Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-55f67697df-xlmdk Total loading time: 0 Render date: 2025-05-08T09:17:31.638Z Has data issue: false hasContentIssue false

Chapter 12 - Anticonvulsants for Mental Disorders: Valproate, Lamotrigine, Carbamazepine and Oxcarbazepine

from Part 2 - Psychopharmacology of the Main Psychotropic Drug Groups

Published online by Cambridge University Press:  29 May 2020

By
Peter S. Talbot
Edited by
Peter M. Haddad  and
David J. Nutt
Peter M. Haddad
Affiliation:
Hamad Medical Corporation, Qatar
David J. Nutt
Affiliation:
Centre for Neuropsychopharmacology, Division of Psychiatry, Department of Brain Sciences, Imperial College London
Get access

Summary

Several anticonvulsants are licensed and used in the treatment of bipolar disorder. However, anticonvulsant activity does not automatically confer benefits for mood disorders on a drug. The anticonvulsant drugs with the strongest evidence for effectiveness in bipolar disorder are valproate, lamotrigine and carbamazepine. Furthermore, the relative effectiveness of these drugs for the different phases of bipolar illness (mania or depression, and acute or maintenance treatment) differs, and none of them has a pattern of effectiveness across the three phases equivalent to lithium. This chapter will describe the basic and clinical psychopharmacology for each of these drugs in turn, as it relates to their use and effectiveness in mental disorders.

Type
Chapter
Information
Seminars in Clinical Psychopharmacology , pp. 362 - 391
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Acharya, S, Bussel, JB (2000). Hematologic toxicity of sodium valproate. J Pediatr Hematol Oncol, 22(1), 62–65.Google Scholar
Aiken, CB, Orr, C (2010). Rechallenge with lamotrigine after a rash: a prospective case series and review of the literature. Psychiatry, 7, 27–32.Google Scholar
Aliyev, NA, Aliyev, ZN (2008). Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: randomized, double-blind placebo-controlled study. Eur Psychiatry, 23, 109–114.Google Scholar
Allen, MH, Hirschfeld, RM, Wozniak, PJ, Baker, JD, Bowden, CL (2006). Linear relationship of valproate serum concentration to response and optimal serum levels for acute mania. Am J Psychiatry, 163, 272–275.Google Scholar
Angus-Lepan, H, Liu, R (2018). Weighing the risks of valproate in women who could become pregnant. BMJ, 361, k1596.Google Scholar
Azorin, JM, Bowden, CL, Garay, RP, et al. (2010). Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Neuropsychiatr Dis Treat, 6, 37–46.Google Scholar
Ballenger, JC, Post, RM (1978). Therapeutic effects of carbamazepine in affective illness: a preliminary report. Commun Psychopharmacol, 2, 159–175.Google Scholar
Ballenger, JC, Post, RM (1980). Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry, 137, 782–790.Google Scholar
Belcastro, V, D’Egidio, C, Striano, P, Verrotti, A (2013). Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res, 107, 1–8.Google Scholar
Bjerkedal, T, Czeizel, A, Goujard, J, et al. (1982). Valproic acid and spina bifida. Lancet, 2, 1096.Google Scholar
BNF (2019). British National Formulary (online). London: BMJ Group and Pharmaceutical Press. Available at: www.medicinescomplete.com (last accessed 13.8.19).Google Scholar
Bond, DJ, Lam, RW, Yatham, LN (2010). Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord, 124, 228–234.Google Scholar
Bowden, CL, Asnis, GM, Ginsberg, LD, et al. (2004). Safety and tolerability of lamotrigine for bipolar disorder. Drug Saf, 27, 173–184.Google Scholar
Brodie, MJ (1992). Lamotrigine. Lancet, 339, 1397–1400.Google Scholar
Brodie, MJ (2010). Antiepileptic drug therapy the story so far. Seizure, 19, 650–655.Google Scholar
Brodie, MJ, Mintzer, S, Pack, AM, et al. (2013). Enzyme induction with antiepileptic drugs: cause for concern? Epilepsia, 54, 11–27.Google Scholar
Bromley, R, Weston, J, Adab, N, et al. (2014). Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst Rev, (10), CD010236.Google Scholar
Campbell, E, Kennedy, F, Russell, A, et al. (2014). Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry, 85, 1029–1034.Google Scholar
Carrigan, PJ, Brinker, DR, Cavanaugh, JH, Lamm, JE, Cloyd, JC (1990). Absorption characteristics of a new valproate formulation: divalproex sodium-coated particles in capsules (Depakote Sprinkle). J Clin Pharmacol, 30, 743–747.CrossRefGoogle ScholarPubMed
Chen, PS, Peng, GS, Li, G, et al. (2006). Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry, 11, 1116–1125.CrossRefGoogle ScholarPubMed
Christensen, J, Gronborg, TK, Sorensen, MJ, et al. (2013). Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA, 309, 1696–1703.CrossRefGoogle ScholarPubMed
Chung, S, Wang, N, Hank, N (2007). Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure, 16, 296–304.CrossRefGoogle ScholarPubMed
Cipriani, A, Barbui, C, Salanti, G, et al. (2011). Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet, 378, 1306–1315.CrossRefGoogle Scholar
Citrome, L, Volavka, J (2011). Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs, 25, 1009–1021.Google Scholar
Cleare, A, Pariante, CM, Young, AH, et al.; Members of the Consensus Meeting (2015). Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol, 29, 459–525.Google Scholar
Cohen, AF, Land, GS, Breimer, DD, et al. (1987). Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans. Clin Pharmacol Ther, 42, 535–541.Google Scholar
Cohen, MJ, Meador, KJ, Browning, N, et al. (2011). Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years. Epilepsy Behav, 22, 240–246.Google Scholar
Cohen, MJ, Meador, KJ, Browning, N, et al.; NEAD study group (2013). Fetal antiepileptic drug exposure: adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav, 29, 308–315.Google Scholar
Correll, CU, Rubio, JM, Inczedy-Farkas, G, et al. (2017). Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry, 74, 675–684.Google Scholar
Crawford, MJ, Sanatinia, R, Barrett, B, et al. (2018). Lamotrigine for people with borderline personality disorder: a RCT. Health Technol Assess, 22, 1–68.Google Scholar
Cummings, C, Stewart, M, Stevenson, M, Morrow, J, Nelson, J (2011). Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child, 96, 643–647.Google Scholar
Davis, LL, Ryan, W, Adinoff, B, Petty, F (2000). Comprehensive review of the psychiatric uses of valproate. J Clin Psychopharmacol, 20, 1S–17S.CrossRefGoogle ScholarPubMed
Dias, VV, Balanza-Martinez, V, Soeiro-de-Souza, MG, et al. (2012). Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview. Acta Psychiatr Scand, 126, 315–331.Google Scholar
Drevets, WC (2000). Neuroimaging studies of mood disorders. Biol Psychiatry, 48, 813–829.CrossRefGoogle ScholarPubMed
Drugbank (2019a). Lamotrigine. Available at: www.drugbank.ca/drugs/DB00555 (last accessed 6.8.19).Google Scholar
Drugbank (2019b). Carbamazepine. Available at: www.drugbank.ca/drugs/DB00564 (last accessed 6.8.19).Google Scholar
electronic Medicines Compendium (2019a). Summary of Product Characteristics: Depakote. SANOFI. Available at: www.medicines.org.uk/emc/product/6113/smpc (last accessed 6.8.19).Google Scholar
electronic Medicines Compendium (2019b). Summary of Product Characteristics: Lamotrigine. Accord Healthcare Limited. Available at: www.medicines.org.uk/emc/product/6091/smpc (last accessed 6.8.19).Google Scholar
electronic Medicines Compendium (2019c). Summary of Product Characteristics: Carbamazepine. Novartis Pharmaceuticals UK Ltd. Available at: www.medicines.org.uk/emc/product/1040/smpc (last accessed 6.8.19).Google Scholar
Elkjaer, LS, Bech, BH, Sun, Y, Laursen, TM, Christensen, J (2018). Association between prenatal valproate exposure and performance on standardized language and mathematics tests in school-aged children. JAMA Neurol, 19, 19.Google Scholar
European Medicines Agency (2018). New measures to avoid valproate exposure in pregnancy endorsed. Press release, 23 March 2018. Available at: www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/03/WC500246391.pdf (last accessed 22.8.19).Google Scholar
Fleming, J, Chetty, M (2005). Psychotropic drug interactions with valproate. Clin Neuropharmacol, 28, 96–101.Google Scholar
Franks, M, Macritchie, KA, Mahmood, T, Young, AH (2008). Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A retrospective naturalistic study. J Psychopharmacol, 22, 452–456.Google Scholar
Frye, MA, Ketter, TA, Kimbrell, TA, et al. (2000). A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol, 20, 607–614.Google Scholar
Geddes, JR, Calabrese, JR, Goodwin, GM (2009). Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry, 194, 4–9.Google Scholar
Geddes, JR, Gardiner, A, Rendell, J, et al.; CEQUEL Investigators and Collaborators (2016). Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): a 2 × 2 factorial randomised trial. Lancet Psychiatry, 3, 31–39.Google Scholar
Ghabrash, MF, Comai, S, Tabaka, J, et al. (2016). Valproate augmentation in a subgroup of patients with treatment-resistant unipolar depression. World J Biol Psychiatry, 17, 165–170.Google Scholar
Ghodke-Puranik, Y, Thorn, CF, Lamba, JK, et al. (2013). Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics, 23, 236–241.Google Scholar
Goodwin, GM, Bowden, CL, Calabrese, JR, et al. (2004). A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry, 65, 432–441.Google Scholar
Goodwin, GM, Haddad, PM, Ferrier, IN, et al. (2016). Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol, 30, 495–553.Google Scholar
Grunze, H, Kotlik, E, Costa, R, et al. (2015). Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I. J Affect Disord, 174, 70–82.Google Scholar
Hammond, CJ, Niciu, MJ, Drew, S, Arias, AJ (2015). Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders. CNS Drugs, 29, 293–311.Google Scholar
Haymond, J, Ensom, MH (2010). Does valproic acid warrant therapeutic drug monitoring in bipolar affective disorder? Ther Drug Monit, 32, 19–29.Google Scholar
Hernandez-Diaz, S, Smith, CR, Shen, A, et al.; North American AED Pregnancy Registry (2012). Comparative safety of antiepileptic drugs during pregnancy. Neurology, 78, 1692–1699.Google Scholar
Huband, N, Ferriter, M, Nathan, R, Jones, H (2010). Antiepileptics for aggression and associated impulsivity. Cochrane Database Syst Rev, (2), CD003499.Google Scholar
Hurley, SC (2002). Lamotrigine update and its use in mood disorders. Ann Pharmacother, 36, 860–873.Google Scholar
Jentink, J, Loane, MA, Dolk, H, et al.; EUROCAT Antiepileptic Study Working Group (2010). Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med, 362, 2185–2193.Google Scholar
Kaye, NS, Graham, J, Roberts, J, Thompson, T, Nanry, K (2007). Effect of open-label lamotrigine as monotherapy and adjunctive therapy on the self-assessed cognitive function scores of patients with bipolar I disorder. J Clin Psychopharmacol, 27, 387–391.Google Scholar
Ketter, TA, Post, RM, Parekh, PI, Worthington, K (1995). Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression. J Clin Psychiatry, 56(10), 471–475.Google Scholar
Kleindienst, N, Greil, W (2000). Differential efficacy of lithium and carbamazepine in the prophylaxis of bipolar disorder: results of the MAP study. Neuropsychobiology, 42(Suppl 1), 2–10.Google Scholar
Klotz, U, Antonin, KH (1977). Pharmacokinetics and bioavailability of sodium valproate. Clin Pharmacol Ther, 21, 736–743.Google Scholar
Kramlinger, KG, Post, RM (1989). The addition of lithium to carbamazepine. Antidepressant efficacy in treatment-resistant depression. Arch Gen Psychiatry, 46, 794–800.Google Scholar
Leach, MJ, Marden, CM, Miller, AA (1986). Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia, 27, 490–497.Google Scholar
Lempérière, T (2001). Brief history of the development of valproate in bipolar disorders. Encephale, 27, 365–372.Google Scholar
Leucht, S, Helfer, B, Dold, M, Kissling, W, McGrath, J (2014). Carbamazepine for schizophrenia. Cochrane Database Syst Rev, (5), CD001258.Google Scholar
Lieb, K, Vollm, B, Rucker, G, Timmer, A, Stoffers, JM (2010). Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials. Br J Psychiatry, 196, 4–12.Google Scholar
Lloyd, KA (2013). A scientific review: mechanisms of valproate-mediated teratogenesis. Biosci Horizons, 6, hzt003-hzt03.Google Scholar
Locharernkul, C, Shotelersuk, V, Hirankarn, N (2011). Pharmacogenetic screening of carbamazepine-induced severe cutaneous allergic reactions. J Clin Neurosci, 18, 1289–1294.Google Scholar
Löscher, W (1999). The discovery of valproate. In Löscher, W, ed., Valproate. Basel: Birkhäuser Basel, pp. 1–3.Google Scholar
Meador, K, Reynolds, MW, Crean, S, Fahrbach, K, Probst, C (2008). Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res, 81, 1–13.Google Scholar
Molgaard-Nielsen, D, Hviid, A (2011). Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA, 305, 1996–2002.Google Scholar
Mula, M, Pini, S, Cassano, GB (2007). The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol, 27, 263–272.Google Scholar
National Institute for Health and Clinical Excellence (NICE) (2009). Borderline personality disorder: recognition and management. Clinical guideline [CG78]. London: National Institute for Health and Care Excellence. Available at: www.nice.org.uk/guidance/cg78 (last accessed 22.8.19).Google Scholar
Nishino, S, Ohtomo, K, Numata, Y, et al. (2012). Divergent effects of lithium and sodium valproate on brain-derived neurotrophic factor (BDNF) production in human astrocytoma cells at therapeutic concentrations. Prog Neuropsychopharmacol Biol Psychiatry, 39, 17–22.Google Scholar
Nugent, AC, Carlson, PJ, Bain, EE, et al. (2013). Mood stabilizer treatment increases serotonin type 1 A receptor binding in bipolar depression. J Psychopharmacol, 27, 894–902.Google Scholar
Okuma, T, Kishimoto, A (1998). A history of investigation on the mood stabilizing effect of carbamazepine in Japan. Psychiatry Clin Neurosci, 52, 3–12.CrossRefGoogle ScholarPubMed
Okuma, T, Kishimoto, A, Inoue, K, Matsumoto, H, Ogura, A (1973). Anti-manic and prophylactic effects of carbamazepine (Tegretol) on manic depressive psychosis. A preliminary report. Folia Psychiatr Neurol Jpn, 27, 283–297.Google Scholar
Ornoy, A (2009). Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Reprod Toxicol, 28, 1–10.Google Scholar
Perugi, G, Toni, C, Frare, F, et al. (2002). Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? J Clin Psychopharmacol, 22, 584–591.Google Scholar
Peterson, GM, Naunton, M (2005). Valproate: a simple chemical with so much to offer. J Clin Pharm Ther, 30, 417–421.Google Scholar
Rajkowska, G (2000). Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry, 48, 766–777.Google Scholar
Ramsay, RE, Pellock, JM, Garnett, WR, et al. (1991). Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy. Epilepsy Res, 10, 191–200.Google Scholar
Rapoport, SI, Basselin, M, Kim, HW, Rao, JS (2009). Bipolar disorder and mechanisms of action of mood stabilizers. Brain Res Rev, 61, 185–209.Google Scholar
Reid, JG, Gitlin, MJ, Altshuler, LL (2013). Lamotrigine in psychiatric disorders. J Clin Psychiatry, 74, 675–684.Google Scholar
Robert, E, Guibaud, P (1982). Maternal valproic acid and congenital neural tube defects. Lancet, 2, 937.Google Scholar
Rosenberg, G (2007). The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci, 64, 2090–2103.Google Scholar
Sahraian, A, Bigdeli, M, Ghanizadeh, A, Akhondzadeh, S (2014). Topiramate as an adjuvant treatment for obsessive compulsive symptoms in patients with bipolar disorder: a randomized double blind placebo controlled clinical trial. J Affect Disord, 166, 201–205.Google Scholar
Sandson, NB, Marcucci, C, Bourke, DL, Smith-Lamacchia, R (2006). An interaction between aspirin and valproate: the relevance of plasma protein displacement drug-drug interactions. Am J Psychiatry, 163, 1891–1896.Google Scholar
Schule, C, Baghai, TC, Eser, D, Nothdurfter, C, Rupprecht, R (2009). Lithium but not carbamazepine augments antidepressant efficacy of mirtazapine in unipolar depression: an open-label study. World J Biol Psychiatry, 10, 390–399.Google Scholar
Seo, HJ, Chiesa, A, Lee, SJ, et al. (2011). Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clin Neuropharmacol, 34, 39–47.Google Scholar
Serrani Azcurra, DJ (2013). Lamotrigine rechallenge after a skin rash. A combined study of open cases and a meta-analysis. Rev Psiquiatr Salud Ment, 6, 144–149.Google Scholar
Sie, M (2014). Mood stabilisers in the management of bipolar affective disorder. Prog Neurol Psychiatry, 18, 22–32.Google Scholar
Smith, LA, Cornelius, VR, Azorin, JM, et al. (2010). Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord, 122, 1–9.Google Scholar
Solmi, M, Veronese, N, Zaninotto, L, et al. (2016). Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials. CNS Spectr, 21, 403–418.Google Scholar
Stoffers, J, Vollm, BA, Rucker, G, et al. (2010). Pharmacological interventions for borderline personality disorder. Cochrane Database Syst Rev, (6), CD005653.Google Scholar
Takezaki, H, Hanaoka, M (1971). The use of carbamazepine (Tegretol) in the control of manic depressive psychosis and other manic depressive states. Saishin Igaku, 13, 1310–1318 (in Japanese).Google Scholar
Tanoshima, M, Kobayashi, T, Tanoshima, R, et al. (2015). Risks of congenital malformations in offspring exposed to valproic acid in utero: a systematic review and cumulative meta-analysis. Clin Pharmacol Ther, 98, 417–441.Google Scholar
Taylor, DM, Cornelius, V, Smith, L, Young, AH (2014). Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis. Acta Psychiatr Scand, 130, 452–469.Google Scholar
Taylor, D, Paton, C, Kapur, S (2015). The Maudsley Prescribing Guidelines in Psychiatry, 12th ed. Hoboken: Wiley Blackwell.Google Scholar
Thomas, SV, Ajaykumar, B, Sindhu, K, et al. (2008). Motor and mental development of infants exposed to antiepileptic drugs in utero. Epilepsy Behav, 13, 229–236.Google Scholar
Thorn, CF, Leckband, SG, Kelsoe, J, et al. (2011). PharmGKB summary: carbamazepine pathway. Pharmacogenet Genomics, 21, 906–910.Google Scholar
Tomson, T, Battino, D, Perucca, E (2016). Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol, 15, 210–218.Google Scholar
Tseng, PT, Chen, YW, Chung, W, et al. (2016). Significant effect of valproate augmentation therapy in patients with schizophrenia: a meta-analysis study. Medicine, 95, e2475.Google Scholar
Uguz, F, Sharma, V (2016). Mood stabilizers during breastfeeding: a systematic review of the recent literature. Bipolar Disord, 18, 325–333.Google Scholar
Vajda, FJ, Donnan, GA, Phillips, J, Bladin, PF (1981). Human brain, plasma, and cerebrospinal fluid concentration of sodium valproate after 72 hours of therapy. Neurology, 31, 486–487.Google Scholar
Vajda, FJ, O’Brien, TJ, Graham, JE, Lander, CM, Eadie, MJ (2013). Dose dependence of fetal malformations associated with valproate. Neurology, 81, 999–1003.Google Scholar
Vasudev, K, Keown, P, Gibb, I, McAllister-Williams, RH (2010). Hematological effects of valproate in psychiatric patients: what are the risk factors? J Clin Psychopharmacol, 30(3), 282–285.Google Scholar
van der Loos, ML, Mulder, PG, Hartong, EG, et al.; LamLit Study Group (2009). Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry, 70, 223–231.Google Scholar
Vella, T, Mifsud, J (2014). Interactions between valproic acid and quetiapine/olanzapine in the treatment of bipolar disorder and the role of therapeutic drug monitoring. J Pharmacy Pharmacol, 66, 747–759.Google Scholar
Veroniki, AA, Cogo, E, Rios, P, et al. (2017a). Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med, 15, 95.Google Scholar
Veroniki, AA, Rios, P, Cogo, E, et al. (2017b). Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open, 7, e017248.Google Scholar
Vieta, E, Manuel Goikolea, J, Martinez-Aran, A, et al. (2006). A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder. J Clin Psychiatry, 67, 473–477.Google Scholar
Wagner, KD, Kowatch, RA, Emslie, GJ, et al. (2006). A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. Am J Psychiatry, 163, 1179–1186. Erratum in: Am J Psychiatry 2006, 163(10), 1843.Google Scholar
Wang, Y, Xia, J, Helfer, B, Li, C, Leucht, S (2008). Valproate for schizophrenia. Cochrane Database Syst Rev, (3), CD004028.Google Scholar
Wegner, C, Nau, H (1992). Alteration of embryonic folate metabolism by valproic acid during organogenesis: implications for mechanism of teratogenesis. Neurology, 42, 17–24.Google Scholar
Weisler, RH, Calabrese, JR, Bowden, CL, et al. (2008). Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence. J Affect Disord, 108, 1–9.Google Scholar
Wieck, A, Jones, S (2018). Dangers of valproate in pregnancy. BMJ, 361, k1609.CrossRefGoogle ScholarPubMed
Yasam, VR, Jakki, SL, Senthil, V, et al. (2016). A pharmacological overview of lamotrigine for the treatment of epilepsy. Expert Rev Clin Pharmacol, 9, 1533–1546.Google Scholar
Yatham, LN, Kennedy, SH, Parikh, SV, et al. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord, 20, 97–170.Google Scholar
Yildiz, A, Nikodem, M, Vieta, E, Correll, CU, Baldessarini, RJ (2015). A network meta-analysis on comparative efficacy and all-cause discontinuation of antimanic treatments in acute bipolar mania. Psychol Med, 45, 299–317.Google Scholar
Zhang, L, Li, H, Li, S, Zou, X (2016). Reproductive and metabolic abnormalities in women taking valproate for bipolar disorder: a meta-analysis. Eur J Obstet Gynecol Reprod Biol, 202, 26–31.Google Scholar
Zhang, ZJ, Tan, QR, Tong, Y, et al. (2008). The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study. J Affect Disord, 109, 91–97.Google Scholar
Zhou, X, Ravindran, AV, Qin, B, et al. (2015). Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry, 76, e487–e498.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×