Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective study on long-term prophlyactic effectiveness

Twenty-two patients affected by bipolar or schizoaffective disorder, in whom carbamazepine was added to lithium after recurrence when on maintenance with lithium alone, were followed up prospectively for 2 to 13 years. The number of episodes, hospitalizations, and cumulative affective morbidity was markedly reduced after carbamazepine augmentation. Seventeen patients presented a better course during combined treatment than during lithium alone, and of these 15 had no further recurrences. Four patients did not appear to improve after carbamazepine augmentation, whereas one featured reemergence of affective episodes after having derived satisfactory benefit from combination for 7 years (delayed tolerance). Carbamazepine augmentation was associated with a reduction of lithium doses in some patients, including a subgroup who had not tolerated lithium at usual therapeutic levels. Carbamazepine significantly reduced serum thyrotropin concentrations, which were abnormally high in approximately one half of patients when on lithium alone. Total serum thyroxine concentrations were also decreased after carbamazepine augmentation, but free thyroid hormone concentrations did not change. Other significant carbamazepine-induced changes in laboratory tests included increases in total cholesterol concentrations and decreases in white blood cell counts.     

Hemodialysis Treatment of Monomorphic Ventricular Tachycardia Associated with Chronic Lithium Toxicity

Introduction

A patient with chronic lithium toxicity developed a life-threatening ventricular arrhythmia that resolved during removal of lithium by hemodialysis. Chronic lithium toxicity commonly results from diminished elimination and can produce neurotoxicity. Cardiovascular complications have been reported and generally affect the sinoatrial node and produce bradyarrhythmias. The majority of these arrhythmias require no emergent intervention. Ventricular arrhythmias associated with lithium toxicity are occasionally mentioned in the literature, but actual cases are rarely reported.

Case Report

A 74-year-old man was brought into the emergency department with a 3-day history of progressive encephalopathy, tremor, and weakness. The lithium level was elevated at 2.2 mmol/L, with a normal serum potassium. Electrocardiography revealed nonsustained monomorphic ventricular tachycardia (120–130 beats/min) lasting up to 1 min, alternating with sinus bradycardia and wandering atrial pacemaker. Episodes of monomorphic ventricular tachycardia recurred >100 times. The patient required a norepinephrine infusion for hypotension. Emergent hemodialysis was initiated to remove lithium and to treat the monomorphic ventricular tachycardia, which was felt to be secondary to lithium toxicity. Episodes of monomorphic ventricular tachycardia abated as hemodialysis progressed. The episodes resolved completely within 4 h of initiating hemodialysis. The patient was discharged home in sinus rhythm on day 5. Lithium was not reinstated.

Conclusion

Monomorphic ventricular tachycardia associated with chronic lithium toxicity is exceptionally rare. Hemodialysis is a treatment option.     

Torsade de pointes: a mechanism for sudden death associated with neuroleptic drug therapy?

An elderly institutionalized woman developed the ventricular arrhythmia torsade de pointes while receiving lithium and thioridazine, 800 mg daily. On hospital admission following a single syncopal episode the electrocardiogram showed sinus bradycardia with first degree AV block, markedly prolonged QT interval, and prominent U waves. Following discontinuation of thioridazine and lithium, episodes of recurrent torsade de pointes gradually subsided. Seven days later the electrocardiogram showed normal sinus rhythm with PR interval of 0.20 seconds and minimal U waves, and the arrhythmia has not recurred.     

Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A retrospective naturalistic study

In bipolar disorder the discontinuation of lithium prophylaxis is associated with early episode precipitation. Is this ;rebound' phenomenon peculiar to lithium? This naturalistic retrospective case note review investigated the frequency of immediate recurrence after discontinuation of any prophylactic treatment. Bipolar patients who stopped at least one medication after at least 6 months of remission were studied. A total of 310 case notes were examined in a systematic search. A total of 53 cases of discontinuation in 48 subjects were found. Discontinued medications included lithium, valproate, carbamazepine, typical and atypical antipsychotics and antidepressants. Recurrence occurred within 3 months of medication withdrawal in 39 cases (74%). Over half of the discontinuation episodes involved lithium: recurrence occurred in 86% of these cases. In the groups stopping other prophylactic agents, a majority of subjects suffered recurrence: anticonvulsants (89%), antipsychotics (64%) and antidepressants (58%). However, these groups were small and the clarity of the data was undermined by the simultaneous withdrawal of other agents. Manic and hypomanic episodes were the most common form of recurrences. Depressive episodes occurred proportionately most frequently following antidepressant withdrawal. More than half of recurrences required hospital admission. This study provides preliminary naturalistic evidence that early episode recurrence in bipolar disorder is not peculiar to lithium withdrawal but may occur following withdrawal of medication from all classes recommended in prophylaxis. These findings, if replicated, have important implications for clinical practice and for research.     

Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.     

Sleep evaluation in the symptomatic episode of recurrent hypersomnia

Recurrent hypersomnia (RH) is a rare disorder characterized by episodes of hypersomnia, variously accompanied by behavioural and cognitive disturbances, compulsive eating behaviour and hypersexuality. Electrophysiologic evaluation of the sleep during symptomatic and asymptomatic periods of RH distinguishes RH from other primary sleep or mental disorders. Unique polysomnographic findings during the hypersomniac attack lasting 96 hours in a 16-year-old boy affected with primary RH are presented in this paper.     

Evaluation of a new lithium dosage-prediction technique

The accuracy of a lithium dosage prediction technique was studied retrospectively. The dosage-prediction technique evaluated is based on lithium body clearance. The medical records of 71 psychiatric patients (30 men, 41 women) were reviewed. Age, sex, height, weight, serum creatinine, and one-compartment intravenous dosage equations were used. The lithium dose that would produce steady-state concentrations equal to those actually attained clinically was calculated. Forty-five (64%) of the predictions were within one capsule/day of the actual dose. There were 42 episodes (59%) of underprediction and 10(14%) of overprediction by one or more capsules per day. Underprediction occurred significantly more often in women than in men (31/41 versus 11/30). Predictions differed from actual doses by three or more capsules per day in 10 cases, nine of which were underpredictions. These patients did not differ significantly from the rest of the study group in age, sex, weight, serum creatinine, creatinine clearance, concurrent medical problems, or other medications. This lithium dosage prediction technique may be reliable, rapid, and inexpensive, but further refinement and prospective evaluation are necessary.     

Long-term outcome of lithium prophylaxis in patients initially classified as complete responders

The long-term outcome of lithium prophylaxis was explored in 43 bipolar and 36 unipolar patients who had been classified as complete responders after the first 2 years of treatment. These patients were followed up prospectively for a further period of 5 years (treatment period II), during which their psychopathological state was assessed monthly or bimonthly. Forty-nine patients completed treatment period II, 2 died during this period, 7 did not attend the unit anymore and could not be traced, and 21 definitively interrupted lithium treatment before the end of the period. In 18 cases the decision to stop lithium was taken by the patient. Twenty-five patients relapsed during the treatment period II. Four relapsers had three or more episodes concentrated during the last 2 years of treatment. These results suggest that the predictive value of an initial favourable response to lithium should not be overrated, and that the impact of the drug on the long-term course of major affective disorders in ordinary clinical conditions might be less dramatic than currently believed.     

Clarithromycin-induced hypersomnia in children

Two cases of hypersomnia in children caused by therapeutic doses of oral clarithromycin are presented. Clarithromycin-induced hypersomnia in children has not been reported before. A 4-year-old girl and 13-year-old boy received clarithromycin as monotherapy. The girl fell into a deep sleep after every dose of the antibiotic. The boy reported daytime sleepiness and prolongation of night-time sleep during the antibiotic therapy. In both cases the hypersomnia receded after cessation of clarithromycin therapy. The onset of hypersomnia after clarithromycin intake, its remission once the drug was stopped, and the absence of other possible causative factors favored the diagnosis of clarithromycin-induced hypersomnia, further supported by the scores on Naranjo's Adverse Drug Reaction Probability Scale in both cases. Clinicians evaluating children receiving clarithromycin and exhibiting suddenly changed behavior should keep in mind that the antibiotic can produce uncommon adverse reactions.     

Quetiapine. A me-too neuroleptic; no panacea

Quetiapine, a so-called atypical neuroleptic, is authorised in the European Union for use in the standard indications of neuroleptics. However, it is the only neuroleptic licensed for the treatment and prevention of depressive episodes in patients with bipolar disorder, and as add-on therapy for depressive episodes inadequately improved by an antidepressant. In patients with schizophrenia, the authors of two meta-analyses, one including 12 trials (3443 patients) and the other 21 trials (4101 patients), concluded that quetiapine was not clearly more effective than other conventional or atypical neuroleptics. In bipolar patients with manic episodes, the results of two trials suggest that quetiapine monotherapy is not more effective than haloperidol or lithium. Two placebo-controlled trials of add-on quetiapine therapy in patients receiving a mood stabiliser (lithium or divalproate sodium) yielded conflicting results. In bipolar patients with a depressive episode, the only available trial, versus placebo and versus paroxetine in 740 patients, failed to provide conclusive evidence. In two trials with controversial designs, in which quetiapine was added to a mood stabiliser in order to prevent new depressive or manic episodes in bipolar patients, quetiapine appeared to be more effective than placebo: about 15% to 20% more patients were stabilised on quetiapine than on placebo. There are no trials to show whether quetiapine is more effective in preventing manic episodes than a neuroleptic. In a trial including 1226 patients in whom quetiapine was effective during a first depressive or manic episode, quetiapine appeared to be more effective than lithium in preventing a depressive episode (relapse rate 8.9% versus 13.5%) but not a manic episode. These comparisons may be biased, however. Two placebo-controlled trials assessed quetiapine add-on therapy in patients in whom an antidepressant was inadequately effective. The conflicting results obtained in these two trials rule out drawing firm conclusions as to the efficacy of quetiapine. Overall, quetiapine has the adverse effect profile common to atypical neuroleptics. However, hypercholesterolaemia is more frequent than with risperidone, and both clinical trials and post-marketing data have shown that quetiapine carries a risk of hypothyroidism. Animal studies suggested a risk of cataracts, but this adverse effect has not yet been confirmed in humans. The risk of sudden cardiovascular death appears similar to that reported with other neuroleptics. A retrospective survey suggests that the consequences of acute overdose are more severe with quetiapine than with other neuroleptics. Quetiapine is metabolised by cytochrome P450 isoenzyme CYP3A4, creating a high risk of pharmacokinetic interactions. In practice, quetiapine has not been shown to provide a therapeutic advantage over other treatments, although additional trials in the prevention of depressive episodes are warranted in selected patients.     

Hypothalamic-pituitary-adrenal axis dysregulation in depersonalization disorder.

BACKGROUND: The purpose of this preliminary study was to investigate HPA axis function in dissociation. METHODS: Nine subjects with DSM-IV depersonalization disorder (DPD), without lifetime Posttraumatic Stress Disorder (PTSD) or current major depression, were compared to nine healthy comparison (HC) subjects of comparable age and gender. RESULTS: DPD subjects demonstrated significant hyposuppression to low-dose dexamethasone administration and significantly elevated morning plasma cortisol levels when covaried for depression scores, but no difference in 24-hour urinary cortisol excretion. Dissociation scores powerfully predicted suppression whereas depression scores did not contribute to the prediction. CONCLUSIONS: Primary dissociative conditions, such as depersonalization disorder, may be associated with a pattern of HPA axis dysregulation that differs from PTSD and merits further study.     

Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.     

Lithium toxicity after switch from fosinopril to lisinopril

There is a small body of literature on the interactions between lithium and angiotensin-converting enzyme inhibitors (ACEIs), but little data documenting the differences between these agents in their impact on serum lithium levels. We present the case of a 46-year-old male who sustained a five-fold increase in his serum lithium level after switching from fosinopril to lisinopril, with a peak serum lithium level of 3.4 meq/l. There was also an increase in serum creatinine from 1.1 on fosinopril to 1.4 after switching to lisinopril. The patient was hospitalized, and intravenously hydrated with 0.5 normal saline, with a reduction of the serum lithium level to 0.7 meq/l by 72 h after admission. The hospital course was marked by two episodes of bradycardia, but was otherwise uneventful, and the patient was discharged without any neurological sequelae. This case demonstrates that ACEIs may have differential effects on renal function, and the potential for significant alterations in lithium clearance that may not be clinically evident for several weeks. Lithium-treated patients who have a change in ACEI, especially those who are older or have below average renal function, must have diligent monitoring for the first 4-6 weeks after switching to detect potentially serious changes in serum lithium levels.     

Are serum lithium levels related to the polarity of recurrence in bipolar disorders? Evidence from a multicenter trial

The primary objective is to test whether the polarity of recurrence (depressive vs manic or mixed), is related to lithium levels. A total of 86 euthymic bipolar patients (DSM-IV) on lithium monotherapy were prospectively followed up for 2.5 years with regular monitoring of both lithium levels and psychopathology. The last lithium level during the free interval that preceded worsening of affective symptoms was related to polarity of symptoms. To account for effects of major confounders, results were corroborated by multivariate analysis. An intervention for manic or mixed symptomatology was required in 27 patients, whereas 22 patients were treated for depressive symptoms. Average lithium levels preceding reappearance of manic or mixed symptomatology were lower than levels preceding reappearance of depressive symptoms (0.53+/-0.13 vs 0.66+/-0.21 mmol/l, P=0.01). This result was confirmed using logistic regression analyses with type of index episode, diagnostic subtype and residual manic and depressive symptoms as covariates. The results indicate that manic or mixed recurrences might rather occur at lower lithium levels, whereas the depressive pole prevails in the higher range. If substantiated by further studies, this finding might indicate that higher lithium levels are needed to prevent manic episodes than to prevent depressive episodes.     

Olanzapine: a review of its use in the management of bipolar I disorder

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder, and for maintenance therapy to prevent recurrence in responders.Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics, such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders, and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated, and although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms (EPS). Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.     

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

We investigated three polymorphisms in the NMDAreceptor 2B subunit gene (GRIN2B) as a candidate gene for lithium response involved in glutamatergic neurotransmission. One hundred five bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as excellent – no affective episodes during lithium treatment; partial – 50% reduction in the episode index; or no response – less than 50% reduction, no change or worsening in the episode index. Genotypes for the -200G/T, 366C/G and rs890G/T GRIN2B polymorphisms were established using the PCR-RFLP method. Genotype distributions were in Hardy-Weinberg equilibrium for all three polymorphisms. No association was found between the three polymorphisms studied and the treatment response to lithium. The authors conclude that polymorphisms of the GRIN2B gene did not show an association with the treatment response to lithium in bipolar patients.     

Effect of chronic lithium and withdrawal from chronic lithium on presynaptic dopamine function in the rat

Bipolar affective disorders can be successfully treated with long-term use of the mood stabilizer lithium. However, discontinuation of lithium treatment is followed by a high incidence of manic episodes. In the present study, we attempted to identify neurobiological changes that might mediate this rebound mania. In vivo microdialysis in the anaesthetized rat and in situ hybridization histochemistry were used to study the effect of chronic lithium treatment and withdrawal from chronic lithium treatment on presynaptic dopamine (DA) function. Rats were maintained for 28 days on a lithium diet or control diet. The lithium-withdrawn treatment group had their lithium diet substituted for control diet from day 25 of the treatment period. Microdialysis probes were implanted in the shell of the nucleus accumbens and both basal extracellular DA levels and DA levels in the presence of the DA uptake inhibitor bupropion (1 microM) were collected. Basal DA levels did not differ between any of the treatment groups. However, during local perfusion of bupropion, the increase in DA was significantly attenuated in the lithium-treated animals compared to controls or lithium-withdrawn animals. In situ hybridization of DA transporter mRNA in the ventral tegmental area revealed no difference in the abundance of this mRNA in any of the groups. These data suggest that there is impaired DA release in rats during chronic lithium treatment, but DA release returns to normal levels on withdrawal from lithium treatment, and is therefore unlikely to underlie the rebound mania associated with lithium withdrawal.     

The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder

OBJECTIVE: To present an economic model and cost-effectiveness estimates for lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes from the pivotal lamotrigine trials. The main comparator treatments in the pivotal trials were lithium and .no maintenance. (acute-only) treatment. A comparison with olanzapine was included as an indirect analysis following publication of data during the course of our research. METHODS: A Markov model was built around the 3 health states of euthymia, mania, and depression. The base-case model simulates a cohort of 1,000 patients with BD-I who have recently stabilized after resolution of a bipolar mania episode. The cohort was modeled for a period of 18 months. Resource-use estimates were derived from best available published data, treatment guidelines, a physician survey, and published unit cost data. Outputs were measured in terms of costs per acute mood episode avoided, costs per euthymic day gained, and costs per quality-adjusted life-years (QALYs). Direct health care payer costs are used in the analyses. RESULTS: The base-case model for patients with a recent manic episode indicated that lamotrigine is the most effective treatment for avoiding both acute depression episodes and all types of acute episodes (depression and mania). It is also the most effective treatment in terms of number of euthymic days achieved (309 days per patient per year). Olanzapine is most effective for avoiding acute mania episodes. Total direct costs of treatment are lowest for the lithium treatment arm (Dollars 8,710 per patient for the 18-month period). All maintenance therapies were cost effective compared with the no-maintenance (acute-only treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided compared with lithium. A QALY analysis indicated that lamotrigine is cost effective in patients with a recent manic episode at Dollars 26,000 per QALY. The base-case model indicated that lamotrigine dominates olanzapine, (that is, lamotrigine costs less and is more effective than olanzapine) in patients with a recent manic episode. In a sensitivity analysis using outcomes from the pivotal trial of recently depressed patients, lamotrigine, in comparison with lithium, was not shown to be as cost effective as in the recently manic patients, but it was still cost effective compared with no maintenance treatment. CONCLUSIONS: For a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that prevention of mood episodes with lithium and lamotrigine is cost effective in patients with a recent manic, mixed, or hypomanic episode. The conclusions with respect to the indirect comparison with olanzapine should be validated if and when direct trial data become available. Cost-effectiveness of maintenance treatments for patients with BD-I (recently depressed as well as recently manic) are likely to improve in models with a broader costing perspective and that take a longer time frame. Further research into the outcome implications of health-related quality of life and other BD subgroups are recommended.     

Spotlight on olanzapine in bipolar I disorder

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder and for maintenance therapy to prevent recurrence in responders. Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated and, although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms. Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.     

Use of a combination of class III and class Ic antiarrhythmic agents in patients with electrical storm

STUDY OBJECTIVE: To determine the efficacy of the combination of class III and class Ic antiarrhythmic agents in suppressing an electrical storm in patients with and without a transvenous implantable cardioverter-defibrillator (ICD). DESIGN: Retrospective medical record review. SETTING: Arrhythmia service of an academic medical center in Zerifin, Israel. PATIENTS: Ten patients who experienced an electrical storm that was not effectively treated with amiodarone or sotalol monotherapy between December 15, 1999, and June 13, 2007. MEASUREMENTS AND MAIN RESULTS: The medical records of 152 patients who received an ICD during the study period were reviewed. Twenty patients experienced an electrical storm, an arrhythmia defined as more than two episodes of hemodynamically unstable ventricular tachycardia during a 24- hour period. Ten of the 20 patients responded favorably to amiodarone or sotalol monotherapy (class III antiarrhythmics), but in 10 patients, the combination of a class III and a class Ic antiarrhythmic agent was needed to effectively eliminate the electrical storm. Of the 10 patients who required both agents, two (20%) developed an electrical storm before implantation of their ICD. In another patient who had ongoing ischemia, ventricular tachycardia recurred, but the drug combination decreased the number of ventricular arrhythmia episodes. One patient with dilated cardiomyopathy had one recurrence of ventricular tachycardia, which was terminated with antitachycardia pacing. Three patients died during a mean +/- SD follow-up of 8.7 +/- 9.9 months. CONCLUSION: Electrical storm can be acutely treated with the combination of a class III and a class Ic antiarrhythmic agent when a class III agent alone is insufficient and when radiofrequency ablation is not an option. Patients receiving this drug combination can be discharged from the hospital only if they have an ICD.