DOCSLIB.ORG

Pregabalin Induced Mood Elevation in Bipolar Patients: Case-Reports

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pregabalin Induced Mood Elevation in Bipolar Patients: Case-Reports Psychiatria Danubina, 2021; Vol. 33, No. 1, pp 60-62 https://doi.org/10.24869/psyd.2021.60 Case report © Medicinska naklada - Zagreb, Croatia PREGABALIN INDUCED MOOD ELEVATION IN BIPOLAR PATIENTS: CASE-REPORTS Seyed Mehdi Samimi Ardestani1 & Pegah Seif2 1Shahid Beheshti University of Medical Science, Imam Hossein Medical Center, Tehran, Iran 2Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran received: 30.10.2020; revised: 22.12.2020; accepted: 30.12.2020 * * * * * INTRODUCTION sleep duration and also her appetite two years earlier. The patient was diagnosed as Bipolar Mood Disorder (BMD) Hagop Souren Akiskal, noticed the patients who exhi- in another center. Pharmacological therapy was started bit hypomania and manic manifestations following taking with lamotrigine, aripiprazole and bupropion and partial antidepressant treatments (Akiskal & Pinto 1999). This remission was obtained. Few months after wards, she condition was more prevalent among those with cyclo- frequently experienced brief periods of depression (lasted thymic temperamental tendencies (Akiskal et al. 1979). for days to few months) with elevated mood intervals. He categorized these group of patients as bipolar type III She visited us and we took a thorough history. When (Akiskal & Pinto 1999). The same phenomena was also asked about the sexual history, she confessed to having recognizable in some patients following the substance or high risk sexual behaviors (unprotected sex, having mul- alcohol use. Bipolar III1/2 type was introduced to tiple sex partners and public sex). She was abusing va- describe these patients (Akiskal & Pinto 1999). Since rious types of stimulant and opioid drugs. She complai- then numerous drugs has been proposed for be the main ned about sleep problems in the form of sleep inversion cause in mood switch among the bipolar patients (Henry and reversal of sleeping tendencies. She reported the & Demotes-Mainard 2003), however the precise under- history of two previous attempted suicide. lying biological mechanism has not discovered yet. Of On mental status examination the only finding was the proven drugs responsible for mood switches in the only finding was a heavy makeup. Other aspects such bipolar disorders can name the TCA (eg, imipramine) as psychomotor activities, form and content of thought, (Prien et al. 1973, 1984), SSRI (eg, Fluoxetine) (Henry cognitive state all were intact. This time we started & Demotes-Mainard 2003), MAOI (Stoll et al. 1994), lithium and lamotrigine with the same diagnosis of BMD. Bupropion (Shopsin 1983, Haykel & Akiskal 1990) and One month afterwards, she was visited again while taking other new antidepressant treatments (eg, Venlafaxine) her medication regularly. The mood fluctuations were (Amsterdam 1998). handled near to completely but she expressed dissatis- Pregabalin is a new synthetic molecule is a derivative faction with moderate level of anxiety. We decided to of the inhibitory neurotransmitter gamma-aminobutyric omit lamotrigine from the treatment plan and added acid (GABA). The drug is used as monotherapy or pregabalin. We recommended to revisit her after one adjunctive treatment in many psychiatric disorder (Marks month but after 2 weeks she came back because of over- et al. 2009), hence few studies has assessed the possible use the prescribed pregabalin as it gave her more energy consequences of this drug in mood disorders. and increased libido. Pregabalin was discontinued and We present two cases of bipolar mood disorder who carbamazepine added to treatment regimen. One month experienced elevated mood switch after receiving prega- later, the mood fluctuations were almost controlled and balin. We obtained written consent from our patients. there was no relapse in pregabalin abuse anymore. Her Ethical approval is not required for case reports mood swings, while being on these medication, became according to our university polices. nearly controlled for the next 4 months. During this period of time, two lapses in pregabalin abuse happened CASE PRESENTATION each time precipitated increased energy level, irritability and high sexual desire. Furthermore she endured brief de- Case 1 pression episodes for 2-3 days without suicidal idea. We asked for the lithium level which came back 0.7, within A 21 years-old woman, university student, presented the therapeutic range. She continued to take lithium and with irritability and depressed mood. In assessing the past carbamazepine and the mood swings nearly stopped. psychiatric disorder two years before coming up to our clinic she experienced a few months period of elevated mood, increased libido and increased rate of speech Case 2 (excessive talkativeness) was noticeable which was A 35 years-old woman came up to outpatient clinic followed by a period of depressed mood, increasing in because of obsession and depression. Her obsessive 60 Seyed Mehdi Samimi Ardestani & Pegah Seif: PREGABALIN INDUCED MOOD ELEVATION IN BIPOLAR PATIENTS: CASE-REPORTS Psychiatria Danubina, 2021; Vol. 33, No. 1, pp 60-62 thoughts began years ago after testing positive for HIV. Sansone 2011). The anticonvulsants with Ȗ-aminobutyric She estimated that she has been infected because of acid (GABAergic) effect, pregabalin and gabapentin, may having unprotected sex with multiple partners due to her be more applicable for some anxiety states (Strawn & high sexual desire. She continued having herself and also Geracioti 2007). her partners tested repeatedly for HIV all theses years. Pregabalin (PGB) is a newer gabapentinoid, adjuvant Besides she reported mood swings for the previous 2 anti epileptic drug, and its structure is similar to gaba- years. Sertraline, 50 mg per day, was prescribed for her pentin (Toth 2014). PGB often use in treatment of anxiety obsessional compulsive disorder (OCD). By passing less (Feltner et al. 2003) and other medical conditions such as than one week, her obsessional thoughts were diminished neuropathic pain (Arezzo 2008). Primary studies indica- significantly but she experienced a rapid mood elevation ted that the pregabalin may have some antidepressant and also mood changes in less than 24 hours. She com- effects (FDA. 2020). However one case was introduced mitted suicide with her medications and also 40 mg of for severe depression and appearance of suicidal thoughts clonazepam at the time she was distressed and frustrated. after taking PGB (Schaffer et al. 2013). In one open study In assessing her family history, we noted a history of it was suggested that pregabalin can be administered as a major depression accompanied by a suicide attempt in her safe and effective mood stabilizing drug in some treat- maternal uncle and also a postpartum depression in her ment-resistant with anti manic effects (Stein et al. 2008). mother. We decided to start lithium carbonate (300 mg However few studies highlighted the mood switch effects twice daily), and carbamazepine (200 mg at night) with of PGB (Kustermann et al. 2014). the BMD diagnosis. She was revisited 28 days later and The development of mania symptoms in our patient we added pregabalin (50 mg three time per day) as she was noticeable following the PGB administration. felt anxious. Ten days later she made a phone call and In our first case, carbamazepine which was started reported having a good feeling toward her recent before PGB could not be the possible agent to be blamed medication regimen since the state of her mood was for mood swing as it is a common mood stabilizer in bi- the same as the time she was taking sertraline. We polar patients and that phenomenon has has not been recommended to stop the pregabalin with the impres- reported following carbamazepine. Likewise, the mania sion of mood switch. She called back 20 days later and symptoms had been subsided after discontinuation of complained about restlessness and anxiety. Her PGB. The same mood elevation symptoms relapsed when condition and medications was asked more in detail she restarted PGB abuse and ultimate mood regulation and we noticed the continuation of taking pregabalin, achieved while PGB was totally omitted from her medi- despite our recommendation, because of the over- cation regimen. The second case we reported had expe- whelming feeling of happiness and joy pregabalin was rienced the mood elevation symptoms following the SSRI giving her. Hence the pregabalin was discontinued and administration which can be categorized as type III bipo- consequently her restlessness and anxiety resolved. lar disorders according to the Akiskal classification (Akis- kal & Pinto). Also the restlessness and anxiety was resol- DISCUSSION ved following the PGB discontinuation in this patient too. The term mood stabilizer has been defined dissi- CONCLUSION milarly in different era. In 1950 mood stabilizers were consisted of amphetamine-barbiturates (Ghaemi 2003). In Our observation showed the emergence of hypomania 1960s, the positive effects of antiepleptic drugs (AEDs) following the PGB administration. This also support the on mood disorder was discovered and gradually it was previous case report in a patient presented with con- used as mood stabilizing agents (Grunze 2008). In 1967, version (Yukawa et al. 2013). As pointed previously this first paper published by Turner and for the first time the effect is similar to antidepressants in bipolar disorder effects of antiepileptic drugs on mood, separated from patients. It is clear that the antidepressant drugs doesn’t their antiepileptic efficacy (Turner 1967). AEDs are clas-
Load more

Recommended publications
  • Valproic Acid and Its Amidic Derivatives As New Antivirals Against Alphaherpesviruses
    viruses Review Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses Sabina Andreu 1,2,* , Inés Ripa 1,2, Raquel Bello-Morales 1,2 and José Antonio López-Guerrero 1,2 1 Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain; [email protected] (I.R.); [email protected] (R.B.-M.); [email protected] (J.A.L.-G.) 2 Centro de Biología Molecular Severo Ochoa, Spanish National Research Council—Universidad Autónoma de Madrid (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain * Correspondence: [email protected] Academic Editor: Maria Kalamvoki Received: 14 November 2020; Accepted: 25 November 2020; Published: 26 November 2020 Abstract: Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/014.3507 A1 Gant Et Al
    US 2010.0143507A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/014.3507 A1 Gant et al. (43) Pub. Date: Jun. 10, 2010 (54) CARBOXYLIC ACID INHIBITORS OF Publication Classification HISTONE DEACETYLASE, GABA (51) Int. Cl. TRANSAMINASE AND SODIUM CHANNEL A633/00 (2006.01) A 6LX 3/553 (2006.01) A 6LX 3/553 (2006.01) (75) Inventors: Thomas G. Gant, Carlsbad, CA A63L/352 (2006.01) (US); Sepehr Sarshar, Cardiff by A6II 3/19 (2006.01) the Sea, CA (US) C07C 53/128 (2006.01) A6IP 25/06 (2006.01) A6IP 25/08 (2006.01) Correspondence Address: A6IP 25/18 (2006.01) GLOBAL PATENT GROUP - APX (52) U.S. Cl. .................... 424/722:514/211.13: 514/221; 10411 Clayton Road, Suite 304 514/456; 514/557; 562/512 ST. LOUIS, MO 63131 (US) (57) ABSTRACT Assignee: AUSPEX The present invention relates to new carboxylic acid inhibi (73) tors of histone deacetylase, GABA transaminase, and/or PHARMACEUTICALS, INC., Sodium channel activity, pharmaceutical compositions Vista, CA (US) thereof, and methods of use thereof. (21) Appl. No.: 12/632,507 Formula I (22) Filed: Dec. 7, 2009 Related U.S. Application Data (60) Provisional application No. 61/121,024, filed on Dec. 9, 2008. US 2010/014.3507 A1 Jun. 10, 2010 CARBOXYLIC ACID INHIBITORS OF HISTONE DEACETYLASE, GABA TRANSAMNASE AND SODIUM CHANNEL 0001. This application claims the benefit of priority of Valproic acid U.S. provisional application No. 61/121,024, filed Dec. 9, 2008, the disclosure of which is hereby incorporated by ref 0004 Valproic acid is extensively metabolised via erence as if written herein in its entirety.
    [Show full text]
  • IJBCP International Journal of Basic & Clinical Pharmacology Antiepileptic
    Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20161495 Review Article Antiepileptic drugs: newer targets and new drugs Vihang S. Chawan, Abhishek M. Phatak*, Kalpesh V. Gawand, Sagar V. Badwane, Sagar S. Panchal Department of Pharmacology, TNMC and BYL Nair Ch. Hospital Mumbai, Maharashtra, India ABSTRACT Received: 10 March 2016 Epilepsy is a common neurological disorder affecting 0.5-1% of the population Accepted: 15 April 2016 in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate *Correspondence to: response to AEDs in addition to various side effects and drug interactions while Dr. Abhishek Madan Phatak, on therapy. Thus there is a need to develop more effective AEDs in drug Email: abhishekphatak9288 resistant epilepsy which have a better safety profile with minimal adverse @gmail.com effects. The United States food and drug administration (USFDA) has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have Copyright: © the author(s), shown a promising future as better AEDs and drugs like ganaxolone, intranasal publisher and licensee Medip diazepam, ICA- 105665, valnoctamide, VX-765, naluzotan are in the pipeline. Academy. This is an open- access article distributed under Keywords: Epilepsy, Newer antiepileptic drugs, Eslicarbazepine Acetate, the terms of the Creative Ezogabine (Retigabine), Perampanel, Brivaracetam, Naluzotan Commons Attribution Non- Commercial License, which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION to AEDs or those patient who have suffered from recurrent seizures, may require surgery.
    [Show full text]
  • Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva
    REVIEW ARTICLE Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva Philip N. Patsalos, FRCPath, PhD*† and Dave J. Berry, FRCPath, PhD† INTRODUCTION Abstract: Blood (serum/plasma) antiepileptic drug (AED) therapeu- Measuring antiepileptic drugs (AEDs) in serum or tic drug monitoring (TDM) has proven to be an invaluable surrogate plasma as an aid to personalizing drug therapy is now a well- marker for individualizing and optimizing the drug management of established practice in the treatment of epilepsy, and guidelines patients with epilepsy. Since 1989, there has been an exponential are published that indicate the particular features of epilepsy and increase in AEDs with 23 currently licensed for clinical use, and the properties of AEDs that make the practice so beneficial.1 recently, there has been renewed and extensive interest in the use of The goal of AED therapeutic drug monitoring (TDM) is to saliva as an alternative matrix for AED TDM. The advantages of saliva ’ fl optimize a patient s clinical outcome by supporting the man- include the fact that for many AEDs it re ects the free (pharmacolog- agement of their medication regimen with the assistance of ically active) concentration in serum; it is readily sampled, can be measured drug concentrations/levels. The reason why TDM sampled repetitively, and sampling is noninvasive; does not require the has emerged as an important adjunct to treatment with the expertise of a phlebotomist; and is preferred by many patients, AEDs arises from the fact that for an individual patient
    [Show full text]
  • Pharmacokinetic and Pharmacodynamic Interactions Between Antiepileptics and Antidepressants Domenico Italiano University of Messina, Italy
    University of Kentucky UKnowledge Psychiatry Faculty Publications Psychiatry 11-2014 Pharmacokinetic and Pharmacodynamic Interactions between Antiepileptics and Antidepressants Domenico Italiano University of Messina, Italy Edoardo Spina University of Messina, Italy Jose de Leon University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/psychiatry_facpub Part of the Psychiatry and Psychology Commons Repository Citation Italiano, Domenico; Spina, Edoardo; and de Leon, Jose, "Pharmacokinetic and Pharmacodynamic Interactions between Antiepileptics and Antidepressants" (2014). Psychiatry Faculty Publications. 40. https://uknowledge.uky.edu/psychiatry_facpub/40 This Article is brought to you for free and open access by the Psychiatry at UKnowledge. It has been accepted for inclusion in Psychiatry Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Pharmacokinetic and Pharmacodynamic Interactions between Antiepileptics and Antidepressants Notes/Citation Information Published in Expert Opinion on Drug Metabolism & Toxicology, v. 10, Issue 11, p. 1457-1489. © 2014 Taylor & Francis Group This is an Accepted Manuscript of an article published by Taylor & Francis Group in Expert Opinion on Drug Metabolism & Toxicology in Nov. 2014, available online: http://www.tandfonline.com/10.1517/ 17425255.2014.956081 Digital Object Identifier (DOI) http://dx.doi.org/10.1517/17425255.2014.956081 This article is available at UKnowledge: https://uknowledge.uky.edu/psychiatry_facpub/40 1 This is an Accepted Manuscript of an article published by Taylor & Francis Group in Expert Opinion on Drug Metabolism & Toxicology in Nov.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0202317 A1 Rau Et Al
    US 20150202317A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0202317 A1 Rau et al. (43) Pub. Date: Jul. 23, 2015 (54) DIPEPTDE-BASED PRODRUG LINKERS Publication Classification FOR ALPHATIC AMNE-CONTAINING DRUGS (51) Int. Cl. A647/48 (2006.01) (71) Applicant: Ascendis Pharma A/S, Hellerup (DK) A638/26 (2006.01) A6M5/9 (2006.01) (72) Inventors: Harald Rau, Heidelberg (DE); Torben A 6LX3/553 (2006.01) Le?mann, Neustadt an der Weinstrasse (52) U.S. Cl. (DE) CPC ......... A61K 47/48338 (2013.01); A61 K3I/553 (2013.01); A61 K38/26 (2013.01); A61 K (21) Appl. No.: 14/674,928 47/48215 (2013.01); A61M 5/19 (2013.01) (22) Filed: Mar. 31, 2015 (57) ABSTRACT The present invention relates to a prodrug or a pharmaceuti Related U.S. Application Data cally acceptable salt thereof, comprising a drug linker conju (63) Continuation of application No. 13/574,092, filed on gate D-L, wherein D being a biologically active moiety con Oct. 15, 2012, filed as application No. PCT/EP2011/ taining an aliphatic amine group is conjugated to one or more 050821 on Jan. 21, 2011. polymeric carriers via dipeptide-containing linkers L. Such carrier-linked prodrugs achieve drug releases with therapeu (30) Foreign Application Priority Data tically useful half-lives. The invention also relates to pharma ceutical compositions comprising said prodrugs and their use Jan. 22, 2010 (EP) ................................ 10 151564.1 as medicaments. US 2015/0202317 A1 Jul. 23, 2015 DIPEPTDE-BASED PRODRUG LINKERS 0007 Alternatively, the drugs may be conjugated to a car FOR ALPHATIC AMNE-CONTAINING rier through permanent covalent bonds.
    [Show full text]
  • A History of the Pharmacological Treatment of Bipolar Disorder
    International Journal of Molecular Sciences Review A History of the Pharmacological Treatment of Bipolar Disorder Francisco López-Muñoz 1,2,3,4,* ID , Winston W. Shen 5, Pilar D’Ocon 6, Alejandro Romero 7 ID and Cecilio Álamo 8 1 Faculty of Health Sciences, University Camilo José Cela, C/Castillo de Alarcón 49, 28692 Villanueva de la Cañada, Madrid, Spain 2 Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute (i+12), Avda. Córdoba, s/n, 28041 Madrid, Spain 3 Portucalense Institute of Neuropsychology and Cognitive and Behavioural Neurosciences (INPP), Portucalense University, R. Dr. António Bernardino de Almeida 541, 4200-072 Porto, Portugal 4 Thematic Network for Cooperative Health Research (RETICS), Addictive Disorders Network, Health Institute Carlos III, MICINN and FEDER, 28029 Madrid, Spain 5 Departments of Psychiatry, Wan Fang Medical Center and School of Medicine, Taipei Medical University, 111 Hsin Long Road Section 3, Taipei 116, Taiwan; [email protected] 6 Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Avda. Vicente Andrés, s/n, 46100 Burjassot, Valencia, Spain; [email protected] 7 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University, Avda. Puerta de Hierro, s/n, 28040 Madrid, Spain; [email protected] 8 Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Crta. de Madrid-Barcelona, Km. 33,600, 28871 Alcalá de Henares, Madrid, Spain; [email protected] * Correspondence: fl[email protected] or [email protected] Received: 4 June 2018; Accepted: 13 July 2018; Published: 23 July 2018 Abstract: In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade’s experiments with lithium and the beginning of the so-called “Psychopharmacological Revolution” in the 1950s.
    [Show full text]
  • An Inventory of Literature on the Relation Between Drug Use, Impaired Driving and Traffic Accidents
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by National Documentation Centre on Drug Use E.M.C.D.D.A. DRUGS MISUSE RESEARCH DIVISION HEALTH RESEARCH BOARD An Inventory of Literature on the Relation between Drug Use, Impaired Driving and Traffic Accidents CT.97.EP.14 Research Team: Colin Gemmell Trinity College, Dublin Rosalyn Moran Drugs Misuse Research Division, Health Research Board James Crowley Professor, Transport Policy Research Institute, University College Dublin Richeal Courtney Medical Expert, for the Health Research Board EMCDDA: Lucas Wiessing February 1999 Please use the following citation: European Monitoring Centre for Drugs and Drug Addiction. An Inventory of Literature on the Relation betweenDrug Use, Impaired Driving and Traffic Accidents. (CT.97.EP.14) Lisbon: EMCDDA, February 1999. Contact Details Drugs Misuse Research Division Health Research Board 73 Lower Baggot Street Dublin 2 Ireland European Monitoring Centre for Drugs and Drug Addiction Rua Cruz de Santa Apolónia 23/25 1100, Lisboa Portugal. Further copies of this bibliography can be obtained from the EMCDDA at the above address. CREDITS Principal Researchers Ms Rosalyn Moran, Project Leader, Health Research Board Professor James Crowley, Professor, Transport Policy Research Institute, UCD Dr Richeal Courtney, Medical Expert, on behalf of the Health Research Board Research Assistants Colin Gemmell (Synthesis and Final Reports) Sarah Heywood (Literature Search and Collaborative Network) For the EMCDDA Lucas Wiessing
    [Show full text]
  • Beyond Lithium in the Treatment of Bipolar Illness Robert M
    Beyond Lithium in the Treatment of Bipolar Illness Robert M. Post, M.D., Mark A. Frye, M.D., Kirk D. Denicoff, M.D., Gabriele S. Leverich, L.C.S.W., Tim A. Kimbrell, M.D., and Robert T. Dunn, M.D. Dramatic changes have recently occurred in the availability lamotrigine, gabapentin, and topiramate have unique of treatment options for bipolar illness. Second generation mechanisms of action and deserve further systematic study, mood stabilizing anticonvulsants carbamazepine and as does the potential role for nonconvulsive brain valproate are now widely used as alternatives or adjuncts to stimulation with repeated transcranial magnetic lithium. High potency benzodiazepines are also used as stimulation (rTMS). These and a host of other potential alternatives to typical neuroleptics, and now atypical treatment options now require a new generation of clinical neuroleptics are demonstrating efficacy and better side- trials to help identify clinical and biological markers of effects profiles than the typicals. Thyroid augmentation response and optimal use alone and in complex combination strategies and dihydropyridine L-type calcium channel therapeutic regimens. [Neuropsychopharmacology blockers require further clinical trials to define their role. 19:206–219, 1998] Published by Elsevier Science Inc. Putative third generation mood stabilizing anticonvulsants KEY WORDS: Carbamazepine; Valproate; Calcium channel al. 1989; O’Connell et al. 1991; Denicoff et al. 1997); a blockers; Lamotrigine; Gabapentin; rTMS history of co-morbid substance abuse; and those pa- tients with a history of head trauma or other such medi- There is increasing recognition of the inadequacy of cal co-morbidities as multiple sclerosis, etc. “lithium treatment” in bipolar illness, even with ad- In addition, it is recognized that patients with initial junctive antidepressants and neuroleptics (Maj et al.
    [Show full text]
  • Clinically Relevant Drug Interactions with Antiepileptic Drugs
    British Journal of Clinical Pharmacology DOI:10.1111/j.1365-2125.2005.02529.x Clinically relevant drug interactions with antiepileptic drugs Emilio Perucca Institute of Neurology IRCCS C. Mondino Foundation, Pavia, and Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy Correspondence Some patients with difficult-to-treat epilepsy benefit from combination therapy with Emilio Perucca MD, PhD, Clinical two or more antiepileptic drugs (AEDs). Additionally, virtually all epilepsy patients will Pharmacology Unit, Department of receive, at some time in their lives, other medications for the management of Internal Medicine and Therapeutics, associated conditions. In these situations, clinically important drug interactions may University of Pavia, Piazza Botta 10, occur. Carbamazepine, phenytoin, phenobarbital and primidone induce many cyto- 27100 Pavia, Italy. chrome P450 (CYP) and glucuronyl transferase (GT) enzymes, and can reduce Tel: + 390 3 8298 6360 drastically the serum concentration of associated drugs which are substrates of the Fax: + 390 3 8222 741 same enzymes. Examples of agents whose serum levels are decreased markedly by E-mail: [email protected] enzyme-inducing AEDs, include lamotrigine, tiagabine, several steroidal drugs, cyclosporin A, oral anticoagulants and many cardiovascular, antineoplastic and psy- chotropic drugs. Valproic acid is not enzyme inducer, but it may cause clinically relevant drug interactions by inhibiting the metabolism of selected substrates, most Keywords notably phenobarbital and lamotrigine. Compared with older generation agents, most antiepileptic drugs, drug interactions, of the recently developed AEDs are less likely to induce or inhibit the activity of CYP enzyme induction, enzyme inhibition, or GT enzymes. However, they may be a target for metabolically mediated drug epilepsy, review interactions, and oxcarbazepine, lamotrigine, felbamate and, at high dosages, topira- mate may stimulate the metabolism of oral contraceptive steroids.
    [Show full text]
  • Stereoselective Anticonvulsant and Pharmacokinetic Analysis of Valnoctamide, a CNS-Active Derivative of Valproic Acid with Low Teratogenic Potential
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Epilepsia Manuscript Author . Author manuscript; Manuscript Author available in PMC 2016 July 28. Published in final edited form as: Epilepsia. 2014 February ; 55(2): 353–361. doi:10.1111/epi.12480. Stereoselective Anticonvulsant and Pharmacokinetic Analysis of Valnoctamide, a CNS-Active Derivative of Valproic Acid with Low Teratogenic Potential Tawfeeq Shekh-Ahmad1, Naama Hen1, Boris Yagen1,2, John H. McDonough3, Richard H. Finnell4, Bogdan J. Wlodarczyk4, and Meir Bialer1,2 1School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel 2David R. Bloom Center for Pharmacy, The Hebrew University of Jerusalem, Israel 3Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Maryland, USA 4Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, Texas, USA Summary Objective—Valnoctamide (VCD), a CNS-active chiral constitutional isomer of valpromide the corresponding amide of valproic acid (VPA), is currently undergoing phase IIb clinical trial in acute mania. VCD exhibits stereoselective pharmacokinetics (PK) in animals and humans. The current study comparatively evaluated the pharmacodynamics (PD; anticonvulsant activity and teratogenicity) and PK of VCD four individual stereoisomers. Methods—The anticonvulsant activity of VCD individual stereoisomers was evaluated in several rodent anticonvulsant models including: maximal electroshock, 6Hz psychomotor, subcutaneous metrazol and the pilocarpine- and soman-induced status epilepticus (SE). The PK- PD (anticonvulsant activity) relationship of VCD stereoisomers was evaluated following ip administration (70mg/kg) to rats. Induction of neural tube defects (NTDs) by VCD stereoisomers was evaluated in a mouse strain highly-susceptible to teratogen-induced neural tube defects.
    [Show full text]
  • Update on Bipolar Disorder: How to Better Predict
    Currentp SYCHIATRY Update on bipolar disorder: How to better predict Paul E. Keck, Jr., MD Erik B. Nelson, MD Susan L. McElroy, MD Biological Psychiatry Program, Department of Psychiatry University of Cincinnati College of Medicine, Cincinnati, Ohio What does current evidence show regarding maintenance treatment with lithium, divalproex, carbamazepine, lamotrigine, or other agents? How well can you predict response? Which therapy will stop subsyndromal symptoms? The answers are here. © John Ritter/Graphistock 40 VOL. 1, NO. 4 / APRIL 2002 response to maintenance therapy hat are we trying to accomplish in the Compared with clinical trials of agents for acute bipolar maintenance treatment of patients mania (and mixed episodes), there are relatively few ran- with bipolar disorder? Given that the domized controlled trials of medications for the maintenance disorder recurs in more than 90% of patients who experience phase of bipolar disorder. Some naturalistic studies have pro- W1 a manic episode, there are 5 important goals: vided data on relapse rates associated with treatment with a 1. Prevention of recurrent episodes; variety of different agents. Even fewer studies have examined 2. Amelioration of subsyndromal symptoms; psychosocial interventions designed specifically to reduce 3. Reduction of suicide risk; relapse rates. 4. Compliance enhancement; But new data are beginning to emerge regarding the 5. Optimization of interpersonal, social, and vocational efficacy of divalproex, lamotrigine, and olanzapine as main- functioning. tenance therapies. A number of clinical predictors of There is a great premium on preventing mood episode response to these agents have begun to be identified, as well recurrence in patients with bipolar disorder. Mood episodes as to lithium and carbamazepine.
    [Show full text]