Bipolar Switching after Carbamazepine Withdrawal

• Introduction
• Case Report
• Discussion
• References

Introduction

Anticonvulsants such as the dibenzazepine derivative carbamazepine (CBZ) are effective alternatives to lithium in phase prophylaxis of bipolar disorder, particularly in the elderly [1], and in case of medical comorbidity [5]. It is well established that lithium withdrawal may precipitate recurrence of manic symptoms in bipolar patients [2]. However, rebound-affective episodes in such patients upon discontinuation of CBZ have not been recognized till to date. Here we describe a case of mania induced in a bipolar depressive patient following cessation of long-term CBZ treatment.

Case Report

Mr. K is a 74-year-old Caucasian man with a more than 20-year history of bipolar I disorder and various psychiatric hospitalizations in the past, predominantly due to depressive episodes. The only certain manic episode during the course of Mr. K's illness was 17 years ago ([Fig. 1]). He had been continuously treated with CBZ for a period of over five years. He currently required intensive inpatient treatment over a 5-month period due to a severe and treatment refractory Major Depressive Episode, diagnosed according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) with depressed mood, anhedonia, loss of energy and goal-directed activity, psychomotor retardation, and an overpowering feeling of emptiness. Ruminating thoughts bordering to delusions of impoverishment were present almost constantly. During the treatment course, he had received high-dose treatment with sertraline, mirtazapine, venlafaxine, and clomipramine (including thyroid hormone augmentation). Moreover, a total of five sleep deprivation treatments had failed to provide enduring response. He was then designated for electroconvulsive therapy (ECT). His concurrent medications at that time were 175 mg/d of clomipramine, 75 m/d of T3, 600 mg/d of CBZ, and 0.5 mg/d of lorazepam. Prior to ECT, clomipramine and T3 were discontinued and lorazepam was tapered off with no effect on the patient's psychopathology during an observation period of ten days. After one additional week, in preparation for the first ECT treatment, CBZ was discontinued over a tapering period of four days. The CBZ plasma level prior to discontinuation was well within therapeutic limits (6.9 mg/l). Thirty-six hours after discontinuation of the last dose, Mr. K.'s mood became elevated and irritable. He exhibited hyperactivity and reduced sleep as well as a verbose, loud, and pressured speech. Within the following 12 hours he completed DSM-IV criteria of a manic episode in further displaying ideas of grandiosity, lack of insight, and distractibility. Thinking showed loose associations and at times incoherence. He was started on olanzapine up to 10 mg/d, and due to severe psychomotor agitation, on perazine up to 150 mg/d. CBZ was not reinstated because of the severe depression that in retrospect paralleled the last five months of its application. Valproate was not applied due to a moderate but persistent elevation of liver enzymes. Instead, lamotrigine was given and titrated to 100 mg/d over four weeks. Symptoms completely remitted within three weeks and Mr. K. remained stable for six additional weeks until discharge under a combination therapy of olanzapine 10 mg/d and lamotrigine 100 mg/d.

Discussion

In this case report, the clear-cut temporal relationship between discontinuation of CBZ and the emergence of manic symptoms following a prolonged and severe depressive episode strongly suggests a causal connection. Moreover, based on the absence of any disturbance of consciousness and cognition and a negative laboratory work-up, a delirium was ruled out. In addition, our patient had no significant medical comorbidity and by the time symptoms developed, there was no condition that might have caused a delirium.

Of interest, two similar cases have been published with rebound mania following sudden CBZ cessation in patients with no previous psychiatric history. A 30-year-old woman was treated with CBZ for complex partial seizures [6], and in a 59-year-old man, the indication was neuropathic pain [3]. To our knowledge, however, emergence of mania in a bipolar patient following CBZ cessation has not yet been reported. In a case series, Macritichie et al. [4] found that among six bipolar patients none had developed manic symptoms when assessed three months after sudden discontinuation of CBZ. The authors speculated on a possible subgroup of patients with a predisposition to suffer recurrence upon withdrawal of prophylaxis that may have been under-represented in their case series. It is conceivable that such vulnerability exists and that old age, as in our patient, may represent a risk factor.

Taken together, our case should heighten the clinician's awareness of a possible CBZ withdrawal syndrome with rebound mania in bipolar disorder. As long as further data are not available, a slow tapering regimen is advisable, particularly in elderly patients.

References

• 1 Akiskal HS, Fuller MA, Hirschfeld RM, Keck Jr PE, Ketter TA, Weisler RH. Reassessing carbamazepine in the treatment of bipolar patients: clinical implications of new data.  CNS Spectr. 2005;  10 ((6 Suppl 5)) 1-13
  PubMedSearch in Google Scholar
• 2 Cavanagh J, Smyth R, Goodwin GM. Relapse into mania or depression following lithium discontinuation: a 7-year follow-up.  Acta Psychiatr Scand. 2004;  109 91-95
  CrossrefPubMedSearch in Google Scholar
• 3 Jess GE, Smith DJ, MacKenzie C, Crawford C. Carbamazepine and rebound mania.  Am J Psychiatry. 2004;  161 2132-2133
  PubMedSearch in Google Scholar
• 4 Macritichie KAN, Hunt NJ. Does “rebound mania” occur after stopping carbamazepine? A pilot study.  J Psychopharmacol. 2000;  14 266-268
  PubMedSearch in Google Scholar
• 5 Mouaffak F, Gourevitch R, Baup N, Loo H, Olie JP. Interrelations between lithium therapy, auto-immune thyroiditis and TSH. A case report.  Pharmacopsychiatry. 2006;  39 77-78
  Thieme ConnectPubMedSearch in Google Scholar
• 6 Scull D, Trimble MR. Mania precipitated by carbamazepine withdrawal.  Br J Psychiatry. 1995;  167 698
  PubMedSearch in Google Scholar

Correspondence

C. Lange-Asschenfeldt

Department of Psychiatry and Psychotherapy

Division of Geriatric Psychiatry

Heinrich Heine University

Bergische Landstr. 2

40629 Düsseldorf

Phone: + 49/211/922 42 15

Fax: + 49/211/922 42 13

Email: christian.lange-asschenfeldt@lvr.de

References

• 1 Akiskal HS, Fuller MA, Hirschfeld RM, Keck Jr PE, Ketter TA, Weisler RH. Reassessing carbamazepine in the treatment of bipolar patients: clinical implications of new data.  CNS Spectr. 2005;  10 ((6 Suppl 5)) 1-13
  PubMedSearch in Google Scholar
• 2 Cavanagh J, Smyth R, Goodwin GM. Relapse into mania or depression following lithium discontinuation: a 7-year follow-up.  Acta Psychiatr Scand. 2004;  109 91-95
  CrossrefPubMedSearch in Google Scholar
• 3 Jess GE, Smith DJ, MacKenzie C, Crawford C. Carbamazepine and rebound mania.  Am J Psychiatry. 2004;  161 2132-2133
  PubMedSearch in Google Scholar
• 4 Macritichie KAN, Hunt NJ. Does “rebound mania” occur after stopping carbamazepine? A pilot study.  J Psychopharmacol. 2000;  14 266-268
  PubMedSearch in Google Scholar
• 5 Mouaffak F, Gourevitch R, Baup N, Loo H, Olie JP. Interrelations between lithium therapy, auto-immune thyroiditis and TSH. A case report.  Pharmacopsychiatry. 2006;  39 77-78
  Thieme ConnectPubMedSearch in Google Scholar
• 6 Scull D, Trimble MR. Mania precipitated by carbamazepine withdrawal.  Br J Psychiatry. 1995;  167 698
  PubMedSearch in Google Scholar

Correspondence

C. Lange-Asschenfeldt

Department of Psychiatry and Psychotherapy

Division of Geriatric Psychiatry

Heinrich Heine University

Bergische Landstr. 2

40629 Düsseldorf

Phone: + 49/211/922 42 15

Fax: + 49/211/922 42 13

Email: christian.lange-asschenfeldt@lvr.de