AboutIvan Goldberg, M.D. Expertise I am a psychiatrist/psychopharmacologist with many years of expereince in treating individuals with depressions, manic-depression (Bipolar Disorder), other mood disorders,. I am especially interested in the psychopharmacologic treatment of individuals with so called "treatment-resistant" syndromes.
Experience I have been on the staff of the National Institute of Mental Health, Columbia's College of Physicians and Surgeons, and the Columbia-Presbyterian Medical Center. I am currently in full-time private practice in New York City.
A.B. Johns Hopkins University M.D. N.Y.U. College of Medicine
I am the creator of Depression Central:http://www.psycom.net/depression.central.html
Question Have you heard about Zonegran being a good medication for the treatment of Bi-polar?
Answer Hi Kisa . . .
The matrerial below is from a book I am bringing out.
Best regards . . .
Ivan
%%%%%%%%%%%%%%%%%%%%%%%%%
Zonisamide (Zonegan)
Indications and Effectiveness
Q: What is zonisamide (Zonegran) and is it useful in treating people with mood disorders?
Zonisamide, became available in the USA in 2000, but has been available in other parts of the world for many years. In open label studies it appeared that it has the ability to improve mood in individuals with Bipolar Disorder. Like topiramate, zonisamide often causes weight loss. It may be its effect on appetite that makes it useful in treating Binge Eating Disorder.
Ref: McElroy SL, Suppes T, Keck PE Jr, et al. Open-label adjunctive zonisamide in the treatment of bipolar disorders: A prospective trial. Journal of Clinical Psychiatry, 2005, 66, 617-624. Vieta E. Bipolar mixed states and their treatment. Expert Review of Neurotherapeutics, 2005, 5, 63-68. McElroy SL, Kotwal R, Hudson JI, et al. Zonisamide in the treatment of binge eating disorder: An open-label, prospective disorder. Journal of Clinical Psychiatry, 2004, 65, 50-56. Gadde KM, Franciscy DM, Wagner HR II, et al. Zonisamide for weight loss in obese adults. Journal of the American Medical Association, 2003, 289, 180-1825. Berigan TR. Zonisamide treatment of bipolar disorder: A case report. Canadian Journal of Psychiatry, 2002, 47, 887. Kanba S, Yagi G, Kamijima K, et al. The first open study of zonisamide, a novel anticonvulsant, shown efficacy in mania. Progress in Neuropsychopharmacology and Biological Psychiatry, 1994, 18, 707-715.
Q: Is there a role for zonisamide (Zonegran) in treating individuals with Bipolar Depression?
A: The usefulness of zonisamide (Zonegran) in treating people with Bipolar Depression is not clear. While there are some reports of the usefulness of zonisamide as an antidepressant for people with Bipolar Depression, it is not yet clear how much antimanic and antidepressant activity it has.
Refs: Anand A, Bukhari L, Jennings SA, et al. A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients. Journal of Clinical Psychiatry, 2005, 66, 195-198. McElroy SL, Suppes T, Keck PE Jr, et al. Open-label adjunctive zonisamide in the treatment of bipolar disorders: A prospective trial. Journal of Clinical Psychiatry, 2005, 66, 617-624. Baldassano CF, Ghaemi SN, Chang A, et al. Acute treatment of bipolar depression with adjunctive zonisamide: A retrospective chart review. Bipolar Disorders, 2004, 6, 432-434. Yatham LN. Newer anticonvulsants in the treatment of bipolar disorder. Journal of Clinical Psychiatry, 2004, 65 (Suppl 10), 28-35. 1Yatham LN, Kusumakar V, Calabrese JR, Rao R, Scarrow G, Kroeker G. Third generation anticonvulsants in bipolar disorder: A review of efficacy and summary of clinical recommendations. Journal of Clinical Psychiatry, 2002, 63, 275-283.
Q: Why might zonisamide (Zonegran) have be a good treatment for a 54-year-old woman with chronic hypomania and painful diabetic neuropathy?
A: As well as having antimanic activity, zonisamide (Zonegran) is useful as a way of controlling neuropathic and thalamic pain.
Refs: Guay DR. Oxcarbazepine, topiramate, zonisamide, and levetiracetam: Potential use in Neuropathic pain. American Journal of Geriatric Pharmacotherapy, 2003, 1, 18-37.Hasegawa H. Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: A retrospective, open label, uncontrolled study in a VA hospital. Current Medical Research and Opinion, 2004, 20, 577-580. Takahashi Y, Hashimoto K, Tsuji S. Successful use of zonisamide fro central poststroke pain. Journal of Pain, 2004, 5, 192-194.
Q: Is zonisamide (Zonegran) a suitable treatment for someone who often engages in binge eating when depressed?
Zonisamide is effective in reducing binge-eating frequency in individuals with binge-eating disorder. We have used zonisamide successfully with some patients who only binge-eat when depressed.
Ref: McElroy SL, Kotwal R, Hudson JI, et al. Zonisamide in the treatment of binge-eating disorder: An open-label prospective trial. Journal of Clinical Psychiatry, 2004, 65, 50-56.
Dosage
Q: When clinicians use zonisamide (Zonegran) to treat psychiatric patients, how should it be start it, and what doses are effective?
A: We usually start Zonisamide at a dose of 100 mg a day. Because of the long half-life it takes about two weeks for the plasma level to reach steady state. We then raise the dose by 100 mg a day at intervals of not less than two-weeks. Final doses are often 200 mg a day or 300 mg a day.
Refs: Anand A, Bukhari L, Jennings SA, et al. A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients. Journal of Clinical Psychiatry, 2005, 66, 195-198. . Baldassano CF, Ghaemi SN, Chang A, et al. Acute treatment of bipolar depression with adjunctive zonisamide: A retrospective chart review. Bipolar Disorders, 2004, 6, 432-434. McElroy SL, Kotwal R, Hudson JI, et al. Zonisamide in the treatment of binge-eating disorder: An open-label prospective trial. Journal of Clinical Psychiatry, 2004, 65, 50-56.
Q: Is the half-life of zonisamide (Zonegran) long enough to allow for once a day administration?
A: Yes. The half-life of zonisamide (Zonegran) is over 60 hours, making once a day administration possible.
Ref: Leppik IE. Zonisamide: Chemistry Mechanism of action, and pharmacokinetics. Seizure, 2004, 13 (Suppl 1), S5-S9. Marson AG, Kadir AZ, Chadwick DW. New antiepileptic drugs: A systematic review of their efficacy and tolerability. British Medical Journal, 1996, 313, 1169-1174.
Side Effects
Q: What are the most common side effects of zonisamide (Zonegran)?
A: The most common side effects of zonisamide (Zonegran), and the percentage of patients reporting them are:
Rarely zonisamide (Zonegran) causes a severe allergic reaction, depression, mania or psychosis.
Refs: Drug Facts and Comparisons, 60th Ed. St. Louis, Mo: Facts and Comparisons; 2006. Mago R, Huege S, Ahuja N, et al. Zonisamide-induced suicidal ideation. Psychosomatics, 2006, 47, 68-69. Anand A, Bukhari L, Jennings SA, et al. A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients. Journal of Clinical Psychiatry, 2005, 66, 195-198. McElroy SL, Suppes T, Keck PE Jr, et al. Open-label adjunctive zonisamide in the treatment of bipolar disorders: A prospective trial. Journal of Clinical Psychiatry, 2005, 66, 617-624. Majeres KD, Suppes T. A cautionary note when using zonisamide in youths: A case report of association with toxic epidermal necrolysis Journal of Clinical Psychiatry, 2004, 65, 1720. Ozaawa K, Kobayashi K, Noda S, et al. Zonisamide-induced depression and mania in patients with epilepsy. Journal of Clinical Psychopharmacology, 2004, 24, 110-111. Miyamoto T, Kohsaka M, Koyama T. Psychotic episodes during zonisamide treatment. Seizure, 2000, 9, 65-70. Charles C, Stoez L, Tollefson G. Zonegran-induced mania. Psychosomatics, 1990, 31, 214-221.
Precautions
(including drug & food interactions, need for monitoring, use during pregnancy and lactation, etc.)
Q: Will zonisamide (Zonegran) interfere with the protection offered by oral contraceptives?
A: A study of the effects of zonisamide (Zonegran) on the pharmacokinetics of an ethinyl estradiol-norethindrone oral contraceptive found that zonisamide had no effect on the concentration in the blood of either ingredient.
Ref: Griffith SG, Dai Y. Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clinical Therapeutics, 2004, 26, 2056-2065. Crawford P. Interactions between antiepileptic drugs and hormonal contraception. CNS Drugs, 2002, 16, 263-272.
Q: Does zonisamide (Zonegran) interact with other anticonvulsants psychiatrists use in treating people with Bipolar Disorder?
A: Zonisamide (Zonegran) has no effect on the plasma levels of carbamazepine (Tegretol), divalproex (Depakote), or lamotrigine (Lamictal). While divalproex has no effect on zonisamide plasma levels, carbamazepine, phenytoin (Dilantin), and Phenobarbital, by inducing drug-metabolizing enzymes, reduces such levels.
Refs: Levy RH, Ragueneau-Majlessi I, Brodie MJ, et al. Lack of clinically significant pharmacokinetic interactions between zonisamide and lamotrigine at steady state in patients with epilepsy. Therapeutic Drug Monitoring, 2005, 27, 193-298. Ragueneau-Majlessi I, Levy RH, Brodie M, et al. Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Clinical Pharmacokinetics, 2005, 44, 517-523. Kothare SV, Valencia I, Khurana DS, et al. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Disorders, 2004, 6, 267-270. Ragueneau-Majlessi I, Levy RH, Bergen D, et al. Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients. Epilepsy Research, 2004, 62, 1-11. Fukuoka N, Tsukamoto T, Uno J, et al. Influence of coadministered antiepileptic drugs on serum zonisamide concentrations in epileptic patients: quantitative analysis based on suitable transforming factor. Biological and Pharmaceutical Bulletin, 2003, 26, 1734-1738. Mimaki T. Clinical pharmacology and therapeutic drug monitoring of zonisamide. Therapeutic Drug Monitoring, 1998, 20, 593-597.
Q: What drugs are likely to increase the plasma level of zonisamide (Zonegran)?
A: The blood level of zonisamide (Zonegran) is likely to be increased by the following inhibitors of CPY450 3A4, among others:
Ref: Nakasa H, Nakamura H, Ono S, et al. Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data. European Journal of Clinical Pharmacology, 1998, 54, 177-183.
Q: Will zonisamide (Zonegran) reduce the effectiveness of oral contraceptives containing estradiol and norethindrone?
A: Zonisamide has no effect on the concentration of estradiol or norethindrone. Because of this, zonisamide (Zonegran) will not reduce the effectiveness of oral contraceptives containing these hormones.
Ref: Griffith SG, Dai Y. Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clinical Therapeutics, 2004, 26, 2056-2065.
