmacokinetic studies using drug phenotypic cocktails in order to determine 95%,95% tolerance intervals of phenotyping indices in healthy volunteers. Then, we applied these phenotypic indices to 46 phenotypic assessments processed in patients having therapeutic issues when treated with painkillers or psychotropic drugs. Patients were given the complete phenotypic cocktail in order to explore the phenotypic activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, and P-glycoprotein (P-gp). P-gp activity was evaluated by determining AUC0–6h for plasma concentrations over time of fexofenadine, a well-known substrate of P-gp. CYP metabolic activities were assessed by measuring the CYP-specific metabolite/parent drug probe plasma concentrations, yielding single-point metabolic ratios at 2 h, 3 h, and 6 h or AUC0–6h ratio after oral administration of the cocktail. The amplitude of phenotyping indices observed in our patients was much wider than those observed in the literature for healthy volunteers. Our study helps define the range of phenotyping indices with “normal” activities in human volunteers and allows classification of patients for further clinical studies regarding CYP and P-gp activities.

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Yoshida, K., B. Smith, and R. Kumar. "Psychotropic drugs in mothers' milk: a comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding." Journal of Psychopharmacology 13, no. 1 (January 1999): 64–80. http://dx.doi.org/10.1177/026988119901300108.

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Lin, Shih-Ku. "Racial/Ethnic Differences in the Pharmacokinetics of Antipsychotics: Focusing on East Asians." Journal of Personalized Medicine 12, no. 9 (August 24, 2022): 1362. http://dx.doi.org/10.3390/jpm12091362.

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Empirical clinical studies have suggested that East Asian patients may require lower dosages of psychotropic drugs, such as antipsychotics, lithium, and antidepressants, than non-Asians. Both the pharmacokinetic and pharmacodynamic properties of a drug can affect the clinical response of an illness. The levels of antipsychotics used for the treatment of schizophrenia may affect patient clinical responses; several factors can affect these levels, including patient medication adherence, body weight (BW) or body mass index, smoking habits, and sex. The cytochrome P450 (CYP) system is a major factor affecting the blood levels of antipsychotics because many antipsychotics are metabolized by this system. There were notable genetic differences between people of different races. In this study, we determined the racial or ethnic differences in the metabolic patterns of some selected antipsychotics by reviewing therapeutic drug monitoring studies in East Asian populations. The plasma concentrations of haloperidol, clozapine, quetiapine, aripiprazole, and lurasidone, which are metabolized by specific CYP enzymes, were determined to be higher, under the same daily dose, in East Asian populations than in Western populations.

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Schjøtt, Jan, Lillan Mo Andreassen, Gro Helen Dale, and Charlotte Lorentze Stokes. "Review of Clinical Questions Submitted to Norwegian Drug Information Centres Concerning Administration and Dosage to Older Patients of Relevance to Patient-Centric Care." Pharmaceutics 13, no. 1 (January 14, 2021): 105. http://dx.doi.org/10.3390/pharmaceutics13010105.

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Patient-centric care entails optimising healthcare provision to patients based on their perspective and opinion. It involves appropriate treatment at a reasonable cost and a focus on patient characteristics in the decision-making process to make it more personally useful. The optimisation of medicines in the older population is a challenge due to physiological changes, comorbidity, and polypharmacy. Furthermore, patient-centric care is difficult to achieve due to the high proportion of patients with dementia and frailty. Decision support concerning the appropriateness of indication, formulation, dose, administration, co-prescribing, and length of treatment to older patients is frequently in demand. In the current study, we aimed to review clinical questions concerning administration and dosage to older patients of relevance to patient-centric care. We analysed questions concerning medicines to patients 65 years or older in the database of the network of Norwegian drug information centres from 2010 to 2020. The analysis included the distribution of drugs, diseases, and recurring topics among the questions. Through a Boolean search that combined the indexed categories of “older” and “administration and dosage”, we retrieved 84 question-answer pairs. Questions about psychotropic and cardiovascular drugs in relation to therapy, adverse drug reactions, and pharmacokinetics dominated, and more than 60% of the questions came from physicians. Topics relevant to patient-centric pharmacotherapy were drug withdrawal (10 questions), drug formulation (8 questions), drug initiation (8 questions), and switching drugs (5 questions). One question concerned drug withdrawal and switching, and one question drug formulation and switching. Answers provided decision support regarding appropriate formulations of drugs to patients with dementia who chew capsules or tablets, the use of parenteral administration in patients who refuse to take oral formulations, and the pharmacokinetics of transdermal or rectal drug administration. The results highlight the importance of including pharmacological factors in the assessment of the acceptability and appropriateness of oral and parenteral medicine to older patients.

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Leonova, M. V. "Drug-induced arrhythmias." Meditsinskiy sovet = Medical Council, no. 21 (January 17, 2021): 26–40. http://dx.doi.org/10.21518/2079-701x-2020-21-26-40.

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The article provides a scientific review based on the proceedings of the 2020 American Heart Association consensus on drugs that may cause arrhythmias on a risk-sensitive basis and a guidance on strategies for monitoring, prevention methods and therapeutic approaches.The risk factors for drug-induced arrhythmias are divided into modifiable and non-modifiable. Among the non-modifiable risk factors are congenital anomalies (changes in the conduction system, ion channel polymorphism) and heart diseases (cavity dilatation, myocardial ischemia). Among the modifiable risk factors are various electrolyte disorders (hypo/hyperkalemia, hypo/hypermagnesemia, hypocalcemia). Certain drugs can lead to electrolyte disorders, which require management with potassium and magnesium supplements. The drug-induced arrhythmias can be caused by conditions leading to altered drug pharmacokinetics and increased plasma concentrations and metabolites having proarrhythmogenic effects, as well as drug-drug interactions.Beta-blockers, non-dihydropyridine calcium channel blockers, other antiarrhythmic drugs, ivabradine, digoxin, anesthetics (bupivacaine, propofol) are the most common culprits in causing drug-induced bradyarrhythmias. The drug-induced atrial fibrillation frequently occurs in patients receiving antiarrhythmics, various sympathomimetics, psychotropic and antineoplastic drugs, anti-inflammatory (NSAIDs, corticosteroids) and immunotropic agents (interleukin-2, fingolimod). Various sympathomimetics and inotropic drugs, some antipsychotic drugs can produce drug-induced atrial and nodal tachyarrhythmias.The drug-induced ventricular tachycardia can be caused by antiarrhythmics, inotropics and various sympathomimetics, antipsychotic and antineoplastic drugs, as well as herbal drugs (aconite, ginkgo biloba). The list of drugs that cause a long QT syndrome includes antiarrhythmics, antimicrobial drugs (macrolides, fluoroquinolones, aminoquinolines, fluconazole), antipsychotics, antineoplastic drugs, antiemetics, etc. For a complete list of drugs that prolong a QT interval, see the CredibleMeds website (Arizona, USA). The drug-induced arrhythmia prevention strategies include rising awareness among doctors about risk factors and potentially dangerous drugs, sufficient monitoring of patients at risk of developing arrhythmias (ECG monitoring, electrolyte balance, kidney and liver function), maintenance of electrolyte balance, primarily potassium and magnesium. The therapeutic approach includes discontinuation of a causative drug; relief and maintenance therapy are carried out based on the modern international clinical guidelines for various forms of arrhythmias.

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Therrien, Rachel. "Managing Psychotropic Drugs with Efavirenz." Canadian Journal of Infectious Diseases and Medical Microbiology 17, suppl d (2006): 15D—16D. http://dx.doi.org/10.1155/2006/736415.

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Efavirenz is in the non-nucleoside reverse transcriptase inhibitor category of HIV antiretroviral medicines. It is an in vivo inducer of the CYP3A4 isoenzyme within the cytochrome P450 (CYP450) system, and an in vitro inhibitor of the system’s CYP2C9/2C19, 3A4 and 2B6 isoenzymes; as a result, concentrations of psychotropic drugs can be increased or decreased depending on the specific enzyme pathway involved in their metabolism. CYP3A4 is responsible for metabolizing many benzodiazepines and other psychotropics, as well as selective serotonin reuptake inhibitors and tricyclic antidepressants. As an inducer of CYP3A4, efavirenz can increase the rate at which these agents are metabolized, resulting in administered psychotropic drug levels that are below their therapeutic thresholds. Conversely, efavirenz is an inhibitor of CYP2B6, which metabolizes agents such as bupropion; consequently, bupropion levels in the blood can increase. Given the existing conflicting data, the clinician may find it impractical to use an evidence-based approach when concomitantly prescribing efavirenz and psychotropic drugs to their HIV patients. Instead, it may be preferable to use a more pragmatic approach that applies knowledge of the most current pharmacological and pharmacokinetic data for psychotropics and non-nucleoside reverse transcriptase inhibitors, which may help better predict their potential interactions.

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Goodlet, Kellie J., Monika T. Zmarlicka, and Alyssa M. Peckham. "Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs." CNS Spectrums 24, no. 03 (October 8, 2018): 287–312. http://dx.doi.org/10.1017/s109285291800113x.

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Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

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Kolyvanov, G. B., A. A. Litvin, R. V. Shevchenko, S. Yu Raskin, P. O. Bochkov, and V. P. Zherdev. "Pharmacokinetic relationships in psychotropic drugs effects." Pharmacokinetics and Pharmacodynamics, no. 4 (June 25, 2021): 3–8. http://dx.doi.org/10.37489/2587-7836-2020-4-3-8.

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The review discusses relationships between pharmacokinetic parameters and effects of psychotropic drugs, both in preclinical studies and clinical practice. The identification of such correlations can serve as a basis for understanding the complex system of relationships between pharmacokinetic and pharmacodynamic mechanisms in the manifestation of the action of this group of drugs and allows us to use the data of pharmacokinetic studies to optimize therapeutic approaches in medical practice.

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Chadwick, Ben, Derek G. Waller, and J. Guy Edwards. "Potentially hazardous drug interactions with psychotropics." Advances in Psychiatric Treatment 11, no. 6 (November 2005): 440–49. http://dx.doi.org/10.1192/apt.11.6.440.

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Of the many interactions with psychotropic drugs, a minority are potentially hazardous. Most interactions are pharmacodynamic, resulting from augmented or antagonistic actions at a receptor or from different mechanisms in the same tissue. Most important pharmacokinetic interactions are due to effects on metabolism or renal excretion. The major enzymes involved in metabolism belong to the cytochrome P450 (CYP) system. Genetic variation in the CYP system produces people who are ‘poor’, ‘extensive’ or ‘ultra-rapid’ drug metabolisers. Hazardous interactions more often result from enzyme inhibition, but the probability of interaction depends on the initial level of enzyme activity and the availability of alternative metabolic routes for elimination of the drug. There is currently interest in interactions involving uridine diphosphate glucuronosyltransferases and the P-glycoprotein cell transport system, but their importance for psychotropics has yet to be defined. The most serious interactions with psychotropics result in profound sedation, central nervous system toxicity, large changes in blood pressure, ventricular arrhythmias, an increased risk of dangerous side-effects or a decreased therapeutic effect of one of the interacting drugs.

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Blier, Pierre. "Generic Substitution for Psychotropic Drugs." CNS Spectrums 14, no. 9 (September 2009): 1–7. http://dx.doi.org/10.1017/s1092852900024706.

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Most antidepressants and other psychotropics in clinical use are available as generic formulations (Table). The availability of lower-priced, generic drugs can benefit patients and third-party payers, but it should not be assumed that all generic drugs are equally beneficial. There are numerous reports in the literature of unexpected and untoward consequences that occur when a generic drug is substituted for the original brand-name drug. A previously stable clinical response may suddenly deteriorate, or the patient may experience new or more severe adverse events (AEs). The United States Food and Drug Administration requires that manufacturers of generic drugs demonstrate that their formulation has pharmacokinetic properties similar (or bioequivalent) to the brand-name drug. Bioequivalency studies are conducted in healthy volunteers, not in patients who would be treated with that drug. Moreover, bioequivalency studies are conducted on a current lot of the branded drug and do not account for variability between lots of the generic formulation. The manufacturer is only required to submit bioequivalency data that support the Abbreviated New Drug Application (ANDA); the FDA does not require disclosure of failed bioequivalence studies. Unlike brand-name drugs, lengthy and costly clinical studies are not required to show that the generic drug is effective and safe.Although the FDA has taken the position that bioequivalence and therapeutic equivalence are equal, many questions related to the use of generic drugs remain unanswered. The following question-and-answer session is an excerpt of an interview with Pierre Blier, MD, PhD, conducted by Diane Sloan, PharmD, which addresses the issue of generic substitution of psychotropic drugs.

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Petrykiv, S., M. Arts, and L. De Jonge. "Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs." European Psychiatry 65, S1 (June 2022): S454. http://dx.doi.org/10.1192/j.eurpsy.2022.1152.

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Introduction Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART). Hepatic metabolism both of AP and ART involves the cytochrome P450 enzyme system, potentially leading to a multitude of pharmacokinetic (PK) interactions and serious adverse side effects. The magnitude and clinical impact of PK-interactions can vary significantly. Objectives The scope of this review is to summarize the currently available data regarding drug-drug interactions (DDI) between AP and ART, and to provide recommendations for their management. Methods A formal search of Embase, Cochrane and Medline was performed, searching for human studies from inception till 2017 on PK-interactions between AP and ART and reporting clinical toxicity as outcomes. Authors also provide their expertise on magnitude and clinical relevance of DDI using PK interaction chart. Results Ten case reports including total of 13 patient were analyzed, comprising following AP: aripiprazole (N=2), risperidone (N=4), quetiapine (N=3) and lurasidone (N=1) in combination with various ART regiments. Significant PK-interactions were to occur in cases when aripiprazole was combined with ritonavir and/or cobicistat or efavirenz and/or darunavir; risperidone with indinavir of ritonavir; quetiapine with ritonavir and atazanavir/ritonavir; lurasidone with atazanavir. Adverse events occurred in combinations of aripiprazole with ritonavir/darunavir, risperidone with ritonavir or indinavir, quetiapine with atazanavir and lurasidone with atazanavir. Conclusions Psychotropics and antiretrovirals may be used safely, particularly when known DDIs are proactively managed. Clinicians should be aware of the pharmacokinetic and pharmacodynamic properties of these agents to best direct therapy and to provide optimal patient care Disclosure No significant relationships.

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Baumann, P. "Clinical effectiveness of psychotropic drugs: Pharmacokinetic and pharmacogenetic determinants." European Psychiatry 25 (2010): 167. http://dx.doi.org/10.1016/s0924-9338(10)70167-x.

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Karimov, Artur Udalisovich, Maxim Leonidovich Maximov, Dmitry Germanovich Semenikhin, and Linar Arturovich Karimov. "Topical issues of interaction of psychotropic drugs." Vrač skoroj pomoŝi (Emergency Doctor), no. 3 (March 1, 2021): 27–38. http://dx.doi.org/10.33920/med-02-2103-02.

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In mental patients with concomitant somatic pathology, psychotropic drugs are prescribed in combination with other drugs used in the treatment of various somatic diseases. As well as a large number of patients with somatic diseases, they receive therapy aimed at correcting mental disorders. At the same time, it is important to take into account the possibility of cross-influence of such pharmacotherapy on the functions of the central nervous system and internal organs, as well as the peculiarities of drug interactions between drugs. According to the mechanism of development, there are pharmaceutical, pharmacokinetic and pharmacodynamic interactions of drugs. The result of the interaction of drugs is more often a change in the intensity of the effect of drugs, less often there are qualitative changes in their action. The review article provides up-to-date practical information on the interaction of drugs for the treatment of mental disorders with drugs of other groups.

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Moran, Michael G., and Troy L. Thompson. "Changes in the Aging Brain as They Affect Psychotropics: A Review." International Journal of Psychiatry in Medicine 18, no. 2 (June 1989): 137–44. http://dx.doi.org/10.2190/p60g-3ctc-26wt-43t8.

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This article reviews a number of neuroanatomic and neurochemical changes that occur in the brain with aging, and focuses specifically on those that may affect the response to psychotropic drugs. We hope to increase physicians' awareness of these “central,” or brain, changes, that occur with aging when prescribing and monitoring psychotropic use, since the traditional emphasis in prescribing for the elderly has rested with the review of pharmacokinetic, or “peripheral” organ changes.

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Hiemke, C. "The interactions between COVID-19 drugs and psychotropic agents." European Psychiatry 64, S1 (April 2021): S15. http://dx.doi.org/10.1192/j.eurpsy.2021.63.

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Coronavirus disease (COVID-19) is a systemic infection targeting multiple organs. Interstitial pneumonia is the landmark feature of this condition. Severe acute respiratory symptoms requiring intensive care support arises for about one out of twenty symptomatic cases. Aminochinolone, antiviral, antibiotic, corticoid, anticoagulant and immunobiological drugs are used, mostly to treat symptoms. Only remdesivir exhibiting weak antiviral activity is approved for COVID-19. Psychotropic medications may interact with medical treatments for COVID-19. The aim of this presentation is to highlight pharmacokinetic and pharmacodynamic drug-drug interactions to be expected for medical treatments of COVID-19. Remdesivir and favipiravir exhibit hepatotoxic properties which may be enhanced under combinations with tricyclic antidepressants or agomelatine. Favipiravir, hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir have QT interval prolongation potential and must be considered for combinations with antidepressant and antipsychotic drugs. For hydroxychloroquine, hypoglycemic activity may give rise to endocrine disturbances. Pharmacokinetic drug-drug interactions can be expected for lopinavir/ritonavir which inhibit cytochrome P-450 (CYP) 3A4 and induce CYP2C9 and CYP2C19. Combinations with psychotropic drugs that are substrates of these enzymes (victim drugs) will affect drug concentrations in blood and lead to supra- or subtherapeutic levels. Moreover, it must be assumed that the COVID-19 infection is associated with an enhanced production of cytokines which has a known impact on CYP enzyme activities. Though studies on interactions between psychotropic medications and medical treatments for COVID-19 are lacking, multiple drug interactions can be predicted and expected considering the side effect profiles and CYP inhibitory, inducing and substrate properties of combined drugs.DisclosureNo significant relationships.

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Wieck, A. "Should we monitor psychotropic drug levels in pregnancy and the postpartum period to reduce risks of recurrence?" European Psychiatry 64, S1 (April 2021): S42—S43. http://dx.doi.org/10.1192/j.eurpsy.2021.142.

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Pregnancy is associated with profound changes in pharmacokinetic processes. This is an important - and until recently neglected - area of research since the majority of women take drugs during pregnancy in addition to vitamin and dietary supplements. Recent evidence has emerged that the changes do not only include absorption, distribution and excretion but also drug metabolism, such as modifications in the regulation of hepatic metabolism and conjugation. Oestradiol is known to have an important role in the expression of cytochrome P450 isoenzymes and glucuronosyltransferase that are involved in the metabolism of psychotropic drugs. Recent studies of different psychotropic drug classes have shown that this can result in profound changes of plasma concentrations that commence early in pregnancy and gradually increase towards delivery. In this presentation pregnancy-induced metabolic changes that have been found so far for several psychotropic drugs will be discussed and the question addressed whether and how we should monitor plasma levels in our pregnant patients.DisclosureNo significant relationships.

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Schlatter, Chantal, Sabin S. Egger, Lydia Tchambaz, and Stephan Krähenbühl. "Pharmacokinetic Changes of Psychotropic Drugs in Patients with Liver Disease." Drug Safety 32, no. 7 (July 2009): 561–78. http://dx.doi.org/10.2165/00002018-200932070-00003.

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Spina, Edoardo, and Emilio Perucca. "Clinical Significance of Pharmacokinetic Interactions Between Antiepileptic and Psychotropic Drugs." Epilepsia 43 (March 19, 2002): 37–44. http://dx.doi.org/10.1046/j.1528-1157.2002.043s2037.x.

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Yasui-Furukori, Norio, Tomonori Tateishi, Tsuyoshi Kondo, Kazuo Mihara, Akihito Suzuki, Shingo Ono, and Sunao Kaneko. "Effect of CYP2D6 genotype on pharmacokinetic interactions with psychotropic drugs." International Congress Series 1244 (July 2002): 21–31. http://dx.doi.org/10.1016/s0531-5131(02)00453-3.

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Pisani, F., E. Perucca, and R. Di Perri. "Clinically Relevant Anti-Epileptic Drug Interactions." Journal of International Medical Research 18, no. 1 (January 1990): 1–15. http://dx.doi.org/10.1177/030006059001800102.

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Anti-epileptic drugs frequently interact due to pharmacokinetic features (induction or inhibition of metabolism, production of active metabolites, low therapeutic indices) and the need for prolonged treatment with possible addition of other drugs to treat concomitant diseases. The most important pharmacokinetic interactions are those that inhibit phenytoin, carbamazepine and phenobarbitone metabolism and thus increase their toxicity. Drugs inhibiting metabolism include antibiotic macrolides, chloramphenicol, isoniazide, some sulphonamides, propoxyphene, cimetidine, valproic acid and sulthiame. Anti-epileptic drugs can induce hepatic microsomal enzymes and, therefore, may increase metabolism of corticosteroids, oral contraceptives, oral anticoagulants, cardiovascular agents, antibiotics, chemotherapeutic agents, psychotropic drugs and non-opiate analgesics, thereby reducing their efficacy. Advantageous pharmacodynamic interactions include synergism of ethosuximide plus valproic acid and of carbamazepine plus valproic acid. A pharmacodynamic mechanism may be responsible for the reduced sensitivity of chronically treated epileptics to some neuromuscular blockers.

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Bishara, Delia, Chris Kalafatis, and David Taylor. "Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents." Therapeutic Advances in Psychopharmacology 10 (January 2020): 204512532093530. http://dx.doi.org/10.1177/2045125320935306.

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As yet, no agents have been approved for the treatment of COVID-19, although several experimental drugs are being used off licence. These may have serious adverse effects and potential drug interactions with psychotropic agents. We reviewed the common agents being used across the world for the treatment of COVID-19 and investigated their drug interaction potential with psychotropic agents using several drug interaction databases and resources. A preliminary search identified the following drugs as being used to treat COVID-19 symptoms: atazanavir (ATV), azithromycin (AZI), chloroquine (CLQ)/hydroxychloroquine (HCLQ), dipyridamole, famotidine (FAM), favipiravir, lopinavir/ritonavir (LPV/r), nitazoxanide, remdesivir, ribavirin and tocilizumab. Many serious adverse effects and potential drug interactions with psychotropic agents were identified. The most problematic agents were found to be ATV, AZI, CLQ, HCLQ, FAM and LPV/r in terms of both pharmacokinetic as well as serious pharmacodynamic drug interactions, including QTc prolongation and neutropenia. Significant caution should be exercised if using any of the medications being trialled for the treatment of COVID-19 until robust clinical trial data are available. An even higher threshold of vigilance should be maintained for patients with pre-existing conditions and older adults due to added toxicity and drug interactions, especially with psychotropic agents.

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Spina, Edoardo, and Achille P. Caputi. "Pharmacogenetic aspects in the metabolism of psychotropic drugs: Pharmacokinetic and clinical implications." Pharmacological Research 29, no. 2 (February 1994): 121–37. http://dx.doi.org/10.1016/1043-6618(94)80036-7.

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Bayanov, A. "A pharmacokinetic study of paradoxical reactions to psychotropic drugs in children with ADHD." European Neuropsychopharmacology 12 (October 2002): 404–5. http://dx.doi.org/10.1016/s0924-977x(02)80690-3.

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Grady, Meghan M., and Stephen M. Stahl. "A Horse of a Different Color: How Formulation Influences Medication Effects." CNS Spectrums 17, no. 2 (May 9, 2012): 63–69. http://dx.doi.org/10.1017/s1092852912000442.

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A medication's pharmacokinetic properties can be as important as its efficacy in determining how successful a treatment is. Formulation plays a critical role in absorption, distribution, and elimination of a drug, which in turn can influence the clinical profile of a medication, including onset and duration of action, consistency of plasma levels, ability to cross the blood-brain barrier, and other factors. Advances in drug delivery technology mean that formulation is now an integral component in the development of a drug. Likewise, formulation is one of the factors that may influence selection of a medication to suit the needs of a particular patient. This article briefly reviews the technologies commonly applied in the development of psychotropic medications, with emphasis on the various oral modified-release formulations, and discusses how formulation can be used to optimize the efficacy and tolerability of psychotropic drugs.

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Santos, Jaqueline Rocha Borges dos, Larrysa de Morais Alves da Cruz, Luís Phillipe Nagem Lopes, and Maria Eline Matheus. "Tobacco consumption during the COVID-19 pandemic and pharmacokinetic interaction involving cytochrome P-450 with psychoactive drugs: an integrative review." Research, Society and Development 11, no. 10 (July 28, 2022): e222111032349. http://dx.doi.org/10.33448/rsd-v11i10.32349.

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This integrative review examines tobacco use related to mental disorders in COVID-19 pandemic and potential interactions involving cytochrome P-450 between tobacco and psychotropic drugs. The five steps of the integrative review development process were considered, namely: elaboration of the guiding question, literature search or sampling, evaluation of data, data analysis, interpretation and presentation of results. A literature search was performed in the Medline and Bireme databases, without language restrictions up to May 2021. Forty-seven articles were found with information on COVID-19, tobacco use and psychiatric illness. Articles were also sought that addressed interactions between major classes of psychotropic drugs and tobacco associated with CYP450 isoforms and genetic polymorphism. Thirty-seven articles were found for interaction among tobacco, cytochrome P450 and antidepressants; 7 including polymorphism; 19 articles involving interaction of tobacco, cytochrome P450 and antipsychotics; 4 including polymorphism; 3 articles describing interaction of tobacco, cytochrome P450 and anxiolytics; 1 including polymorphism; 2 articles regarding interaction of tobacco, cytochrome P450 and mood stabilizers; and 1 including polymorphism. These findings reinforce the importance of recognizing the role of tobacco associated with drug use in mental disorders; indicating the need for monitoring to prevent worsening clinical conditions.

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Prisco, V., T. Iannaccone, A. Capuano, M. Fabrazzo, and F. Catapano. "Drug safety warnings in psychiatry: Adverse drug reactions’ signaling from 2002 to 2014." European Psychiatry 41, S1 (April 2017): S758. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1420.

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Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and co-morbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in ADRs (adverse drug reactions). This study performs an analysis of the Italian medicine agency (AIFA) data, in the section “signal analysis”, to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (anti-epileptics), N05 (anti-psychotics), N06 (psycho-analectic drugs). Then we analyzed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to anti-psychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical anti-spychotics. Other correlations (6 above all) were found among anti-epileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs’ signaling is a classical system to provide the required attention in relation to a potential risk.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Woroń, Jarosław. "Pharmacotherapy of breakthrough pain, what else can we do to improve the effectiveness of treatment." BÓL 20, no. 4 (April 7, 2020): 1–11. http://dx.doi.org/10.5604/01.3001.0014.0914.

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Breakthrough pain in cancer patients (BTP), also called episodic or incidental, occurs in a significant percentage of patients (40–60%) with cancer. Compared to patients who did not have BTP, patients with a diagnosis of breakthrough pain more often show functional disorders, a higher level of anxiety and depression, and a much worse quality of life. What’s more, in this group of patients, the consumption of sleeping pills and other groups of psychotropic drugs increases, which in turn can lead to a decrease in the effectiveness of analgesic therapy and escalate the risk of adverse interactions with analgesics. The key to improving effectiveness and reducing complications is the choice of drugs used to treat pain breakthrough so that the pharmacokinetic profile of the selected drug is compatible with the breakthrough pain characteristics.

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Chen, LiZhu, DeQiu Zhu, and Ping Xiang. "Recent advances in chiral analysis for biosamples in clinical research and forensic toxicology." Bioanalysis 13, no. 6 (March 2021): 493–511. http://dx.doi.org/10.4155/bio-2020-0330.

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This article covers current methods and applications in chiral analysis from 2010 to 2020 for biosamples in clinical research and forensic toxicology. Sample preparation for aqueous and solid biological samples prior to instrumental analysis were discussed in the article. GC, HPLC, capillary electrophoresis and sub/supercritical fluid chromatography provide the efficient tools for chiral drug analysis coupled to fluorescence, UV and MS detectors. The application of chiral analysis is discussed in the article, which involves differentiation between clinical use and drug abuse, pharmacokinetic studies, pharmacology/toxicology evaluations and chiral inversion. Typical chiral analytes, including amphetamines and their analogs, anesthetics, psychotropic drugs, β-blockers and some other chiral compounds, are also reviewed.

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Curto, Martina, Luana Lionetto, Maria Chiara David, Aniello Maiese, Stefano Ferracuti, Maurizio Simmaco, and Ross J. Baldessarini. "Sudden Death Associated with Complex Treatment of Acute Mania: Case Report and Toxicological Findings." Current Psychopharmacology 8, no. 3 (December 13, 2019): 238–43. http://dx.doi.org/10.2174/2211556008666190916093915.

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Background: Antipsychotic drugs, mood-stabilizers, and sedatives are used routinely to treat acute mania, sometimes in combinations, most of which are poorly evaluated for efficacy and safety. Objective: We report a case of sudden death in a 40-year-old man with acute mania treated aggressively with combinations of drugs that resulted in in potentially toxic, high serum drug concentrations. Method: After the autopsy, analysis were conducted to determine levels of the administered medications using GC-MS and LC-MS/MS. Results: Although dosed within recommended ranges, circulating concentrations of some antipsychotic drugs given were excessive, suggesting possible pharmacokinetic interactions. In particular, valproate may have increased serum levels of haloperidol, clozapine, and promazine. The proposed cause of death was cardiac arrest, to which the high concentrations of antipsychotics may have contributed. Conclusion: This case suggests caution in the aggressive treatment of mania with combinations of psychotropic drugs and highlights the need of further clinical studies to identify consequences of drug-drug interactions of antimanic drugs, even when given at recommended doses.

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Boyce, Richard D., Carol Collins, Marc Clayton, John Kloke, and John R. Horn. "Inhibitory Metabolic Drug Interactions with Newer Psychotropic Drugs: Inclusion in Package Inserts and Influences of Concurrence in Drug Interaction Screening Software." Annals of Pharmacotherapy 46, no. 10 (October 2012): 1287–98. http://dx.doi.org/10.1345/aph.1r150.

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Background: Food and Drug Administration (FDA) regulations mandate that package inserts (Pls) include observed or predicted clinically significant drug-drug interactions (DDIs), as well as the results of pharmacokinetic studies that establish the absence of effect. Objective: To quantify how frequently observed metabolic inhibition DDIs affecting US-marketed psychotropics are present in FDA-approved Pls and what influence the source of DDI information has on agreement between 3 DDI screening programs. Methods: The scientific literature and Pls were reviewed to determine all drug pairs for which there was rigorous evidence of a metabolic inhibition interaction or noninteraction. The DDIs were tabulated noting the source of evidence and the strength of agreement over chance. Descriptive statistics were used to examine the influence of source of DDI information on agreement among 3 DDI screening tools. Logistic regression was used to assess the influence of drug class, indication, generic status, regulatory approval date, and magnitude of effect on agreement between the literature and PI as well as agreement among the DDI screening tools. Results: Thirty percent (13/44) of the metabolic inhibition DDIs affecting newer psychotropics were not mentioned in Pls. Drug class, indication, regulatory approval date, generic status, or magnitude of effect did not appear to be associated with more complete DDI information in Pls. DDIs found exclusively in Pls were 3.25 times more likely to be agreed upon by all 3 DDI screening tools than were those found exclusively in the literature. Generic status was inversely associated with agreement among the DDI screening tools (odds ratio 0.11; 95% CI 0.01 to 0.89). Conclusions: The presence in Pls of DDI information for newer psychotropics appears to have a strong influence on agreement among DDI screening tools. Users of DDI screening software should consult more than 1 source when considering interactions involving generic psychotropics.

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Baumann, Pierre, and Gilles Bertschy. "Pharmacodynamic and pharmacokinetic interactions of selective serotonin re-uptake inhibiting antidepressants (SSRIs) with other psychotropic drugs." Nordic Journal of Psychiatry 47, sup30 (January 1993): 13–19. http://dx.doi.org/10.3109/08039489309104120.

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Fagiolini, A. "Advanced Psychopharmacology: Practical Strategies for Rational Polypharmacy in Mood Disorders." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70254-8.

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Patients with mood disorders frequently present with treatment resistant syndromes or develop tolerance to once effective first line medications. Refractory depressive, manic or mixed episodes challenge psychiatrists to find means of augmenting traditional therapies, despite the paucity of evidence based data that support this practice. The balance between risks and benefits in most cases seems acceptable, provided that the physician and the patients have a clear understanding of the possible adverse and therapeutic interactions and that treatment resistance is not the result of inadequate (dose/time) prescription of a first line monotherapy. The workshop will review the pharmacokinetic and pharmacodynamic interactions among the psychotropic drugs and the strategies to safely and successfully use a rational polypharmacy for the management of treatment resistant mood disorders.

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Sabaté, M. Betriu, A. González-Rodríguez, A. Guàrdia, E. Pérez-Macho, A. Alvarez Pedrero, S. Acebillo, J. A. Monreal, D. Palao Vidal, and J. Labad. "Pharmacokinetic interactions of psychotropic medications in patients with schizophrenia suffering from atypical mycobacterial infections." European Psychiatry 64, S1 (April 2021): S649—S650. http://dx.doi.org/10.1192/j.eurpsy.2021.1725.

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IntroductionMycobacterium kansasii is a nontuberculous mycobacterium that causes infection associated with past or current tuberculosis disease. Clinical syndromes and radiological findings are mostly indistinguishable from that of Mycobacterium tuberculosis, thus requiring microbiological confirmation.ObjectivesWe report a case of a 44-year-old man diagnosed with schizophrenia and Mycobacterium kansasii infection.MethodsCase report and non-systematic narrative review from PubMed.ResultsCase report: Patient with schizophrenia who was admitted at the inpatient unit presenting psychotic exacerbation with high levels of excitement. Risperidone 6 mg/day and valproate 500 mg/day were initiated. He was also diagnosed with a M. kansasii lung infection, with radiological findings of past tuberculosis disease. Before the microbiological confirmation, it was necessary to start rifampicin, requiring an increase in doses of both psychotropic drugs. Review: (1)Comorbidity of mycobacterial infections and schizophrenia. Several studies have shown that people with severe mental illness have higher rates of tuberculosis compared with the general population. Although the relationship between tuberculosis and M. Kansasii infection is known, few literature is available with regard to the association of M. Kansasii and schizophrenia. (2)Interactions between antipsychotics and mood stabilizers with rifampicin. Rifampicin is mainly metabolized by CYP3A4 and transported by P-glycoprotein. Add-on with rifampicin have been reported to reduce clozapine and olanzapine plasma levels (despite both are metabolized by CYP1A2), reduce haloperidol and risperidone levels (possible role of P-glycoprotein in this interaction), as well as for valproate.ConclusionsTreatment of comorbid infections in people with schizophrenia remains a challenge. Antibiotics used to treat mycobacterial infections can modify the pharmacokinetic of psychotropic drugs.DisclosureNo significant relationships.

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Kadasah, Sultan F., Abdulaziz M. S. Alqahtani, Abdullah Alkhammash, and Mohamed O. Radwan. "Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy." International Journal of Molecular Sciences 25, no. 12 (June 7, 2024): 6314. http://dx.doi.org/10.3390/ijms25126314.

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Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood–brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.

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Baumann, P., and W. Greil. "Clinical pharmacological management of polypharmacy in old age depression." European Psychiatry 33, S1 (March 2016): S39. http://dx.doi.org/10.1016/j.eurpsy.2016.01.881.

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Polypharmacy is the rule in psychogeriatric patients, as they present frequently comorbidities such as depression, dementia [often including Behavioral and Psychological Symptoms of Dementia (BPSD)] and somatic diseases. Recommended treatments for geriatric depression are antidepressant medications, psychotherapy and psychosocial interventions [1]. Besides antidepressants, other psychotropic drugs are often co-prescribed, but somatic drugs are also needed for the treatment of other concomitant diseases. This situation increases the risk for adverse effects due to pharmacokinetic and pharmacodynamic interactions, especially since the organism of elderly patients displays a lowered homeostatic reserve and a decrease of functions, which allows resisting to xenobiotic influences.On the other hand, there are also studies which suggest that in hospitalized psychogeriatric patients, the incidence of severe adverse reactions is lower in patients > 60 y than in those < 60 y [2]. This is one of the results of the AMSP-study group, which in German speaking countries has developed a pharmacovigilance program in psychiatric hospitals.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Englisch, Susanne, Hanna Jung, Antje Lewien, Anna Becker, Ulrike Nowak, Hanna Braun, Sarah Eisenacher, Jascha Thiem, Andreas Meyer-Lindenberg, and Mathias Zink. "Response to Agomelatine Treatment is Independent of Smoking Status and Dosage: Results From the AGOPSYCH Study." Pharmacopsychiatry 52, no. 03 (May 7, 2018): 142–46. http://dx.doi.org/10.1055/a-0606-5240.

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Abstract Introduction Cigarette smoking influences response to antidepressant treatment. It accelerates the metabolism of several cytochrome P450 (CYP) subtypes, including CYP1A2, and therefore bears the risk of pharmacokinetic interactions with psychotropic drugs using that pathway. Agomelatine is a substrate of CYP1A2; the association between nicotine use and agomelatine dosage, however, has never been studied before. Methods Smoking habits were correlated with agomelatine doses and treatment outcomes in a sample of 27 patients with lifetime diagnoses within the schizophrenia spectrum who received agomelatine treatment in addition to their stable antipsychotic treatment regimen because of depressive symptoms. Results No interactions were found between smoking status and agomelatine dosage, and treatment outcomes did not differ between smokers and nonsmokers. Discussion Agomelatine efficacy appears to be independent of dosage and smoking status, pointing toward mechanisms beyond mere dose-response relationships. Further research will be necessary to validate these findings.

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Gillman, Peter Kenneth, Vincent Van den Eynde, Lila Godet, Charles Redhead, Alexander Horwitz, and Brian Barnett. "Monoamine Oxidase Inhibitors and Clinically Relevant Drug Interactions: A Guide for Preventing Serotonin Toxicity and Hypertensive Reactions." Psychiatric Annals 53, no. 8 (August 2023): 353–58. http://dx.doi.org/10.3928/00485713-20230713-02.

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This article describes and clarifies the two significant interactions encountered with monoamine oxidase inhibitors (MAOIs): serotonin toxicity and the tyramine pressor response. This is important because of the amount of inaccurate and misleading information (including in United States Food and Drug Administration-approved product information sheets and online resource and database systems) promulgated over the last few decades, which continues to cause confusion and undue concern. There are few if any clinically relevant CYP450 interactions with psychotropic drugs and no significant pharmacokinetic interactions. Serotonin toxicity is now well understood and only occurs in a problematic form when MAOIs are given in conjunction with serotonin reuptake inhibitors. Major prolonged elevations of blood pressure from tyramine are now less of a concern because of greatly reduced tyramine levels in foods. Therefore, MAOIs are safer and simpler to use in clinical practice than has usually been stated and should be considered earlier in the treatment algorithm for both atypical and melancholic depression. [ Psychiatr Ann . 2023;53(8):353–358.]

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Journal articles on the topic 'Psychotropic drugs – pharmacokinetics'

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