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Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up
European Psychiatry 21 (2006) 280–281 http://france.elsevier.com/direct/EURPSY/
Case report
Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up Sherif Karama a, Samarthji Lal b,* a
b
Resident in Psychiatry, Douglas Hospital Research Center, McGill University, 6875 LaSalle Blvd., Verdun, Que., Canada H4H 1R3 Professor of Psychiatry, Director, McGill Center for Research in Schizophrenia, Douglas Hospital Research Center, McGill University, 6875 LaSalle Blvd., Verdun, Que., Canada H4H 1R3 Received 19 August 2004; accepted 15 July 2005 Available online 19 December 2005
Abstract A patient with a treatment-refractory bipolar disorder with ultradian cycling responded to adjunctive topiramate. Response was maintained during 3-year follow-up. © 2005 Elsevier SAS. All rights reserved. Keywords: Bipolar disorder; Ultradian cycling; Topiramate
1. Introduction There is evidence that adjunctive topiramate may have antimanic or anti-cycling effects [2,3,8] as well as an antidepressant action in bipolar disorder [4,9]. A beneficial effect has been observed in rapid cyclers [5,7]. Some data suggest that adjunctive topiramate may be useful in treatment-resistant bipolar spectrum disorders [10]. Long-term follow-up of topiramate responders has been brief, though some patients have been followed for 6–12 months [8,10]. Letmaier et al. [6] reported a patient with a 10-year history of bipolar disorder refractory to treatment who became mostly asymptomatic for approximately 17 months on addition of topiramate. We report a patient with a refractory ultradian cycling bipolar disorder who has been euthymic for 3 years on adjunctive topiramate. The patient provided informed consent for all treatments and agreed to anonymous publication of this report.
2. Case report A 43-year-old male with a history of multiple hospitalizations for a bipolar disorder both in the manic and depressive * Corresponding author. E-mail address: [email protected] (S. Lal). 0924-9338/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2005.07.002
phase, with or without psychotic features since the age of 18, was re-hospitalized for the 18th time because of increasing withdrawal, neglect of his basic hygiene, and talking about death. In the past he had made several suicide attempts including an overdose of lithium (resulting in renal toxicity), hanging, drinking chlorine dioxide and jumping in front of a garbage truck. Past treatments included lithium, valproic acid, carbamazapine, clonazepam, antidepressants (clomipramine, nefazodone), neuroleptics (haloperidol, risperidone, perphenazine, fluphenazine) in various combinations and three courses of ECT. For the previous 18 years it had been difficult to stabilize him. Between hospitalizations, he remained symptomatic even when discharged to a supervised setting. Soon after each discharge deterioration quickly followed. At the time of admission he was taking risperidone 5 mg bid, carbamazepine 400 mg am and 800 mg hs and nefazodone 300 mg bid. Diagnosis was bipolar depression. He was treated with venlafaxine and carbamazepine but became manic necessitating referral to a locked ward. When transferred he was receiving loxapine 25 mg bid and carbamazepine 400 mg am and hs and was in a depressed state. He was uncommunicative, sat in a flexed posture with furrowed brow. His speech was slowed and interrupted with pauses. He was withdrawn, irritable, hostile and resentful if disturbed. He spent most of his time in bed. At times he would urinate and defecate in his bed. He talked about the Mafia wanting to kill him because he deserved to die and felt the T.V. talked about him reveal-
S. Karama, S. Lal / European Psychiatry 21 (2006) 280–281
ing that he was a bad person. During the day he would briefly emerge from his withdrawn state and become good-humored and communicative before reverting to his depressed state. On valproic acid and olanzapine, psychotic features (other than delusions of guilt) resolved but an extreme diurnal variation in mood became evident. When lithium was added he became less withdrawn and stopped defecating and urinating in his bed but diurnal variation in mood was unchanged. In the morning he expressed delusions of guilt, feelings of unworthiness, loss of self-esteem, preoccupation with all the miseries of the world and at times, suicidal ideation. In the evenings he would be over-active, mischievous, tease the other patients, interfere with their care, become disruptive, angry and, at times, physically aggressive if the staff tried to intervene. A diagnosis of bipolar disorder with ultradian cycling was made. Over a period of 11 months, he received lithium (750–900 mg hs), valproic acid (1000–1250 mg hs), together with either chlorpromazine (up to 800 mg/day) or olanzapine 15 mg/day with minimal benefit. During this time, for a 4-month period, paroxetine was added to treat his suicidal ideation following a suicide attempt but this increased his disruptive behavior and was discontinued. After being in hospital for 23 months and manifesting an ultradian bipolar rhythm for 14 months he was started on topiramate in a dose of 25 mg bid as an adjunct to lithium, valproic acid and loxapine. Topiramate was progressively increased over a 5-week period to 100 mg bid. On this dose, within a week, improvement in the diurnal mood variation was apparent. Over the ensuing 8 months instead of frequent outbursts of anger or disruptive behavior, only eight incidents were noted. He was discharged 3 months later without incident and has remained stable in the community with regular follow-up for 25 months on topiramate 100 mg bid, lithium (750–900 mg hs), valproic acid (1000–1250 mg/day), loxapine 25 mg am and hs and benztropine 1 mg am and hs. 3. Discussion The psychotic symptoms experienced by the patient were mood congruent with his depressive state and lifted with his diurnal change to a manic mood. Delusions were not present in the absence of prominent mood symptoms. These findings point to a diagnosis of bipolar disorder with psychotic features rather than a schizoaffective disorder. Improvement with adjunctive topiramate has been described in rapid cycling bipolar patients with psychotic symptoms [2] or patients with schizoaffective disorder [7] but follow-up has been short. Antidepressants may induce or accelerate rapid cycling [1] so that it is possible that antidepressants triggered the ultra-
281
dian rhythm and simply stopping antidepressants led to improvement. However, onset of ultradian cycling occurred 7 months after venlafaxine was discontinued and was present for 8 months before paroxetine was started. Improvement with topiramate occurred 6–7 weeks after paroxetine was discontinued so that it is possible that paroxetine enhanced mood congruent psychopathology although it did not induce ultradian cycling. Though a spontaneous remission cannot be discounted, this is unlikely given the chronicity of the condition, poor response to previous treatments, temporal association of response with the addition of topiramate and improvement extending to 3 years in a patient requiring repeated admissions in the past. McElroy et al. [8] included patients with ultradian cycling in their study but the effect of topiramate in this subgroup was not specified. Aside from the latter paper, published data on topiramate in ultradian cycling bipolar patients is lacking. The dose of topiramate used and time of onset of improvement in our patient is similar to that described by others [5,8] in the treatment of rapid cycling bipolar disorders. The present case report suggests that in refractory cases with ultradian rapid cycling a trial with topiramate in increasing doses up to 200 mg/day may be of therapeutic benefit.
References [1]
Barrios C, Chaudhry TA, Goodnick PJ. Rapid cycling bipolar disorder. Expert Opin Pharmacother 2001;2:1963–73. [2] Chengappa R, Rathore D, Levine J, Atzert R, Solai L, Parepally H, et al. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord 1999;1:42–53. [3] Evins AE. Efficacy of newer anticonvulsant medications in bipolar spectrum mood disorders. J Clin Psychiatr 2003;64(S8):9–14. [4] Hussain MZ. Treatment of bipolar depression with topiramate. Eur Neuropsychopharmacol 1999;9(Suppl. 5):S222. [5] Kusumakar V, Yatham L, Kutcher S, O’Donovan C. Preliminary, open-label study of topiramate in rapid cycling bipolar women. Eur Neuropsychopharmacol 1999;9(Suppl. 5):S357. [6] Letmaier M, Schreinzer D, Wolf R, Kasper S. Topiramate as a mood stabilizer. Intern Clin Psychopharmacol 2001;16:295–8. [7] Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Dis 1998;50:245–51. [8] McElroy SL, Suppes T, Keck PE, Frye MA, Denicoff KD, Altshuler LL, et al. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatr 2000;47:1025–33. [9] McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Bipolar Disord 2002;4:207–13. [10] Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, Garcia-Parés G, Rodriguez A, et al. Use of topiramate in treatment-resistant bipolar spectrum disorders. J Clin Psychopharmacol 2002;22:431–5.
Case report
Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up Sherif Karama a, Samarthji Lal b,* a
b
Resident in Psychiatry, Douglas Hospital Research Center, McGill University, 6875 LaSalle Blvd., Verdun, Que., Canada H4H 1R3 Professor of Psychiatry, Director, McGill Center for Research in Schizophrenia, Douglas Hospital Research Center, McGill University, 6875 LaSalle Blvd., Verdun, Que., Canada H4H 1R3 Received 19 August 2004; accepted 15 July 2005 Available online 19 December 2005
Abstract A patient with a treatment-refractory bipolar disorder with ultradian cycling responded to adjunctive topiramate. Response was maintained during 3-year follow-up. © 2005 Elsevier SAS. All rights reserved. Keywords: Bipolar disorder; Ultradian cycling; Topiramate
1. Introduction There is evidence that adjunctive topiramate may have antimanic or anti-cycling effects [2,3,8] as well as an antidepressant action in bipolar disorder [4,9]. A beneficial effect has been observed in rapid cyclers [5,7]. Some data suggest that adjunctive topiramate may be useful in treatment-resistant bipolar spectrum disorders [10]. Long-term follow-up of topiramate responders has been brief, though some patients have been followed for 6–12 months [8,10]. Letmaier et al. [6] reported a patient with a 10-year history of bipolar disorder refractory to treatment who became mostly asymptomatic for approximately 17 months on addition of topiramate. We report a patient with a refractory ultradian cycling bipolar disorder who has been euthymic for 3 years on adjunctive topiramate. The patient provided informed consent for all treatments and agreed to anonymous publication of this report.
2. Case report A 43-year-old male with a history of multiple hospitalizations for a bipolar disorder both in the manic and depressive * Corresponding author. E-mail address: [email protected] (S. Lal). 0924-9338/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2005.07.002
phase, with or without psychotic features since the age of 18, was re-hospitalized for the 18th time because of increasing withdrawal, neglect of his basic hygiene, and talking about death. In the past he had made several suicide attempts including an overdose of lithium (resulting in renal toxicity), hanging, drinking chlorine dioxide and jumping in front of a garbage truck. Past treatments included lithium, valproic acid, carbamazapine, clonazepam, antidepressants (clomipramine, nefazodone), neuroleptics (haloperidol, risperidone, perphenazine, fluphenazine) in various combinations and three courses of ECT. For the previous 18 years it had been difficult to stabilize him. Between hospitalizations, he remained symptomatic even when discharged to a supervised setting. Soon after each discharge deterioration quickly followed. At the time of admission he was taking risperidone 5 mg bid, carbamazepine 400 mg am and 800 mg hs and nefazodone 300 mg bid. Diagnosis was bipolar depression. He was treated with venlafaxine and carbamazepine but became manic necessitating referral to a locked ward. When transferred he was receiving loxapine 25 mg bid and carbamazepine 400 mg am and hs and was in a depressed state. He was uncommunicative, sat in a flexed posture with furrowed brow. His speech was slowed and interrupted with pauses. He was withdrawn, irritable, hostile and resentful if disturbed. He spent most of his time in bed. At times he would urinate and defecate in his bed. He talked about the Mafia wanting to kill him because he deserved to die and felt the T.V. talked about him reveal-
S. Karama, S. Lal / European Psychiatry 21 (2006) 280–281
ing that he was a bad person. During the day he would briefly emerge from his withdrawn state and become good-humored and communicative before reverting to his depressed state. On valproic acid and olanzapine, psychotic features (other than delusions of guilt) resolved but an extreme diurnal variation in mood became evident. When lithium was added he became less withdrawn and stopped defecating and urinating in his bed but diurnal variation in mood was unchanged. In the morning he expressed delusions of guilt, feelings of unworthiness, loss of self-esteem, preoccupation with all the miseries of the world and at times, suicidal ideation. In the evenings he would be over-active, mischievous, tease the other patients, interfere with their care, become disruptive, angry and, at times, physically aggressive if the staff tried to intervene. A diagnosis of bipolar disorder with ultradian cycling was made. Over a period of 11 months, he received lithium (750–900 mg hs), valproic acid (1000–1250 mg hs), together with either chlorpromazine (up to 800 mg/day) or olanzapine 15 mg/day with minimal benefit. During this time, for a 4-month period, paroxetine was added to treat his suicidal ideation following a suicide attempt but this increased his disruptive behavior and was discontinued. After being in hospital for 23 months and manifesting an ultradian bipolar rhythm for 14 months he was started on topiramate in a dose of 25 mg bid as an adjunct to lithium, valproic acid and loxapine. Topiramate was progressively increased over a 5-week period to 100 mg bid. On this dose, within a week, improvement in the diurnal mood variation was apparent. Over the ensuing 8 months instead of frequent outbursts of anger or disruptive behavior, only eight incidents were noted. He was discharged 3 months later without incident and has remained stable in the community with regular follow-up for 25 months on topiramate 100 mg bid, lithium (750–900 mg hs), valproic acid (1000–1250 mg/day), loxapine 25 mg am and hs and benztropine 1 mg am and hs. 3. Discussion The psychotic symptoms experienced by the patient were mood congruent with his depressive state and lifted with his diurnal change to a manic mood. Delusions were not present in the absence of prominent mood symptoms. These findings point to a diagnosis of bipolar disorder with psychotic features rather than a schizoaffective disorder. Improvement with adjunctive topiramate has been described in rapid cycling bipolar patients with psychotic symptoms [2] or patients with schizoaffective disorder [7] but follow-up has been short. Antidepressants may induce or accelerate rapid cycling [1] so that it is possible that antidepressants triggered the ultra-
281
dian rhythm and simply stopping antidepressants led to improvement. However, onset of ultradian cycling occurred 7 months after venlafaxine was discontinued and was present for 8 months before paroxetine was started. Improvement with topiramate occurred 6–7 weeks after paroxetine was discontinued so that it is possible that paroxetine enhanced mood congruent psychopathology although it did not induce ultradian cycling. Though a spontaneous remission cannot be discounted, this is unlikely given the chronicity of the condition, poor response to previous treatments, temporal association of response with the addition of topiramate and improvement extending to 3 years in a patient requiring repeated admissions in the past. McElroy et al. [8] included patients with ultradian cycling in their study but the effect of topiramate in this subgroup was not specified. Aside from the latter paper, published data on topiramate in ultradian cycling bipolar patients is lacking. The dose of topiramate used and time of onset of improvement in our patient is similar to that described by others [5,8] in the treatment of rapid cycling bipolar disorders. The present case report suggests that in refractory cases with ultradian rapid cycling a trial with topiramate in increasing doses up to 200 mg/day may be of therapeutic benefit.
References [1]
Barrios C, Chaudhry TA, Goodnick PJ. Rapid cycling bipolar disorder. Expert Opin Pharmacother 2001;2:1963–73. [2] Chengappa R, Rathore D, Levine J, Atzert R, Solai L, Parepally H, et al. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord 1999;1:42–53. [3] Evins AE. Efficacy of newer anticonvulsant medications in bipolar spectrum mood disorders. J Clin Psychiatr 2003;64(S8):9–14. [4] Hussain MZ. Treatment of bipolar depression with topiramate. Eur Neuropsychopharmacol 1999;9(Suppl. 5):S222. [5] Kusumakar V, Yatham L, Kutcher S, O’Donovan C. Preliminary, open-label study of topiramate in rapid cycling bipolar women. Eur Neuropsychopharmacol 1999;9(Suppl. 5):S357. [6] Letmaier M, Schreinzer D, Wolf R, Kasper S. Topiramate as a mood stabilizer. Intern Clin Psychopharmacol 2001;16:295–8. [7] Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Dis 1998;50:245–51. [8] McElroy SL, Suppes T, Keck PE, Frye MA, Denicoff KD, Altshuler LL, et al. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatr 2000;47:1025–33. [9] McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Bipolar Disord 2002;4:207–13. [10] Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, Garcia-Parés G, Rodriguez A, et al. Use of topiramate in treatment-resistant bipolar spectrum disorders. J Clin Psychopharmacol 2002;22:431–5.